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	<title>Collection : COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv</title>
	<link>https://biorxiv.org</link>
	<description>
	This feed contains articles for Collection "COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv"
	</description>

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		</rdf:Seq>
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	<prism:publicationName>bioRxiv</prism:publicationName>
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	<title>bioRxiv/medRxiv</title>
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	<link>https://biorxiv.org</link>
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	<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.05.08.723928v1?rss=1">
<title>
<![CDATA[
AI-discovered protein fragments as generalizable regulators of biomolecular condensates 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.05.08.723928v1?rss=1"
</link>
<dc:creator>Savinov, A.</dc:creator>
<dc:creator>Sadasivan, J.</dc:creator>
<dc:creator>White, K. J.</dc:creator>
<dc:creator>Rubien, J. D.</dc:creator>
<dc:creator>Li, G.-W.</dc:creator>
<dc:creator>Case, L. B.</dc:creator>
<dc:date>2026-05-12</dc:date>
<dc:identifier>doi:10.64898/2026.05.08.723928</dc:identifier>
<dc:title><![CDATA[AI-discovered protein fragments as generalizable regulators of biomolecular condensates]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-12</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Biomolecular condensates are a major driver of cellular organization; however, we lack a predictable and systematic approach to modulate the multivalent interactions underlying their formation. Here, we demonstrate that the AI-driven FragFold method enables robust and generalizable design of protein fragments to control biomolecular condensate formation. We apply this approach across diverse proteins: G3BP1, SARS-CoV-2 nucleocapsid, TDP-43, and focal adhesion kinase (FAK). Computationally screening 2,235 fragments, we selected 18 candidates for further investigation. Overall, we attain a 50% success rate (9/18 designs) in discovering condensate-controlling protein fragments, experimentally testing just 3-5 candidates per protein. For each condensate-forming protein, the success rate is at least 40%. Furthermore, FragFold-predicted fragment binding modes align with their condensate-inhibitory or enhancing activities, revealing both known and newly identified interactions underlying condensate formation. In FAK, a condensate-inhibitory fragment uncovered a domain interaction required for phase separation, and mutational analysis validated its importance. Notably, this inhibitory fragment also suppresses FAK condensate formation in living mammalian cells. Together, these results establish AI-guided protein fragment discovery as a generalizable strategy to dissect and control the molecular interactions that govern biomolecular condensates.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.05.07.723385v1?rss=1">
<title>
<![CDATA[
Crude Fucus vesiculosus fucoidan demonstrates superior SARS-CoV-2 antiviral activity compared to its pure form: binding kinetics and functional studies 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.05.07.723385v1?rss=1"
</link>
<dc:creator>Dudek, A.</dc:creator>
<dc:creator>Janapatla, R. P.</dc:creator>
<dc:creator>Chen, C. L.</dc:creator>
<dc:creator>Chiu, C. H.</dc:creator>
<dc:date>2026-05-12</dc:date>
<dc:identifier>doi:10.64898/2026.05.07.723385</dc:identifier>
<dc:title><![CDATA[Crude Fucus vesiculosus fucoidan demonstrates superior SARS-CoV-2 antiviral activity compared to its pure form: binding kinetics and functional studies]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-12</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Fucoidans have been widely reported to show SARS-CoV-2 antiviral activity. In this study, we observed a striking difference in the inhibitory potency between two commercially available fucoidans: Fucus vesiculosus crude (Fvc) and pure (Fvp). SEC-MALS analysis revealed two molecular weight populations for Fvc (1098 kDa, 58.58 kDa) and one for Fvp (40.48 kDa). At micromolar concentrations of fucoidans, the binding affinities (KDs) of Fvc_1098 (223 nM) and Fvc_58 (4.27 M) for the amine-biotinylated SARS-CoV-2 receptor binding domain (RBD) were higher than that of Fvp (76.5 M). At nanomolar concentrations, binding was observed only to the Avi-tag-, but not amine-biotinylated RBDs, suggesting better accessibility of their binding sites. The association rates (kon) were faster for Fvc than for Fvp. Similarly, affinities of Fvc_1098 (23.4 nM) and Fvc_58 (4.48 M) for ACE2 were greater than that of Fvp (66.8 M), indicating that Fvc can bind directly to both RBD and ACE2. Fvc demonstrated enhanced inhibitory potency (IC50 = 58 g/mL) compared to Fvp (IC50 > 239 g/mL) in the pseudovirus entry assay and did not induce cytotoxicity in HEK293T cells. In conclusion, crude fucoidan with high fucose content and high molecular weight shows promising antiviral activity.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.05.07.723210v1?rss=1">
<title>
<![CDATA[
Temperature-Dependent Replication and Sensitivity to Innate Immunity of Human Coronavirus HKU1 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.05.07.723210v1?rss=1"
</link>
<dc:creator>Buchrieser, J.</dc:creator>
<dc:creator>Thuillier, E.</dc:creator>
<dc:creator>Postal, J.</dc:creator>
<dc:creator>Wileveau, A.</dc:creator>
<dc:creator>Guivel-Benhassine, F.</dc:creator>
<dc:creator>Staropoli, I.</dc:creator>
<dc:creator>Saunders, N.</dc:creator>
<dc:creator>Planas, D.</dc:creator>
<dc:creator>Sugrue, J.</dc:creator>
<dc:creator>Bondet, V.</dc:creator>
<dc:creator>Fernandez, I.</dc:creator>
<dc:creator>Bontems, F.</dc:creator>
<dc:creator>Porrot, F.</dc:creator>
<dc:creator>Petiot, C.</dc:creator>
<dc:creator>Prot, M.</dc:creator>
<dc:creator>Jungbauer-Groznica, M.</dc:creator>
<dc:creator>Arowas, L.</dc:creator>
<dc:creator>Michel, V.</dc:creator>
<dc:creator>Blanc, C.</dc:creator>
<dc:creator>Trouillet-Assant, S.</dc:creator>
<dc:creator>Bruel, T.</dc:creator>
<dc:creator>Rey, F. A.</dc:creator>
<dc:creator>Rameix-Welti, M.-A.</dc:creator>
<dc:creator>Casartelli, N.</dc:creator>
<dc:creator>Fontanet, A.</dc:creator>
<dc:creator>White, M.</dc:creator>
<dc:creator>Duffy, D.</dc:creator>
<dc:creator>Simon-Loriere, E.</dc:creator>
<dc:creator>Schwartz, O.</dc:creator>
<dc:date>2026-05-12</dc:date>
<dc:identifier>doi:10.64898/2026.05.07.723210</dc:identifier>
<dc:title><![CDATA[Temperature-Dependent Replication and Sensitivity to Innate Immunity of Human Coronavirus HKU1]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-12</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
The human coronavirus HKU1, causing common colds and occasionally severe illness, remains largely uncharacterized because it has not been successfully grown on immortalized cells. Here, we identified Caco2 cells overexpressing TMPRSS2, the HKU1 receptor, as being highly permissive to infection. HKU1 replicated efficiently, formed syncytia and released infectious progeny in these cells at 33{degrees}C, the temperature of the nasal cavity, but was attenuated at 37{degrees}C. Viral entry occurred similarly at both temperatures, but subsequent viral RNA synthesis was enhanced at 33{degrees}C. Released virions displayed higher stability at 33{degrees}C. In Caco2 and primary epithelial nasal cells, HKU1 was sensitive to interferons (IFN), but induction of IFN stimulated genes, such as IFN-Induced Transmembrane Proteins (IFITMs), was delayed at 33{degrees}C. Once expressed, IFITMs comparably inhibited HKU1 fusion at both temperatures. In contrast, SARS-CoV-2 robustly replicated at 37{degrees}C. Thus, cellular permissiveness, innate immunity and viral properties collectively explain why HKU1 replicates more efficiently at nasal temperature. Our results highlight temperature-sensitivity disparities between coronaviruses, likely associated to different pathogenic outcomes.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.05.07.26352639v1?rss=1">
<title>
<![CDATA[
SARS CoV 2 Associated Shifts in the Upper Respiratory Tract Mycobiome in Non Hospitalized Cases 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.05.07.26352639v1?rss=1"
</link>
<dc:creator>Tomar, S. S.</dc:creator>
<dc:creator>Khairnar, K.</dc:creator>
<dc:date>2026-05-10</dc:date>
<dc:identifier>doi:10.64898/2026.05.07.26352639</dc:identifier>
<dc:title><![CDATA[SARS CoV 2 Associated Shifts in the Upper Respiratory Tract Mycobiome in Non Hospitalized Cases]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-10</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
SARS{square}CoV{square}2 infection is associated with marked changes of the upper respiratory tract mycobiome. URT mycobiome Changes in non-hospitalized patients however, remains poorly defined. We performed shotgun metagenomic sequencing of 95 upper respiratory tract swab samples from 48 symptomatic SARS{square}CoV{square}2-positive individuals and 47 healthy controls from central India. Fungal diversity and community structure were compared using alpha- and beta-diversity analyses, while differential taxa were identified using prevalence-based testing and LEfSe. SARS{square}CoV{square}2-positive samples showed significantly higher fungal alpha diversity than controls, with increased Shannon diversity (p = 0.000319) and Simpson diversity (p = 0.017). Beta-diversity analysis showed significant separation between groups for both Bray-Curtis and Jaccard distances (PERMANOVA p = 0.001), with significant dispersion effects as well (PERMDISP p = 0.001). Differential analysis identified more SARS{square}CoV{square}2-enriched than control-enriched taxa, including Candida orthopsilosis, Malassezia furfur, M. sympodialis, M. globosa, Aspergillus niger, A. terreus, and A. nidulans. Aspergillus sydowii was the main control-enriched taxon. LEfSe and concordant multi-test analysis supported these findings, and sensitivity analysis confirmed robustness across thresholds. Certain SARS{square}CoV{square}2-enriched taxa were linked to confirmed or probable COVID{square}19-associated fungal infections, whereas no such pathogens were detected in controls. These findings indicate that SARS{square}CoV{square}2 infection is associated with URT mycobiome dysbiosis and enrichment of clinically relevant opportunistic fungi in community cases.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.05.07.26352649v1?rss=1">
<title>
<![CDATA[
Delayed humoral kinetics but stabilization of IgG responses in common variable immunodeficiency after SARS-CoV-2 mRNA booster vaccination 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.05.07.26352649v1?rss=1"
</link>
<dc:creator>Federico, L.</dc:creator>
<dc:creator>Loeken, R. O.</dc:creator>
<dc:creator>Quy, K. L.</dc:creator>
<dc:creator>Osen, J. R.</dc:creator>
<dc:creator>Chaban, V.</dc:creator>
<dc:creator>Nordoey, I.</dc:creator>
<dc:creator>Skarpengland, T.</dc:creator>
<dc:creator>Lundin, K. E.</dc:creator>
<dc:creator>Fjellgaard Joergensen, S.</dc:creator>
<dc:creator>Fraz, M. S. A.</dc:creator>
<dc:creator>Aukrust, P.</dc:creator>
<dc:creator>Lund, K. P.</dc:creator>
<dc:creator>Tran, T. T.</dc:creator>
<dc:creator>Nygaard Osnes, L. T.</dc:creator>
<dc:creator>Lund-Johansen, F.</dc:creator>
<dc:creator>Kared, H.</dc:creator>
<dc:creator>Fevang, B.</dc:creator>
<dc:creator>Munthe, L. A.</dc:creator>
<dc:date>2026-05-08</dc:date>
<dc:identifier>doi:10.64898/2026.05.07.26352649</dc:identifier>
<dc:title><![CDATA[Delayed humoral kinetics but stabilization of IgG responses in common variable immunodeficiency after SARS-CoV-2 mRNA booster vaccination]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-08</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
PurposePatients with common variable immunodeficiency (CVID) frequently exhibit impaired antibody responses to vaccination, yet the dynamics of humoral and cellular immunity following mRNA immunisation remain incompletely defined. This study aimed to characterise the temporal evolution of anti-SARS-CoV-2 antibody and T cell responses across successive vaccine doses in a well-characterised CVID cohort, and to identify key determinants of vaccine responsiveness in this population.

MethodsWe performed a longitudinal and cross-sectional analysis of serum and peripheral blood mononuclear cell (PBMC) samples collected from 88 CVID patients after two, three, or four doses of mRNA vaccine (Moderna/mRNA-1273 or Pfizer-BioNTech/BNT162b2). Anti-receptor-binding domain (RBD) IgG titers were quantified in relation to vaccine dose, time since last vaccination, and clinical characteristics. Vaccine-specific CD4+ and CD8+ T cell responses were assessed ex vivo using an activation-induced marker (AIM) assay by flow cytometry.

ResultsThe proportion of patients with detectable anti-RBD IgG increased from 35% after two doses to more than 80% after four doses. Boosting-dependent increases in IgG titers were observed exclusively in samples collected more than three months after the last dose, and antibody levels correlated positively with time since vaccination, consistent with delayed but progressive humoral kinetics that stabilised after the third dose. In contrast, spike-specific CD4+ and CD8+ T cell responses were rapidly induced and remained stable across all timepoints.

ConclusionVaccine-induced immunity in CVID is characterised by delayed humoral responses alongside preserved cellular immunity. Early post-vaccination serology may systematically underestimate vaccine responsiveness, and booster vaccination supports stabilisation of antibody responses in this population.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.05.06.26352506v1?rss=1">
<title>
<![CDATA[
Positive Registration Rate as a Key Determinant of COCOA Effectiveness: Empirical Evidence from Individual-Level Key-Match Data during the Sixth and Seventh COVID-19 Waves in Japan 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.05.06.26352506v1?rss=1"
</link>
<dc:creator>Nakagawa, S.</dc:creator>
<dc:creator>Kumagai, S.</dc:creator>
<dc:creator>Yamamoto, A.</dc:creator>
<dc:date>2026-05-08</dc:date>
<dc:identifier>doi:10.64898/2026.05.06.26352506</dc:identifier>
<dc:title><![CDATA[Positive Registration Rate as a Key Determinant of COCOA Effectiveness: Empirical Evidence from Individual-Level Key-Match Data during the Sixth and Seventh COVID-19 Waves in Japan]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-08</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundCOCOA, Japans Bluetooth-based COVID-19 contact tracing app, was widely regarded as ineffective due to persistently low key-match counts. However, this assessment may have conflated two distinct phenomena: (1) a structurally suppressed positive registration rate caused by administrative friction in the HER-SYS linkage, and (2) genuine epidemiological inefficacy.

ObjectiveTo empirically examine whether the correlation between individual COCOA key-match counts and regional COVID-19 case numbers depended on positive registration rate, using a unique longitudinal dataset from a single observer with a rigorously controlled behavioral pattern.

MethodsThe corresponding author (S.N.) recorded daily key-match counts from his personal iPhone from January 10 to October 8, 2022, encompassing the Sixth Wave (January 10-April 20, 2022) and Seventh Wave (July 9-September 2, 2022). Daily reported COVID-19 cases in Tokyo were obtained from publicly available NHK data. Pearson correlation coefficients were calculated for each wave period separately.

ResultsDuring the Sixth Wave, no meaningful correlation was observed between key-match counts and daily case numbers (r2 = 0.018, p = 0.059, n = 194). In contrast, during the Seventh Wave, a strong positive correlation emerged (r2 = 0.530, p < 0.001, n = 56). This correlation disappeared abruptly after September 12, 2022, coinciding with Japans revision of the mandatory full case reporting (Zenshu Todokedashi) policy, which substantially reduced positive registrations in COCOA.

ConclusionsCOCOAs utility as an individual infection risk indicator was critically dependent on positive registration rate rather than app installation rate. These findings provide the first real-world empirical evidence supporting the threshold effect predicted by prior simulation studies, and offer important lessons for the design of digital tools in future pandemic preparedness.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.05.08.26352596v1?rss=1">
<title>
<![CDATA[
Safety first: should the high tolerability of intramuscular anti-spike COVID-19 monoclonal antibody change our expectations of vaccine safety? 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.05.08.26352596v1?rss=1"
</link>
<dc:creator>Putrino, D.</dc:creator>
<dc:creator>Curtis, A.</dc:creator>
<dc:creator>Leston, M.</dc:creator>
<dc:creator>Yalcin, I.</dc:creator>
<dc:creator>Gerlach, R.</dc:creator>
<dc:creator>Elia, M.</dc:creator>
<dc:creator>Mina, M.</dc:creator>
<dc:date>2026-05-08</dc:date>
<dc:identifier>doi:10.64898/2026.05.08.26352596</dc:identifier>
<dc:title><![CDATA[Safety first: should the high tolerability of intramuscular anti-spike COVID-19 monoclonal antibody change our expectations of vaccine safety?]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-08</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
IntroductionPublic and regulatory scrutiny of immunization safety has intensified in recent years. The COVID-19 pandemic has been instrumental in this. The accelerated timeline of COVID-19 vaccine development combined with the amplification of resultant side effects have proven corrosive to confidence. Unsurprisingly, COVID-19 vaccine uptake has declined year-on-year. This conflicts with the threat that infection still presents: predictors and prognoses of post-acute complications remain uncertain. Restoring public trust in these technologies will require meaningful progress in the availability and accessibility of clinical safety and pharmacovigilance data.

MethodsExpanding upon recent comparisons of COVID-19 vaccine reactogenicity, we present a post-hoc safety analysis of adintrevimab, an intramuscular (IM) anti-SARS-CoV-2 spike recombinant investigational monoclonal antibody (mAb) for the pre-exposure and post-exposure prophylaxis of COVID-19, as assessed by the multi-center, double-blind, Phase 2/3 randomized placebo-controlled EVADE study (NCT04859517). Exploratory endpoints included the incidence of [&ge;]1 systemic symptoms within 7 days of study drug administration as well as symptom number, duration and severity. Safety reporting encompassed solicited and unsolicited treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), vital signs, and clinical laboratory assessments.

ResultsEVADE study participants (n=2582) were randomized between April 2021 - January 2022. Baseline characteristics were balanced across treatment groups. Within the 7 day post-dose period, 25/1241 (2.0%) of adintrevimab recipients and 12/1242 (1.0%) of placebo recipients reported at least one systematic TEAE. Multiple systemic TEAEs were less prevalent, with 0.3% and 0.1% reporting two systemic TEAEs, and 0.1% and 0.1% reporting three TEAEs in adintrevimab and placebo groups, respectively. The majority of TEAEs reported were mild to moderate in severity, primarily involving headache (0.4% adintrevimab, 0.8% placebo), fatigue (adintrevimab 0.4%, placebo 0.2%), and nausea/vomiting (adintrevimab 0.4%, placebo 0.1%). For those participants who experienced any TEAEs in the 7 day post-dose period, mean (+/-standard deviation) number of systemic symptoms was 1.2 (0.5) for adintrevimab and 1.3 (0.6) for placebo with symptoms consistently resolving within 3 days.

ConclusionsIncreased expectations for pharmaceutical safety data generation are to be welcomed, offering patients the information they need to appropriately weigh the benefits and risks of any novel therapeutic. These analysis results support the high tolerability of IM-administered adintrevimab, with reactogenicity data broadly comparable to placebo. While the co-administration of vaccines and monoclonal antibodies limit direct comparisons between historical safety reports, findings such as these demonstrate the potential clinical value of controlled head-to-head studies such as the anticipated LIBERTY trial.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.05.06.723356v1?rss=1">
<title>
<![CDATA[
The Effect of Vaccination on the Evolution of the SARS-CoV-2 B.1.351 Variant 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.05.06.723356v1?rss=1"
</link>
<dc:creator>Wang, Z.</dc:creator>
<dc:creator>Raeihle, M.</dc:creator>
<dc:creator>Braun-Gorman, S.</dc:creator>
<dc:creator>Leung, I.</dc:creator>
<dc:creator>Richards, C.</dc:creator>
<dc:creator>Gabbay, L.</dc:creator>
<dc:creator>Shamoon-Pour, M.</dc:creator>
<dc:date>2026-05-08</dc:date>
<dc:identifier>doi:10.64898/2026.05.06.723356</dc:identifier>
<dc:title><![CDATA[The Effect of Vaccination on the Evolution of the SARS-CoV-2 B.1.351 Variant]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-08</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Since the initial distribution of the SARS-CoV-19 vaccine, its widespread use has been hypothesized to act as a selective pressure that drives the COVID-19 virus to mutate. This study aims to investigate the correlation between global vaccination rates and the mutation rate of the SARS-CoV-2 Beta variant (B.1.351). From January to July 2021, nucleotide diversity increased in tandem with vaccination rates, demonstrating that the virus evolved more rapidly in response to selective pressure from mass vaccination. Statistical analysis revealed statistically significant positive correlations between both vaccination rates and vaccine doses administered with nucleotide diversity. Thus, our findings indicate a positive correlation between rising vaccination rates and nucleotide diversity, suggesting that increased vaccination coverage acted as a selective pressure that accelerated viral evolution of SARS CoV2.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.05.07.723425v1?rss=1">
<title>
<![CDATA[
Site-Specific Entry Factors Define Cellular Susceptibility to SARS-CoV-2 in Human Tissues 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.05.07.723425v1?rss=1"
</link>
<dc:creator>Vivas-Roca, M.</dc:creator>
<dc:creator>Mancebo-Perez, C.</dc:creator>
<dc:creator>Abdalfttah, M.</dc:creator>
<dc:creator>Balafkir, I.</dc:creator>
<dc:creator>Benitez-Martinez, A.</dc:creator>
<dc:creator>Montal, V.</dc:creator>
<dc:creator>Gonzalez, A.</dc:creator>
<dc:creator>Mota-Gomez, I.</dc:creator>
<dc:creator>Grau-Exposito, J.</dc:creator>
<dc:creator>Pieren, D. K.</dc:creator>
<dc:creator>Planas, B.</dc:creator>
<dc:creator>Rosado, J.</dc:creator>
<dc:creator>Semidey, M. E.</dc:creator>
<dc:creator>Landolfi, S.</dc:creator>
<dc:creator>Espin-Bassany, E.</dc:creator>
<dc:creator>Trilla, E.</dc:creator>
<dc:creator>Falco, V.</dc:creator>
<dc:creator>Curran, A.</dc:creator>
<dc:creator>Burgos, J.</dc:creator>
<dc:creator>Buzon, M. J.</dc:creator>
<dc:creator>Guallar, V.</dc:creator>
<dc:creator>Heyn, H.</dc:creator>
<dc:creator>Genesca, M.</dc:creator>
<dc:date>2026-05-08</dc:date>
<dc:identifier>doi:10.64898/2026.05.07.723425</dc:identifier>
<dc:title><![CDATA[Site-Specific Entry Factors Define Cellular Susceptibility to SARS-CoV-2 in Human Tissues]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-08</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
SARS-CoV-2 primarily infects the respiratory epithelium through entry factors ACE2 and TMPRSS2. However, alternative viral entry receptors and/or modulators of viral entry factors expression may contribute to infection in respiratory as well as non-respiratory tissues, including the kidneys and colon. Using single-cell analyses, we identified novel candidates for spike-mediated viral entry in epithelial cells from diverse fresh human tissues exposed to a labeled spike-pseudotyped virus. Systematic viral tracking revealed tissue-specific membrane receptors that contribute to viral entry, functionally validated in human tissues and partially predicted by molecular modeling. We found ADAM17 and IL1R1, together with canonical molecules, to significantly facilitate viral entry in the lung parenchyma, while entry into the renal cortex was less dependable on canonical factors, but strongly modulated by JAK1/2 engagement. These findings uncover distinct viral entry mechanisms across tissues and suggest novel organ-specific therapeutic targets for patients at risk.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.05.06.723221v1?rss=1">
<title>
<![CDATA[
Helminth-remodeled microbial indole-3-lactic acid drives AhR-dependent disease tolerance 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.05.06.723221v1?rss=1"
</link>
<dc:creator>Sun, R.</dc:creator>
<dc:creator>Liu, Y.</dc:creator>
<dc:creator>Wang, Y.</dc:creator>
<dc:creator>Xu, N.</dc:creator>
<dc:creator>Ma, X.</dc:creator>
<dc:creator>Lv, Q.</dc:creator>
<dc:creator>Zhao, X.</dc:creator>
<dc:creator>Vallee, I.</dc:creator>
<dc:creator>Boireau, P.</dc:creator>
<dc:creator>Wu, Z.</dc:creator>
<dc:creator>Liu, M.</dc:creator>
<dc:creator>Liu, X.</dc:creator>
<dc:creator>Jin, X.</dc:creator>
<dc:date>2026-05-08</dc:date>
<dc:identifier>doi:10.64898/2026.05.06.723221</dc:identifier>
<dc:title><![CDATA[Helminth-remodeled microbial indole-3-lactic acid drives AhR-dependent disease tolerance]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-08</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Helminths systemically suppress host immunity, yet whether they impose immune tolerance by rewiring host-associated microbial metabolism remains unclear. Here we show that Trichinella spiralis infection remodels intestinal tryptophan metabolism to generate an AhR-dependent regulatory immune state. T. spiralis infection enriched the commensal bacterium Ligilactobacillus murinus, which converted tryptophan into indole-3-lactic acid (ILA), a microbial metabolite that directly engaged the aryl hydrocarbon receptor. Antibiotic-mediated microbiota depletion abolished infection-induced ILA accumulation, AhR activation and Treg/Th17 rebalancing, whereas fecal microbiota transplantation from infected donors or supplementation with L. murinus or ILA restored these effects. Pharmacological blockade or genetic deletion of AhR eliminated the ability of T. spiralis, L. murinus and ILA to restrain LPS-induced cytokine-storm-like lung inflammation, establishing AhR as an essential host node in this circuit. Extending these findings to viral inflammatory disease, oral ILA improved survival and reduced pulmonary immunopathology in SARS-CoV-2-infected K18-hACE2 mice. Re-analysis of human COVID-19 metabolomic data further revealed reduced circulating ILA in severe disease. These findings define a helminth-remodeled microbial tryptophan metabolic pathway that promotes disease tolerance and identify the ILA-AhR axis as a candidate postbiotic strategy for limiting hyperinflammatory tissue injury.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.05.06.723370v1?rss=1">
<title>
<![CDATA[
vartracker: an end-to-end tool for pathogen longitudinal variant analysis and visualisation 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.05.06.723370v1?rss=1"
</link>
<dc:creator>Foster, C. S. P.</dc:creator>
<dc:creator>Rawlinson, W. D.</dc:creator>
<dc:date>2026-05-08</dc:date>
<dc:identifier>doi:10.64898/2026.05.06.723370</dc:identifier>
<dc:title><![CDATA[vartracker: an end-to-end tool for pathogen longitudinal variant analysis and visualisation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-08</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Longitudinal sequencing can reveal fine-grained pathogen evolution during acute and chronic infections and inform public health responses. However, integrating ordered pathogen genomic data into a coherent evolutionary and clinical framework can be tedious and error-prone. We present vartracker, an open-source tool for longitudinal pathogen variant analysis and visualisation. Given an ordered sample manifest, vartracker supports three entry points: raw sequence reads, reference-aligned BAM files, or user-supplied VCF and coverage inputs. Raw-read and BAM inputs are processed through an integrated Snakemake workflow, whereas VCF mode starts from precomputed files. Variants are normalised and annotated relative to a reference genome, tracked across timepoints, and classified as original or newly emerging and as transient or persistent. Inferred amino acid changes are reported, and for SARS-CoV-2 analyses, relevant published literature for key mutations can be automatically linked through a functional database. vartracker outputs a schema-documented results table, provenance metadata for reproducibility, publication-quality static figures, and an interactive heatmap for data exploration. Although packaged with SARS-CoV-2 reference assets and initially developed for SARS-CoV-2 datasets, vartracker is pathogen-agnostic when appropriate reference data are supplied. We demonstrate its utility using SARS-CoV-2 and respiratory syncytial virus A (RSV-A) datasets. vartracker is freely available through GitHub, PyPI and Bioconda.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.05.06.26352509v1?rss=1">
<title>
<![CDATA[
Determinants and long-term outcomes of COVID-19 undervaccination: a cohort study of 6.8 million individuals in Lombardy, Italy 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.05.06.26352509v1?rss=1"
</link>
<dc:creator>Corbetta, A.</dc:creator>
<dc:creator>Logan, K. M.</dc:creator>
<dc:creator>Ieva, F.</dc:creator>
<dc:creator>Di Angelantonio, E.</dc:creator>
<dc:date>2026-05-07</dc:date>
<dc:identifier>doi:10.64898/2026.05.06.26352509</dc:identifier>
<dc:title><![CDATA[Determinants and long-term outcomes of COVID-19 undervaccination: a cohort study of 6.8 million individuals in Lombardy, Italy]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-07</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundReceiving fewer COVID-19 vaccine doses than recommended ("undervaccination") may increase risks of death, severe COVID-19, and post-COVID condition. However, population-scale evidence from Italy remains limited. We aimed to characterise determinants of undervaccination in Lombardy and to quantify its association with mortality, severe COVID-19, and long COVID outcomes.

MethodsWe conducted a population-based study including all residents of Lombardy aged [&ge;]30 years who were alive on June 1, 2022 (n=6,836,566), and followed them until Dec 31, 2024. Vaccine deficit was defined as the difference between age-specific recommended doses (three for <60 years; four for [&ge;]60 years) and doses received, and was modelled as a time-varying exposure. Outcomes were all-cause mortality, severe COVID-19 (hospitalisation or COVID-19-related death), and long COVID defined using symptom-based ICD codes recorded [&ge;]1 month after infection. Determinants of undervaccination were assessed using multivariable logistic regression. Age-stratified Cox models estimated adjusted hazard ratios (HRs). Counterfactual vaccination scenarios were simulated using fitted survival models.

ResultsOn June 1, 2022, 1,668,014 individuals (24{middle dot}4%) were not up to date with recommended vaccination. Undervaccination was more frequent in younger adults, women, individuals born outside Europe, rural residents, and those with high comorbidity burden. During follow-up, 265,383 deaths, 52,121 severe COVID-19 events, and 23,780 long COVID events occurred. In adults aged [&ge;]60 years, increasing vaccine deficit was associated with progressively higher risks of mortality (HR up to 1{middle dot}63) and severe COVID-19 (HR up to 2{middle dot}16). Associations were weaker in younger adults. For long COVID, effect estimates were modest and sensitive to outcome definition. Simulated universal booster coverage in adults [&ge;]60 years was associated with substantial reductions in expected deaths and severe COVID-19 events.

ConclusionAbout one in four adults in Lombardy was undervaccinated by mid-2022. An increasing vaccine deficit was associated with a higher risk of severe COVID-19 and mortality, particularly in older adults. Sustaining booster uptake in high-risk groups remains central to mitigating the COVID-19 burden.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.05.06.723222v1?rss=1">
<title>
<![CDATA[
SARS-CoV-2 Nsp2 reprograms host immunity to drive pathogenic inflammation 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.05.06.723222v1?rss=1"
</link>
<dc:creator>Lacasse, E.</dc:creator>
<dc:creator>Dubuc, I.</dc:creator>
<dc:creator>Leclerc, J.</dc:creator>
<dc:creator>Gravel, A.</dc:creator>
<dc:creator>Gudimard, L.</dc:creator>
<dc:creator>Joly-Beauparlant, C.</dc:creator>
<dc:creator>Faure, M.</dc:creator>
<dc:creator>Fortin, P.</dc:creator>
<dc:creator>Blanchet, M.-R.</dc:creator>
<dc:creator>Droit, A.</dc:creator>
<dc:creator>Flamand, L.</dc:creator>
<dc:date>2026-05-07</dc:date>
<dc:identifier>doi:10.64898/2026.05.06.723222</dc:identifier>
<dc:title><![CDATA[SARS-CoV-2 Nsp2 reprograms host immunity to drive pathogenic inflammation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-07</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Despite the end of the COVID-19 pandemic, SARS-CoV-2 continues to circulate endemically, highlighting the need to better understand the viral determinants of pathogenesis. Non-structural protein 2 (Nsp2) has been implicated in host-virus interactions, yet its function remains poorly defined in the context of infection.

Here, we generated a recombinant SARS-CoV-2 lacking Nsp2 ({Delta}Nsp2) to investigate its role in viral replication and disease. While {Delta}Nsp2 replicated comparably to wild-type virus in vitro and in vivo, its deletion resulted in markedly attenuated disease in K18-hACE2 mice.

Wild-type infection induced a strong pro-inflammatory response associated with increased recruitment of monocytes and macrophages, whereas {Delta}Nsp2 infection promoted a more balanced antiviral response characterized by enhanced lymphocyte and NK cell recruitment. This was accompanied by reduced pulmonary and systemic inflammation and distinct transcriptional programs, including downregulation of pathways related to RNA processing and translation.

Mechanistically, CLIP-seq and proximity labeling suggest that Nsp2 interacts with host RNA and components of the translational machinery.

Together, our findings identify Nsp2 as a key virulence factor that drives immunopathology by skewing host immune responses, highlighting its role as a regulator of host-pathogen interactions.

Graphical Abstract

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=98 SRC="FIGDIR/small/723222v1_ufig1.gif" ALT="Figure 1">
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org.highwire.dtl.DTLVardef@540e40org.highwire.dtl.DTLVardef@73c663org.highwire.dtl.DTLVardef@e5c535org.highwire.dtl.DTLVardef@f62d7f_HPS_FORMAT_FIGEXP  M_FIG C_FIG
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.05.06.723231v1?rss=1">
<title>
<![CDATA[
Functional Landscape of Motifs within the Sarbecovirus Spike Cytoplasmic Tail 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.05.06.723231v1?rss=1"
</link>
<dc:creator>Zhou, S.</dc:creator>
<dc:creator>Chen, C.</dc:creator>
<dc:creator>Liu, C.</dc:creator>
<dc:creator>Zheng, X.</dc:creator>
<dc:creator>Shi, L.</dc:creator>
<dc:creator>Ma, L.</dc:creator>
<dc:creator>Cheng, P.</dc:creator>
<dc:creator>Wang, Q.</dc:creator>
<dc:creator>Liu, L.</dc:creator>
<dc:date>2026-05-07</dc:date>
<dc:identifier>doi:10.64898/2026.05.06.723231</dc:identifier>
<dc:title><![CDATA[Functional Landscape of Motifs within the Sarbecovirus Spike Cytoplasmic Tail]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-07</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Sarbecoviruses exhibit extensive diversity in host range and zoonotic potential. Although the ectodomain of the viral spike protein has been well characterized, the functional landscape of the cytoplasmic tail (CT) remains poorly defined. To address this gap, we systematically generated CT truncation variants of representative spike proteins from all major ACE2-utilizing clades to define the roles of conserved host factor-interacting motifs associated with COPI, COPII, FERM, and SNX27. Using vesicular stomatitis virus (VSV)- and lentivirus-based pseudotyping systems, we evaluated viral entry in cells expressing varying levels of ACE2 and TMPRSS2. Our results demonstrate that CT-associated motifs differentially regulate viral infectivity. Specifically, truncation of the COPI- or SNX27-binding motifs markedly reduces entry efficiency, whereas disruption of the COPII-binding motif produces the opposite outcome. By contrast, removal of the FERM-binding motif consistently enhances infectivity across lineages. Mechanistically, truncation of this motif increases spike expression, cell surface localization, incorporation into virions, and particle stability. Importantly, despite these pronounced effects on viral infectivity, deletion of the FERM-binding motif does not affect antigenicity, receptor dependence, or sensitivity to protease inhibitors, as demonstrated by neutralization and inhibition assays. In addition, this approach substantially increases spike protein density on virus-like particles (VLPs). Collectively, by extending the analysis beyond SARS-CoV-1 and SARS-CoV-2, our study reveals a generalizable mechanism in which cytoskeletal anchoring mediated by the FERM-binding motif acts as a limiting determinant of viral assembly. These findings provide a practical framework for optimizing pseudovirus platforms and guiding vaccine development against emerging viral threats.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.05.04.722688v1?rss=1">
<title>
<![CDATA[
The conserved QTQTX motif in the SARS-CoV-2 spike protein is dispensable for cleavage and lung cell entry of the emerging variant BA.3.2 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.05.04.722688v1?rss=1"
</link>
<dc:creator>Zhang, L.</dc:creator>
<dc:creator>Chen, N.</dc:creator>
<dc:creator>Eichmann, A.</dc:creator>
<dc:creator>Nehlmeier, I.</dc:creator>
<dc:creator>Hisner, R.</dc:creator>
<dc:creator>Happle, C.</dc:creator>
<dc:creator>Behrens, G. M. N.</dc:creator>
<dc:creator>Hoffmann, M.</dc:creator>
<dc:creator>Pöhlmann, S. H.</dc:creator>
<dc:date>2026-05-07</dc:date>
<dc:identifier>doi:10.64898/2026.05.04.722688</dc:identifier>
<dc:title><![CDATA[The conserved QTQTX motif in the SARS-CoV-2 spike protein is dispensable for cleavage and lung cell entry of the emerging variant BA.3.2]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-07</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
The furin motif in the SARS-CoV-2 spike (S) protein is important for lung cell entry. It is embedded in an extended loop structure and preceded by a highly conserved QTQTX motif that is required for efficient furin cleavage of the SARS-CoV-2 WA-1 S protein. BA.3.2 is an emerging SARS-CoV-2 saltation variant that is spreading globally in April 2026 and encodes for a highly mutated S protein. Here, we analyzed whether the QTQTX motif is also required for spike protein cleavage and lung cell entry of BA.3.2. We report that two patient-derived spike sequences of the BA.3.2 subvariant BA.3.2.2 lack the first QT repeat of the QTQTX motif and show that this motif is largely dispensable for both cleavage and lung cell entry of BA.3.2.2, which we found to depend on TMPRSS2. Our results suggest that the reconfiguration of the BA.3.2 S protein during persistent infection may have significantly altered the determinants of furin cleavage.

IMPORTANCEThe furin motif in the SARS-CoV-2 spike (S) protein is unique among sarbecoviruses and constitutes a virulence determinant. A QTQTX motif located immediately upstream of the furin motif is required for furin cleavage of the S protein of the virus that circulated early in the pandemic. Here, we show that the QTQTX motif is largely dispensable for S protein processing and S protein-driven lung cell entry of the emerging saltation variant BA.3.2, which is currently spreading globally. Thus, BA.3.2 evolution within immunocompromised individuals may have relaxed the requirements for furin processing of the spike protein.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.30.26352025v1?rss=1">
<title>
<![CDATA[
Inequalities in early childhood developmental concerns before, during and after the COVID-19 pandemic in Scotland: a retrospective cohort study 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.30.26352025v1?rss=1"
</link>
<dc:creator>Hardie, I.</dc:creator>
<dc:creator>Marryat, L.</dc:creator>
<dc:creator>Murray, A.</dc:creator>
<dc:creator>King, J.</dc:creator>
<dc:creator>Okelo, K.</dc:creator>
<dc:creator>Fenton, L.</dc:creator>
<dc:creator>Boardman, J. P.</dc:creator>
<dc:creator>Wilson, P.</dc:creator>
<dc:creator>Wood, R. P.</dc:creator>
<dc:creator>Auyeung, B.</dc:creator>
<dc:date>2026-05-06</dc:date>
<dc:identifier>doi:10.64898/2026.04.30.26352025</dc:identifier>
<dc:title><![CDATA[Inequalities in early childhood developmental concerns before, during and after the COVID-19 pandemic in Scotland: a retrospective cohort study]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-06</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundThe COVID-19 pandemic was associated with increased child developmental concerns in Scotland. However, it is not known whether this increase was uniform across social groups, and there is particular concern that children from low-income households, urban areas and ethnic minority groups may have been disproportionately affected. This retrospective, population-based, cohort study aimed to examine whether the pandemic was associated with changes in developmental inequalities in Scotland.

Study designWe linked national birth records, the COVID-19 in Pregnancy in Scotland (COPS) dataset, and 13-15 month and 27-30 month child health review records, covering all children born in Scotland who undertook reviews between January 2019 and August 2023 and had full developmental data. Logistic regression models estimated inequalities in odds of developmental concerns, before, during and after the pandemic and across Scottish Index of Multiple Deprivation (SIMD) quintiles, parental National Statistics Socioeconomic Classification (NS-SEC), urban-rural classification, child ethnicity and child sex. Interaction analysis formally tested for any significant changes in inequalities.

FindingsThe analyses included 254,367 children, covering 13-15 month child health review records for 183,439 children and 27-30 month child health review records for 184,689 children. Children in more deprived SIMD quintiles and lower parental NS-SEC categories had significantly higher odds of developmental concerns, as did African and Asian children (at 27-30 months only). Children who were female and in rural areas (27-30 months only) had significantly lower odds of developmental concerns. Developmental inequalities were broadly consistent at each time point and interaction analysis suggested that there was no widening of inequalities during or after the pandemic.

ConclusionsDevelopmental inequalities in Scotland did not widen during or after the COVID-19 pandemic. However, substantial pre-existing inequalities persist, underscoring the need for interventions to reduce disparities and support national policy goals on child development.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.05.05.26352439v1?rss=1">
<title>
<![CDATA[
Identifying the determinants of health protective behaviors during the COVID-19 pandemic using machine learning: an analysis of six countries 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.05.05.26352439v1?rss=1"
</link>
<dc:creator>Chevalier, J. M.</dc:creator>
<dc:creator>Stellbrink, L. M.</dc:creator>
<dc:creator>Steijvers, L.</dc:creator>
<dc:creator>Wijnen, S.</dc:creator>
<dc:creator>van Daalen, F.</dc:creator>
<dc:creator>Kojan, L.</dc:creator>
<dc:creator>Li, N.</dc:creator>
<dc:creator>Jahn, B.</dc:creator>
<dc:creator>Siebert, U.</dc:creator>
<dc:creator>Calero Valdez, A.</dc:creator>
<dc:creator>Hiligsmann, M.</dc:creator>
<dc:creator>Crutzen, R.</dc:creator>
<dc:creator>Dukers-Muijrers, N. H.</dc:creator>
<dc:creator>Kretzschmar, M. E.</dc:creator>
<dc:date>2026-05-06</dc:date>
<dc:identifier>doi:10.64898/2026.05.05.26352439</dc:identifier>
<dc:title><![CDATA[Identifying the determinants of health protective behaviors during the COVID-19 pandemic using machine learning: an analysis of six countries]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-06</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Individuals adapt their behavior in response to infectious disease epidemics. Understanding the determinants of behavior, particularly the impact of infections themselves, can help model the feedback loop between disease and behavior in epidemic models. We combined the Imperial College London YouGov COVID-19 behavior survey with hospitalization data and the Oxford COVID-19 government response tracker stringency index to identify the key predictors of three health behaviors--social distancing, masking, and personal protective measures (e.g. handwashing)-- during an early phase of the COVID-19 pandemic in six different countries. We compared two machine learning algorithms--logistic regression with stepwise Akaike Information Criterion and extreme gradient boosting (XGBoost). Top predictors of health behavior were perceived disease severity, hospitalizations, willingness to isolate, and intervention effectiveness, across the six countries. Logistic regression and XGBoost had comparable performance. Machine learning algorithms trained on real-world data could be used to predict individual behavior uptake in agent-based network models.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.05.05.723025v1?rss=1">
<title>
<![CDATA[
Tocilizumab induces significant changes in longitudinal proteomes of blood serum from patients with severe COVID-19 pneumonia 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.05.05.723025v1?rss=1"
</link>
<dc:creator>Cordero, J.</dc:creator>
<dc:creator>Bravo, G.</dc:creator>
<dc:creator>Silva, P. H.</dc:creator>
<dc:creator>Lozano, B.</dc:creator>
<dc:creator>Rivas, E.</dc:creator>
<dc:creator>Labra, V.</dc:creator>
<dc:creator>Villalobos, D.</dc:creator>
<dc:creator>Saldivia, P.</dc:creator>
<dc:creator>Hernandez, M.</dc:creator>
<dc:creator>Koch, E. S.</dc:creator>
<dc:creator>Vargas, C.</dc:creator>
<dc:creator>Nova-Lamperti, E.</dc:creator>
<dc:creator>Barrera, N. P.</dc:creator>
<dc:creator>Retamal, J.</dc:creator>
<dc:date>2026-05-06</dc:date>
<dc:identifier>doi:10.64898/2026.05.05.723025</dc:identifier>
<dc:title><![CDATA[Tocilizumab induces significant changes in longitudinal proteomes of blood serum from patients with severe COVID-19 pneumonia]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-06</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Coronavirus disease 2019 (COVID-19) shows highly variable clinical outcomes that are not fully explained by age or comorbidities, underscoring the importance of host molecular responses in determining disease severity. Proteomic and multi-omics studies have linked severe COVID-19 to profound dysregulation of immune, inflammatory, and coagulation pathways, and have shown that circulating protein signatures can predict clinical trajectories. Tocilizumab (TCZ), a monoclonal antibody targeting the interleukin-6 receptor (IL-6R), is an established therapy for IL-6-driven inflammatory diseases and can normalize aberrant molecular profiles. Here, we applied longitudinal serum proteomics to patients with severe SARS-CoV-2 pneumonia treated with TCZ to further characterize how IL-6R blockade reshapes the systemic inflammatory milieu. After TCZ administration, several clinical and inflammatory markers, including C-reactive protein (CRP), CCL5 and CXCL10, decreased. Proteomic profiling revealed that TCZ exerts a sustained effect on the serum proteome, with the most pronounced changes emerging 7 days after treatment. These changes were associated with a broad reconfiguration of the proteomic profile toward a pattern resembling a healthy physiological state, characterized by the restoration of key protein abundances to levels comparable to those observed under homeostatic conditions. Collectively, our findings support that TCZ treatment contributes to the normalization of the inflammatory state in severe COVID-19 and represents a viable therapeutic option for managing the acute inflammatory phase of the disease, while also highlighting additional pathways and biomarkers involved in this recovery process.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.05.04.722452v1?rss=1">
<title>
<![CDATA[
Longitudinal analysis reveals myeloid cell contributions to neuroPASC pathogenesis 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.05.04.722452v1?rss=1"
</link>
<dc:creator>Tan, L.</dc:creator>
<dc:creator>Lowery, S.</dc:creator>
<dc:creator>Verma, A. K.</dc:creator>
<dc:creator>Thurman, A. L.</dc:creator>
<dc:creator>Sariol, A.</dc:creator>
<dc:creator>Fain, C.</dc:creator>
<dc:creator>Harty, J.</dc:creator>
<dc:creator>Perlman, S.</dc:creator>
<dc:date>2026-05-06</dc:date>
<dc:identifier>doi:10.64898/2026.05.04.722452</dc:identifier>
<dc:title><![CDATA[Longitudinal analysis reveals myeloid cell contributions to neuroPASC pathogenesis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-06</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Neurological and neuropsychiatric symptoms, collectively termed neuroPASC, are among the most prevalent Post-Acute Sequelae of COVID-19 (PASC). Neuroinflammation - particularly microglia reactivity - has been implicated in neuroPASC. Current insights are largely derived from post-mortem tissues of acutely infected patients and may not reflect PASC-related neuropathology. We previously established a PASC model in which SARS-CoV-2-infected mice developed persistent behavioral alterations and prolonged neuroinflammation for up to 120 days post-infection (dpi) in the absence of viral neuroinvasion. Here, we extended these results to a longitudinal single-cell RNA sequencing analysis of brain immune cells collected at 0, 6, 30, and 100 dpi. We identified a coordinated contribution of infiltrating and resident myeloid cells to the initiation and persistence of neuroinflammation. In specific, microglia displayed sustained expansion of subclusters characterized by inflammatory, stress response, and metabolic signatures. Border-associated macrophages upregulated monocyte attractants during acute infection. Concurrently, monocytes and neutrophils showed marked brain recruitment and mounted transient inflammatory responses at 6 dpi, potentially triggering long-term microglial reactivity. Together, these findings provide a high-resolution atlas of brain myeloid immune dynamics during neuroPASC and highlight a central role for microglia in sustaining chronic neuroinflammation.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.30.721843v1?rss=1">
<title>
<![CDATA[
The redesign of the molecular scaffold of viral ion channel blockers 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.30.721843v1?rss=1"
</link>
<dc:creator>Zsido, B.</dc:creator>
<dc:creator>Mernyak, E.</dc:creator>
<dc:creator>Földes, F.</dc:creator>
<dc:creator>Kopasz, Z.</dc:creator>
<dc:creator>Leiner, K.</dc:creator>
<dc:creator>Madai, M.</dc:creator>
<dc:creator>Zana, B.</dc:creator>
<dc:creator>Kuczmog, A.</dc:creator>
<dc:creator>Hetenyi, C.</dc:creator>
<dc:date>2026-05-06</dc:date>
<dc:identifier>doi:10.64898/2026.04.30.721843</dc:identifier>
<dc:title><![CDATA[The redesign of the molecular scaffold of viral ion channel blockers]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-06</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
The rise of new, rapidly mutating viruses presents increasing challenges for drug developers. Traditional methods, such as high-throughput screening and drug repurposing against mutagenic viral targets, have recently shown their limitations. Our current rational molecular engineering approach offers a sustainable solution by targeting viral ion channels, which generally have low mutation rates. First, extending the amantadine molecule led to the development of new compounds that better match the alternating hydrophobic and hydrophilic patterns of the inner walls of ion channels--a common feature across many viruses. Then, simplifying the structure yielded a cyclohexylamine-based minimalist scaffold that effectively blocks the ion channel and demonstrates improved antiviral activity compared to well-known agents such as amantadine and arterolane. SARS-CoV-2 variants served as test systems in laboratory experiments. The new molecular scaffolds presented here provide a strong foundation for designing potent, broad-spectrum viral ion channel blockers.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.05.03.26351251v1?rss=1">
<title>
<![CDATA[
Ethnic Inequalities in COVID-19 Vaccination Uptake Among Older Adults in Australia: A Nationwide Linked Data Study 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.05.03.26351251v1?rss=1"
</link>
<dc:creator>Xu, P.</dc:creator>
<dc:creator>Khalatbari-Soltani, S.</dc:creator>
<dc:creator>Sheel, M.</dc:creator>
<dc:creator>Laaksonen, M. A.</dc:creator>
<dc:creator>Zhu, L.</dc:creator>
<dc:creator>Lin, Y.</dc:creator>
<dc:creator>Abdel Shaheed, C.</dc:creator>
<dc:creator>Sawan, M.</dc:creator>
<dc:creator>Mussagulova, A.</dc:creator>
<dc:creator>Gnjidic, D.</dc:creator>
<dc:creator>Patu, P.</dc:creator>
<dc:creator>Liu, B.</dc:creator>
<dc:creator>Stanaway, F. F.</dc:creator>
<dc:date>2026-05-05</dc:date>
<dc:identifier>doi:10.64898/2026.05.03.26351251</dc:identifier>
<dc:title><![CDATA[Ethnic Inequalities in COVID-19 Vaccination Uptake Among Older Adults in Australia: A Nationwide Linked Data Study]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-05</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundInternational evidence has documented ethnic inequalities in COVID-19 vaccine uptake, but national evidence for Australia remains limited. We aimed to quantify ethnic inequalities in COVID-19 vaccine uptake in the first 6 months of 2024 and examine retrospective trends in Dose 1-4 (2021-22) across detailed ethnic groups among older adults.

MethodsWe conducted a nationwide cohort study of Australian residents aged [&ge;]75 years who were not Aboriginal or Torres Strait Islander (N=2,038,522) by linking the 2021 Census, Australian Immunisation Register, death, and migration data. Age-standardized uptake of any COVID-19 vaccine dose by ethnic group was calculated (Jan 1-June 30, 2024). Stratified descriptive analyses were conducted to explore intersections between ethnicity and other key sociodemographic characteristics. Uptake of Dose 1-4 during 2021-22 was also assessed across ethnic groups.

ResultsIn the first 6 months of 2024, 31.1% of the cohort received a COVID-19 vaccine. Uptake was substantially lower in several ethnic groups, including Central Asian (<10.0%, 95% CI <10.0-10.7), North African and Middle Eastern (<10.0%, 95% CI <10.0-<10.0), Pasifika (13.0%, 95% CI 11.7-14.4), and South Eastern European (10.5%, 95% CI 10.3-10.7) groups. These differences persisted even among individuals born in Australia, with higher English proficiency, higher educational attainment, and living in less disadvantaged areas. Similar inequalities were observed across earlier vaccine doses.

ConclusionsSubstantial ethnic inequalities in COVID-19 vaccination uptake persist among older Australians. Reliance on country of birth, language, or socioeconomic factors alone does not fully identify groups with the lowest uptake. Incorporating more detailed ethnicity information may improve identification of under-served groups and inform more targeted and culturally appropriate vaccination strategies.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.05.05.722935v1?rss=1">
<title>
<![CDATA[
Targeted metagenomic recovery of coronaviruses from wildlife samples 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.05.05.722935v1?rss=1"
</link>
<dc:creator>Johnston, C. M.</dc:creator>
<dc:creator>Gunalan, V.</dc:creator>
<dc:creator>Baagoe, H. J.</dc:creator>
<dc:creator>Elmeros, M.</dc:creator>
<dc:creator>Fjederholt, E. T.</dc:creator>
<dc:creator>Quaade, M. L.</dc:creator>
<dc:creator>Hansen, M. J. S.</dc:creator>
<dc:creator>Lohse, L.</dc:creator>
<dc:creator>Rasmussen, T. B.</dc:creator>
<dc:date>2026-05-05</dc:date>
<dc:identifier>doi:10.64898/2026.05.05.722935</dc:identifier>
<dc:title><![CDATA[Targeted metagenomic recovery of coronaviruses from wildlife samples]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-05</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Coronaviruses (CoVs) are diverse RNA viruses infecting a wide range of hosts, with significant implications for public health, animal production and welfare. Bats are key reservoirs of mammalian CoVs and have contributed to the emergence and circulation of several zoonotic viruses in a wildlife context, while mustelids represent important hosts at the human-animal interface, as highlighted by SARS-CoV-2 outbreaks in farmed mink.

Using metagenomic next-generation sequencing, we screened bats and wild mustelids and recovered and characterized full-length CoV genomes. Building on previous findings in Danish wildlife, including alpha-CoVs and a MERS-related beta-CoV in bats, this study expands current knowledge of coronavirus diversity and evolution in wildlife, emphasizing their relevance for zoonotic emergence.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.30.721971v1?rss=1">
<title>
<![CDATA[
Condensate-Like Organization in Respiratory Aerosols Modulates the Dynamics of an Airborne Virus 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.30.721971v1?rss=1"
</link>
<dc:creator>Wauer, N.</dc:creator>
<dc:creator>Calvo-Tusell, C.</dc:creator>
<dc:creator>Dommer, A.</dc:creator>
<dc:creator>Casalino, L.</dc:creator>
<dc:creator>Kearns, F.</dc:creator>
<dc:creator>Caparotta, M.</dc:creator>
<dc:creator>Rosenfeld, M.</dc:creator>
<dc:creator>Morris, C.</dc:creator>
<dc:creator>Amaro, R. E.</dc:creator>
<dc:date>2026-05-04</dc:date>
<dc:identifier>doi:10.64898/2026.04.30.721971</dc:identifier>
<dc:title><![CDATA[Condensate-Like Organization in Respiratory Aerosols Modulates the Dynamics of an Airborne Virus]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-04</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
The molecular behavior of viruses within respiratory aerosols plays a critical role in airborne disease transmission yet remains largely inaccessible to experimental characterization. Here, we use a billion-atom all-atom molecular dynamics simulation of a virus-laden respiratory aerosol to uncover how respiratory proteins, lipids, ions, and water collectively assemble around SARS-CoV-2, giving rise to structured microenvironments that influence viral stability and spike dynamics. We find that respiratory components rapidly evolve into heterogeneous networks characterized by protein-rich aggregates, patchy lipid assemblies, and spatially structured ion and water dynamics. These features create distinct microenvironments that constrain molecular transport and stabilize regions surrounding the virion. Within this crowded aerosol context, we observe sustained and selective interactions between aerosol components and the viral spike protein, including preferential recruitment of surfactant lipids and persistent coordination by divalent cations. These interactions modulate spike conformational dynamics, enhancing domain breathing motions and flexibility at key hinge regions while preserving a stable membrane anchor. Together, these observations reveal a condensate-like physical regime in which multivalent aerosol components coalesce into a soft, heterogeneous matrix that selectively modulates viral protein dynamics under extreme crowding. By framing virus-laden respiratory aerosols within this physical context, this work establishes an in situ molecular framework for understanding how aerosols influence viral persistence and offers a platform for exploring mechanisms relevant to airborne disease transmission and mitigation strategies.

TOC Graphic

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=115 SRC="FIGDIR/small/721971v1_ufig1.gif" ALT="Figure 1">
View larger version (58K):
org.highwire.dtl.DTLVardef@4d0f60org.highwire.dtl.DTLVardef@12c9d1forg.highwire.dtl.DTLVardef@1ff6c29org.highwire.dtl.DTLVardef@15feec_HPS_FORMAT_FIGEXP  M_FIG C_FIG SynopsisRespiratory aerosols exhibit condensate-like physical properties that govern the evolution of the particle and modulate the behavior of airborne SARS-CoV-2.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.05.02.722415v1?rss=1">
<title>
<![CDATA[
Connecting Cryo-EM and Crystallographic Views of RNA Folding through Ionic Conditions and Structural Flexibility 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.05.02.722415v1?rss=1"
</link>
<dc:creator>Mainan, A.</dc:creator>
<dc:creator>Roy, S.</dc:creator>
<dc:creator>Kirmizialtin, S.</dc:creator>
<dc:date>2026-05-04</dc:date>
<dc:identifier>doi:10.64898/2026.05.02.722415</dc:identifier>
<dc:title><![CDATA[Connecting Cryo-EM and Crystallographic Views of RNA Folding through Ionic Conditions and Structural Flexibility]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-04</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Discrepancies between biomolecular structures resolved by cryo-electron microscopy (cryo-EM) and X-ray crystallography (XRD) often arise from differences in ionic conditions and construct design, yet their mechanistic impact on RNA folding remains unclear. In the SARS-CoV-2 frameshifting stimulatory element, cryo-EM and XRD structures reveal distinct pseudoknot conformations--a bent and a coaxially stacked state--complicating its structure-function relationship. Here, combining all-atom explicit-solvent simulation results with a structure-based electrostatic model, we show that Mg{superscript 2} ions drive transitions between these states by stabilizing long-range tertiary interactions and modulating local dynamical coupling involving the slippery site and stem 3. Energy landscape analysis reveals distinct folding pathways, while deletion of the slippery segment in crystallographic constructs alters intermediates and produces pathways inconsistent with single-molecule optical tweezer experiments. This study demonstrates how condition-dependent experiments encode complementary interaction-level information and how physics-based computational approaches integrate these to yield a coherent, mechanistic picture of RNA folding.

TOC GRAPHICS

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/722415v1_ufig1.gif" ALT="Figure 1">
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org.highwire.dtl.DTLVardef@1a7c324org.highwire.dtl.DTLVardef@fcabceorg.highwire.dtl.DTLVardef@736704org.highwire.dtl.DTLVardef@7061e6_HPS_FORMAT_FIGEXP  M_FIG C_FIG
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.05.03.722459v1?rss=1">
<title>
<![CDATA[
SARS-CoV-2 (E)-protein induces rapid TLR2-mediated T cell activation in mouse lungs revealed by intravital lung microscopy 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.05.03.722459v1?rss=1"
</link>
<dc:creator>Shaalan, Y.</dc:creator>
<dc:creator>Kuruppu, N.</dc:creator>
<dc:creator>Orinska, Z.</dc:creator>
<dc:creator>Li, C.</dc:creator>
<dc:creator>Koops, F.</dc:creator>
<dc:creator>Wasnick, R.</dc:creator>
<dc:creator>Noessner, E.</dc:creator>
<dc:creator>Stoeger, T.</dc:creator>
<dc:creator>Meiners, S.</dc:creator>
<dc:creator>Rehberg, M.</dc:creator>
<dc:date>2026-05-04</dc:date>
<dc:identifier>doi:10.64898/2026.05.03.722459</dc:identifier>
<dc:title><![CDATA[SARS-CoV-2 (E)-protein induces rapid TLR2-mediated T cell activation in mouse lungs revealed by intravital lung microscopy]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-04</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Mounting evidence indicates that T cells can operate in an innate-like mode challenging the classical description of T cells as strictly adaptive immune effectors. T cells can engage innate pattern recognition receptors to mount rapid but antigen-nonspecific responses to infection or cellular stress. This study observed that CD8+ T cells, and to a lesser extent also CD4+ T cells, responded to viral proteins in the mouse lung quickly in an innate-like fashion.

We employed intravital lung microscopy to visualize infiltration of CD8+ T cells into the lung following intratracheal instillation of the SARS-CoV-2 envelope (E)-protein. Here, we demonstrate acute recruitment of CD8+ from the pulmonary microcirculation into the lung as early as 4 and 24 hours after (E)-protein instillation. The acute infiltration of CD8+ T cells was not observed in Tlr2-/- mice. Immunohistochemistry analysis of mouse lungs revealed T cell accumulation in nodular inflammatory foci (NIF) of the lung at perivascular regions and around large airways. Stimulating spleen-derived CD8+ T cells from wild-type mice with (E)-protein ex vivo in combination with cytokines or TCR agonists significantly upregulated CD69 and activated secretion of interferon (IFN){gamma} which was not observed with CD8+ T cells isolated from Tlr2-/- mice.

These findings indicate rapid bystander activation of CD8+ T cells by the SARS-CoV-2 envelope (E)-protein that depends on (E)-protein sensing by TLR2. This innate-like CD8+ T cell response to SARS-CoV-2 (E)-protein may offer novel opportunities for diagnostic and therapeutic development, warranting further investigation.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.30.721889v1?rss=1">
<title>
<![CDATA[
Single-cell atlas of transcript usage remodelling in antiviral immune responses across human populations 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.30.721889v1?rss=1"
</link>
<dc:creator>Chazarra-Gil, R.</dc:creator>
<dc:creator>Ripoll-Cladellas, A. R.-C.</dc:creator>
<dc:creator>Sopena-Rios, M.</dc:creator>
<dc:creator>Mestres-Pascual, I.</dc:creator>
<dc:creator>Calvo, M.</dc:creator>
<dc:creator>Reverter, F.</dc:creator>
<dc:creator>Garrido-Martin, D.</dc:creator>
<dc:creator>Mele, M.</dc:creator>
<dc:date>2026-05-04</dc:date>
<dc:identifier>doi:10.64898/2026.04.30.721889</dc:identifier>
<dc:title><![CDATA[Single-cell atlas of transcript usage remodelling in antiviral immune responses across human populations]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-04</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Humans exhibit substantial interindividual variation in their immune responses to infection, yet the contribution of transcript usage --the relative abundance of gene isoforms-- to this variation remains poorly understood. Here, we generate the first single-cell atlas of transcript usage variation during early responses to influenza A virus and SARS-CoV-2 across 160 individuals of African and European ancestry. We show that viral stimulation induces widespread remodelling of transcript usage across all major immune lineages, with changes that are largely lineage-restricted and frequently undetected at the gene expression level. We further find that ancestry-associated effects on transcript usage are predominantly cell type-specific and contribute to population differences in antiviral responses. In addition, the genetic regulation of transcript usage during stimulation differs between influenza A and SARS-CoV-2, pointing to virus-dependent regulatory architectures. Together, our findings establish transcript usage as a dynamic regulatory layer shaping responses to viral infection across immune cell types and human populations, providing new insights into the molecular basis of variation in human antiviral immunity.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.30.26352163v1?rss=1">
<title>
<![CDATA[
Early functional maturation of anti-Spike antibodies predicts SARS-CoV-2 RNA clearance in mild infection 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.30.26352163v1?rss=1"
</link>
<dc:creator>Rodrigues, D.</dc:creator>
<dc:creator>Araujo, B.</dc:creator>
<dc:creator>Pestana, J.</dc:creator>
<dc:creator>da Costa, L.</dc:creator>
<dc:creator>Andrade, M.</dc:creator>
<dc:creator>de Freitas, L.</dc:creator>
<dc:creator>Nery, B.</dc:creator>
<dc:creator>Bozza, V.</dc:creator>
<dc:creator>Conde, L.</dc:creator>
<dc:creator>Raposo, L.</dc:creator>
<dc:creator>Gama, A.</dc:creator>
<dc:creator>Mendes, V.</dc:creator>
<dc:creator>Cobos, E.</dc:creator>
<dc:creator>Higa, L.</dc:creator>
<dc:creator>Galliez, R.</dc:creator>
<dc:creator>Tanuri, A.</dc:creator>
<dc:creator>Ferreira, O.</dc:creator>
<dc:creator>Castilho, L.</dc:creator>
<dc:creator>Castineiras, T.</dc:creator>
<dc:creator>Echevarria, J.</dc:creator>
<dc:creator>Bozza, M.</dc:creator>
<dc:creator>Vale, A. M.</dc:creator>
<dc:date>2026-05-03</dc:date>
<dc:identifier>doi:10.64898/2026.04.30.26352163</dc:identifier>
<dc:title><![CDATA[Early functional maturation of anti-Spike antibodies predicts SARS-CoV-2 RNA clearance in mild infection]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-03</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
SARS-CoV-2 infection exhibits heterogeneous viral clearance kinetics even in individuals with mild disease. The immunological determinants underlying rapid versus prolonged viral RNA detection remain incompletely defined. Here, we performed a three-year longitudinal analysis of 77 healthcare professionals infected with the ancestral Wuhan strain. Participants were stratified according to viral RNA clearance kinetics into non-persistent ([&le;]21 days) and persistent (>21 days) groups. Non-persistent individuals exhibited accelerated seroconversion to Spike and receptor-binding domain (RBD) antigens during the first 11 days after symptom onset. Early antibody responses were characterized by higher functional activity, including significantly greater neutralizing activity against the ancestral strain. In contrast, persistent individuals displayed delayed seroconversion, prolonged IgM responses, and weaker coordination among IgG subclasses, with less synchronized subclass responses, during early infection. Importantly, total immunoglobulin levels did not distinguish the groups. Cross-variant antibody recognition during acute infection was limited and largely strain-focused in both groups. During convalescence, durable anti-Spike IgG responses were maintained independently of persistence status, without significant differences in cross-variant breadth. Vaccination robustly amplified antibody titers, enhanced variant recognition, and sustained high-affinity responses in both groups. Together, our findings demonstrate that the timing and functional quality of early humoral maturation, reflected by neutralizing antibody activity, rather than antibody magnitude or breadth, are key determinants of SARS-CoV-2 RNA clearance in mild infection. These results highlight the importance of early neutralizing antibody generation in shaping acute viral control and the long-term immune architecture.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.30.722013v1?rss=1">
<title>
<![CDATA[
Modeling healthy proteomic profiles for anomaly detection using subspace learning based one-class classification 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.30.722013v1?rss=1"
</link>
<dc:creator>Sohrab, F.</dc:creator>
<dc:creator>Kumar, A.</dc:creator>
<dc:creator>Ahola, V.</dc:creator>
<dc:creator>Magis, A.</dc:creator>
<dc:creator>Hautamaki, V.</dc:creator>
<dc:creator>Heinaniemi, M.</dc:creator>
<dc:creator>Huang, S.</dc:creator>
<dc:date>2026-05-01</dc:date>
<dc:identifier>doi:10.64898/2026.04.30.722013</dc:identifier>
<dc:title><![CDATA[Modeling healthy proteomic profiles for anomaly detection using subspace learning based one-class classification]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-05-01</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
High-throughput plasma proteomics provides sensitive and scalable measurements of thousands of systemic protein profiles from minimally invasive blood samples, creating new opportunities for disease detection and population-scale health monitoring. However, robust statistical modeling remains challenging due to high dimensionality, limited availability and high diversity of diseased samples, resulting in class imbalance in clinical cohorts. Here, we present a subspace One-Class Classification (OCC) framework for proteomics-driven anomaly detection that models healthy proteomic profiles as a reference distribution. To address the limitations of conventional hyperparameter tuning in severely imbalanced data settings, we introduce a fully data-driven parameter estimation strategy that infers all model parameters directly from intrinsic properties of the healthy training data, without using any disease labels. Using plasma proteomics data generated with Olink, we evaluate a family of subspace and graph-embedded subspace extensions of Support Vector Data Description, in which all models operate on learned low-dimensional representations rather than the original feature space. Models are trained exclusively on a healthy reference cohort and evaluated on heterogeneous disease conditions, including multiple cancer types and an independent COVID-19 cohort, with all disease samples withheld from training to enable unbiased assessment of cross-disease generalization. Across disease contexts, the evaluated one-class models yield stable and balanced detection performance, demonstrating that learning structured low-dimensional representations of healthy proteomic variation captures intrinsic biological organization that generalizes across disease-specific perturbations. These results establish healthy-profile-based, subspace one-class learning as a robust and disease-agnostic framework for screening in high-dimensional plasma proteomics.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.29.26352072v1?rss=1">
<title>
<![CDATA[
Global burden of foreign bodies and impact of COVID-19 pandemic 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.29.26352072v1?rss=1"
</link>
<dc:creator>Simayi, F.</dc:creator>
<dc:date>2026-04-30</dc:date>
<dc:identifier>doi:10.64898/2026.04.29.26352072</dc:identifier>
<dc:title><![CDATA[Global burden of foreign bodies and impact of COVID-19 pandemic]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-30</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundForeign bodies (FBs) can cause obstruction, infection, or injury, yet comprehensive global assessments remain limited. This study evaluated the burden of FBs from 1990-2021, projected trends to 2050, and identified high-risk populations.

MethodsUsing Global Burden of Disease 2021 data, we estimated age-standardized incidence ratio (ASIR), death ratio (ASDR), and disability-adjusted life years (DALYs) by age, sex, and region. Temporal trends were assessed with estimated annual percentage change (EAPC) and Joinpoint regression; projections applied Bayesian age-period-cohort models; decomposition quantified the effects of aging, population, and epidemiological change.

ResultsFrom 1990-2021, global ASIR declined from 660.75 to 561.16 per 100,000 (EAPC: -0.84), ASDR from 2.11 to 1.41 (-1.47), and DALYs from 145.14 to 77.87 (- 2.13). Males had consistently higher burden (2021: 725.96 versus 394.11 per 100,000 in females). Children under 5 and adults over 80 bore the highest risks, with intraocular FBs dominating incidence and pulmonary aspiration/airway FBs driving mortality. Western Europe had the highest ASIR, Andean Latin America the highest ASDR. Since 2019, the onset of the COVID-19 pandemic, intraocular FBs incidence has surged in East Asia, mainly China. Projections suggest ASIR will continue to rise through 2050, while ASDR and DALYs continue to decline, driven by global population growth (187.27%) and aging (46.82%) but offset by epidemiological improvements (-134.09%).

ConclusionsDespite long-term declines, FB incidence is rebounding, with marked disparities across sex, age, and region. Targeted interventions, including workplace safety, pediatric and geriatric care, and region-specific policies, are needed to mitigate risks and reduce inequalities.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.29.721712v1?rss=1">
<title>
<![CDATA[
Proof-of-concept of targeted degradation of p38α/β MAPK host-kinase as a potent inhibitor of coronaviruses. 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.29.721712v1?rss=1"
</link>
<dc:creator>Cooper, G.</dc:creator>
<dc:creator>Snape, T. J.</dc:creator>
<dc:creator>Shivkumar, M.</dc:creator>
<dc:date>2026-04-30</dc:date>
<dc:identifier>doi:10.64898/2026.04.29.721712</dc:identifier>
<dc:title><![CDATA[Proof-of-concept of targeted degradation of p38α/β MAPK host-kinase as a potent inhibitor of coronaviruses.]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-30</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Host-targeting antivirals offer a promising strategy for combating emerging viral threats by targeting cellular pathways required for infection. The p38 mitogen-activated protein kinase (MAPK) pathway has been implicated as a host dependency factor exploited by multiple viruses, including coronaviruses, making it an attractive antiviral target. Here, we show for the first time that targeted degradation of p38 using the proteolysis-targeting chimera (PROTAC) NR-7h potently inhibits coronavirus infection. NR-7h induced substantial degradation of p38 in multiple cell lines and inhibited infection of two seasonal coronaviruses OC43 and 229E, providing broad pan-coronavirus activity. Infectious viral titres and viral RNA levels were significantly reduced without any detectable cytotoxicity. NR-7h exhibited greater antiviral potency than conventional p38 small-molecule inhibitors, with an IC50 of 1.0 nM compared with 648.4 nM for LY2228820, while the parent kinase inhibitor PH-797804 did not achieve 50% inhibition at the highest concentration tested. Pseudovirus and time-of-addition studies indicated that antiviral activity occurred at a post-entry stage of infection. Importantly, antiviral activity was eliminated by inhibition of proteasome function or E3 ligase activity, demonstrating dependence on PROTAC-mediated degradation. Our findings provide a proof-of-concept that targeted degradation of host kinase p38 can function as an antiviral modality and suggest PROTAC-based host-directed therapeutics may offer advantages over conventional kinase inhibition for broad-spectrum antiviral development.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.27.26351870v1?rss=1">
<title>
<![CDATA[
Changing COVID-19 vaccine eligibility could reshape disease burden for all 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.27.26351870v1?rss=1"
</link>
<dc:creator>Larsen, S. L.</dc:creator>
<dc:creator>Martinez, P. P.</dc:creator>
<dc:creator>Mahmud, A.</dc:creator>
<dc:date>2026-04-29</dc:date>
<dc:identifier>doi:10.64898/2026.04.27.26351870</dc:identifier>
<dc:title><![CDATA[Changing COVID-19 vaccine eligibility could reshape disease burden for all]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-29</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
COVID-19 vaccine recommendations are evolving in the United States. While older adults are most at risk of severe COVID-19 outcomes and therefore experience the greatest direct benefits of vaccination, limiting vaccination to only this age group could worsen outcomes in this higher-risk population. Here, we leveraged data from a statewide survey in Illinois to inform transmission models accounting for contact and vaccination rates across age. Simulating a single season of COVID-19 transmission, we compared deaths under existing vaccination coverage against counterfactual scenarios where individuals under 5 or under 65 were never vaccinated. We find substantial indirect vaccine impacts for older adults. Our results suggest that existing vaccination coverage among younger people is mitigating COVID-19 mortality for older populations. These findings can provide insights into the long-term consequences of deprioritizing young adults and children from vaccination campaigns, and suggest that a lack of vaccine-induced immunity may impact outcomes in other age groups. This underscores the importance of considering indirect vaccine impacts when developing policy.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.28.26351941v1?rss=1">
<title>
<![CDATA[
Detection and characterization of single SARS-CoV-2 viral particles by flow virometry 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.28.26351941v1?rss=1"
</link>
<dc:creator>Jungbauer-Groznica, M.</dc:creator>
<dc:creator>Commere, P.-H.</dc:creator>
<dc:creator>Cottignies-Calamarte, A.</dc:creator>
<dc:creator>De Cruz, A.</dc:creator>
<dc:creator>Fantin, A.</dc:creator>
<dc:creator>Planchais, C.</dc:creator>
<dc:creator>Guivel-Benhassine, F.</dc:creator>
<dc:creator>Staropoli, I.</dc:creator>
<dc:creator>Schmutz, S.</dc:creator>
<dc:creator>Novault, S.</dc:creator>
<dc:creator>Veyer, D.</dc:creator>
<dc:creator>Pere, H.</dc:creator>
<dc:creator>Mouquet, H.</dc:creator>
<dc:creator>Schwartz, O.</dc:creator>
<dc:creator>Bruel, T.</dc:creator>
<dc:date>2026-04-29</dc:date>
<dc:identifier>doi:10.64898/2026.04.28.26351941</dc:identifier>
<dc:title><![CDATA[Detection and characterization of single SARS-CoV-2 viral particles by flow virometry]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-29</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Virus infected cells release viral particles, which have variable protein content and are functionally diverse. Deciphering this heterogeneity remains a challenge. Here, we adapt flow virometry to detect and phenotype severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) particles. In supernatants of infected cells, we observe particles measuring 70-100 nm. The appearance of these particles is associated to the increase in viral RNA and infectivity. Sample inactivation using temperature or detergent leads to the disappearance of these particles. Using antibodies and dyes for lipid membranes and nucleic acids, we detect the spike protein, the lipid envelope and the RNA genome. We further confirm the presence of viral particles by electron microscopy. Analyzing different viral preparations demonstrate that spike detection in particles outcompetes particle concentration to predict infectivity. Antibodies against different spike epitopes enable probing of spike conformation changes in the presence of soluble ACE2. Lastly, we detect SARS-CoV-2 particles in PCR-confirmed patient nasal swabs without prior purification steps. In summary, we developed an efficient framework to detect and characterize single SARS-CoV-2 particles.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.28.26351994v1?rss=1">
<title>
<![CDATA[
COVID-19 onset, stay-at-home orders, and racialized inequities in homicide mortality across the US 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.28.26351994v1?rss=1"
</link>
<dc:creator>Tanveer, M.</dc:creator>
<dc:creator>Santaularia Gomez, N. J.</dc:creator>
<dc:creator>Vinita Fitch, K.</dc:creator>
<dc:creator>Holmes, M.</dc:creator>
<dc:creator>Moracco, K. E.</dc:creator>
<dc:creator>Dolan, M.</dc:creator>
<dc:creator>Fulcher, N.</dc:creator>
<dc:creator>Ranapurwala, S. I.</dc:creator>
<dc:date>2026-04-29</dc:date>
<dc:identifier>doi:10.64898/2026.04.28.26351994</dc:identifier>
<dc:title><![CDATA[COVID-19 onset, stay-at-home orders, and racialized inequities in homicide mortality across the US]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-29</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
We examined the impact of COVID-19 pandemic onset (2020 April) on homicide mortality in the United States.

We conducted a single interrupted time series analysis using homicide events from the National Vital Statistics System that occurred over six years (2017-2022), with COVID-19 onset as an interruption. Monthly homicide deaths rates were calculated per 100,000 person-years to create a monthly time series. We used autoregressive integrated moving average regression, adjusted for seasonality, to model the immediate and sustained trend changes in the homicide mortality rate ratios due to the pandemic. We stratified models by length of stay-at-home order, race and ethnicity, sex, age, and weapon used to examine effect measure modification.

In Jan 2017, the US homicide mortality rate was 5.9/100,000 PY. While there were annual seasonal changes, the overall time trend before April 2020 was stable. However, with COVID-19 onset, the overall homicide mortality rate ratio increased by 32% (95% CI: 0.23, 0.41), which persisted through 2022 without additional trend changes, but with seasonal variations. Immediate increases with stable sustained trends in homicide rates were also observed in most stratified analyses.

COVID-19 pandemic onset is associated with US homicide mortality rates immediately increasing and remaining stable and higher afterwards.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.27.721131v1?rss=1">
<title>
<![CDATA[
Naturally occurring ACE2 stalk variants are differentially released from the cell. 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.27.721131v1?rss=1"
</link>
<dc:creator>Wiersch, F.</dc:creator>
<dc:creator>Lux, C.</dc:creator>
<dc:creator>Vanderliek-Kox, J.</dc:creator>
<dc:creator>Schun, K.</dc:creator>
<dc:creator>Ludwig, A.</dc:creator>
<dc:creator>Dusterhoft, S.</dc:creator>
<dc:date>2026-04-29</dc:date>
<dc:identifier>doi:10.64898/2026.04.27.721131</dc:identifier>
<dc:title><![CDATA[Naturally occurring ACE2 stalk variants are differentially released from the cell.]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-29</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Angiotensin-converting enzyme 2 (ACE2) is a key regulator of the renin-angiotensin-aldosterone system (RAAS). It also acts as a receptor for SARS-CoV-2 and stabilises the B0AT1 amino acid transporter at the cell surface. Therefore, surface expression of ACE2 is crucial for these physiological processes. ACE2 is released as a soluble, catalytically active form, partly through ectodomain shedding. This process mainly involves the sheddases ADAM10 and ADAM17, but the exact regulatory mechanisms remain unclear.

We assessed 11 naturally occurring single-point mutations in the ACE2 stalk region. Most variants showed significantly reduced release compared to wild-type (WT) ACE2; however, the single point mutations P734L and G726R significantly increased their release. ACE2_P734L also exhibits higher surface expression, directly increasing the surface levels of B0AT1. Despite B0AT1 and ACE2 forming a tight tetrameric complex, this did not affect ACE2 shedding. This suggests that complex formation does not restrict sheddase access.

Overall, these data identify the ACE2 stalk region as a major determinant of shedding efficiency. Naturally occurring variants in this region can substantially affect the release of soluble ACE2, potentially contributing to interindividual differences that are relevant for pathophysiological processes.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.27.721205v1?rss=1">
<title>
<![CDATA[
T-cell repertoire response in individuals with post-acute sequelae of COVID-19 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.27.721205v1?rss=1"
</link>
<dc:creator>Montague, Z.</dc:creator>
<dc:creator>Grover, R. M.</dc:creator>
<dc:creator>Baumgartner, A.</dc:creator>
<dc:creator>Trofimov, A.</dc:creator>
<dc:creator>Hadlock, J.</dc:creator>
<dc:creator>Nourmohammad, A.</dc:creator>
<dc:date>2026-04-29</dc:date>
<dc:identifier>doi:10.64898/2026.04.27.721205</dc:identifier>
<dc:title><![CDATA[T-cell repertoire response in individuals with post-acute sequelae of COVID-19]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-29</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
T-cells are central to SARS-CoV-2 clearance and immunological memory, yet their contribution to the persistence of post-acute sequelae of COVID-19 (PASC) remains poorly understood. The immunological features that distinguish individuals who develop PASC from those who recover fully are unresolved, in part due to the phenotypic heterogeneity of the condition and the likely multiplicity of its underlying mechanisms. Here, we profiled longitudinal bulk TCR{beta} repertoires from 120 individuals in the INCOV cohort-71 with PASC and 49 without-sampled at two to three time points spanning the acute and post-acute phases of infection. Using robust statistical modeling of repertoire composition and clonal dynamics, we found that global statistics such as V, J gene usage and CDR3 length do not differ between groups, but that locally enriched sequence motifs and differentially dynamic clones reveal distinct T-cell signatures associated with PASC status. Clones contracting following the peak of the acute response were significantly enriched for SARS-CoV-2 specificity in both groups. Interestingly, Influenza A-specific TCRs were disproportionately enriched among contracting clones in PASC+ repertoires, implicating viral co-infection as a potential contributor to early disease severity and, possibly, PASC pathogenesis. Rare public TCR clones were markedly enriched for SARS-CoV-2 specificity, with PASC+ individuals harboring a modestly but significantly higher proportion than PASC- individuals. Together, we identified over 1,000 candidate TCR{beta} receptors potentially discriminating PASC+ from PASC- immune responses, opening a path toward the identification of disease-relevant T-cell specificities and the development of T-cell-based immunological biomarkers for long COVID.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.27.26351858v1?rss=1">
<title>
<![CDATA[
A Deterministic-Stochastic Model for COVID-19 and Malaria Co-Infection with Malaria-Acquired Partial Immunity 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.27.26351858v1?rss=1"
</link>
<dc:creator>Idowu, K. O.</dc:creator>
<dc:creator>Lin, G.</dc:creator>
<dc:date>2026-04-28</dc:date>
<dc:identifier>doi:10.64898/2026.04.27.26351858</dc:identifier>
<dc:title><![CDATA[A Deterministic-Stochastic Model for COVID-19 and Malaria Co-Infection with Malaria-Acquired Partial Immunity]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-28</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Coinfection of COVID-19 and malaria in endemic regions may generate complex epidemiological interactions that influence susceptibility patterns, disease burden, and outbreak risk. Although malaria-acquired immunity has been hypothesized to modulate host responses to other infections, its population-level implications for COVID-19 transmission under uncertainty remain insufficiently understood. In this study, we develop a deterministic-stochastic compartmental model for the coupled dynamics of COVID-19, malaria, and their co-infection. Malaria-acquired partial immunity is incorporated through a relative susceptibility parameter that reduces the risk of COVID-19 infection among malaria-recovered individuals.

For the deterministic system, we establish positivity, boundedness, an invariant feasible region, and basic reproduction numbers for the COVID-19-only and malaria-only subsystems. We then use numerical simulations to examine how immunity-mediated reductions in susceptibility may influence COVID-19 incidence, peak burden, hospitalization, and cumulative mortality. To account for environmental and transmission variability, we extend the deterministic model to an Ito stochastic differential equation framework and use repeated realizations to characterize uncertainty in epidemic trajectories, peak distributions, and outbreak risk. In addition, global sensitivity analysis based on partial rank correlation coefficients (PRCCs) is performed to identify the parameters with the greatest influence on COVID-19 outcomes.

Our results suggest that, under the assumed modeling framework, malaria-acquired partial immunity may reduce the peak infectious burden and cumulative mortality associated with COVID-19. The stochastic simulations further show substantial variability around deterministic trajectories and indicate a non-negligible probability of large outbreak events that are not fully captured by mean-field predictions alone. Overall, the proposed framework provides an uncertainty-aware, mechanistic basis for studying COVID-19-malaria co-dynamics and for assessing how interacting disease processes may shape epidemic outcomes in endemic settings.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.28.721328v1?rss=1">
<title>
<![CDATA[
Distinct virus-derived circular RNA molecule influences host response during SARS-CoV-2 infection 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.28.721328v1?rss=1"
</link>
<dc:creator>Grossi-Soyster, E. N.</dc:creator>
<dc:creator>Gullberg, R. C.</dc:creator>
<dc:creator>Rustagi, A.</dc:creator>
<dc:creator>Lee, J. S.</dc:creator>
<dc:creator>Blish, C. A.</dc:creator>
<dc:creator>Cherry, S.</dc:creator>
<dc:creator>Salzman, J.</dc:creator>
<dc:creator>Sarnow, P.</dc:creator>
<dc:date>2026-04-28</dc:date>
<dc:identifier>doi:10.64898/2026.04.28.721328</dc:identifier>
<dc:title><![CDATA[Distinct virus-derived circular RNA molecule influences host response during SARS-CoV-2 infection]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-28</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Virus-derived circular RNA molecules (VcircRNAs) are expressed by many RNA viruses during infection. Putative functions include modulating viral replication and interacting with the host immune response. Some function as non-coding RNA fragments that regulate gene expression through binding to complementary RNA sequences, whereas others contain internal ribosomal entry site (IRES) sequences or non-canonical modifications that allow them to be translated. Here, we confirm the expression of a distinct SARS-CoV-2 VcircRNA molecule, circ7b8N, that has not been previously identified. We found that circ7b8N is expressed and detectable in cell culture infections and in acute infections across SARS-CoV-2 variants and shows promise for detection in post-acute clinical samples. Conservation of circ7b8N junctions is limited to the nearest phylogenetic relatives within the betacoronavirus genus but are present in other human and bat-infecting coronaviruses. Host cell gene expression is modulated by the treatment with circ7b8N agnostic of viral infection. The discovery and subsequent confirmation of circ7b8N expressed by SARS-CoV-2 provides a new biomarker for infection, and its conservation across variants suggests functional importance.

Author SummaryCircular RNAs are a well-documented class of molecules expressed by mammalian cells. However, circular RNA molecules expressed by RNA viruses remain largely uncharacterized regarding their generation, specific functions, and roles in host-pathogen interactions. Our computational predictions discovered thousands of distinct circular RNA molecules expressed by SARS-CoV-2. Among these, we confirmed the presence of circ7b8N, the most abundant SARS-CoV-2-derived circular RNA identified in our sequencing data. We found that circ7b8N localizes outside the nucleus and is detectable in clinical samples collected both during and after acute SARS-CoV-2 infection. Although overexpression of circ7b8N was not found to alter viral titers, it modulated the expression of host genes related to immune response activation and membrane remodeling. This suggests that circ7b8N may simultaneously provide pro- and anti-viral functions independent of influencing viral replication. Phylogenetic analyses of coronaviruses suggest that the expression of circ7b8N is a relatively recent evolutionary event, and it is conserved across SARS-CoV-2 variants from the first five years of the pandemic. The abundant presence of circ7b8N across variants in both sequencing data and clinical samples implies it plays a multifaceted role in SARS-CoV-2 pathogenesis.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.24.26351694v1?rss=1">
<title>
<![CDATA[
Disentangling Fatigue from Depression among Survivors of Severe COVID-19 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.24.26351694v1?rss=1"
</link>
<dc:creator>Cabrera, J. R.</dc:creator>
<dc:creator>Pham, P.</dc:creator>
<dc:creator>Boscardin, W. J.</dc:creator>
<dc:creator>Makam, A. N.</dc:creator>
<dc:date>2026-04-27</dc:date>
<dc:identifier>doi:10.64898/2026.04.24.26351694</dc:identifier>
<dc:title><![CDATA[Disentangling Fatigue from Depression among Survivors of Severe COVID-19]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-27</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
PurposeSurvivors of severe COVID-19 commonly experience post-intensive care syndrome (PICS), which includes depression and fatigue. Fatigue is far more common and may inflate depression severity given overlapping symptoms. We sought to disentangle fatigue from depression in PICS.

MethodsWe conducted a cross-sectional analysis of the RAFT COVID study, a national multicenter longitudinal cohort of severe prolonged COVID-19 survivors. We included participants who completed validated surveys at 1-year from hospitalization for depression (PHQ-9) and fatigue (FACIT-Fatigue). We described correlation of FACIT-fatigue with the PHQ9, and separately with PHQ-2 and PHQ-7, which both omit the two items we hypothesized are influenced by fatigue--tiredness and sleeping. Using a MIMIC model, we performed differential item functioning to evaluate the impact of fatigue on depression directly through these two questions and indirectly with the latent depression construct. We then compared PHQ-7 to PHQ-9 scores by fatigue status.

ResultsAmong 82 participants, 61.0% reported fatigue (reverse-scored FACIT-Fatigue [&ge;]9), and 15.9% moderately severe depression (PHQ-9 [&ge;]10). FACIT-fatigue was strongly correlated with PHQ-9 (r=.87, p<.001), but less so for PHQ-2 (r=.76, p<.001) and PHQ-7 (r=.82, p<.001). The MIMIC model identified significant direct effects on tiredness ({lambda}=.89, p<.001) and sleep ({lambda}=.52, p<.001). Among fatigued participants, the rescaled PHQ-7 was lower than the PHQ-9 (median of 4.5, IQR 1.50-9.75, vs 7, IQR 4-9.75).

ConclusionsFatigue significantly inflated depression symptoms in severe COVID-19 survivors through tiredness and sleeping PHQ-9 items. PHQ-2 may better screen for true depressive symptoms in PICS, minimizing the risk of misdiagnosis and overtreatment.

PLAIN ENGLISH SUMMARYSurvivors of severe COVID-19 illness commonly experience post-intensive care syndrome (PICS), which includes depression and fatigue. Fatigue is far more common and may inflate depression severity given overlapping symptoms. We sought to disentangle fatigue from depression in PICS. We found that the presence of fatigue inflated depression severity through symptoms of tiredness and difficulty sleeping, which are two of the nine items of a commonly used depression screening tool, known as the Patient Health Questionnaire-9 (PHQ-9). Depression screening tools that omit these two items, such as the PHQ-2, may better screen for depressive symptoms in PICS, minimizing the risk of overestimating depression symptoms and potentially misdiagnosis.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.27.721040v1?rss=1">
<title>
<![CDATA[
Inhibiting the interaction between the mitochondrial receptor Tom70 and SARS CoV 2 Orf9b with small molecules 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.27.721040v1?rss=1"
</link>
<dc:creator>San Felipe, C.</dc:creator>
<dc:creator>Verba, K. A.</dc:creator>
<dc:creator>Krogan, N. J.</dc:creator>
<dc:creator>Grabe, M.</dc:creator>
<dc:creator>Fraser, J. S.</dc:creator>
<dc:date>2026-04-27</dc:date>
<dc:identifier>doi:10.64898/2026.04.27.721040</dc:identifier>
<dc:title><![CDATA[Inhibiting the interaction between the mitochondrial receptor Tom70 and SARS CoV 2 Orf9b with small molecules]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-27</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
The SARS CoV 2 accessory protein Orf9b is in a complex monomer-dimer equilibrium that influences its interactions with the host mitochondrial receptor Tom70. This interaction is critical for viral suppression of a Type-1 interferon response during infection. Modulating this equilibrium with a small molecule, either by stabilizing the Orf9b dimer or blocking its interaction with Tom70, represents a promising strategy for restoring interferon signaling and the antiviral response. To build tool molecules that could test this concept, we performed two screens: a crystallographic fragment screen against the Orf9b homodimer and a high-throughput fluorescence polarization screen for competitors of an Orf9b-derived peptide binding to Tom70. Fragment screening revealed two binding sites with potential to be developed into an inhibitor: one located at the peripheral dimer interface and the other just outside the lipid-binding channel that defines the central dimer interface. Functionalization of the fragments outside of the lipid-binding channel with hydrophobic moieties stabilized the Orf9b dimer thereby indirectly inhibiting association with Tom70. In parallel, the high throughput screen for competitive inhibitors of the Tom70:Orf9b interaction discovered a separate series of molecules. These molecules display dynamic structure activity relationship (SAR) and could be improved in the future to modulate the interaction between Tom70 and potentially a wide range of substrates. Collectively, these results demonstrate the feasibility of two distinct strategies to manipulate the Orf9b-Tom70 equilibrium, which is critical to the host response to SARS CoV 2 infection.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.21.26350610v1?rss=1">
<title>
<![CDATA[
Identifying clinician perceived priorities for a real-time wearable system for in-hospital monitoring: findings and evolutions following the COVID-19 pandemic 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.21.26350610v1?rss=1"
</link>
<dc:creator>Vollam, S.</dc:creator>
<dc:creator>Roman, C.</dc:creator>
<dc:creator>King, E.</dc:creator>
<dc:creator>Tarassenko, L.</dc:creator>
<dc:date>2026-04-24</dc:date>
<dc:identifier>doi:10.64898/2026.04.21.26350610</dc:identifier>
<dc:title><![CDATA[Identifying clinician perceived priorities for a real-time wearable system for in-hospital monitoring: findings and evolutions following the COVID-19 pandemic]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-24</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
A Wearable Monitoring System (WMS), comprising a chest patch, wrist-worn pulse oximeter, and arm-worn blood pressure device, was developed in preparation for a pilot Randomised Controlled Trial (RCT) on a UK surgical ward. The system was designed to support continuous physiological monitoring and early detection of deterioration.

An initial prototype user interface was developed by the research team based on prior clinical experience and engineering knowledge. To ensure suitability for clinical practice, iterative user-centred refinement was undertaken through a series of clinician focus groups and wearability assessments. Six focus groups were conducted between November 2019 and May 2021 involving multidisciplinary healthcare professionals. Feedback from these sessions informed successive interface and system modifications.

System development spanned the COVID-19 pandemic, during which the WMS was rapidly adapted and deployed to support clinical care on isolation wards. Feedback obtained during this period was incorporated into later versions of the system and provided a unique opportunity to examine changes in clinician priorities under pandemic conditions.

Clinicians consistently prioritised alert visibility, alarm fatigue mitigation, parameter flexibility, and centralised monitoring. Notably, preferences regarding alert modality and access mechanisms evolved over time: early enthusiasm for mobile or smartphone-type devices shifted towards a preference for fixed, ward-based displays and audible alerts at the nurses station following pandemic deployment.

Building on previous wearability testing in healthy volunteers, wearability testing using a validated questionnaire was completed by 169 patient participants during the RCT. The chest patch and pulse oximeter demonstrated high tolerability, whereas the blood pressure cuff showed poor wearability and was removed from the final system.

These findings demonstrate the importance of iterative, clinician-led design for wearable WMS and highlight how extreme clinical contexts such as the COVID-19 pandemic can significantly reshape perceived requirements for safety-critical monitoring technologies.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.22.26351531v1?rss=1">
<title>
<![CDATA[
Identifying SARS-CoV-2 Lineages that Share the Same Relative Effective Reproduction Numbers 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.22.26351531v1?rss=1"
</link>
<dc:creator>Musonda, R.</dc:creator>
<dc:creator>Ito, K.</dc:creator>
<dc:creator>Omori, R.</dc:creator>
<dc:creator>Ito, K.</dc:creator>
<dc:date>2026-04-24</dc:date>
<dc:identifier>doi:10.64898/2026.04.22.26351531</dc:identifier>
<dc:title><![CDATA[Identifying SARS-CoV-2 Lineages that Share the Same Relative Effective Reproduction Numbers]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-24</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continuously evolved since its emergence in the human population in 2019. As of 1st August 2025, more than 1,700 Omicron subvariants have been designated by the Pango nomenclature system. The Pango nomenclature system designates a new lineage based on genetic and epidemiological information of SARS-CoV-2 strains. However, there is a possibility that strains that have similar genetic backgrounds and the same phenotype are given different Pango lineage names. In this paper, we propose a new algorithm, called FindPart-w, which can identify groups of viral lineages that share the same relative effective reproduction numbers. We introduced a new lineage replacement model, called the constrained RelRe model, which constrains groups of lineages to have the same relative effective reproduction numbers. The FindPart-w algorithm searches the equality constraints that minimise the Akaike Information Criterion of constrained RelRe models. Using hypothetical observation count data created by simulation, we found that the FindPart-w algorithm can identify groups of lineages having the same relative effective reproduction number in a practical computational time. Applying FindPart-w to actual real-world data of time-stamped lineage counts from the United States, we found that the Pango lineage nomenclature system may have given different lineage names to SARS-CoV-2 strains even if they have the same relative effective reproduction number and similar genetic backgrounds. In conclusion, this study showed that viruses that had the same relative effective reproduction number were identifiable from temporal count data of viral sequences. These findings will contribute to the future development of lineage designation systems that consider both genetic backgrounds and transmissibilities of lineages.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.22.720035v1?rss=1">
<title>
<![CDATA[
Bacteriocin Diversity and Antiviral Potential of Lactiplantibacillus pentosus from Fermented Rice. 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.22.720035v1?rss=1"
</link>
<dc:creator>Cheruvari, A.</dc:creator>
<dc:creator>kammara, R.</dc:creator>
<dc:date>2026-04-24</dc:date>
<dc:identifier>doi:10.64898/2026.04.22.720035</dc:identifier>
<dc:title><![CDATA[Bacteriocin Diversity and Antiviral Potential of Lactiplantibacillus pentosus from Fermented Rice.]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-24</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Fermentation is a long-standing tradition on the Indian subcontinent, shaped by local cultures and resources. Regional ingredients create a variety of fermented foods rich in probiotics. Lactiplantibacillus pentosus, found in foods like olives, grains, and vegetables, is a key strain. We studied the genome of L. pentosus from traditional fermented rice in Himachal Pradesh, India, and compared it to 95 global genomes. Our focus was on antimicrobial compounds, especially bacteriocins, which improve food safety. KEGG analysis revealed important metabolic proteins, while BPGA showed genome sizes of 3.4-4 Mb and GC content of 45.5-46%. The Indian L. pentosus strain (krglsrbmofpi2) uniquely contains three bacteriocins: Pentoplantaricin-EF, Pentobovicin, and Pentopediocin. Docking studies assessed their antiviral potential. Pentoplantaricin-EF showed the strongest binding to the prefusion 2019-nCoV spike glycoprotein (PDB 6VSB), while Pentobovicin had the highest affinity for the Omicron spike protein (PDB 7T9J) and the Hepatitis E virus E2 domain (PDB 3RKC).
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.22.720112v1?rss=1">
<title>
<![CDATA[
Proximity proteomics reveals a role for IFI16 during human coronavirus infection 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.22.720112v1?rss=1"
</link>
<dc:creator>Languon, S.</dc:creator>
<dc:creator>Bailey, I.</dc:creator>
<dc:creator>Sorensen, M.</dc:creator>
<dc:creator>Miller, Z. D.</dc:creator>
<dc:creator>Sha, J.</dc:creator>
<dc:creator>Dearborn, J.</dc:creator>
<dc:creator>Dowell, W.</dc:creator>
<dc:creator>Kirch, T.</dc:creator>
<dc:creator>Wohlschlegel, J.</dc:creator>
<dc:creator>MAJUMDAR, D.</dc:creator>
<dc:date>2026-04-23</dc:date>
<dc:identifier>doi:10.64898/2026.04.22.720112</dc:identifier>
<dc:title><![CDATA[Proximity proteomics reveals a role for IFI16 during human coronavirus infection]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-23</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Viruses rely on the infected host cell to ensure successful replication and propagation of infection. This is achieved through interactions between virus-encoded proteins and proteins expressed in infected cells. All human coronaviruses (HCoVs) encode 16 non-structural proteins (NSPs) which exhibit some level of similarity in identity and function among the HCoVs. To identify host proteins that are potential interacting partners of HCoV NSPs, we utilized split-TurboID along with mass spectrometry and identified IFN-{gamma}-inducible protein-16 (IFI16) as a proximal partner of SARS-CoV-2 NSP8 and NSP10. To investigate the significance of the association between the NSP8/NSP10 complex and IFI16, we utilized CRISPR-Cas9 to knockout and CRISPRi to knockdown IFI16 in A549 cells and demonstrated that loss or reduced expression of IFI16 leads to a decrease in human coronavirus infection. We further demonstrated that there is reduced viral RNA replication and viral protein synthesis upon loss of IFI16. Interestingly, the loss of IFI16 results in reduced expression of type I IFNs. Taken together, these data suggests that IFI16 promotes human coronavirus infection, and the role IFI16 plays in coronavirus replication is independent of its role as a regulator of type I IFN gene expression.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.21.26351402v1?rss=1">
<title>
<![CDATA[
Diagnostic Classification for Long Covid Patients identifying Persistent Virus and Hyperimmune Pathophysiologies 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.21.26351402v1?rss=1"
</link>
<dc:creator>James-Pemberton, P.</dc:creator>
<dc:creator>Harper, D.</dc:creator>
<dc:creator>Wagerfield, P.</dc:creator>
<dc:creator>Watson, C.</dc:creator>
<dc:creator>Hervada, L.</dc:creator>
<dc:creator>Kohli, S.</dc:creator>
<dc:creator>Alder, S.</dc:creator>
<dc:creator>Shaw, A.</dc:creator>
<dc:date>2026-04-22</dc:date>
<dc:identifier>doi:10.64898/2026.04.21.26351402</dc:identifier>
<dc:title><![CDATA[Diagnostic Classification for Long Covid Patients identifying Persistent Virus and Hyperimmune Pathophysiologies]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-22</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
A multiplex diagnostic test is evaluated for self-reported long COVID associated persistent symptoms and a poor recovery from a SARS-CoV-2 infection. A mass-standardised concentration of total antibodies (AC), high-quality (HQ) antibodies and percentage of HQ antibodies (HQ%) is assessed against a spectrum of spike proteins to the SARS-CoV-2 variants: Wuhan, , {delta}, and the Omicron variants BA.1, BA.2, BA.2.12.1, BA.2.75, BA.5, CH.1.1, BQ.1.1 and XBB.1.5 in three cohorts. A cohort of control patients (n = 46) recovered (CC) and a cohort of self-declared long COVID patients (n = 113) (LCC). A nested Receiver Operating Characteristic (ROC) analysis, performed for the variant with lowest HQ concentration in the spectrum, produced an area under the curve and AUC = 0.61 (0.53-0.70) for the CC vs LCC cohorts. For the LCC cohort, the cut-off thresholds for AC = 0.8 mg/L, HQ = 1.5 mg/L and HQ% of 34% were determined, leading to a 71% sensitivity and 66% specificity derived by the Youden metric. The cohorts may be fully classified based on ROC and outlier analysis to give an incidence of persistent virus 62% (95% CI 52% - 71%), hyperimmune 12% (95% CI 7% - 20%) and unclassified, 26% (95% CI 18% - 35%). The overall diagnostic accuracy for both the hyper and hypo immune is 69%. All clinical interventions can now be tailored for the heterogenous long COVID patient cohort.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.20.719671v1?rss=1">
<title>
<![CDATA[
Unique nasal cell states induced by common pediatric respiratory viruses 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.20.719671v1?rss=1"
</link>
<dc:creator>Walsh, J. M. L.</dc:creator>
<dc:creator>Juttukonda, L. J.</dc:creator>
<dc:creator>Tang, Y.</dc:creator>
<dc:creator>Chatterjee, A.</dc:creator>
<dc:creator>Elosua-Bayes, M.</dc:creator>
<dc:creator>Langan, E.</dc:creator>
<dc:creator>Frischmann, A.</dc:creator>
<dc:creator>Taliaferro, F.</dc:creator>
<dc:creator>Matthews, H. R.</dc:creator>
<dc:creator>Kimler, K.</dc:creator>
<dc:creator>Lent, C. M.</dc:creator>
<dc:creator>Purna Keya, D.</dc:creator>
<dc:creator>Chondrow Dev, P.</dc:creator>
<dc:creator>Rajib Malaker, A.</dc:creator>
<dc:creator>Tanvia, L.</dc:creator>
<dc:creator>Mohammad Tanmoy, A.</dc:creator>
<dc:creator>Ghosh, S.</dc:creator>
<dc:creator>Maitra, A.</dc:creator>
<dc:creator>Ghosh, A.</dc:creator>
<dc:creator>Basu, S.</dc:creator>
<dc:creator>Kane, A. S.</dc:creator>
<dc:creator>Coomer, C. A.</dc:creator>
<dc:creator>Shalek, A. K.</dc:creator>
<dc:creator>de Silva, T. I.</dc:creator>
<dc:creator>Sesay, A. K.</dc:creator>
<dc:creator>Edwards, J.</dc:creator>
<dc:creator>Sin Quee, C.</dc:creator>
<dc:creator>Gonzalez, W. I.</dc:creator>
<dc:creator>Yonker, L. M.</dc:creator>
<dc:creator>Glover, S. C.</dc:creator>
<dc:creator>Majumder, P.</dc:creator>
<dc:creator>Hooda, Y.</dc:creator>
<dc:creator>Saha, S.</dc:creator>
<dc:creator>Ordovas-Montanes, J.</dc:creator>
<dc:creator>Horwitz, B. H.</dc:creator>
<dc:date>2026-04-22</dc:date>
<dc:identifier>doi:10.64898/2026.04.20.719671</dc:identifier>
<dc:title><![CDATA[Unique nasal cell states induced by common pediatric respiratory viruses]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-22</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Respiratory viral infections in early childhood are major drivers of acute morbidity and long-term airway disease, yet how distinct viruses remodel the pediatric nasal mucosa at cellular resolution remains unresolved. Here, we generated a single-cell RNA sequencing atlas of 335,174 nasal epithelial and immune cells from 132 children under five years of age with SARS-CoV-2, rhinovirus, or respiratory syncytial virus (RSV) infection, alongside uninfected controls. Mapping viral transcripts to individual cells revealed virus-specific infected epithelial states: an NF-kB-responsive ciliated subset in SARS-CoV-2 and a previously undescribed KRT17+ squamous-like subset in RSV. We delineated divergent mucosal response programs, including a robust interferon (IFN) response in SARS-CoV-2, an IL-13-responsive secretory program in rhinovirus, and heightened inflammatory and cytotoxic immune activation in RSV. In RSV, specific immune subsets and elevated IFN-response signatures were associated with disease severity, whereas rhinovirus-induced wheeze was marked by expansion of a CST1+ goblet cell subset. Integration of asthma genome-wide association data with our atlas revealed a KRT13+ hillock-like squamous epithelial subset enriched for expression of childhood-onset asthma risk loci. Finally, we demonstrate that this resource enables high-resolution annotation of independent pediatric cohorts in Kolkata, India and rural Bangladesh. Together, this atlas establishes a comprehensive view of antiviral immunity in the pediatric nasal mucosa and defines virus-specific mucosal immune programs relevant to disease severity and asthma risk in early life.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.20.719543v1?rss=1">
<title>
<![CDATA[
Long-range allosteric communication, double mutant cycles, and energetic coupling in SARS-CoV-2 spike protein 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.20.719543v1?rss=1"
</link>
<dc:creator>Lucas, A.</dc:creator>
<dc:creator>Rayaprolu, V.</dc:creator>
<dc:creator>Mallela, K.</dc:creator>
<dc:date>2026-04-22</dc:date>
<dc:identifier>doi:10.64898/2026.04.20.719543</dc:identifier>
<dc:title><![CDATA[Long-range allosteric communication, double mutant cycles, and energetic coupling in SARS-CoV-2 spike protein]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-22</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
SARS-CoV-2 spike protein is continuously evolving, leading to new variants. While mutations in the receptor-binding domain (RBD) enhance binding to the ACE2 receptor and evade neutralizing antibodies, the function of mutations in the N-terminal domain (NTD) remains poorly understood. Using two independent methods, surface plasmon resonance (SPR) and cryo-EM, we show that NTD mutations increase the population of spike protein with the RBD in the "up" conformational state. SPR association and dissociation kinetics of spike binding to ACE2 and antibodies, analyzed using a coupled equilibrium model, determined the relative populations and indicated that the RBD-up-to-down transition is rate-limiting relative to the RBD-down-to-up transition. Advanced model fitting of cryo-EM Coulomb potential maps confirmed the populations. The combined effect of NTD and RBD mutations exceeds the sum of their individual effects, indicating long-range allosteric communication and energetic coupling within the spike protein.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.21.719937v1?rss=1">
<title>
<![CDATA[
A High-Throughput Platform for Rapidly Adapting DNA Aptamers to SARS-CoV-2 Evolution 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.21.719937v1?rss=1"
</link>
<dc:creator>He, Y.</dc:creator>
<dc:creator>Yang, Z.</dc:creator>
<dc:creator>Kuo, Y.-A.</dc:creator>
<dc:creator>Wu, Y.</dc:creator>
<dc:creator>Fonseca-Albert, D.</dc:creator>
<dc:creator>Le, K. K.</dc:creator>
<dc:creator>Guo, J. G.</dc:creator>
<dc:creator>Wang, Y.</dc:creator>
<dc:creator>Nguyen, A.-T.</dc:creator>
<dc:creator>Chen, Y.-I.</dc:creator>
<dc:creator>Kim, S.</dc:creator>
<dc:creator>Chen, W.-R.</dc:creator>
<dc:creator>Seifi, S.</dc:creator>
<dc:creator>Hong, S.</dc:creator>
<dc:creator>Nguyen, T. D.</dc:creator>
<dc:creator>Chen, Y.</dc:creator>
<dc:creator>Ren, P.</dc:creator>
<dc:creator>Lu, Y.</dc:creator>
<dc:creator>Yeh, H.-C.</dc:creator>
<dc:date>2026-04-22</dc:date>
<dc:identifier>doi:10.64898/2026.04.21.719937</dc:identifier>
<dc:title><![CDATA[A High-Throughput Platform for Rapidly Adapting DNA Aptamers to SARS-CoV-2 Evolution]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-22</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Rapid pathogen evolution threatens public health by eroding the effectiveness of vaccines, therapeutics, and diagnostic tools. Although spike protein targeting monoclonal antibodies (mAbs) were developed within 10-12 months of the initial outbreak to serve as key theranostic agents, their redesign has struggled to keep pace with viral evolution, rendering many neutralizing antibodies ineffective. Here we demonstrate a novel platform that combines a random-rational hybrid library diversification with high-throughput MiSeq screening to rapidly reprogram aptamers against emerging SARS-CoV-2 spike variants. Interactions between 3 different spike proteins and 11,806 unique aptamer variant designs were profiled within a few days. Starting from a 40-nt aptamer originally selected against wild-type (WT) spike protein, our screen identified a Delta-binding mutant with a 4-fold affinity improvement and an Omicron-binding mutant that converted undetectable binding into nanomolar affinity. We also identified a WT-selective mutant with substantially reduced affinity for Delta, as well as previously unrecognized bases that critically contribute to spike recognition. Integrating high-throughput binding data with molecular dynamics simulations further revealed sequence-dependent structural features underlying variant-specific aptamer-spike interactions. Finally, we developed a sensor based on the identified WT-selective aptamer mutant, enabling highly specific detection of the WT spike protein with robust performance. Together, this work establishes a rapid and adaptable aptamer engineering platform for rapid adaptation of aptamers to evolving pathogens in future pandemics.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.14.26350639v1?rss=1">
<title>
<![CDATA[
Modeling the impact of adherence to U.S. isolation and masking guidance on SARS-CoV-2 transmission in office workplaces in 2021-2022 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.14.26350639v1?rss=1"
</link>
<dc:creator>Garcia Quesada, M.</dc:creator>
<dc:creator>Wallrafen-Sam, K.</dc:creator>
<dc:creator>Kiti, M. C.</dc:creator>
<dc:creator>Ahmed, F.</dc:creator>
<dc:creator>Aguolu, O. G.</dc:creator>
<dc:creator>Ahmed, N.</dc:creator>
<dc:creator>Omer, S. B.</dc:creator>
<dc:creator>Lopman, B. A.</dc:creator>
<dc:creator>Jenness, S. M.</dc:creator>
<dc:date>2026-04-21</dc:date>
<dc:identifier>doi:10.64898/2026.04.14.26350639</dc:identifier>
<dc:title><![CDATA[Modeling the impact of adherence to U.S. isolation and masking guidance on SARS-CoV-2 transmission in office workplaces in 2021-2022]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-21</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Non-pharmaceutical interventions (NPIs) have been important for controlling SARS-CoV-2 transmission, particularly before and during initial vaccine rollout. During the pandemic, the US Centers for Disease Control and Prevention issued isolation and masking guidance in case of COVID-19-like illness, a positive SARS-CoV-2 test, or known exposure to SARS-CoV-2. However, the impact of this guidance on mitigating transmission in office workplaces is unclear. We used a network-based mathematical model to estimate the impact of this guidance on SARS-CoV-2 transmission among office workers and their communities. The model represented social contacts in the home, office, and community. We used data from the CorporateMix study to parametrize social contacts among office workers and calibrated the model to represent the COVID-19 epidemic in Georgia, USA from January 2021 through August 2022. In the reference scenario (58% adherence to guidance among office workers and the broader population), workplace transmission accounted for a small fraction of total infections. Reducing adherence among office workers to 0% increased workplace transmissions by 27.1% and increasing adherence to 75% reduced workplace transmission by 7.0%. Increasing adherence to 75% among office workers had minimal impact on symptomatic cases and deaths; increasing it among the broader population was more effective in reducing office worker cases and deaths. In our model, moderate adherence to recommended NPIs in workplaces was effective in reducing transmission, but increasing adherence had limited benefit given workplaces that have low contact intensity and hybrid work arrangements. These results underscore the public health benefits of community-wide adoption of recommended NPIs.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.19.719510v1?rss=1">
<title>
<![CDATA[
SARS-CoV-2 spike protein-associated sialoglycoconjugates induce nanoscale filipodia to facilitate micro-size platelet clotting 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.19.719510v1?rss=1"
</link>
<dc:creator>Bake, A.</dc:creator>
<dc:creator>Sanaubarova, A.</dc:creator>
<dc:creator>Spillings, B. L.</dc:creator>
<dc:creator>Bremaud, E.</dc:creator>
<dc:creator>Masic, V.</dc:creator>
<dc:creator>Dirr, L.</dc:creator>
<dc:creator>von Itzstein, M.</dc:creator>
<dc:creator>Mak, J.</dc:creator>
<dc:date>2026-04-20</dc:date>
<dc:identifier>doi:10.64898/2026.04.19.719510</dc:identifier>
<dc:title><![CDATA[SARS-CoV-2 spike protein-associated sialoglycoconjugates induce nanoscale filipodia to facilitate micro-size platelet clotting]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-20</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
COVID-19 disease is associated with thrombosis, but the pathogenic mechanism remains unclear. Here, we investigate how SARS-CoV-2 spike protein causes platelet activation and aggregation. Our three-dimensional ultrastructural analyses showed that invaginated platelet structures, open canalicular system (OCS), expanded upon activation, trapping viral particles in the process. Binding with platelet OCS concealed SAR-CoV-2 spike-coated particles from virion detection in platelet-depleted blood plasma. Both SARS-CoV-2 spike coated-particles and recombinant spikes specifically induced platelet aggregation with nanoscale filipodia extensions, with the terminal sialic acids of the SARS-CoV-2 spike protein-associated sialoglycoconjugates being the key determinant in platelet activation. Our work illustrates that virus-associated sialic acids, not proteins, are functionally responsible for SARS-CoV-2 induced thrombotic events, providing a mechanistic insight on how glycosylation contributes to disease severity in COVID-19. This study lays the foundation for the development of glycan-modified vaccines with reduced risks of thrombosis.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.17.716662v1?rss=1">
<title>
<![CDATA[
Conserved metabolic vulnerabilities across pathogenic coronaviruses nominate host-directed therapeutic targets 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.17.716662v1?rss=1"
</link>
<dc:creator>Dohai, B.</dc:creator>
<dc:creator>El Assal, D. C.</dc:creator>
<dc:creator>Kang, M.</dc:creator>
<dc:creator>Jaiswal, A.</dc:creator>
<dc:creator>Poulet, C.</dc:creator>
<dc:creator>Daakour, S.</dc:creator>
<dc:creator>Nelson, D. R.</dc:creator>
<dc:creator>Falter-Braun, P.</dc:creator>
<dc:creator>Twizere, J.-C.</dc:creator>
<dc:creator>Salehi-Ashtiani, K.</dc:creator>
<dc:date>2026-04-20</dc:date>
<dc:identifier>doi:10.64898/2026.04.17.716662</dc:identifier>
<dc:title><![CDATA[Conserved metabolic vulnerabilities across pathogenic coronaviruses nominate host-directed therapeutic targets]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-20</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Pathogenic coronaviruses profoundly rewire host cell metabolism to support viral replication, yet whether these metabolic alterations expose shared and actionable vulnerabilities remains unclear. By integrating transcriptomic profiles from cells infected with SARS-CoV, SARS-CoV-2, and MERS-CoV with genome-scale metabolic models, we identify conserved and virus-specific metabolic perturbations affecting mitochondrial transport, nucleotide biosynthesis, fatty acid metabolism, and redox balance. Despite distinct transcriptional responses, all three viruses converge on a limited set of metabolic reactions whose flux ranges deviate strongly from healthy states. Using a network-based predictive framework, we systematically identify gene-pair perturbations that restore perturbed reaction fluxes toward non-infected metabolic states. Predicted rescue mechanisms reveal shared metabolic dependencies across coronaviruses, as well as time-dependent virus-specific vulnerabilities, and nominate druggable host targets. Notably, several top predictions align with independent experimental and clinical evidence, including metabolic interventions shown to reduce viral replication or disease severity in COVID-19 patients. Together, our results define conserved metabolic rescue pathways in coronavirus infection and provide a general strategy for identifying host-directed therapeutic opportunities from transcriptomic data.

HighlightsO_LICoronaviruses converge on shared metabolic vulnerabilities in host cells
C_LIO_LINiTRO predicts gene pairs that rescue viral-induced metabolic states
C_LIO_LIMitochondrial transport emerges as a key pan-coronavirus target
C_LIO_LITop predictions validated by clinical trials and in vitro evidence
C_LI

eTOC BlurbDohai et al. develop NiTRO, a network-based algorithm that integrates coronavirus-induced transcriptomic changes with genome-scale metabolic models to identify gene-pair perturbations capable of rescuing infected metabolic states. The approach reveals shared and virus-specific druggable metabolic vulnerabilities, with top predictions corroborated by clinical evidence.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.16.719115v1?rss=1">
<title>
<![CDATA[
Systematic evaluation of 24 extraction and library preparation combinations for metagenomic sequencing of SARS-CoV-2 in saliva 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.16.719115v1?rss=1"
</link>
<dc:creator>Qian, K.</dc:creator>
<dc:creator>Abhyankar, V.</dc:creator>
<dc:creator>Keo, D.</dc:creator>
<dc:creator>Zarceno, P.</dc:creator>
<dc:creator>Toy, T.</dc:creator>
<dc:creator>Eskin, E.</dc:creator>
<dc:creator>Arboleda, V. A.</dc:creator>
<dc:date>2026-04-20</dc:date>
<dc:identifier>doi:10.64898/2026.04.16.719115</dc:identifier>
<dc:title><![CDATA[Systematic evaluation of 24 extraction and library preparation combinations for metagenomic sequencing of SARS-CoV-2 in saliva]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-20</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Sequencing the respiratory tract transcriptome has the potential to provide insights into infectious pathogens and the hosts immune response. While DNA-based sequencing is more standard in clinical laboratories due to its stability, RNA assays offer unique advantages. RNA reflects dynamic physiological changes, and for RNA viruses, viral RNA particles directly represent copies of the viral genome, enabling greater diagnostic sensitivity. However, RNAs susceptibility to degradation remains a significant challenge, particularly in RNase-rich specimens like saliva. To address this, we conducted a systematic, combinatorial evaluation of 24 distinct mNGS workflows, crossing eight nucleic acid extraction methods with three RNA-Seq library preparation protocols. Remnant saliva samples (n = 6) were pooled and spiked with MS2 phage as a control. The SARS-CoV-2 virus was spiked into half of the samples, which were extracted using the eight different extraction methods (n = 3) and compared using RNA Integrity Number equivalent (RINe) scores and RNA concentration. The extracted RNA was then processed across the three library construction methods and subjected to short-read sequencing to assess all 24 combinations head-to-head. We compared methods based on viral read recovery and found that RINe and concentration did not correlate with viral detection. The Zymo Quick-RNA Magbead kit and the Tecan Revelo RNA-Seq High-Sensitivity RNA library kit were the extraction and library-preparation kits that yielded the most SARS-CoV-2 reads, respectively. Importantly, our combinatorial analysis revealed that any small variability attributable to different nucleic acid extraction methods was heavily overshadowed by differences in quality attributable to the RNA-Seq library preparation methods. These findings challenge the reliance on conventional RNA quality metrics for clinical metagenomics and underscore the need to redefine extraction quality standards for mNGS applications.

IMPORTANCEmNGS is a powerful and unbiased approach towards pathogen detection that has mostly been applied to blood and cerebrospinal fluid samples. However mNGS has recently been applied to more areas including the respiratory pathogen detection space, with potential applications in both in-patient diagnostics and public health surveillance. Saliva samples are an ideal sample type for these use cases since they can be collected non-invasively. However, saliva is also a challenging sample type due to its high RNase activity and often yields low-quality nucleic acid. This study explores the feasibility of using saliva specimens in mNGS with contrived SARS-CoV-2 samples to optimize the combination of two factors: nucleic acid extraction and RNA-seq library preparation. Exploration in this area could enhance the sensitivity of saliva-based mNGS assays, with the goal of future expansion of this specimen type in clinical diagnostics and public health surveillance.

Key PointsO_LIThe choice of RNA-Seq library preparation kit has a greater impact on pathogen detection than the nucleic acid extraction method.
C_LIO_LIThe combination of Zymo Quick-RNA Magbead extraction kit and TECAN Revelo RNA-Seq High Sensitivity RNA library kit recovered the highest percentage of total SARS-CoV-2 reads.
C_LIO_LIRNA quantity and RINe score do not correlate with viral read capture, indicating a need for an alternative metric to assess RNA quality for downstream mNGS clinical diagnostics.
C_LI
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.16.26351013v1?rss=1">
<title>
<![CDATA[
Evolving concerns about the COVID-19 pandemic: A content analysis of free-text reports from the UK COVID-19 Public Experiences (COPE) study cohort over a two-year period 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.16.26351013v1?rss=1"
</link>
<dc:creator>Phillips, R.</dc:creator>
<dc:creator>Wood, F.</dc:creator>
<dc:creator>Torrens-Burton, A.</dc:creator>
<dc:creator>Glennan, C.</dc:creator>
<dc:creator>Sellars, P.</dc:creator>
<dc:creator>Lowe, S.</dc:creator>
<dc:creator>Caffoor, A.</dc:creator>
<dc:creator>Hallingberg, B.</dc:creator>
<dc:creator>Gillespie, D.</dc:creator>
<dc:creator>Shepherd, V.</dc:creator>
<dc:creator>Poortinga, W.</dc:creator>
<dc:creator>Wahl-Jorgensen, K.</dc:creator>
<dc:creator>Williams, D.</dc:creator>
<dc:date>2026-04-19</dc:date>
<dc:identifier>doi:10.64898/2026.04.16.26351013</dc:identifier>
<dc:title><![CDATA[Evolving concerns about the COVID-19 pandemic: A content analysis of free-text reports from the UK COVID-19 Public Experiences (COPE) study cohort over a two-year period]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-19</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
ObjectivesConcerns about COVID-19 were a key driver of infection-prevention behaviour during the pandemic. The aim of this study was to gain an in-depth longitudinal understanding of the type and frequency of concerns experienced throughout the first two years of the COVID-19 pandemic.

DesignContent analysis of qualitative descriptions provided in a prospective longitudinal online survey as part of the COVID-19 UK Public Experiences (COPE) Study.

MethodAt baseline (March/April 2020), when the UK entered its first national lockdown, 11,113 adults completed the COPE survey. Follow-up surveys were conducted at 3, 12, 18 and 24 months. Participants were recruited via the HealthWise Wales research registry and social media. Baseline surveys collected demographic and health data, and all waves included an open-ended question about COVID-19 concerns. Content analysis was used to identify the type and frequency of concerns at each time point.

ResultsA total of 41,564 open-text responses were coded into six categories: personal harm (n=16,353), harm to others (n=11,464), social/economic impact (n=6,433), preventing transmission (n=4,843), government/media (n=1,048), and general concerns (n=1,423). The proportion of respondents reporting any concern declined from 75.3% at baseline to 65.8% at 24 months. Over time, concerns about personal harm increased (baseline 41.8% vs. 24-months 52.7%) whereas concerns about harm to others decreased (baseline 48.5% vs. 24-months 28.6%). Concerns about harm were also expressed in relation to clinical vulnerability, lack of trust in government/media, and perceived lack of adherence by others. These were balanced against concerns about wider social and economic impacts of restrictions.

ConclusionsPublic concerns about COVID-19 evolved substantially over the first two years of the pandemic, reflecting changing perceptions of risk and responsibility. Monitoring concerns longitudinally is vital to help guide effective communication and behavioural interventions during future pandemics.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.16.26350989v1?rss=1">
<title>
<![CDATA[
Impact of COVID-19 pandemic on childhood immunization coverage in Indonesia: lesson learned from a nationwide analysis of the Expanded Programme on Immunization 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.16.26350989v1?rss=1"
</link>
<dc:creator>Nurina, A.</dc:creator>
<dc:creator>Puspaningrum, E.</dc:creator>
<dc:creator>Tandy, G.</dc:creator>
<dc:creator>Pattilima, D.</dc:creator>
<dc:creator>Hegar, B.</dc:creator>
<dc:creator>Wangge, G.</dc:creator>
<dc:creator>Hamers, R.</dc:creator>
<dc:creator>Elyazar, I.</dc:creator>
<dc:creator>Surendra, H.</dc:creator>
<dc:date>2026-04-18</dc:date>
<dc:identifier>doi:10.64898/2026.04.16.26350989</dc:identifier>
<dc:title><![CDATA[Impact of COVID-19 pandemic on childhood immunization coverage in Indonesia: lesson learned from a nationwide analysis of the Expanded Programme on Immunization]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-18</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundThe COVID-19 pandemic disrupted childhood immunization programmes in many countries worldwide. However, evidence on its impact in low and middle-income countries remains limited. This study examined the impact of the COVID-19 pandemic on childhood immunization coverage across 514 districts in Indonesia and identified district-level associated factors.

MethodsWe conducted a nationwide longitudinal analysis of the Expanded Programme on Immunization to compare immunization coverage before and after the pandemic. The outcome variable was the annual childhood immunization coverage (proportion of children aged 0-12 months who have received all recommended doses of childhood immunization as per the national immunization schedule). The explanatory variables include COVID-19 burden and vaccination rates, health system and human development indicators. Mixed-effect logistic regression was done to assess association between the explanatory and outcome variables.

ResultsAt the national level, the coverage was 83.2% in pre-pandemic, 75.0% in the first year of pandemic, and 88.6%, in the second. In the first year, 69.3% of districts experienced significant decline, with a lower national coverage ratio of 0.92 (95% confidence interval 0.89-0.94). In the second year, 36.2% districts were still affected. The multivariable analysis showed that a significant decline in coverage during the first pandemic year was associated with high COVID-19 incidence (adjusted odds ratio 2.19, 95%CI 1.01-4.73 for the highest vs. lowest group), low midwife adequacy (5.84, 2.40-14.16 for the lowest vs. the highest group, 2.61, 1.26-5.40 for low-middle vs. the highest group), and a high proportion of health facility-based births (2.98, 1.49-5.98 for middle-high vs. the lowest group).

ConclusionsThe COVID-19 pandemic negatively and unevenly impacted childhood immunization in Indonesia, with greatest impacts in districts facing a higher COVID-19 burden and weaker health system capacity. These findings underscore the need for targeted efforts to strengthen the local health system for future health crises.

Summary boxO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIAccording to the WHO Pulse Survey, routine immunizations were the most disrupted essential health services during the COVID-19 pandemic, reported by 70% of countries. Southeast Asia experienced the steepest drop in childhood immunization coverage compared to the other regions.
C_LIO_LIIndonesia had the highest number of COVID-19 cases and related mortality in Southeast Asia. However, the magnitude and heterogeneity of the impact of COVID-19 pandemic on childhood immunization coverage across all 514 districts in Indonesia has not been evaluated.
C_LI

What this study addsO_LIThis study affirmed that the COVID-19 pandemic greatly impacted childhood immunization coverage, disproportionately impacting district with vulnerable health systems capacity.
C_LI

How this study might affect research, practice, or policyO_LIThis study highlights the critical need of addressing health inequity to strengthen health system resilience for future global health crises.
C_LIO_LIIn the context of a decentralised health system such as in Indonesia, coordination and prioritisation of available resources and public health intervention will be critical to ensure optimal health outcomes for children living in districts with weak health systems.
C_LI
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.14.26350918v1?rss=1">
<title>
<![CDATA[
Combined Effects of Severe Immunocompromise and Prolonged Virus Shedding on Within-Host SARS-CoV-2 Evolution in COVID-19 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.14.26350918v1?rss=1"
</link>
<dc:creator>Hirata, Y.</dc:creator>
<dc:creator>Takahashi, K.</dc:creator>
<dc:creator>Iwamoto, N.</dc:creator>
<dc:creator>Dam Jeong, Y.</dc:creator>
<dc:creator>Miyamoto, S.</dc:creator>
<dc:creator>Kawasaki, J.</dc:creator>
<dc:creator>Mine, S.</dc:creator>
<dc:creator>Iida, S.</dc:creator>
<dc:creator>Saito, S.</dc:creator>
<dc:creator>Ainai, A.</dc:creator>
<dc:creator>Kanno, T.</dc:creator>
<dc:creator>Katano, H.</dc:creator>
<dc:creator>Sasaki, N.</dc:creator>
<dc:creator>Horiba, K.</dc:creator>
<dc:creator>Ishikane, M.</dc:creator>
<dc:creator>Kamegai, K.</dc:creator>
<dc:creator>Harrison, M. T.</dc:creator>
<dc:creator>Itoh, N.</dc:creator>
<dc:creator>Akazawa, N.</dc:creator>
<dc:creator>Okumura, N.</dc:creator>
<dc:creator>Haraguchi, M.</dc:creator>
<dc:creator>Sakoh, T.</dc:creator>
<dc:creator>Morishima, M.</dc:creator>
<dc:creator>Araoka, H.</dc:creator>
<dc:creator>Uchida, N.</dc:creator>
<dc:creator>Hase, R.</dc:creator>
<dc:creator>Marumo, Y.</dc:creator>
<dc:creator>Adachi, T.</dc:creator>
<dc:creator>Matsue, K.</dc:creator>
<dc:creator>Saito, T.</dc:creator>
<dc:creator>Ohmagari, N.</dc:creator>
<dc:creator>Iwami, S.</dc:creator>
<dc:creator>Suzuki, T.</dc:creator>
<dc:date>2026-04-17</dc:date>
<dc:identifier>doi:10.64898/2026.04.14.26350918</dc:identifier>
<dc:title><![CDATA[Combined Effects of Severe Immunocompromise and Prolonged Virus Shedding on Within-Host SARS-CoV-2 Evolution in COVID-19]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-17</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundProlonged SARS-CoV-2 infection in immunocompromised individuals may accelerate virus evolution within the host, raising concerns about the virus evading immunity, developing resistance, and forming novel variants of concern. However, the determinants and public health implications of within-host viral evolution in this population remain incompletely understood.

MethodsWe performed longitudinal analyses of SARS-CoV-2 genomes from 91 patients with COVID-19 who were classified as being severely or moderately immunocompromised. Using serial measurements of viral RNA loads and infectious titers, we modeled the shedding dynamics of the virus and stratified the infected cases by upper respiratory virus shedding duration to assess associations with within-host evolutionary dynamics.

ResultsShedding modeling identified two profiles of shedding duration: intermediate and long. The long shedding profile (shedding lasting >21 days) was found in 14.8% of moderately immunocompromised cases and 72.1% of severely immunocompromised cases. Frequent single-nucleotide variants accumulated specifically in severely immunocompromised individuals with the long shedding phenotype, correlating positively with shedding duration. By contrast, mutations remained limited in moderately immunocompromised individuals with the long shedding phenotype and in severely immunocompromised individuals with the intermediate shedding phenotype. We identified mutations in the spike receptor-binding domain associated with monoclonal antibody resistance; however, we found no fitness-enhancing mutations for inter-host transmission, and antiviral drug resistance mutations were rare. Instead, mutations were introduced frequently and randomly across the entire viral genome.

ConclusionsProlonged upper respiratory virus shedding exceeding 21 days combined with severe immunocompromise is a risk factor of the accumulation of within-host SARS-CoV-2 mutations. Although no variants of concern emerged, the introduction of genome-wide random mutations suggests that the risk for novel variant generation cannot be excluded. These findings highlight the need for intensive antiviral strategies to limit shedding duration to less than 21 days in severely immunocompromised patients, and for immunological investigations to elucidate the host factors underlying residual shedding control in those who achieve clearance within this threshold.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.15.26350844v1?rss=1">
<title>
<![CDATA[
Understanding inequalities in COVID-19 vaccination between migrants and non-migrants in Germany: The role of psychological factors of vaccine behaviour 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.15.26350844v1?rss=1"
</link>
<dc:creator>Bartig, S.</dc:creator>
<dc:creator>Siegert, M.</dc:creator>
<dc:creator>Hoevener, C.</dc:creator>
<dc:creator>Michalski, N.</dc:creator>
<dc:date>2026-04-17</dc:date>
<dc:identifier>doi:10.64898/2026.04.15.26350844</dc:identifier>
<dc:title><![CDATA[Understanding inequalities in COVID-19 vaccination between migrants and non-migrants in Germany: The role of psychological factors of vaccine behaviour]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-17</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundUnderstanding the underlying mechanisms for differences in vaccine uptake between migrants and non-migrants is crucial in order to design targeted interventions encouraging vaccination and to ensure vaccine-related equity. Therefore, this study examined to what extent migration-related disparities in COVID-19 vaccination were associated with psychological factors, based on the established 5C model of vaccine behaviour (Confidence, Complacency, Constraints, Calculation, Collective Responsibility).

MethodsData were obtained from the German study "Corona Monitoring Nationwide - Wave 2" (RKI-SOEP-2 study), which was carried out between November 2021 and March 2022. The association between COVID-19 vaccination and migration status, while considering the psychological factors, was investigated using multivariable binary logistic regressions. A decomposition analysis (Karlson-Holm-Breen method) was conducted to examine the extent to which migration-related disparities in vaccine uptake were associated with the psychological factors of the 5C framework.

ResultsMigrants were less likely to be vaccinated against COVID-19 compared to non-migrants, especially participants from the Middle East and North Africa (MENA) region. Our decomposition showed that almost two-thirds of the disparities in COVID-19 vaccine uptake between migrants and non-migrants were associated with the psychological factors (first-generation: 61.2%, second-generation: 64.2%). Confidence in safety of the vaccine was the most relevant factor in the 5C framework. Furthermore, the results highlighted the importance of a differentiated analysis regarding country of origin: While the 5C model accounted for only 19.4% of the difference between participants from the MENA region and non-migrants, the proportion for participants from Eastern Europe was 73.5%, suggesting that the underlying mechanisms for the lower uptake in the MENA group need further investigation.

ConclusionsOverall, migration-related disparities in COVID-19 vaccination were significantly associated with differences in psychological factors of vaccine behaviour. To increase vaccine acceptance within the heterogeneous group of migrants in general, tailored and proactive health communication interventions are needed.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.16.26351004v1?rss=1">
<title>
<![CDATA[
Transmission dynamics of the COVID-19 pandemic across the emerging variants in mainland China: a hypergraph-based spatiotemporal modeling study 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.16.26351004v1?rss=1"
</link>
<dc:creator>Wang, Y.</dc:creator>
<dc:creator>WANG, D.</dc:creator>
<dc:creator>Lau, Y. C.</dc:creator>
<dc:creator>Du, Z.</dc:creator>
<dc:creator>Cowling, B. J.</dc:creator>
<dc:creator>Zhao, Y.</dc:creator>
<dc:creator>Ali, S. T.</dc:creator>
<dc:date>2026-04-17</dc:date>
<dc:identifier>doi:10.64898/2026.04.16.26351004</dc:identifier>
<dc:title><![CDATA[Transmission dynamics of the COVID-19 pandemic across the emerging variants in mainland China: a hypergraph-based spatiotemporal modeling study]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-17</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Mainland China experienced multiple waves of COVID-19 pandemic during 2020-2022, driven by emerging variants and changes in public health and social measures (PHSMs). We developed a hypergraph-based Susceptible-Vaccinated-Exposed-Infectious-Recovered-Susceptible (SVEIRS) model to reconstruct epidemic dynamics across 31 provinces, capturing transmission heterogeneity associated with clustered contacts. We assessed key characteristics of transmission at national and provincial levels during four outbreak periods: initial, localized pre-delta, Delta, and widespread Omicron, which accounted for 96.7% of all infections. We found significant diversity in transmission contributions across cluster sizes, with a small fraction of larger clusters responsible for a disproportionate share of infections. Counterfactual analyses showed that reducing cluster-size heterogeneity, while holding overall exposure constant, could have lowered national infections by 11.70-30.79%, with the largest effects during Omicron period. Ascertainment rates increased over time but remained spatially heterogeneous with a range: (14.40, 71.93)%. Population susceptibility declined following mass vaccination (to 42.49% in Aug 2021, nationally) and rebounded (to 89.89% in Nov 2022) due to waning immunity with variations across the provinces. Effective reproduction numbers displayed marked temporal and spatial variability, with higher estimates during Omicron. Overall, these results highlight critical role of group contact heterogeneity in shaping epidemic dynamics.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.16.26351029v1?rss=1">
<title>
<![CDATA[
SARS-CoV-2 neutralising antibody profiles reveal variant specific antibody dynamics and regional differences in infection histories in Malawi 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.16.26351029v1?rss=1"
</link>
<dc:creator>McCormack, M. J.</dc:creator>
<dc:creator>Banda, L.</dc:creator>
<dc:creator>Kasenda, S.</dc:creator>
<dc:creator>Hughes, E. C.</dc:creator>
<dc:creator>Crampin, A. C.</dc:creator>
<dc:creator>Amoah, A. S.</dc:creator>
<dc:creator>Read, J. M.</dc:creator>
<dc:creator>Ho, A.</dc:creator>
<dc:creator>Willett, B. J.</dc:creator>
<dc:creator>Hay, J. A.</dc:creator>
<dc:date>2026-04-17</dc:date>
<dc:identifier>doi:10.64898/2026.04.16.26351029</dc:identifier>
<dc:title><![CDATA[SARS-CoV-2 neutralising antibody profiles reveal variant specific antibody dynamics and regional differences in infection histories in Malawi]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-17</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Serological data provide important insights into SARS-CoV-2 transmission and immunity, particularly in regions with limited routine surveillance such as sub-Saharan Africa. However, antibody waning and boosting following reinfection or vaccination remain poorly characterised, complicating interpretation of serological measurements. Improved understanding of these dynamics is critical for accurate epidemiological inference. Modelling longitudinal serological data provides a means to quantify antibody kinetics and reconstruct infection histories. We analysed 15,679 neutralising antibody (nAb) titres from 1,675 unvaccinated, HIV-uninfected participants in urban (Lilongwe) and rural (Karonga) Malawi (February 2021 - April 2022). NAb titres against ancestral B.1, Beta, Delta, and Omicron (BA.1/BA.2) viruses were measured using an HIV-based SARS-CoV-2 pseudotyped virus neutralisation assay. A multi-level Bayesian model was used to reconstruct infection histories and antibody kinetics. The model identified 429 infections (95% credible interval 417-441), including 39 (9{middle dot}1%) that had not been identified by traditional seroconversion-based thresholds. Antibody levels waned rapidly, with 48% (0{middle dot}403-0{middle dot}560) of the acute boost remaining after three months and only 5% (0{middle dot}027-0{middle dot}098) after one year. Pre-Omicron infections generated stronger antibody boosts than Omicron infections. Responses varied, with individuals clustering into low and high responders. Cross-reactive responses extended across substantial antigenic distances - Omicron infections induced broader immunity. Seroincidence was higher in Lilongwe than in Karonga (0{middle dot}41 vs. 0{middle dot}27 infections per person per three months), driven by the early 2022 Omicron wave. Reinfections were common, particularly among adults and urban residents. SARS-CoV-2 nAb responses following infection were heterogeneous and declined rapidly. This rapid waning underscores the importance of vaccination for sustained protection, while cross-reactivity suggests only partial immunity from prior variants. Identifying reinfections is essential for understanding transmission and finding populations at higher repeat infection risk, particularly where routine surveillance is limited.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.12.26350701v1?rss=1">
<title>
<![CDATA[
SPLIT: Safety Prioritization for Long COVID Drug Repurposing via a Causal Integrated Targeting Framework 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.12.26350701v1?rss=1"
</link>
<dc:creator>Pinero, S. L.</dc:creator>
<dc:creator>Li, X.</dc:creator>
<dc:creator>Lee, S. H.</dc:creator>
<dc:creator>Liu, L.</dc:creator>
<dc:creator>Li, J.</dc:creator>
<dc:creator>Le, T. D.</dc:creator>
<dc:date>2026-04-16</dc:date>
<dc:identifier>doi:10.64898/2026.04.12.26350701</dc:identifier>
<dc:title><![CDATA[SPLIT: Safety Prioritization for Long COVID Drug Repurposing via a Causal Integrated Targeting Framework]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-16</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Long COVID affects millions of people worldwide, yet no disease-modifying treatment has been approved, and existing interventions have shown only modest and inconsistent benefits. A key reason for this limited progress is that current computational drug repurposing pipelines do not match well with the clinical reality of Long COVID. These patients often have persistent, multi-systemic symptoms and may already be taking multiple medications, making treatment safety a primary concern. However, most repurposing workflows still treat safety as a downstream filter and rely on disease-associated targets rather than causal drivers. They also assume that the findings of one analysis would generalize across the diverse presentations of Long COVID. We introduce SPLIT, a safety-first repurposing framework that addresses these limitations. SPLIT prioritizes safety at the start of the candidate evaluation, integrates complementary causal inference strategies to identify likely driver genes, and uses a counterfactual substitution design to compare drugs within specific cohort contexts. When applied to cognitive and respiratory Long COVID cohorts, SPLIT revealed three main findings. First, drugs with similar predicted efficacy could have very different predicted safety profiles. Second, the drugs flagged as unfavorable were often different between the two cohorts, showing that drug prioritization is phenotype-specific. Third, SPLIT flagged 18 drugs currently under active investigation in Long COVID trials as having unfavorable predicted profiles. SPLIT provides a practical framework to identify safer, more context-appropriate candidates earlier in the process, supporting more targeted and better-tolerated treatment strategies for Long COVID.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.13.26350772v1?rss=1">
<title>
<![CDATA[
Effectiveness of 2025-2026 mRNA-1283 and BNT162b2 COVID-19 Vaccines Against COVID-19 Related Hospitalizations and Medically-Attended COVID-19 Among Adults Aged >= 65 years in the United States 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.13.26350772v1?rss=1"
</link>
<dc:creator>Vicic, N.</dc:creator>
<dc:creator>Bogdanov, A.</dc:creator>
<dc:creator>Hensler, H.</dc:creator>
<dc:creator>Ryan, T.</dc:creator>
<dc:creator>Zeng, N.</dc:creator>
<dc:creator>Beck, E.</dc:creator>
<dc:creator>Patry, E.</dc:creator>
<dc:creator>Bonafede, M.</dc:creator>
<dc:creator>Araujo, A. B.</dc:creator>
<dc:creator>Wilson, A.</dc:creator>
<dc:date>2026-04-16</dc:date>
<dc:identifier>doi:10.64898/2026.04.13.26350772</dc:identifier>
<dc:title><![CDATA[Effectiveness of 2025-2026 mRNA-1283 and BNT162b2 COVID-19 Vaccines Against COVID-19 Related Hospitalizations and Medically-Attended COVID-19 Among Adults Aged >= 65 years in the United States]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-16</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundThe 2025-2026 COVID-19 vaccine season introduced updated formulations targeting the LP.8.1 lineage. This study assessed the absolute vaccine effectiveness (aVE) of mRNA-1283 and BNT162b2 on COVID-19 outcomes in adults aged [&ge;]65 years.

MethodsThis retrospective study used linked electronic health record and administrative claims data through Jan 31, 2026. Adults [&ge;]65 years who received the mRNA-1283 or BNT162b2 2025-2026 COVID-19 vaccine were matched to unvaccinated individuals. Inverse probability of treatment weighting was applied to each vaccines matched cohorts to balance covariates. Each vaccine was evaluated independently against its own unvaccinated comparator group. aVE against COVID-19 related hospitalization and medically-attended COVID-19 was estimated using Cox proportional hazards models; aVE = 100 x (1 - hazard ratio [HR]).

ResultsWe identified 233,072 mRNA-1283 recipients and 422,610 BNT162b2 recipients [&ge;]65 years. The aVE (95% confidence interval) of mRNA-1283 against COVID-19 related hospitalization and medically-attended COVID-19 was 59.3% (39.0%, 72.9%) and 42.0% (35.0%, 48.3%) among adults [&ge;]65 years and 66.9% (45.9 %, 79.8%) and 50.2% (42.1%, 57.2%) in [&ge;]75 years, respectively. The aVE of BNT162b2 against COVID-19 related hospitalization and medically-attended COVID-19 was 48.3% (32.4%, 60.5%) and 41.2% (36.2%, 45.8%) in [&ge;]65 years and 45.9% (26.0%, 60.4%) and 44.0% (37.8%, 49.6%) in [&ge;]75 years, respectively.

ConclusionsThis is the first real-world evidence showing that mRNA-1283 prevents COVID-19-related hospitalizations and medically attended events in vulnerable older adults at highest risk of severe disease. These findings support mRNA-1283 as an important public health tool for reducing the ongoing burden of COVID-19.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.14.26350862v1?rss=1">
<title>
<![CDATA[
Cognitive Profiling and Validation of a Digital Cognitive Assessment Tool in Post-COVID-19 Condition: Protocol for a Single-Center, Cross-Sectional Study (DigiCog Study) 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.14.26350862v1?rss=1"
</link>
<dc:creator>Lacomba-Arnau, E.</dc:creator>
<dc:creator>Da Rocha Oliveira, R.</dc:creator>
<dc:creator>Monteiro, S.</dc:creator>
<dc:creator>Pauly, C.</dc:creator>
<dc:creator>Vaillant, M.</dc:creator>
<dc:creator>Celebic, A.</dc:creator>
<dc:creator>Bulaev, D.</dc:creator>
<dc:creator>Fischer, A.</dc:creator>
<dc:creator>Fagherazzi, G.</dc:creator>
<dc:creator>Fernandez, G.</dc:creator>
<dc:creator>Shulz, M.</dc:creator>
<dc:creator>Perquin, M.</dc:creator>
<dc:date>2026-04-16</dc:date>
<dc:identifier>doi:10.64898/2026.04.14.26350862</dc:identifier>
<dc:title><![CDATA[Cognitive Profiling and Validation of a Digital Cognitive Assessment Tool in Post-COVID-19 Condition: Protocol for a Single-Center, Cross-Sectional Study (DigiCog Study)]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-16</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundCognitive impairment is among the most frequently reported and disabling persistent symptoms following SARS-CoV-2 infection. Despite growing evidence of its prevalence, the characterization of domain-specific cognitive profiles and the identification of modifiable factors influencing cognitive outcomes in post-COVID-19 condition (PCC) remains scarce. Digital cognitive assessment tools have emerged as scalable and examiner-independent alternatives to traditional neuropsychological testing, but their validation in post-infectious contexts is still limited.

ObjectiveThe DigiCog study aims to characterize cognitive profiles associated with PCC, to evaluate a novel digital cognitive assessment technology (ViewMind, VMTech) against standardized neuropsychological measures, and to explore the potential role of cognitive reserve (CR) proxies in shaping cognitive outcomes following SARS-CoV-2 infection.

MethodsDigiCog is a single-center cross-sectional study conducted within the Luxembourgish Predi-COVID cohort (NCT04380987). Participants aged 25-65 years, with and without persistent COVID-19 symptoms, are invited to participate. Cognitive assessments are performed during face-to-face sessions by trained nurses and neuropsychologists using both the VMTech device and standardized neuropsychological tests. Additional data on PCC symptom status, CR, sociodemographic characteristics, fatigue, and psychological factors are also collected. Agreement between digital and standard cognitive assessments will be evaluated using Cohens kappa coefficient, with sensitivity, specificity, and receiver operating characteristic analyses as secondary measures. Cognitive performance will be compared between participants with and without PCC, and associations with CR proxies will be explored.

ResultsParticipant recruitment began in May 2023. As of March 2025, 199 participants had been enrolled. Data collection has been completed. Data processing and statistical analyses are ongoing.

ConclusionsThe DigiCog study will provide new insights into cognitive functioning in PCC and evaluate the validity of a novel digital cognitive assessment approach. By integrating neuropsychological testing, digital assessment, and cognitive reserve, the study may inform scalable and more personalized approaches to cognitive screening and monitoring in post-infectious conditions.

Study registrationClinicalTrials.gov NCT06391970; Luxembourg National Research Ethics Committee approval No. 202208/05.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.15.718804v1?rss=1">
<title>
<![CDATA[
Repeated SARS-CoV-2 Antigenic Exposures from Prior Vaccinations and Infections Demonstrate Limits of Antibody Durability and Breadth Against Newer Variants 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.15.718804v1?rss=1"
</link>
<dc:creator>WANG, W.</dc:creator>
<dc:creator>Goguet, e.</dc:creator>
<dc:creator>Lusvarghi, S.</dc:creator>
<dc:creator>Paz, S.</dc:creator>
<dc:creator>Shrestha, L.</dc:creator>
<dc:creator>Vassell, R.</dc:creator>
<dc:creator>Pollett, S.</dc:creator>
<dc:creator>Mitre, E.</dc:creator>
<dc:creator>Weiss, C. D.</dc:creator>
<dc:date>2026-04-16</dc:date>
<dc:identifier>doi:10.64898/2026.04.15.718804</dc:identifier>
<dc:title><![CDATA[Repeated SARS-CoV-2 Antigenic Exposures from Prior Vaccinations and Infections Demonstrate Limits of Antibody Durability and Breadth Against Newer Variants]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-16</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundWidespread immunity from vaccination and infection has reduced COVID-19 morbidity and mortality, but this immunity varies across the population. Understanding how repeated antigenic exposures influence antibody responses helps to inform future vaccination strategies.

MethodsSerum samples collected one and six months after XBB.1.5 vaccination from 25 generally healthy healthcare workers with varying exposure histories were assessed for neutralizing activity against a range of variants, from pre-Omicron variants to latest Omicron JN.1 sublineage variants and divergent BA.3.2 variants, using lentiviral pseudoviruses. Participants were stratified by vaccination and infection history.

ResultsXBB.1.5 vaccination elicited broad neutralizing responses, with strong boosting against previously encountered antigens relative to vaccine-matched XBB.1.5 and newer variants. Geometric mean neutralization titers were generally comparable across exposure groups, indicating limited influence of prior Omicron infection or bivalent vaccination, though intra-group heterogeneity was observed. At six months, overall titers declined by 36-62%. Titers remained highest against the pre-Omicron and lowest against JN.1 sublineage variants. N-terminal glycosylation (DelS31, T22N) modestly affected neutralization.

ConclusionsXBB.1.5 vaccination elicited broad neutralizing antibody responses against previously encountered and vaccine-matched antigens regardless of exposure history, but titers waned after six months. This waning, compounded by continued emergence of immune-evasive variants and heterogenous population immunity, underscores the need for continually monitoring neutralizing antibody durability and breadth to guide evidence-based COVID-19 vaccine formulation updates.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.15.718757v1?rss=1">
<title>
<![CDATA[
Mechanistic insights into the association and activation of the SARS-CoV-2 2'-O-Methyltransferase (NSP16) 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.15.718757v1?rss=1"
</link>
<dc:creator>Ma, H.</dc:creator>
<dc:creator>Brace, A.</dc:creator>
<dc:creator>Lemus, M. R.</dc:creator>
<dc:creator>Chennubhotla, S. C.</dc:creator>
<dc:creator>Satchell, K. J.</dc:creator>
<dc:creator>Ramanathan, A.</dc:creator>
<dc:date>2026-04-16</dc:date>
<dc:identifier>doi:10.64898/2026.04.15.718757</dc:identifier>
<dc:title><![CDATA[Mechanistic insights into the association and activation of the SARS-CoV-2 2'-O-Methyltransferase (NSP16)]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-16</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
The nsp16 2-O-Methyltransferase is an essential non-structural protein of SARS-CoV-2, which methylates the viral mRNA cap structure, enabling it to evade the host immune response for higher translation efficiency. However, nsp16 is only active when it is bound to its cofactor, namely the non-structural protein-10 (nsp10). Understanding how nsp10 binds to and activates nsp16 function can help to develop targeted inhibitors; however, given the varying degree of disorder in both nsp10 and nsp16, characterizing this interaction has been challenging. Using long-timescale molecular dynamics simulations and AI/ML methods, we posit that the nsp16/nsp10 binding process is mediated by a hydrophobic latch formed with Leu4298 from nsp10 and a hydrophobic concave on the nsp16 protein surface. Our study highlights how the nsp16 S-adenosyl-L-methionine (SAM) pocket closes in its monomer state, which in turn deactivates the MTase function. We also observe that the nsp16/nsp10 complex allows for the RNA binding site to open with the empty SAM pocket. The results reveal how the SAM pocket loops facilitate SAM binding while allowing for the by-product S-adenosyl-L-homocysteine (SAH) to exit. Our study thus provides valuable atomistic-level mechanistic insights into understanding the activation of nsp16 MTase function while highlighting the challenges of studying protein-protein interactions mediated by largely flexible/disordered regions.

SIGNIFICANCENsp16 carries out the methylation of the viral mRNA to gain immune evasion and translation efficiency. Understanding its complex molecular machinery can help us develop better therapeutic treatments. Here, we explore the key activation conditions for the SARS-CoV-2 nsp16 function via molecular dynamics simulation and AI/ML methods. The results demonstrate the role of nsp16 loops in different stages preparing for the methylation reaction from nsp16/nsp10 binding, (de)activation of nsp16 function and how the nsp16 SAM binding pocket can affect the RNA binding loops. This research explains the role of the nsp16 loops, which orchestrate its molecular function, and provides valuable insight to develop more targeted therapeutic approaches to disrupt viral immune evasion activity.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.14.718551v1?rss=1">
<title>
<![CDATA[
Tracing cell communication programs across conditions at single cell resolution with CCC-RISE 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.14.718551v1?rss=1"
</link>
<dc:creator>Ramirez, A.</dc:creator>
<dc:creator>Thomas, N.</dc:creator>
<dc:creator>Calabrese, D. R.</dc:creator>
<dc:creator>Greenland, J. R.</dc:creator>
<dc:creator>Meyer, A. S.</dc:creator>
<dc:date>2026-04-15</dc:date>
<dc:identifier>doi:10.64898/2026.04.14.718551</dc:identifier>
<dc:title><![CDATA[Tracing cell communication programs across conditions at single cell resolution with CCC-RISE]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-15</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Cell-cell communication (CCC) mediates coordinated cellular activities that vary dynamically across time, location, and biological context. While various tools exist to infer CCC, they typically aggregate data according to pre-defined cell types, obscuring critical single-cell heterogeneity. Furthermore, because signaling pathways and cell populations operate in a coordinated manner, an integrative analytical approach is essential. To address these challenges, we developed CCC-RISE, an extension of the tensor-based method Reduction and Insight in Single-cell Exploration (RISE). CCC-RISE identifies integrative patterns of single-cell variation by deconvolving communication into interpretable modules defined by unique sender cells, receiver cells, ligands, and condition associations. We applied this framework to a COVID-19 cohort with varying disease severity and a lung transplant cohort with acute allograft dysfunction. In both contexts, CCC-RISE successfully identified disease-relevant communication programs and traced them to specific cellular subpopulations, often crossing conventional cell-type boundaries. This approach offers a robust pipeline enabling the identification of disease-relevant signaling subpopulations that are invisible to aggregate methods.

HighlightsO_LICCC-RISE enables integrative analysis of cell-cell communication across multiple conditions at single-cell resolution
C_LIO_LICCC-RISE deconvolves signaling patterns into modules defined by their sender cells, receiver cells, LR pairs, and experimental conditions/samples
C_LIO_LIAnalysis at single-cell resolution uncovers signaling activity within and across conventional cell types
C_LI
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.11.26350682v1?rss=1">
<title>
<![CDATA[
Risk of Post-acute Symptoms and Conditions After SARS-CoV-2 Compared to Other Respiratory Viral Infections: A Systematic Review and Meta-Analysis 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.11.26350682v1?rss=1"
</link>
<dc:creator>Pinto, T. F.</dc:creator>
<dc:creator>Santoro, A.</dc:creator>
<dc:creator>Oliveira, A. L. G.</dc:creator>
<dc:creator>Tavares, T. S.</dc:creator>
<dc:creator>Almeida, A.</dc:creator>
<dc:creator>Incardona, F.</dc:creator>
<dc:creator>Marchetti, G.</dc:creator>
<dc:creator>Cozzi-Lepri, A.</dc:creator>
<dc:creator>Pinto, J.</dc:creator>
<dc:creator>Caporali, J. F. M.</dc:creator>
<dc:date>2026-04-13</dc:date>
<dc:identifier>doi:10.64898/2026.04.11.26350682</dc:identifier>
<dc:title><![CDATA[Risk of Post-acute Symptoms and Conditions After SARS-CoV-2 Compared to Other Respiratory Viral Infections: A Systematic Review and Meta-Analysis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-13</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundHow post-COVID-19 condition (PCC) differs from post-acute infection syndromes (PAIS) caused by other respiratory viruses remains uncertain. Comparing these conditions may clarify whether post-acute symptoms reflect specific consequences of SARS-CoV-2 infection or broader post-viral mechanisms.

MethodsWe conducted a systematic review and meta-analysis of cohort studies comparing persistent symptoms or conditions in adults after SARS-CoV-2 infection with those following other acute respiratory viral infections. PubMed, Embase, and Scopus were searched. Random-effects models were used to estimate pooled risks.

ResultsAmong 9,371 records screened, 22 studies were included and 14 contributed to the meta-analysis. Increased risk after SARS-CoV-2 infection was observed for pulmonary embolism, abnormal breathing, fatigue, hemorrhagic stroke, memory loss/brain fog, and palpitations; heart rate abnormalities showed borderline significance. For most other outcomes pooled estimates were inconclusive.

ConclusionsOnly a subset of outcomes appears more frequent after SARS-CoV-2 infection, suggesting many symptoms attributed to PCC may reflect broader post-viral syndromes.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.09.26350495v1?rss=1">
<title>
<![CDATA[
Classifying and Differentiating Individuals with Respiratory Syncytial Virus, Influenza, and COVID-19 Cases in OpenSAFELY 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.09.26350495v1?rss=1"
</link>
<dc:creator>Prestige, E.</dc:creator>
<dc:creator>Warren-Gash, C.</dc:creator>
<dc:creator>Quint, J. K.</dc:creator>
<dc:creator>Evans, D.</dc:creator>
<dc:creator>Costello, R. E.</dc:creator>
<dc:creator>Mehrkar, A.</dc:creator>
<dc:creator>Bacon, S.</dc:creator>
<dc:creator>Goldacre, B.</dc:creator>
<dc:creator>Barley-McMullen, S.</dc:creator>
<dc:creator>Yameen, F.</dc:creator>
<dc:creator>Shah, P.</dc:creator>
<dc:creator>Natt, M.</dc:creator>
<dc:creator>Alder, Y.</dc:creator>
<dc:creator>Hulme, W.</dc:creator>
<dc:creator>Parker, E. P. K.</dc:creator>
<dc:creator>Eggo, R. M.</dc:creator>
<dc:date>2026-04-13</dc:date>
<dc:identifier>doi:10.64898/2026.04.09.26350495</dc:identifier>
<dc:title><![CDATA[Classifying and Differentiating Individuals with Respiratory Syncytial Virus, Influenza, and COVID-19 Cases in OpenSAFELY]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-13</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Electronic health records (EHRs) are a rich source of data which can be used to analyse health outcomes using computable phenotypes. With the approval of NHS England we used the OpenSAFELY secure analytics platform to design and assess phenotypes to classify three key respiratory viruses - respiratory syncytial virus (RSV), influenza, and COVID-19 - in English coded health data between September 2016 and August 2024. We compared specific and sensitive phenotypes to one another and to publicly available surveillance data. Cases from both phenotypes showed similar seasonal patterns to surveillance data. Sensitive phenotypes led to increased risk of misclassification than specific phenotypes for mild cases. For severe cases the risk of misclassification was higher in infants than for older adults, irrespective of the phenotype used. The phenotypes presented here offer a solution to classifying respiratory viruses from coded health records in the absence of testing information.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.09.26349480v1?rss=1">
<title>
<![CDATA[
SARS-CoV-2 Introductions into Lao PDR Revealed by Genomic Surveillance, 2021-2024 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.09.26349480v1?rss=1"
</link>
<dc:creator>Panapruksachat, S.</dc:creator>
<dc:creator>Troupin, C.</dc:creator>
<dc:creator>Souksavanh, M.</dc:creator>
<dc:creator>Keeratipusana, C.</dc:creator>
<dc:creator>Vongsouvath, M.</dc:creator>
<dc:creator>Vongphachanh, S.</dc:creator>
<dc:creator>Vongsouvath, M.</dc:creator>
<dc:creator>Phommasone, K.</dc:creator>
<dc:creator>Somlor, S.</dc:creator>
<dc:creator>Robinson, M. T.</dc:creator>
<dc:creator>Chookajorn, T.</dc:creator>
<dc:creator>Kochakarn, T.</dc:creator>
<dc:creator>Day, N. P.</dc:creator>
<dc:creator>Mayxay, M.</dc:creator>
<dc:creator>Letizia, A. G.</dc:creator>
<dc:creator>Dubot-Peres, A.</dc:creator>
<dc:creator>Ashley, E. A.</dc:creator>
<dc:creator>Buchy, P.</dc:creator>
<dc:creator>Xangsayarath, P.</dc:creator>
<dc:creator>Batty, E. M.</dc:creator>
<dc:date>2026-04-13</dc:date>
<dc:identifier>doi:10.64898/2026.04.09.26349480</dc:identifier>
<dc:title><![CDATA[SARS-CoV-2 Introductions into Lao PDR Revealed by Genomic Surveillance, 2021-2024]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-13</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
We used 2492 whole genome sequences from Laos to investigate the molecular epidemiology of SARS-CoV-2 from 2021 through 2024, covering the major waves of COVID-19 disease in Laos including time periods of travel restrictions and after relaxation of travel across international borders. We identify successive waves of COVID-19 caused by shifts in the dominant lineage, beginning with the Alpha variant in April 2021 and continuing through the Delta and Omicron variants. We quantify a shift from a small number of viral introductions responsible for widespread transmission in early waves to a larger number of introductions for each variant after travel restrictions were lifted, and identify potential routes of introduction into the country. Our study underscores the importance of genomic surveillance to public health responses to characterize viral transmission dynamics during pandemics.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.10.26350587v1?rss=1">
<title>
<![CDATA[
Comparative LUSZ Therapeutic Study (LUSZ_AVIST) of Antiviral, Antiretroviral, and Immunosuppressive Treatments in Hospitalized COVID-19 Patients with High-Risk Factors, Biomarkers, and Disease Progression. 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.10.26350587v1?rss=1"
</link>
<dc:creator>Makdissy, N.</dc:creator>
<dc:creator>Makdessi, E. W.</dc:creator>
<dc:creator>Fenianos, F.</dc:creator>
<dc:creator>Nasreddine, N.</dc:creator>
<dc:creator>Daher, W.</dc:creator>
<dc:creator>El Hamoui, S.</dc:creator>
<dc:date>2026-04-13</dc:date>
<dc:identifier>doi:10.64898/2026.04.10.26350587</dc:identifier>
<dc:title><![CDATA[Comparative LUSZ Therapeutic Study (LUSZ_AVIST) of Antiviral, Antiretroviral, and Immunosuppressive Treatments in Hospitalized COVID-19 Patients with High-Risk Factors, Biomarkers, and Disease Progression.]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-13</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
COVID-19 has spread rapidly and caused a global pandemic making it one of the deadliest in history. Early identification of patients with coronavirus disease 2019 who may develop critical illness is of immense importance. Therefore, novel biomarkers were needed to identify patients who will suffer rapid disease progression to severe complications and death. Many treatments were adopted including the antiviral Remdesivir, the antiretroviral Lopinavir /Ritonavir and Tocilizumab. Our study aimed not only to specify high-risk factors and biomarkers of fatal outcome in hospitalized subjects with coronavirus but also to compare the efficacy of the three considered treatments to help clinicians better choose a therapeutic strategy and reduce mortality. We divided the population (n=711) into four main groups based according to the WHO ordinal severity scale. The percentage of mortality, in and out the hospital, the length of stay in the hospital, the pulmonary inflammatory lesion and its distribution, the SARS-CoV-2 IgM and IgG variations at admission, the inflammatory markers, the complete blood count, the coagulation factors and enzymes, proteins and electrolytes profile, glucose and lipid profile, and other relevant markers were measured. The significance of the observed variation was assessed by multivariate and ANOVA analyses. We succeeded to establish a novel predictive scoring model of disease progression based on a cohort of Lebanese hospitalized patients relying on the pulmonary inflammatory lesions, inflammation biomarkers such as LDH, D-Dimer, CRP, IL-6 and the lymphocyte count, the number of comorbidities and the age of the patient which all were significantly correlated with the illness severity showing best outcomes with immunomodulatory and anticoagulant treatments by the results. As top tier, Tocilizumab was more efficient than the two other treatments in non-severe cases but none of the used treatments was insanely effective alone to reduce mortality in severe cases.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.10.717462v1?rss=1">
<title>
<![CDATA[
Loss of host factor-mediated m6Am methylation of the viral RNA cap impairs SARS CoV-2 replication 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.10.717462v1?rss=1"
</link>
<dc:creator>Pandey, R. R.</dc:creator>
<dc:creator>Ebert, N.</dc:creator>
<dc:creator>Homolka, D.</dc:creator>
<dc:creator>Barut, T.</dc:creator>
<dc:creator>Trueeb, B.</dc:creator>
<dc:creator>Stalder, H.</dc:creator>
<dc:creator>Delfino, E.</dc:creator>
<dc:creator>Vagbo, C.</dc:creator>
<dc:creator>Veiga, I.</dc:creator>
<dc:creator>Leidel, S.</dc:creator>
<dc:creator>Thiel, V.</dc:creator>
<dc:creator>Pillai, R.</dc:creator>
<dc:date>2026-04-13</dc:date>
<dc:identifier>doi:10.64898/2026.04.10.717462</dc:identifier>
<dc:title><![CDATA[Loss of host factor-mediated m6Am methylation of the viral RNA cap impairs SARS CoV-2 replication]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-13</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Eukaryotic mRNAs are co-transcriptionally capped at the 5' end with a methylated m7G moiety (cap0)1, which in higher eukaryotes is further methylated on the ribose (Nm) of the transcription start site (TSS) nucleotide to create the cap1 structure (m7GpppNm). Coronaviruses that replicate in the cytoplasm encode their own capping enzymes to acquire this cap1 structure which facilitates translation and shields them from the host innate immune system2-5. Here we report the identification of an additional N6-methyladenosine (m6A) methylation on the 5' cap (m7Gpppm6Am) of the human coronavirus SARS-CoV-2 RNA. It is catalysed by the host m6A methylase PCIF16-9 following capping by virus-encoded non-structural protein NSP 14 and NSP1610. Human cell cultures lacking PCIF1 accumulate reduced levels of the viral RNA and support reduced viral replication. Furthermore, Pcif1 mutant mice infected with SARS CoV-2 display milder symptoms. We identify the host RNA methyltransferase PCIF1 as a critical ally of SARS CoV-2 for viral replication.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.10.717575v1?rss=1">
<title>
<![CDATA[
Integrated Computational and Experimental Evaluation of selected Flavonoids as a Multi-Target Modulator of Viral Entry and Protease Activity. 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.10.717575v1?rss=1"
</link>
<dc:creator>Mohseni-Motlagh, A.</dc:creator>
<dc:creator>Alereza, T.</dc:creator>
<dc:creator>Mozaffari, L.</dc:creator>
<dc:creator>Rozbeh, M.</dc:creator>
<dc:date>2026-04-13</dc:date>
<dc:identifier>doi:10.64898/2026.04.10.717575</dc:identifier>
<dc:title><![CDATA[Integrated Computational and Experimental Evaluation of selected Flavonoids as a Multi-Target Modulator of Viral Entry and Protease Activity.]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-13</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Flavonoids have been widely investigated for their antiviral and anti-inflammatory properties, but their mechanisms of action often remain insufficiently defined. In the present study, high-purity flavonoids were evaluated using an integrated workflow combining molecular docking, LigPlot+ interaction mapping, surface plasmon resonance (SPR), fluorescence-based TMPRSS2 inhibition assays, and cell-based viability studies. Docking with AutoDock Vina identified Hesperidin as the strongest overall candidate among the compounds evaluated. Hesperidin showed strong active-site engagement with TMPRSS2, including interactions with catalytic residues His296, Asp345, and Ser441, and stable binding within the SARS-CoV-2 main protease (Mpro) pocket. Comparative docking showed weaker or more peripheral interaction patterns for Rutin and moderate Spike binding for Hesperidin and Rutin. Experimental validation demonstrated dose-dependent inhibition of TMPRSS2 activity with an IC50 of 79.1 {micro}M for Hesperidin and 43.5 {micro}M for Hesperetin, while Rutin showed partial inhibition without a defined IC50 in the tested range. In Calu-3 cells, pre-treatment with Hesperidin or Rutin reduced SARS-CoV-2 Spike-induced cytotoxicity by approximately 30% without detectable intrinsic toxicity at the concentrations tested Docking analysis of Hesperidin and Rutin with the SARS-CoV-2 Spike protein revealed moderate interaction patterns involving residues such as Asn343, Ser371, and Val367. Hydrogen bond distances were generally in the range of approximately 2.9-3.3 [A], indicating moderate stabilization compared with the stronger active-site interactions observed for Hesperidin in TMPRSS2. The resulting binding poses suggest that these flavonoids can associate with structurally relevant regions of the Spike receptor-binding domain; however, they do not strongly overlap with the key residues required for ACE2 interaction. Rutin, in particular, exhibited a more peripheral and distributed binding mode within the Spike-ACE2 complex, indicating limited potential for direct disruption of the binding interface. In addition to SARS-CoV-2 targets, docking analysis extended to influenza viral proteins revealed moderate interaction of Hesperidin with hemagglutinin (HA) and strong catalytic-pocket binding of Rutin to neuraminidase (NA), involving key residues associated with enzymatic activity. These findings broaden the scope of the study to include influenza viral entry and release mechanisms, supporting a multi-virus, multi-target framework.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.11.716570v1?rss=1">
<title>
<![CDATA[
Serial vaccination expands and refines human CD4+ T cell memory 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.11.716570v1?rss=1"
</link>
<dc:creator>Lai, Y.-H.</dc:creator>
<dc:creator>Su, X.</dc:creator>
<dc:creator>Awad, S.</dc:creator>
<dc:creator>Ansari, A.</dc:creator>
<dc:creator>Jang, J.</dc:creator>
<dc:creator>Saber, A. O.</dc:creator>
<dc:creator>Chen, H.-W.</dc:creator>
<dc:creator>Jung, H.</dc:creator>
<dc:creator>Sarkar, A.</dc:creator>
<dc:creator>Drapeau, E. M.</dc:creator>
<dc:creator>Bilker, W. B.</dc:creator>
<dc:creator>Hensley, S. E.</dc:creator>
<dc:creator>Su, L. F.</dc:creator>
<dc:date>2026-04-13</dc:date>
<dc:identifier>doi:10.64898/2026.04.11.716570</dc:identifier>
<dc:title><![CDATA[Serial vaccination expands and refines human CD4+ T cell memory]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-13</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
CD4+ T cells coordinate protective immunity against pathogens. However, a major unresolved question is how human CD4+ T cell memory is established and evolves following primary and repeated vaccination. Using COVID-19 mRNA vaccination as a model, we tracked 50 distinct antigen-specific populations directly ex vivo with peptide-MHC class II tetramers in eight SARS-CoV-2-naive individuals from pre-vaccine baseline through memory time points after three mRNA doses. Our findings identify the primary vaccine series as the main driver of memory pool size. It leverages pre-existing memory while preferentially recruiting high-avidity T cells, establishing an immunodominance hierarchy dominated by a small subset of precursors. Booster vaccination refines both the magnitude and quality of T cell memory. It increases select populations and enhances differentiation of subdominant CD4+ T cells. Populations that did not become more abundant after boosting retained their polyfunctional potential. Beyond establishing memory to the ancestral spike, vaccinations broadened responses by recruiting cross-reactive T cells recognizing viral variants. Collectively, these findings reveal how human CD4+ T cell memory evolves through sequential immunizations to generate a functionally diverse and broadly responsive memory repertoire against future viral challenges.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.10.717770v1?rss=1">
<title>
<![CDATA[
MIMIQ: Fast mutual information calculation and significance testing for single-cell RNA sequencing analysis 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.10.717770v1?rss=1"
</link>
<dc:creator>O'Hanlon, D.</dc:creator>
<dc:creator>Garcia Busto, S.</dc:creator>
<dc:creator>Perez Carrasco, R.</dc:creator>
<dc:date>2026-04-13</dc:date>
<dc:identifier>doi:10.64898/2026.04.10.717770</dc:identifier>
<dc:title><![CDATA[MIMIQ: Fast mutual information calculation and significance testing for single-cell RNA sequencing analysis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-13</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Mutual information is a fundamental quantity in information theory that describes the non-linear dependency between two variables, and has numerous applications within bioinformatics and beyond. However, its exploitation is hampered by a trade-off between computational intensity and accuracy. Here we present an adaptive binning approach to computing the pairwise mutual information, optimized for small integer counts such as those observed in single-cell RNA sequencing. By assuming a sampling distribution such as the negative binomial, a {chi}2 test statistic for hypothesis testing can be computed simultaneously via a copula transformation. Using these quantities, we show how gene rewiring of CD4+ naive T-cells during SARS-CoV-2 infection can be studied using a single-cell sequencing dataset of healthy and COVID-19 donors.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.10.26350613v1?rss=1">
<title>
<![CDATA[
Comprehensive Immunophenotyping of Monocytes and Dendritic Cells Suggests Distinct Pathophysiology in Chronic Fatigue Syndrome and Long COVID 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.10.26350613v1?rss=1"
</link>
<dc:creator>Petrov, S. I.</dc:creator>
<dc:creator>Bozhkova, M.</dc:creator>
<dc:creator>Ivanovska, M.</dc:creator>
<dc:creator>Kalfova, T.</dc:creator>
<dc:creator>Dudova, D.</dc:creator>
<dc:creator>Todorova, Y.</dc:creator>
<dc:creator>Dimitrova, R.</dc:creator>
<dc:creator>Murdjeva, M.</dc:creator>
<dc:creator>Taskov, H.</dc:creator>
<dc:creator>Nikolova, M.</dc:creator>
<dc:creator>Maes, M.</dc:creator>
<dc:date>2026-04-12</dc:date>
<dc:identifier>doi:10.64898/2026.04.10.26350613</dc:identifier>
<dc:title><![CDATA[Comprehensive Immunophenotyping of Monocytes and Dendritic Cells Suggests Distinct Pathophysiology in Chronic Fatigue Syndrome and Long COVID]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-12</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID are complex chronic conditions that often follow infectious triggers with overlapping clinical features but poorly defined pathophysiological relationships. This study aimed to identify disease-specific immune signatures through multiparameter immunophenotyping of monocytes, dendritic cells, and T-cell subsets. A total of 207 participants were included (ME/CFS: n = 103; long COVID: n = 63; healthy controls: n = 41). Peripheral blood mononuclear cells were analyzed using multiparameter flow cytometry. Statistical analyses included non-parametric testing, age-adjusted ANCOVA, correlation network analysis, and principal component analysis (PCA). Long COVID was characterized by increased M2-like monocyte polarization, elevated CD80 expression across monocyte subsets, expansion of dendritic cells, and reduced expression of activation markers, indicating persistent immune activation with features of immune exhaustion. In contrast, ME/CFS exhibited reduced costimulatory molecule expression, impaired CCR7-mediated immune cell trafficking, and less coordinated activation patterns, consistent with a state of immune suppression. Correlation network analysis revealed more extensive and integrated immune interactions in long COVID, while PCA identified distinct immunophenotypic components and enabled moderate discrimination between the two conditions. These findings demonstrate that ME/CFS and long COVID are characterized by distinct immune profiles, supporting the concept of divergent immunopathological mechanisms. The identified signatures may contribute to biomarker development and guide targeted therapeutic approaches.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.10.26350608v1?rss=1">
<title>
<![CDATA[
Minor Consent state policies and COVID-19 vaccination in adolescents 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.10.26350608v1?rss=1"
</link>
<dc:creator>Litchy, C.</dc:creator>
<dc:creator>Semprini, J.</dc:creator>
<dc:date>2026-04-11</dc:date>
<dc:identifier>doi:10.64898/2026.04.10.26350608</dc:identifier>
<dc:title><![CDATA[Minor Consent state policies and COVID-19 vaccination in adolescents]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-11</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundEver since the COVID-19 vaccine became available, vaccinations in adolescents lagged behind adults. Whether adolescent vaccination rates were higher in states with "Minor Consent" policies remains unknown.

MethodsWe accessed adolescent (aged 12-17) county-level vaccine administration data from the CDC (12/2020-05/2023) Our outcomes were COVID-19 vaccination counts for 1) initial dose, 2) completed series doses, 3) booster doses. Panel Poisson regression models with state and time random effects, seasonal fixed-effects, log-population offsets, and adult vaccination rates were estimated to calculate incidence rate ratios (IRR), testing the association between residing in a state with a Minor Consent policy and COVID-19 vaccine uptake.

ResultsOverall, for the initial dose and complete series, there was no difference in adolescent COVID-19 vaccination between states with or without Minor Consent policies. However, we found that Minor Consent policies were associated with lower COVID-19 booster doses (IRR = 0.582; 95% CI: 0.409, 0.828; p=0.0026). This association was not found in urban (IRR = 0.867; CI = 0.722, 1.043; p = 0.1295), but only in rural counties (IRR 0.541; CI 0.401, 0.730; p<0.0001).

ConclusionsMinor Consent policies were not associated with higher adolescent COVID-19 vaccination. Rather, we found that Minor Consent policies were associated with lower adolescent vaccination for booster doses in rural counties. Despite minimal evidence of impact, states continue to implement Minor Consent vaccination policies. Future research on the topic should investigate, not just other vaccines, but how Minor Consent policies impact parental trust in public health more broadly.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.09.717495v1?rss=1">
<title>
<![CDATA[
Phagocytic Clearance of SARS-CoV-2 Nucleocapsid- and RNA-Containing Immune Complexes Drives Inflammatory Cytokine Production and Endothelial Dysfunction 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.09.717495v1?rss=1"
</link>
<dc:creator>Gach, J. S.</dc:creator>
<dc:creator>Kim, D.</dc:creator>
<dc:creator>Vu, K.</dc:creator>
<dc:creator>Marshall, M. E.</dc:creator>
<dc:creator>Cachay, C.</dc:creator>
<dc:creator>Rangwala, A. A.</dc:creator>
<dc:creator>Kerster, G.</dc:creator>
<dc:creator>Tifrea, D.</dc:creator>
<dc:creator>Pearlman, E.</dc:creator>
<dc:creator>van Gils, M.</dc:creator>
<dc:creator>Hughes, C. C.</dc:creator>
<dc:creator>Forthal, D. N.</dc:creator>
<dc:date>2026-04-10</dc:date>
<dc:identifier>doi:10.64898/2026.04.09.717495</dc:identifier>
<dc:title><![CDATA[Phagocytic Clearance of SARS-CoV-2 Nucleocapsid- and RNA-Containing Immune Complexes Drives Inflammatory Cytokine Production and Endothelial Dysfunction]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-10</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
The aberrant inflammation that characterizes severe COVID-19 is incompletely understood. Given the persistence of SARS-Cov-2 RNA and nucleocapsid protein (N) and the presence of anti-N antibody during the course of severe infection, we investigated the role of RNA-containing immune complexes (ICs) in driving inflammation. We found that ICs consisting of SARS-CoV-2 RNA, N, and anti-N IgG1 stimulate primary human monocytes in vitro to produce inflammatory cytokines and chemokines in a manner dependent on Fc{gamma} receptors and partially dependent on toll-like receptor-8. In addition, the inflammatory response induced in monocytes by RNA-containing ICs caused endothelial dysfunction in vascularized micro-organs. Using nasopharyngeal samples from SARS-CoV-2-infected individuals, SARS-CoV-2 RNA and N were captured by anti-N monoclonal antibody in the absence of lysing reagents, indicating that SARS-CoV-2 RNA and N complexes are present outside of virions and cells. Finally, we found that during an early wave of COVID-19, the anti-N IgG:IgM ratio predicted severe clinical outcomes, consistent with a role for inflammatory, IgG-mediated phagocytic clearance of nucleic acid-containing ICs in SARS-CoV-2 pathogenesis, perhaps mitigated by non-inflammatory, IgM-mediated clearance. We conclude that RNA-containing ICs may play a role in the pathogenesis of severe COVID-19. Since all pathogenic viruses encode nucleic acid-binding proteins, such as N, and these proteins often elicit an antibody response, inflammatory clearance of nucleic acid-containing ICs may also contribute to disease severity in other viral infections.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.08.717316v1?rss=1">
<title>
<![CDATA[
Role of Nonneutralizing Antibodies and Fc Effector Functions in Inhibiting SARS-CoV-2 Infection 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.08.717316v1?rss=1"
</link>
<dc:creator>Sun, H.</dc:creator>
<dc:creator>Esqueda, A.</dc:creator>
<dc:creator>Steinkellner, H.</dc:creator>
<dc:creator>Chen, Q.</dc:creator>
<dc:date>2026-04-09</dc:date>
<dc:identifier>doi:10.64898/2026.04.08.717316</dc:identifier>
<dc:title><![CDATA[Role of Nonneutralizing Antibodies and Fc Effector Functions in Inhibiting SARS-CoV-2 Infection]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-09</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Neutralizing monoclonal antibodies (mAbs) are a key component of antiviral therapeutics against SARS-CoV-2; however, the contribution of Fc-mediated effector functions remains underexplored. Here, we compare the antiviral activities of the neutralizing and non-neutralizing mAbs CB6 and CR3022, respectively. The Fc regions of both plant-produced mAbs carried nonfucosylated, non-galactosylated complex glycans (pCB6 and pCR3022), and CR3022 was also produced with mammalian-typical galactosylated, fucosylated glycans (mCR3022). pCR3022 exhibited markedly enhanced antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cell-mediated virus inhibition (ADCVI) compared to mCR3022, indicating a significant impact of Fc glycosylation on antiviral activity despite the lack of neutralization. pCB6 exhibited potent neutralization while further enhancing virus clearance through synergistic Fc effector activity. Our findings suggest that Fc-mediated mechanisms, especially ADCC and ADCVI, can contribute substantially to viral control and may be particularly valuable against immune-evasive variants. These results advance our understanding of the functional roles that non-neutralizing antibodies can play in SARS-CoV-2 infection and highlight the potential of Fc glycoengineering to modulate the antiviral efficacy of both neutralizing and non-neutralizing mAbs.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.09.717442v1?rss=1">
<title>
<![CDATA[
An imaging flow cytometry method to study platelet-monocyte aggregates using Long COVID as a model 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.09.717442v1?rss=1"
</link>
<dc:creator>Thompon, A.</dc:creator>
<dc:creator>Venter, C.</dc:creator>
<dc:creator>de Villiers, W. J.</dc:creator>
<dc:creator>De Swardt, D.</dc:creator>
<dc:creator>Laubscher, G. J.</dc:creator>
<dc:creator>Kell, D. B.</dc:creator>
<dc:creator>Pretorius, E.</dc:creator>
<dc:date>2026-04-09</dc:date>
<dc:identifier>doi:10.64898/2026.04.09.717442</dc:identifier>
<dc:title><![CDATA[An imaging flow cytometry method to study platelet-monocyte aggregates using Long COVID as a model]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-09</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundLong COVID is characterised by persistent systemic inflammation and endothelial dysfunction, with increasing evidence implicating thromboinflammatory mechanisms. Platelet-monocyte aggregates (PMA) represent a sensitive marker of platelet activation and immune-vascular interactions, but their role in Long COVID remains incompletely defined.

MethodsThis study quantified circulating PMA in 20 Long COVID patients and 20 healthy controls using a two-colour imaging flow cytometry assay targeting CD14 (a monocyte receptor for pathogen-associated molecular patterns, PAMPs) and CD62P (P-selectin). PMA were expressed as a percentage of total monocytes, and platelet attachment patterns were classified into single versus multiple platelet binding. Statistical analyses included Shapiro-Wilk normality testing, unpaired t-tests, Mann-Whitney U tests or two-way ANOVA as appropriate, and linear regression for correlation analysis.

ResultsCirculating PMA were significantly elevated in Long COVID patients compared with controls (29.19 [20.02-37.26] vs 4.59 [2.67-7.16], p < 0.0001). Long COVID samples showed a reduced proportion of monocytes with single platelet attachment and a corresponding increase in multiple platelet binding (p < 0.0001). In controls, %PMA increased with age (p < 0.01), whereas no age association was observed in Long COVID, indicating an elevated baseline independent of age.

ConclusionsLong COVID is associated with markedly increased platelet-monocyte aggregation and altered platelet attachment dynamics, consistent with sustained thromboinflammatory activity. PMA represent a sensitive cellular marker of platelet-driven immune activation and may have utility as an accessible biomarker for stratifying thromboinflammatory burden in Long COVID.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.08.717307v1?rss=1">
<title>
<![CDATA[
Myeloma and therapy reshape the bone marrow niche to durably constrain immune reconstitution and vaccine responsiveness 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.08.717307v1?rss=1"
</link>
<dc:creator>Chander, A.</dc:creator>
<dc:creator>Rachid Zaim, S.</dc:creator>
<dc:creator>Dillon, M. A.</dc:creator>
<dc:creator>Genge, P. C.</dc:creator>
<dc:creator>Moss, N.</dc:creator>
<dc:creator>McGrath, P. I.</dc:creator>
<dc:creator>Kopp, M. S.</dc:creator>
<dc:creator>Lee, K. J.</dc:creator>
<dc:creator>Kuan, E. L.</dc:creator>
<dc:creator>Reading, J.</dc:creator>
<dc:creator>Hernandez, V.</dc:creator>
<dc:creator>Song, X.</dc:creator>
<dc:creator>Singh, M.</dc:creator>
<dc:creator>Garber, J.</dc:creator>
<dc:creator>LaFrance, C. M.</dc:creator>
<dc:creator>Kong, G. L.</dc:creator>
<dc:creator>Glass, M. C.</dc:creator>
<dc:creator>Davis, E. L. W.</dc:creator>
<dc:creator>Glass, D.</dc:creator>
<dc:creator>He, Y. D.</dc:creator>
<dc:creator>Heubeck, A. T.</dc:creator>
<dc:creator>Kawelo, E. K.</dc:creator>
<dc:creator>Krishnan, U.</dc:creator>
<dc:creator>Lord, C.</dc:creator>
<dc:creator>Meijer, P.</dc:creator>
<dc:creator>Mettey, R. R.</dc:creator>
<dc:creator>Musgrove, B.</dc:creator>
<dc:creator>Okada, L. Y.</dc:creator>
<dc:creator>Parthasarathy, V.</dc:creator>
<dc:creator>Peng, T.</dc:creator>
<dc:creator>Phalen, C. G.</dc:creator>
<dc:creator>Riddell, S.</dc:creator>
<dc:creator>Roll, C. R.</dc:creator>
<dc:creator>Stuckey, T. J.</dc:creator>
<dc:creator>Swanson, E. G.</dc:creator>
<dc:creator>Thomson, Z. J.</dc:creator>
<dc:creator>Weiss, M. D. A.</dc:creator>
<dc:creator>Wittig, P. J.</dc:creator>
<dc:creator>Anover-Sombke, S. D.</dc:creator>
<dc:creator>Coffey, E. M.</dc:creator>
<dc:creator>Becker, L. A.</dc:creator>
<dc:creator>Bumol, T. F.</dc:creator>
<dc:creator>Goldrath, A. W.</dc:creator>
<dc:creator>Newell, E. W.</dc:creator>
<dc:creator>Greenberg, P. D.</dc:creator>
<dc:creator>Li, X.-j.</dc:creator>
<dc:creator>Kaech, S. M.</dc:creator>
<dc:creator>Skene, P. J.</dc:creator>
<dc:creator>Graybuck, L. T.</dc:creator>
<dc:creator>Tatting, L.</dc:creator>
<dc:creator>Sigvardsson, M.</dc:creator>
<dc:creator>Kwok, M.</dc:creator>
<dc:creator>Green, D. J.</dc:creator>
<dc:creator>Torgerson, T. R.</dc:creator>
<dc:creator>Angus-Hill, M. L.</dc:creator>
<dc:date>2026-04-09</dc:date>
<dc:identifier>doi:10.64898/2026.04.08.717307</dc:identifier>
<dc:title><![CDATA[Myeloma and therapy reshape the bone marrow niche to durably constrain immune reconstitution and vaccine responsiveness]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-09</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Infections are the most common cause of non-relapse mortality in multiple myeloma (MM), but the basis of persistent immune dysfunction is obscured by patient heterogeneity and complex treatment regimens, including autologous stem cell transplant (ASCT). We performed longitudinal multi-omic profiling of matched bone marrow and peripheral blood from MM patients across diagnosis, induction, ASCT, and recovery. We found the tumor imposes a compartment-specific immune program where the marrow exhibits metabolic and inflammatory changes that bias hematopoiesis and alter cytotoxic effector programs not mirrored in blood. Adaptive immune reconstitution is impaired up to two years post-ASCT. Half of patients fail to mount IgG responses to high-dose non-adjuvanted influenza vaccine, a defect overcome by the lipid nanoparticle (LNP) adjuvanted COVID mRNA vaccine, which elicited responses in all patients, supporting adjuvanted influenza vaccine strategies in MM. Together these findings define how myeloma and its treatment durably reshape immunity from the marrow outward.

HighlightsO_LIMultiple Myeloma marrow and blood show opposing metabolic and inflammatory states
C_LIO_LIInduction therapy selects durable myeloma plasma-cell transcriptional states
C_LIO_LIB cell and follicular helper T deficits blunt antigen responses after transplant
C_LIO_LICOVID-19 vaccination builds immune memory with variable responses to flu vaccination
C_LI

eTOCMultiple myeloma and its treatment leave a lasting imprint on the bone marrow niche. By profiling bone marrow and blood longitudinally at diagnosis, through induction, autologous transplant, and recovery, we show that marrow-local metabolic and inflammatory constraints persist and help explain why influenza vaccination often fails while mRNA vaccination succeeds.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.04.07.26349269v1?rss=1">
<title>
<![CDATA[
Assessing the Impact of Timing and Coverage of United States COVID-19 Vaccination Campaigns: A Multi-Model Approach 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.04.07.26349269v1?rss=1"
</link>
<dc:creator>Nande, A.</dc:creator>
<dc:creator>Larsen, S. L.</dc:creator>
<dc:creator>Turtle, J.</dc:creator>
<dc:creator>Davis, J. T.</dc:creator>
<dc:creator>Bandekar, S. R.</dc:creator>
<dc:creator>Lewis, B.</dc:creator>
<dc:creator>Chen, S.</dc:creator>
<dc:creator>Contamin, L.</dc:creator>
<dc:creator>Jung, S.-m.</dc:creator>
<dc:creator>Howerton, E.</dc:creator>
<dc:creator>Shea, K.</dc:creator>
<dc:creator>Bay, C.</dc:creator>
<dc:creator>Ben-Nun, M.</dc:creator>
<dc:creator>Bi, K.</dc:creator>
<dc:creator>Bouchnita, A.</dc:creator>
<dc:creator>Chen, J.</dc:creator>
<dc:creator>Chinazzi, M.</dc:creator>
<dc:creator>Fox, S. J.</dc:creator>
<dc:creator>Hill, A. L.</dc:creator>
<dc:creator>Hochheiser, H.</dc:creator>
<dc:creator>Lemaitre, J. C.</dc:creator>
<dc:creator>Loo, S. L.</dc:creator>
<dc:creator>Marathe, M.</dc:creator>
<dc:creator>Meyers, L. A.</dc:creator>
<dc:creator>Pearson, C. A. B.</dc:creator>
<dc:creator>Porebski, P.</dc:creator>
<dc:creator>Przykucki, E.</dc:creator>
<dc:creator>Smith, C. P.</dc:creator>
<dc:creator>Venkatramanan, S.</dc:creator>
<dc:creator>Vespignani, A.</dc:creator>
<dc:creator>Willard, T. C.</dc:creator>
<dc:creator>Yan, K.</dc:creator>
<dc:creator>Viboud, C.</dc:creator>
<dc:creator>Lessler, J.</dc:creator>
<dc:creator>Truelove, S.</dc:creator>
<dc:date>2026-04-08</dc:date>
<dc:identifier>doi:10.64898/2026.04.07.26349269</dc:identifier>
<dc:title><![CDATA[Assessing the Impact of Timing and Coverage of United States COVID-19 Vaccination Campaigns: A Multi-Model Approach]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-08</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Six years after its emergence, SARS-CoV-2 continues to have a substantial burden, however, the impact of vaccination and the optimal timing of its rollout remain uncertain. To explore these uncertainties, the US Scenario Modeling Hub convened its 19th round of ensemble projections for COVID-19 hospitalizations and deaths in the United States. Eight teams provided outcomes for each US state and nationally from April 2025 to April 2026 under five scenarios regarding vaccine recommendations and timing. We assessed recommendations with two eligibility scenarios (high-risk individuals only and all-eligible) and two timing scenarios (classic start: mid-August, earlier start: late June). These were crossed to create four scenarios and were compared against a counterfactual scenario with no vaccination. We found that compared to no vaccination, our ensemble projections estimated 90,000 (95% PI 53,000-126,000) hospitalizations averted in the high-risk and classic timing scenario across the US. Expanding coverage averted an additional 26,000 (95% PI 14,000-39,000) hospitalizations, which when coupled with earlier vaccination timing further reduced national hospitalizations by 15,000 (95% PI -3,000-33,000). These findings estimate significant benefits from a broad all-eligible vaccination recommendation, and suggest an additional benefit is likely to be gained from an earlier vaccination campaign.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.07.716934v1?rss=1">
<title>
<![CDATA[
Intranasal Anti-CD3 Antibody Treatment Attenuates Post-COVID Neuroinflammation and Enhances Hippocampal Neurogenesis and Cognitive Function in Mice 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.07.716934v1?rss=1"
</link>
<dc:creator>Lu, P.</dc:creator>
<dc:creator>Izzy, S.</dc:creator>
<dc:creator>Da Silva, P.</dc:creator>
<dc:creator>Imkamp, H. T.</dc:creator>
<dc:creator>Christenson, J. R.</dc:creator>
<dc:creator>Yahya, T.</dc:creator>
<dc:creator>Mansi, M. H. A.</dc:creator>
<dc:creator>Alawi, A.</dc:creator>
<dc:creator>Moreira, T. G.</dc:creator>
<dc:creator>Monje, M.</dc:creator>
<dc:creator>Weiner, H. L.</dc:creator>
<dc:creator>Iwasaki, A.</dc:creator>
<dc:date>2026-04-08</dc:date>
<dc:identifier>doi:10.64898/2026.04.07.716934</dc:identifier>
<dc:title><![CDATA[Intranasal Anti-CD3 Antibody Treatment Attenuates Post-COVID Neuroinflammation and Enhances Hippocampal Neurogenesis and Cognitive Function in Mice]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-08</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Cognitive impairment is a disabling feature of Long COVID, with data supporting neuroinflammation and maladaptive glial responses as primary drivers. Nasal administration of an anti-CD3 monoclonal antibody (aCD3 mAb) has shown therapeutic benefits in autoimmune and CNS disease models. Using a respiratory-restricted mild SARS-CoV-2 mouse model of Long COVID, we show that nasal anti-CD3 mAb, administered shortly after infection or during chronic neuroinflammation, increased brain FoxP3+ IL-10+ Tregs, reduced microglial and astrocytic gliosis in the white matter and hippocampus, restored neurogenesis, and improved short-term memory. Nasal aCD3 mAb reprogrammed microglia from an antigen-presenting, NF-{kappa}B-driven inflammatory state toward chemokine signaling, phagosome, and TGF {beta}-related regulatory phenotype. Patients with Long COVID with neurological symptoms had lower circulating Treg populations. These findings identify nasal administration of aCD3 mAb as a noninvasive strategy to control neuroinflammation, restore the neurogenic niche, and offer a novel approach to treating cognitive impairment in Long COVID.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.07.717019v1?rss=1">
<title>
<![CDATA[
SKIN AS A POTENTIAL ENTRY POINT FOR SARS-COV-2 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.07.717019v1?rss=1"
</link>
<dc:creator>Trubestskoy, D.</dc:creator>
<dc:creator>Grudzien, P.</dc:creator>
<dc:creator>Chudakova, D.</dc:creator>
<dc:creator>Klopot, A.</dc:creator>
<dc:creator>Bhalla, P.</dc:creator>
<dc:creator>Perez-White, B.</dc:creator>
<dc:creator>Budunova, I.</dc:creator>
<dc:date>2026-04-08</dc:date>
<dc:identifier>doi:10.64898/2026.04.07.717019</dc:identifier>
<dc:title><![CDATA[SKIN AS A POTENTIAL ENTRY POINT FOR SARS-COV-2]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-08</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
The primary route of SARS-CoV-2 entry is via respiratory epithelium. However, many COVID-19 patients developed dermatological lesions, and SARS-CoV-2 RNA has been detected in the patients skin. Inflammatory skin diseases, psoriasis and atopic dermatitis (AD), significantly increased the risk of COVID-19. To evaluate the potential role of skin in SARS-CoV-2 host interactions, we utilized 3D human skin organoids (HSO) generated from human epidermal keratinocytes, as well as neonatal skin explants. HSO were treated with cytokines involved in acute and chronic skin inflammation and cytokine storm in severe COVID-19 disease, TNF-, IL-6, IL-1{beta}, and IFN-{gamma}, individually and in combination. HSO were also treated with Th1 (TNF- + IL-17) and Th2 (IL-4 + IL-13) cocktails inducing pro-psoriasis and pro-AD HSO changes, respectively. All individual cytokines, and especially their combinations, elevated the expression of ACE2 and TMPRSS2 at mRNA/protein levels. The Th2 induced only TMPRSS2, the Th1 predominantly induced ACE2. Topically applied Spike-pseudotyped lentiviral Tomato reporter, which binds ACE2 similarly to SARS-CoV-2, successfully infected control and cytokine-treated HSO as well as neonatal skin explants. Cytokine treatment, especially TNF- + IL-6 + IL-1{beta} + IFN-{gamma} and the Th1, significantly increased viral entry. Transcriptomic analysis further revealed partial overlap between gene expression signatures induced by Spike-mediated entry in inflamed HSO and those observed in lung tissue from COVID-19 patients, supporting the biological relevance of skin models. Together, these findings demonstrate that inflammation enhances the permissiveness of human skin to SARS-CoV-2 entry, suggesting that the skin may represent a previously underappreciated interface in viral host interactions.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.03.716319v1?rss=1">
<title>
<![CDATA[
High-speed 3D single-virus tracking reveals actin-aided viral trafficking of SARS-CoV-2 on the plasma membrane 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.03.716319v1?rss=1"
</link>
<dc:creator>Lin, Y.</dc:creator>
<dc:creator>Lu, X.</dc:creator>
<dc:creator>Exell, J.</dc:creator>
<dc:creator>Lin, H.</dc:creator>
<dc:creator>Johnson, C.</dc:creator>
<dc:creator>Welsher, K.</dc:creator>
<dc:date>2026-04-06</dc:date>
<dc:identifier>doi:10.64898/2026.04.03.716319</dc:identifier>
<dc:title><![CDATA[High-speed 3D single-virus tracking reveals actin-aided viral trafficking of SARS-CoV-2 on the plasma membrane]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-06</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Early interactions between viruses and live cells are difficult to resolve due to rapid extracellular motion, 3D nature of the cell membrane, and the fast, nanoscale interactions involved. While actin is a central regulator of viral entry, direct observations of actin-aided trafficking have been restricted to membrane protrusions on glass surfaces given the limitations of conventional methods. Here, high-speed 3D Tracking and Imaging microscopy (3D-TrIm) is integrated with highly photostable StayGold-labeled SARS-CoV-2 virus-like particles to capture long-term, high-resolution single-virus trajectories in live cells. This approach revealed distinct regimes of viral dynamics, including extracellular diffusion, protrusion-based surfing, and an unreported linear trafficking mode along the plasma membrane that precedes viral internalization. This work demonstrates that this membrane trafficking is actin-driven and positively correlated with ACE2 expression. These findings reveal new actin exploitation by viruses and demonstrate the utility of 3D-TrIm for dissecting dynamic virus-cell interactions at high spatiotemporal resolution.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.02.716254v1?rss=1">
<title>
<![CDATA[
Frustration Landscapes of Broadly Neutralizing SARS-CoV-2 Spike Antibodies Targeting Conserved Epitopes Reveal Energetic Logic of Escape-Proof and Escape-Prone Mechanisms 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.02.716254v1?rss=1"
</link>
<dc:creator>Alshahrani, M.</dc:creator>
<dc:creator>Gatlin, W.</dc:creator>
<dc:creator>Ludwick, M.</dc:creator>
<dc:creator>Turano, L.</dc:creator>
<dc:creator>Foley, B.</dc:creator>
<dc:creator>Verkhivker, G.</dc:creator>
<dc:date>2026-04-03</dc:date>
<dc:identifier>doi:10.64898/2026.04.02.716254</dc:identifier>
<dc:title><![CDATA[Frustration Landscapes of Broadly Neutralizing SARS-CoV-2 Spike Antibodies Targeting Conserved Epitopes Reveal Energetic Logic of Escape-Proof and Escape-Prone Mechanisms]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-03</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
The continued evolution of SARS-CoV-2 has enabled escape from most monoclonal antibodies, yet a subset of broadly neutralizing antibodies targeting three newly identified super-conserved RBD epitopes--SCORE-A, SCORE-B, and SCORE-C--retains remarkable activity against even the most recent JN.1-derived sublineages. Here we employed an integrated computational framework combining conformational dynamics, mutational scanning, MM-GBSA binding energetics, and frustration profiling to dissect the molecular mechanisms by which XGI antibodies achieve broad neutralization and resistance to immune escape. Structural analysis revealed that all three SCORE epitopes share a common architecture: a highly conserved, minimally frustrated core that provides stable anchoring, flanked by peripheral regions that accommodate antibody-specific variations. Conformational dynamics showed that SCORE-A antibodies (XGI-183) rigidify the lateral epitope while leaving the RBM partially mobile; SCORE-B antibodies (XGI-198, XGI-203) clamp the RBM apex, directly blocking ACE2; and SCORE-C antibodies (XGI-171) allosterically loosen the RBM loop, impairing receptor engagement indirectly. Mutational scanning identified a hierarchical hotspot organization where primary hotspots (e.g., K356, T500, Y380, T385) are evolutionarily constrained and minimally frustrated, while secondary hotspots (e.g., V503, Y508, S383) are neutrally frustrated and represent the principal sites of immune-driven mutations. MM-GBSA decomposition revealed that van der Waals-driven hydrophobic packing dominates binding, with electrostatic interactions providing auxiliary stabilization. Critically, frustration analysis demonstrated that immune escape hotspots reside precisely in zones of neutral frustration--"energetic playgrounds" that permit mutational exploration without destabilizing the RBD--while minimally frustrated cores are evolutionarily locked. The comparative analysis of conformational versus mutational frustration distributions revealed a unifying principle: aligned neutral frustration yields permissive, escape-prone interfaces; decoupling enables targeting of constrained cores; and convergence of minimal frustration in both distributions creates invulnerable interfaces. These findings establish that broad neutralization arises not from ultra-high-affinity anchors but from strategic energy distribution across rigid, evolutionarily informed interfaces, providing a roadmap for designing next-generation therapeutics that target the invulnerable cores of viral surface proteins.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.03.716256v1?rss=1">
<title>
<![CDATA[
The transmembrane domain regulates the kinetics of the SARS-CoV-2 spike conformational transition 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.03.716256v1?rss=1"
</link>
<dc:creator>Kulshrestha, A.</dc:creator>
<dc:creator>Banerjee, A.</dc:creator>
<dc:creator>Lall, S.</dc:creator>
<dc:creator>Gosavi, S.</dc:creator>
<dc:date>2026-04-03</dc:date>
<dc:identifier>doi:10.64898/2026.04.03.716256</dc:identifier>
<dc:title><![CDATA[The transmembrane domain regulates the kinetics of the SARS-CoV-2 spike conformational transition]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-03</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
ABSTRACTThe homotrimeric SARS-CoV-2 spike glycoprotein comprises two subunits: S1, which recognizes host-receptors through its receptor-binding domains (RBDs), and S2, anchored to the viral membrane through its transmembrane domain (TMD), which facilitates the fusion of the viral envelope with the host cell membrane. Upon host-receptor engagement and proteolytic activation, S1 dissociates and triggers a large conformational transition in S2, involving structural rearrangements in the S2 ectomembrane-domains and the TMD. While studies have focused on the ectomembrane-domain dynamics, the TMD has typically been modeled as being in a trimeric state. Here, we use molecular dynamics simulations of a coarse-grained structure-based model (SBM) with an implicit membrane to investigate the role of TMD dynamics in modulating S2 conformational conversion. We first recapitulate previous results from an all-atom SBM with a trimeric TMD and re-emphasize that the extended pre-hairpin intermediate state of S2, which brings the two membranes into apposition, is a byproduct of the prefusion-to-postfusion transition. Next, by introducing dynamics into the TMD, we find a late fusion intermediate structurally similar to a recent cryo-EM structure. A dynamic TMD also makes the conformational transition faster. Simulations including the S1/S2 complex reveal coupled RBD-TMD dynamics: when all three RBDs are in the closed state, they can stabilize the TMD in a trimeric configuration, whereas the opening of a single RBD can trigger a transition to a dynamic TMD. So, the dynamics and the conformational preferences of the TMD can be tuned by the presence and conformation of S1. There is some evidence that the TMDs of class I viral fusion proteins, such as spike, contribute to viral fusion by modulating membrane properties. Our simulations indicate an expanded role for the function of the TMD, where it can directly regulate the kinetics of S2 conformational transitions.

SIGNIFICANCE STATEMENTThe SARS-CoV-2 fusion protein, spike, undergoes a large conformational transition, which facilitates the fusion of the viral and host-cell membranes and the delivery of the viral genome into the host cell. Despite extensive studies of the spike conformational conversion, its transmembrane domain (TMD) has largely been viewed as a viral membrane anchor. Using coarse-grained structure-based model simulations, we show that TMD dynamics can modulate the timing of the spike-S2 (fusion subunit) prefusion-to-postfusion conformational conversion. The presence of spike-S1 (receptor-recognition subunit) can suppress TMD dynamics, potentially reducing the rate of spike conformational conversion and viral fusion. Thus, the spike TMD regulates the kinetics of spike-mediated membrane fusion, and TMD-targeting strategies can be an additional avenue for antiviral intervention.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.02.716054v1?rss=1">
<title>
<![CDATA[
Machine Learning-Driven Antigen Selection Reveals Conserved T-Cell Targets for Broad Coronavirus Vaccination 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.02.716054v1?rss=1"
</link>
<dc:creator>Federico, L.</dc:creator>
<dc:creator>Odainic, A.</dc:creator>
<dc:creator>Lund, K. P.</dc:creator>
<dc:creator>Egner, I. M.</dc:creator>
<dc:creator>Wiese, K. E.</dc:creator>
<dc:creator>Cornelissen, L. A. H. M.</dc:creator>
<dc:creator>Kared, H.</dc:creator>
<dc:creator>Stratford, R.</dc:creator>
<dc:creator>Kapell, S.</dc:creator>
<dc:creator>Malone, B.</dc:creator>
<dc:creator>Gheorghe, M.</dc:creator>
<dc:creator>Machart, P.</dc:creator>
<dc:creator>Siarheyeu, R.</dc:creator>
<dc:creator>Tanaka, Y.</dc:creator>
<dc:creator>Clancy, T.</dc:creator>
<dc:creator>Bendjama, K.</dc:creator>
<dc:creator>Munthe, L. A.</dc:creator>
<dc:date>2026-04-03</dc:date>
<dc:identifier>doi:10.64898/2026.04.02.716054</dc:identifier>
<dc:title><![CDATA[Machine Learning-Driven Antigen Selection Reveals Conserved T-Cell Targets for Broad Coronavirus Vaccination]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-03</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundCoronavirus outbreaks remain a persistent threat to global health, and vaccines based primarily on spike-specific immune responses are susceptible to antigenic variation. T-cell immunity directed against conserved internal viral proteins may provide a complementary and more variant-tolerant strategy for next-generation coronavirus vaccines.

MethodsWe combined machine learning-guided antigen prioritization with ex vivo functional immunological validation to identify conserved non-spike T-cell targets across betacoronaviruses. Candidate sequences were screened for immunogenicity using primary human peripheral blood mononuclear cells from healthy donors using intracellular cytokine staining and activation-induced marker assays. Top-ranked conserved regions were incorporated into multiepitope mRNA constructs, and their intracellular expression and HLA class I presentation were confirmed by immunopeptidomics. Immunogenicity was further evaluated ex vivo and in vivo using mRNA immunization of mice and T-cell FluoroSpot assays.

FindingsAcross a panel of 97 peptides derived from 19 viral proteins, evolutionary conservation across distinct betacoronavirus taxa was strongly associated with functional T-cell immunogenicity in human donors. Highly conserved peptides elicited significantly stronger and more frequent CD4 and CD8 T-cell responses than taxon-restricted peptides. Multiepitope mRNA constructs encoding conserved regions were efficiently expressed and presented on HLA class I molecules and induced T-cell responses in human PBMCs. In mice, mRNA immunization with conserved multiepitope constructs generated robust interferon-{gamma}- and interleukin-2-producing T-cell responses that exceeded those induced by unconserved control constructs.

InterpretationThese results link evolutionary conservation to functional cellular immunogenicity and demonstrate the feasibility of multiepitope mRNA delivery for inducing conserved coronavirus-directed T-cell responses. Although protective efficacy remains to be established, conservation-guided antigen selection represents a scalable strategy for developing T-cell-focused vaccines with broad lineage coverage, supporting pandemic preparedness beyond spike-centered immunity.

FundingThe research was supported by CEPI, NEC, University of Oslo and Oslo university hospital.

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSPrior coronavirus vaccine development has focused predominantly on spike protein-directed neutralizing antibodies. While highly effective against matched strains, spike-centered immunity is vulnerable to antigenic drift and lineage-specific escape. Multiple observational and experimental studies have shown that T-cell responses, particularly against internal viral proteins, are more conserved and correlate with reduced disease severity and cross-variant recognition. Epitope prediction algorithms and immunoinformatics approaches have been widely used to nominate candidate T-cell targets; however, systematic functional validation of conserved non-spike antigens across betacoronaviruses in primary human immune systems, combined with antigen presentation data and in vivo vaccine testing, has remained limited. Searches of PubMed and bioRxiv up to December 2025 using terms including "coronavirus T-cell vaccine," "conserved coronavirus epitopes," "betacoronavirus cross-reactive T cells," and "mRNA T-cell vaccine" identified studies demonstrating cross-reactive T-cell immunity and computational epitope selection, but few integrated machine-learning-guided antigen prioritization with ex vivo human functional screening, immunopeptidomics, and in vivo mRNA immunization in a unified workflow.

Added value of this studyThis study provides an integrated experimental and computational framework for identifying and validating conserved non-spike T-cell antigens across betacoronaviruses. We functionally screened a panel of candidate peptides derived from multiple viral proteins and demonstrated that evolutionary conservation across species is strongly associated with T-cell immunogenicity. We further demonstrate that multiepitope mRNA constructs encoding these top-ranked conserved regions can be intracellularly expressed, presented on HLA class I molecules to induce polyfunctional T-cell responses in primary human PBMCs. Finally, in vivo mRNA immunization in mice induces robust interferon-{gamma} and interleukin-2 T-cell responses exceeding those induced by unconserved control constructs. Together, these findings link evolutionary conservation to functional cellular immunogenicity and extend beyond in silico prediction by demonstrating antigen processing, presentation, and immunogenicity across human and murine systems.

Implications of all the available evidenceCollectively, the available evidence indicates that T-cell immunity directed toward conserved internal coronavirus proteins represents a complementary and potentially more variant-tolerant axis of vaccine design than spike-only strategies. Our findings suggest that evolutionary conservation can serve as a practical selection principle for prioritizing T-cell antigens with broad lineage coverage and that multiepitope mRNA delivery is a feasible platform for inducing such responses. While direct protection and heterologous challenge studies will be required to establish clinical efficacy, the integration of computational prioritization with functional validation supports a scalable approach to pandemic preparedness that may be applicable to other rapidly evolving viral families.
]]></description>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.04.02.716024v1?rss=1">
<title>
<![CDATA[
TF-IDF k-mer-based Classical and Hybrid Machine Learning Models for SARS-CoV-2 Variant Classification under Imbalanced Genomic Data 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.04.02.716024v1?rss=1"
</link>
<dc:creator>Haque, N.</dc:creator>
<dc:creator>Mazed, A.</dc:creator>
<dc:creator>Ankhi, J. N.</dc:creator>
<dc:creator>Uddin, M. J.</dc:creator>
<dc:date>2026-04-02</dc:date>
<dc:identifier>doi:10.64898/2026.04.02.716024</dc:identifier>
<dc:title><![CDATA[TF-IDF k-mer-based Classical and Hybrid Machine Learning Models for SARS-CoV-2 Variant Classification under Imbalanced Genomic Data]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-04-02</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
Accurate classification of SARS-CoV-2 genomic variants is essential for effective genomic surveillance, yet it is challenged by extreme class imbalance, limited representation of rare variants, and distribution shifts in real-world sequencing data. In this study, we employed hybrid RF-SVM framework designed for robust detection of rare SARS-CoV-2 variants. It integrates a random forest and a polynomial-kernel based support vector machine to enhance sensitivity to minority classes while maintaining overall predictive stability. We systematically compared classical machine learning models, deep learning approaches, and hybrid strategies under both standard and distribution-shifted evaluation settings. Our results show that classical models using TF-IDF-based k-mer features outperform deep learning methods on macro-averaged performance metrics. The Random Forest classifier using TF-IDF Feature achieved the best overall performance, with a macro-averaged F1-score of 0.8894 and an accuracy of 96.3%. The model also demonstrated strong generalization ability, as evidenced by stable cross-validation performance (CV accuracy = 0.9637). Hybrid RF-SVM model further improves rare variant detection under severe class imbalance. Calibration analysis indicates reliable probability estimates for common variants, although challenges persist for minority classes. Overall, this study highlights the limitations of deep learning in highly imbalanced genomic settings and demonstrates that carefully designed hybrid machine learning approaches provide an effective and interpretable solution for rare SARS-CoV-2 variant detection.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.03.24.26349101v1?rss=1">
<title>
<![CDATA[
An Assessment of Correctional Officer's Health Beliefs in Relationship to COVID-19 Vaccine Uptake and Hesitancy. 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.03.24.26349101v1?rss=1"
</link>
<dc:creator>Hedden-Clayton, B.</dc:creator>
<dc:creator>Roddy, A. L.</dc:creator>
<dc:creator>Roddy, J. K.</dc:creator>
<dc:creator>Ngassa, Y.</dc:creator>
<dc:creator>Pickard, B.</dc:creator>
<dc:creator>Tam, R. A.</dc:creator>
<dc:creator>Wurcel, A. G.</dc:creator>
<dc:date>2026-03-26</dc:date>
<dc:identifier>doi:10.64898/2026.03.24.26349101</dc:identifier>
<dc:title><![CDATA[An Assessment of Correctional Officer's Health Beliefs in Relationship to COVID-19 Vaccine Uptake and Hesitancy.]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-03-26</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
IntroductionDuring the COVID-19 pandemic, incarcerated populations faced heightened risk of exposure due to healthcare barriers, restrictive environments, and pre-existing health conditions. Consequently, Correctional Officers (COs) faced increased risk of COVID-19 exposure. Given the health benefits of COVID-19 vaccination and the rise in vaccine hesitancy, this study examined the relationship between COs health beliefs and COVID-19 vaccine uptake.

MethodsA health beliefs survey was administered to Massachusetts-based COs (n=118). Chi-squared Automatic Interaction Detection modeling and logistic regression was utilized to analyze the survey data.

ResultsCOs with higher trust in vaccines and a prior positive COVID-19 test were most likely to get vaccinated voluntarily. Those with low trust in vaccines and no previous positive COVID-19 test were least likely to receive the vaccine.

ConclusionDespite the severe impact of COVID-19 in correctional settings, and the evidence of vaccine efficacy against hospitalization and death, vaccine uptake among COs remains low.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.03.21.26348591v1?rss=1">
<title>
<![CDATA[
Disentangling the Shared and Differential Genetic Architecture Between COVID-19 and Other Respiratory Disorders: A Multi-Omics Genome-Wide Analysis 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.03.21.26348591v1?rss=1"
</link>
<dc:creator>Xue, X.</dc:creator>
<dc:creator>LIN, Y.-P.</dc:creator>
<dc:creator>FENG, Y.</dc:creator>
<dc:creator>SO, H.-C.</dc:creator>
<dc:date>2026-03-26</dc:date>
<dc:identifier>doi:10.64898/2026.03.21.26348591</dc:identifier>
<dc:title><![CDATA[Disentangling the Shared and Differential Genetic Architecture Between COVID-19 and Other Respiratory Disorders: A Multi-Omics Genome-Wide Analysis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-03-26</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundA bidirectional relationship has been observed between COVID-19 and respiratory disorders, where respiratory comorbidities increase severity and COVID-19 induces respiratory sequelae. The underlying biological and genetic mechanisms remain unclear. While previous studies have identified overlapping genetic loci, few have systematically disentangled the genetic factors shared between these conditions versus those specific to COVID-19, particularly at a multi-omics level.

MethodsWe developed and applied a unified analytical framework to compare three COVID-19 phenotypes with eight respiratory disorders (including asthma, COPD, IPF, and pneumonia). Utilizing the cofdr method for shared genetic signal analysis and DDx/mtCOJO for differentiation, we integrated genome-wide association statistics with multi-omics data (transcriptome, splicing, and proteome). This approach allowed for the simultaneous identification of shared genetic signals (concordant or discordant) and disease-specific variants across expression (TWAS), alternative splicing (spTWAS), and protein abundance (PWAS).

ResultsWe delineated a comprehensive atlas of 214 differential and numerous shared loci across 24 pairwise comparisons. The shared genetic architecture was characterized by pleiotropic effects in genes such as ATP11A (exhibiting opposing effects in COVID-19 vs. IPF) and GSDMB (shared with COPD). Crucially, differentiation analysis revealed that severe COVID-19 is genetically distinct from other respiratory infections (e.g., pneumonia and influenza) through dysregulated Type I/III interferon signaling and specific defects in alveolar epithelial and macrophage function, as well as GM-CSF/surfactant metabolism pathways. These findings provide direct genetic evidence supporting the use of GM-CSF modulators and interferon-lambda for COVID-19 treatment, therapies that have already entered clinical trials. Furthermore, multi-trait conditional analysis prioritized FYCO1 and HCN3 as potential COVID-19-specific risk genes. Splicing analysis underscored the critical role of alternative splicing in both shared and differential architectures, highlighting IFNAR2 isoform regulation as a key discriminator between COVID-19 and other respiratory traits.

ConclusionThis study provides the first genome-wide, multi-omics map revealing the shared and differential genetic landscapes of COVID-19 and other respiratory phenotypes. By uncovering specific molecular mechanisms that distinguish COVID-19 pathology, specifically involving surfactant homeostasis and interferon pathways, our findings offer novel insights for targeted drug repurposing and precision risk stratification.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.03.23.26349092v1?rss=1">
<title>
<![CDATA[
Higher SARS-CoV-2 Transmission Burden Among Racialized Individuals: Evidence from Canadian Serology Data 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.03.23.26349092v1?rss=1"
</link>
<dc:creator>Mann, S. K.</dc:creator>
<dc:creator>Wilson, N. J.</dc:creator>
<dc:creator>Lee, C. E.</dc:creator>
<dc:creator>Fisman, D.</dc:creator>
<dc:date>2026-03-25</dc:date>
<dc:identifier>doi:10.64898/2026.03.23.26349092</dc:identifier>
<dc:title><![CDATA[Higher SARS-CoV-2 Transmission Burden Among Racialized Individuals: Evidence from Canadian Serology Data]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-03-25</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
IntroductionCOVID-19 transmission has not been evenly distributed across racial groups, with exposure being shaped by social and structural factors. The emergence of highly transmissible variants (i.e., Omicron) dramatically increased infection rates. However, it remains unclear whether racial disparities in transmission disappeared or persisted over the course of the pandemic.

ObjectiveTo understand how SARS-CoV-2 transmission differed by race in Canada and whether those disparities changed with the Omicron variant.

MethodsWe analyzed cross-sectional SARS-CoV-2 seroprevalence data from the Canadian Blood Services serosurveillance program (June 2020 to April 2023) using a previously described dynamic susceptible-infection model, while accounting for seroreversion. Race-specific force of infection was estimated for the pre-Omicron and Omicron periods (with the emergence of Omicron defined as beginning December 26, 2021).

ResultsPrior to Omicron, racialized individuals had a 74% higher force of infection (IRR = 2.205; 95% CI: 2.115-2.299). During the Omicron period, infection rates rose significantly within each racial group relative to the pre-Omicron period, with a 55.52-fold increase among White individuals and a 31.27-fold increase among racialized individuals. Despite this, racialized individuals remained disproportionately affected following the emergence of Omicron, with 24% higher infection rates than those of their White counterparts (IRR = 1.242; 95% CI: 1.231-1.253).

ConclusionWidespread transmission during Omicron did not result in epidemiologic equity, as racialized populations continued to experience higher infection risk despite crude seroprevalence depicting convergence.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.03.23.26349084v1?rss=1">
<title>
<![CDATA[
Beyond COVID-19 Deaths: Cause-Specific Analysis of Excess Mortality in Russia 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.03.23.26349084v1?rss=1"
</link>
<dc:creator>Degtiareva, E.</dc:creator>
<dc:creator>Timonin, S.</dc:creator>
<dc:creator>Tilstra, A.</dc:creator>
<dc:creator>Aburto, J. M.</dc:creator>
<dc:date>2026-03-25</dc:date>
<dc:identifier>doi:10.64898/2026.03.23.26349084</dc:identifier>
<dc:title><![CDATA[Beyond COVID-19 Deaths: Cause-Specific Analysis of Excess Mortality in Russia]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-03-25</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
During the COVID-19 pandemic, European mortality exhibited a marked East-West divide in both timing and magnitude, echoing longstanding longevity disparities in this region. Russia sits on the Eastern side: early restrictions were short-lived, and vaccine uptake remained low amid historically limited trust in government and science. Using weekly national and monthly regional mortality data disaggregated by age, sex, and cause of death, we estimated excess mortality from March 2020 to December 2021 using generalised additive models. We identify two major mortality peaks (late 2020-early 2021 and late 2021) and estimate 1,044,914 excess deaths, well above the 595,815 officially registered COVID-19 deaths. Non-COVID-19 excess was larger during the first peak, especially at ages 15-44. Cardiovascular diseases accounted for roughly 60% of the non-COVID-19 excess and we find no evidence of excess mortality from cancer or external causes. Among women, excess deaths were concentrated at older ages, whereas among men they clustered at working and older working ages, only partly reflecting differences in age structure. The highest excess mortality was found in the most populous regions, particularly the Central European and Volga parts. Temporal and spatial inconsistencies in cause-of-death coding may obscure indirect mortality burden and hinder the associated policy response.

Highlights- Russia had 1,044,914 excess deaths in 2020-21, about twice official COVID-19 deaths.
- These discrepancies varied over time and across regions.
- Cardiovascular deaths drove most non-COVID excess mortality.
- We find no evidence of excess mortality from external causes of death.
- Autopsy-based COVID-19 assignment may have increased misclassification
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.03.23.26349096v1?rss=1">
<title>
<![CDATA[
Wastewater-Based Genomic Surveillance of SARS-CoV-2 Variant Circulation in Two Informal Urban Settlements in Nairobi, Kenya 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.03.23.26349096v1?rss=1"
</link>
<dc:creator>Kingwara, L.</dc:creator>
<dc:creator>Madada, R. S.</dc:creator>
<dc:creator>Morangi, V.</dc:creator>
<dc:creator>Akasa, S.</dc:creator>
<dc:creator>Kiprutto, V.</dc:creator>
<dc:creator>Julie, O.</dc:creator>
<dc:creator>Muthoka, R.</dc:creator>
<dc:creator>Rombo, C.</dc:creator>
<dc:creator>Kimonye, K.</dc:creator>
<dc:creator>Okunga, E.</dc:creator>
<dc:creator>Masika, M.</dc:creator>
<dc:creator>Ochieng, E.</dc:creator>
<dc:creator>Nyaga, R.</dc:creator>
<dc:creator>Otieno, O.</dc:creator>
<dc:creator>Cham, F.</dc:creator>
<dc:creator>Hull, N.</dc:creator>
<dc:creator>Kimenye, K.</dc:creator>
<dc:date>2026-03-25</dc:date>
<dc:identifier>doi:10.64898/2026.03.23.26349096</dc:identifier>
<dc:title><![CDATA[Wastewater-Based Genomic Surveillance of SARS-CoV-2 Variant Circulation in Two Informal Urban Settlements in Nairobi, Kenya]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-03-25</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundSARS-CoV-2 genomic surveillance data remain limited in most low and middle-income countries (LMICs), resulting in significant gaps in the understanding of variant circulation and evolution. Wastewater-based epidemiology (WBE) presents a non-invasive, cost-effective, and population-representative surveillance approach that can complement clinical testing, particularly in densely populated urban informal settlements with limited healthcare access. This study aimed to pilot wastewater-based genomic surveillance as a multifaceted public health tool in Kenya.

MethodsA prospective study was conducted using wastewater samples collected from two WHO-validated environmental surveillance sites -- Eastleigh A (Kamukunji sub-county) and Mathare (Starehe sub-county) -- in Nairobi, Kenya, between December 2022 and October 2023. A total of 272 samples were collected using Moore swabs at a frequency of two to three times per week. Samples were concentrated using Nanotrap(R) Magnetic Virus Particles, and nucleic acid was extracted using the Qiagen QIAamp Viral RNA Mini Kit. SARS-CoV-2 was detected using RT-PCR (TaqPath COVID-19 CE-IVD RT-PCR Kit). Library preparation for whole-genome sequencing was performed using the Illumina COVIDSeq kit, and sequencing was conducted on the Illumina MiSeq platform. Bioinformatic analysis was performed using Terra.bio and RStudio, and phylogenetic analysis included sequences abstracted from GISAID.

ResultsOf 272 samples, 238 (87.5%) tested positive with a cycle threshold (Ct) value of less than 36. Genomic analysis of 181 sequences identified Omicron as the predominant circulating variant, detected in 59% of samples. Other variants included XBB (16%), XBB.2.3(10%), XBB.1.9.X (5%), and additional minor variants. These findings were concordant with clinical sequencing data from Kenya over the same period.

ConclusionsWastewater-based genomic surveillance reliably reflected SARS-CoV-2 variant trends observed in clinical data. This approach provides early signals of variant emergence and evolution, offering a cost-effective complement to clinical surveillance in resource-limited settings.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.03.23.26349117v1?rss=1">
<title>
<![CDATA[
Household Size and Age as Primary Drivers of COVID-19 Infection Among Priority Populations in Australia 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.03.23.26349117v1?rss=1"
</link>
<dc:creator>Narayanasamy, S.</dc:creator>
<dc:creator>Altermatt, A.</dc:creator>
<dc:creator>Tse, W. C.</dc:creator>
<dc:creator>Gibbs, L.</dc:creator>
<dc:creator>Wilkinson, A.</dc:creator>
<dc:creator>Heath, K.</dc:creator>
<dc:creator>Stoove, M.</dc:creator>
<dc:creator>Scott, N.</dc:creator>
<dc:creator>Gibney, K.</dc:creator>
<dc:creator>Hellard, M.</dc:creator>
<dc:creator>Pedrana, A.</dc:creator>
<dc:date>2026-03-25</dc:date>
<dc:identifier>doi:10.64898/2026.03.23.26349117</dc:identifier>
<dc:title><![CDATA[Household Size and Age as Primary Drivers of COVID-19 Infection Among Priority Populations in Australia]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-03-25</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundThe COVID-19 pandemic exacerbated health disparities globally, with certain populations experiencing disproportionate disease burdens. In Australia, COVID-19 deaths occurred disproportionately among first-generation migrants. This study examined risk factors for COVID-19 infection in a Victorian cohort recruited from priority populations, including healthcare workers, people with chronic health conditions, and culturally and linguistically diverse (CALD) communities.

MethodsWe conducted a cross-sectional analysis of participants from the Optimise longitudinal cohort study (September 2020-December 2023). The primary outcome was the self-reported count of confirmed COVID-19 infections (PCR or rapid antigen test positive) from December 2019 to December 2023. We used Poisson regression to examine associations between baseline sociodemographic characteristics and infection count, calculating unadjusted and adjusted incidence rate ratios (IRRs) with 95% confidence intervals (CIs).

ResultsOf 433 participants (median age 51 years, 75% female), 25% reported no infections, 48% reported one infection, and 27% reported two or more infections. In univariate analysis, CALD status (IRR=1.24,95%CI:1.02-1.50) and larger household size (2-5 people, IRR=1.71,95%CI:1.14-2.50) were associated with higher infection rates, while chronic health conditions (IRR=0.73, 95%CI:0.61-0.88) and older age (IRR=0.54, 95%CI:0.43-0.67) were associated with lower infection rates. In adjusted analysis, younger age (18-34 years vs [&ge;]55 years: aIRR=0.63,95%CI:0.48-0.82) and medium household size (living alone vs 2-5 person household: aIRR=1.42, 95%CI:1.11-1.83) remained significant predictors. CALD status and socioeconomic status showed no independent association with infection risk after adjustment for household size and age.

ConclusionCOVID-19 infection risk in this Victorian cohort was driven by younger age and larger household size rather than CALD status or socioeconomic status, suggesting that housing density and age, rather than cultural or socioeconomic characteristics, determined infection patterns. Future pandemic preparedness should prioritise policies enabling safe quarantine and isolation for individuals in larger households and workplace protections and economic security for younger essential workers.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.03.23.26349139v1?rss=1">
<title>
<![CDATA[
Phylogenetic Insights into SARS-CoV-2 Introductions and Spread in Georgia 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.03.23.26349139v1?rss=1"
</link>
<dc:creator>Veytsel, G. E.</dc:creator>
<dc:creator>Lyu, L.</dc:creator>
<dc:creator>Stott, G.</dc:creator>
<dc:creator>Carmola, L.</dc:creator>
<dc:creator>Dishman, H.</dc:creator>
<dc:creator>Bahl, J.</dc:creator>
<dc:date>2026-03-25</dc:date>
<dc:identifier>doi:10.64898/2026.03.23.26349139</dc:identifier>
<dc:title><![CDATA[Phylogenetic Insights into SARS-CoV-2 Introductions and Spread in Georgia]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-03-25</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
The spread of successive novel COVID-19 variants presented a challenge for outbreak surveillance, epidemiology, and emergency responses. Monitoring the emergence and spread of SARS-CoV-2 variants is essential to allocate limited public health resources and optimize control efforts. Global collaboration among the scientific community enabled large-scale viral surveillance and sequencing efforts. However, translating these vast datasets into actionable public health inferences requires rapid statistical methodologies, scalable workflows, and robust frameworks.

In this study, we focused on the Delta epidemic wave in Georgia by applying a hybrid maximum likelihood (ML) and Bayesian phylodynamic approach. We characterized the Delta variant introduction to Georgia and its subsequent local spread. Our analysis of 9,783 Delta sequences collected between August 1, 2020 and January 25, 2022 detected at least 344 introductions into Georgia, resulting in 34 highly-supported local clusters. On average, clusters circulated for one month before the earliest detected sequence, highlighting critical delays in detection. While most clusters remained small, a few introduction events led to large, sustained outbreaks. We jointly inferred the statewide transmission network, estimated from all locally circulating clusters with a modified Bayesian discrete trait phylogeographic reconstruction of statewide health districts. We showed that South Central, Georgia was a major source of transmission, despite having smaller numbers of infected people, compared to major metropolitan areas.

Our study addresses the urgent need for methodologies and data-driven recommendations for public health practice, particularly given large, dynamic, and integrated datasets. By identifying key geographic sources and sinks of transmission, our findings can guide resource allocation and prepare for future epidemics among high-risk populations. Additionally, by characterizing introduction events, local circulation, and detection lags, we highlight critical gaps in surveillance. These gaps can inform outbreak investigation and response, such as targeted contact tracing and testing.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.03.20.26348947v1?rss=1">
<title>
<![CDATA[
Shifts in the pathogen spectrum and epidemiology of respiratory tract infections in the post-COVID-19 era: A study from Quzhou, Eastern China 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.03.20.26348947v1?rss=1"
</link>
<dc:creator>Yang, R.</dc:creator>
<dc:creator>Wang, M.</dc:creator>
<dc:creator>Lyu, L.</dc:creator>
<dc:creator>You, J.</dc:creator>
<dc:creator>Huang, S.</dc:creator>
<dc:creator>Zhan, B.</dc:creator>
<dc:date>2026-03-24</dc:date>
<dc:identifier>doi:10.64898/2026.03.20.26348947</dc:identifier>
<dc:title><![CDATA[Shifts in the pathogen spectrum and epidemiology of respiratory tract infections in the post-COVID-19 era: A study from Quzhou, Eastern China]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-03-24</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundAlthough the relaxation of COVID-19 containment measures in China has altered the transmission dynamics of respiratory pathogens, regional data on post-pandemic epidemiological characteristics remain limited.

ObjectiveThis study aimed to investigate the pathogen spectrum and epidemiological characteristics of acute respiratory infections (ARIs) in Quzhou City from 2023 to 2024, providing a scientific basis for local prevention and control strategies.

MethodsA total of 2,800 respiratory specimens were collected from November 2023 to July 2024, comprising 1,960 influenza-like illness (ILI) cases from outpatient/emergency departments and 840 severe acute respiratory infection (SARI) cases from inpatient departments. All samples were tested for 13 common respiratory pathogens using multiplex fluorescence quantitative PCR. Etiological and epidemiological analyses were performed based on detection results and case information.

ResultsThe overall ARI positivity rate was 59.28% (1,660/2,800), with a male-to-female ratio of 1.07:1 (1,447/1,353). The three most prevalent pathogens were influenza virus (Flu, 23.21%, 650/2,800), Streptococcus pneumoniae (SP, 13.14%, 368/2,800), and adenovirus (ADV, 8.39%, 235/2,800). Single pathogen infections accounted for 73.55% (1,221/1,660) of positive cases, while co-infections with two or more pathogens accounted for 26.45% (439/1,660), yielding an overall co-infection rate of 15.68% (439/2,800). No significant gender difference was observed in detection rates. However, significant differences were found across case types, temporal periods, age groups, and geographic regions (P < 0.01). Children aged [&le;]5 years exhibited the highest positivity rate (78.00%, 378/525), while adults aged [&ge;]65 years showed the lowest (34.53%, 144/417). Among surveillance regions, Kaihua County had the highest positivity rate (72.47%), and Changshan County the lowest (40.55%).

ConclusionsMultiple respiratory pathogens and co-infections are prevalent in Quzhou City, with distinct age-specific and seasonal patterns. These findings underscore the need for continuous multi-pathogen surveillance and integrated prevention strategies for influenza and other respiratory infectious diseases in the post-pandemic era.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.03.18.26348530v1?rss=1">
<title>
<![CDATA[
Microtesla Magnetic Therapy for cognitive impairment in post-acute sequelae of SARS CoV-2: A randomized controlled feasibility study 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.03.18.26348530v1?rss=1"
</link>
<dc:creator>Canori, A.</dc:creator>
<dc:creator>Watson, E.</dc:creator>
<dc:creator>Patel, D.</dc:creator>
<dc:creator>Fiorentino, A.</dc:creator>
<dc:creator>Santiago, C.</dc:creator>
<dc:creator>Maltz, D.</dc:creator>
<dc:creator>Gurfein, B.</dc:creator>
<dc:creator>Putrino, D.</dc:creator>
<dc:creator>Becker, J.</dc:creator>
<dc:date>2026-03-23</dc:date>
<dc:identifier>doi:10.64898/2026.03.18.26348530</dc:identifier>
<dc:title><![CDATA[Microtesla Magnetic Therapy for cognitive impairment in post-acute sequelae of SARS CoV-2: A randomized controlled feasibility study]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-03-23</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundCognitive impairment has significant implications for function and quality of life and is common in individuals with post-acute sequelae of SARS CoV-2, also known as long COVID (LC). Emerging evidence suggests that sustained neuroinflammation, cerebrovascular dysfunction, and mitochondrial impairment are contributors to cognitive symptoms. Microtesla Magnetic Therapy (MMT) is a low-amplitude radiofrequency magnetic field intervention that has demonstrated anti-inflammatory and neuroprotective effects in preclinical models, suggesting it may be valuable in the management of cognitive impairment from LC and other neurological disorders. This study is the first randomized controlled trial to evaluate MMT for LC-related cognitive impairment.

ObjectiveTo evaluate the feasibility, safety, and preliminary efficacy of an at-home MMT intervention in individuals with moderate-to-severe cognitive impairment from LC.

MethodsIn this prospective feasibility study, 30 participants with LC-related cognitive impairment were randomized (2:1) to receive active or sham MMT. Participants self-administered 15-minute treatments at home with remote monitoring twice weekly for 4 weeks using a head-worn device that delivered a nonthermal radiofrequency magnetic field to the whole brain. Feasibility was defined as completion of at least 80% of prescribed treatments and all study visits. Secondary outcomes included safety, cognitive function, and self-reported mood and quality of life assessed at baseline, post-treatment (Week 4), and follow-up (Week 8).

ResultsFeasibility was high, with 100% treatment adherence among participants who completed the study and strong usability ratings for at-home administration. There were no device-related adverse events. Compared with sham, participants receiving active MMT showed significantly greater improvements from baseline to Week 8 in WAIS-IV Digit Span Sequencing (p= 0.026), HVLT-R Recall (p= 0.044), and D-KEFS Color Naming (p= 0.049). Additional measures of attention, processing speed, and executive function demonstrated favorable trends in the active group. Emotional well-being, assessed by the SF-36, improved significantly in the active group at Week 8 compared with sham (p= 0.017), and mood symptoms showed clinically meaningful improvement.

ConclusionsAdministration of the MMT intervention at home was feasible, safe, and well tolerated in individuals with cognitive impairment from LC. Preliminary findings suggest sustained clinically meaningful improvements in multiple cognitive domains and mood following treatment.

Trial RegistrationClinicalTrials.gov NCT06739668, https://clinicaltrials.gov/study/NCT06739668, 2024-12-17
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.03.16.26348020v1?rss=1">
<title>
<![CDATA[
Feasibility, Acceptability, and Cost of Community-Based Self-monitoring among Sex Workers Testing Positive for COVID-19 in Zimbabwe: A Mixed-methods Study. 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.03.16.26348020v1?rss=1"
</link>
<dc:creator>Kabonga, I.</dc:creator>
<dc:creator>Mangenah, C.</dc:creator>
<dc:creator>Watadzaushe, C.</dc:creator>
<dc:creator>Madanhire, C.</dc:creator>
<dc:creator>Ruhode, N.</dc:creator>
<dc:creator>Dunkley, Y.</dc:creator>
<dc:creator>Karin, H.</dc:creator>
<dc:creator>Corbett, E. L.</dc:creator>
<dc:creator>Cowan, F. M.</dc:creator>
<dc:creator>Sibanda, E. L.</dc:creator>
<dc:date>2026-03-23</dc:date>
<dc:identifier>doi:10.64898/2026.03.16.26348020</dc:identifier>
<dc:title><![CDATA[Feasibility, Acceptability, and Cost of Community-Based Self-monitoring among Sex Workers Testing Positive for COVID-19 in Zimbabwe: A Mixed-methods Study.]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-03-23</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundSex workers struggled to adhere to isolation guidelines following COVID-19 diagnosis because of financial pressure to keep working. We co-developed and evaluated for feasibility, acceptability, and cost an intervention for promoting isolation and community-based self-monitoring for COVID-19.

MethodsSex workers testing positive for COVID-19 received the following co-developed intervention: i) risk-differentiated support, including immediate hospitalization and/or treatment for serious illness, and community-based self-monitoring for those at risk of progressing to severe illness, ii) food packs lasting two weeks. Using Proctors Framework, we interviewed purposively selected health-workers and sex workers before intervention implementation (26 sex workers and 24 health workers) and during implementation (8 sex workers of whom 5 tested positive, and 5 health workers) to evaluate the intervention. We determined intervention development and implementation costs using program data.

ResultsThe intervention was implemented between March-June 2023. Sex workers and health workers reported that the intervention was highly acceptable and was implemented with fidelity. Food packs were highly appreciated; participants said they promoted isolation although vulnerability to non-food financial pressures persisted. Unanticipated impacts were increased testing uptake following introduction of food packs. Self-monitoring at home was acceptable although fear of stigma prevented some participants from seeking the needed support. The cost per sex worker testing positive was $49 and $54 respectively excluding/including intervention co-development costs.

ConclusionA co-developed intervention for promoting isolation and community-based self-monitoring for COVID-19 was feasible and acceptable, with costs comparing favorably with similar interventions. Addressing stigma could optimise implementation and potential for future pandemics.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.03.19.26348776v1?rss=1">
<title>
<![CDATA[
Physiotherapy service during the COVID-19 pandemic in Nepal: An onsite survey and the lived experience among clinicians 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.03.19.26348776v1?rss=1"
</link>
<dc:creator>Shakya, N. R.</dc:creator>
<dc:creator>Dahal, S.</dc:creator>
<dc:creator>Shrestha, N.</dc:creator>
<dc:creator>Webb, G.</dc:creator>
<dc:creator>Stensdotter, A.-K.</dc:creator>
<dc:date>2026-03-22</dc:date>
<dc:identifier>doi:10.64898/2026.03.19.26348776</dc:identifier>
<dc:title><![CDATA[Physiotherapy service during the COVID-19 pandemic in Nepal: An onsite survey and the lived experience among clinicians]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-03-22</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundThe COVID-19 pandemic significantly disrupted healthcare services globally, particularly in low-resource settings. This study explores the impact of the pandemic on physiotherapy services in Nepal.

MethodsA cross-sectional study was conducted. Qualitative data were collected through semi-structured interviews with 12 physiotherapists, while quantitative data were gathered from an onsite survey of 29 health facilities at six different districts of Province III of Nepal. Inductive thematic analysis approach was used to analyze the qualitative data, and descriptive statistics were used for the closed ended questions.

ResultsThe findings were categorized into sub-themes under two major themes: i) Pandemic effect on physiotherapy services and patient care and ii) Adaptation, innovation and collaboration. The study revealed a significant disruption in physiotherapy services with a notable decline in patient flow and service availability. Most patients, especially those with disabilities and post-operative needs, experienced worsening conditions due to limited access to care. There was an increased recognition of the role of physiotherapy in acute respiratory care and post-COVID-19 recovery. Tele-rehabilitation was explored as an alternative care method but faced challenges in implementation. More than half (62.07%) of the centers reported uninterrupted physiotherapy services, whereas almost one third (31.03%) experienced service suspension. Most centers (89.7%) had personal protective equipment available, and majority (86.2%) of the physiotherapists worked in multidisciplinary team: fever clinics, triage, emergency care, respiratory physical therapy, and nursing and administrative support were among the expanded roles. Several centers (37.9%) used virtual care with telephone consultation serving as the primary modality. Virtual service was mostly absent in centers where in-person services persisted.

ConclusionThe COVID-19 pandemic significantly impacted physiotherapy services in Nepal, leading to service disruptions and compromised patient care. It highlighted the need to further incorporate physiotherapy into the healthcare system and enhance rehabilitation services to improve continued patient care.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.03.19.26348823v1?rss=1">
<title>
<![CDATA[
SARS-CoV-2 and the Pandemic Surge in Invasive Group A Streptococcal Disease 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.03.19.26348823v1?rss=1"
</link>
<dc:creator>Fisman, D.</dc:creator>
<dc:creator>Lee, C. E.</dc:creator>
<dc:creator>Wilson, N.</dc:creator>
<dc:creator>Barton, M.</dc:creator>
<dc:creator>Mann, S. K.</dc:creator>
<dc:creator>Tuite, A.</dc:creator>
<dc:date>2026-03-22</dc:date>
<dc:identifier>doi:10.64898/2026.03.19.26348823</dc:identifier>
<dc:title><![CDATA[SARS-CoV-2 and the Pandemic Surge in Invasive Group A Streptococcal Disease]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-03-22</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundMultiple countries reported unprecedented increases in invasive group A streptococcal (iGAS) disease following widespread SARS-CoV-2 circulation. Whether this surge reflects reduced pathogen exposure during non-pharmaceutical interventions ("immunity debt") or effects of SARS-CoV-2 infection on host immunity remains unresolved.

MethodsWe conducted a population-based time-series analysis of weekly iGAS incidence in central Ontario, Canada (population {approx}11 million) from March 2011 through March 2024 (676 weeks). Using negative binomial panel regression, we modeled acute (2-week lagged) and cumulative SARS-CoV-2 exposure while adjusting for seasonality, secular trends, age, and sex. Population attributable fractions (PAFs) were estimated by counterfactual prediction. Specificity was assessed through negative control analyses (influenza, RSV). The immunity debt hypothesis was evaluated using cumulative streptococcal exposure as a predictor of iGAS.

ResultsAmong 2,906 iGAS episodes, 34.3% during the pandemic period were associated with acute SARS-CoV-2 effects (range by age group: 16.5-39.1%). Models incorporating cumulative SARS-CoV-2 burden showed markedly better fit ({Delta}AIC=-157.5); cumulative exposure was strongly associated with iGAS (IRR 1.193, 95% CI 1.151-1.235), increasing the estimated PAF to 66.7%. Cumulative effects were strongest in children (IRR 1.309). SARS-CoV-2 was comparably associated with non-invasive streptococcal disease, with no increase in invasion propensity. Cumulative streptococcal exposure was not protective (overall IRR 1.000, p=0.730); where significant, the association was positive, opposite to immunity debt predictions.

ConclusionsCumulative SARS-CoV-2 burden was strongly associated with pandemic-era iGAS incidence. Cumulative streptococcal exposure did not support the immunity debt hypothesis. These ecological findings are consistent with SARS-CoV-2-associated immune dysregulation and warrant individual-level confirmation.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.03.19.26348833v1?rss=1">
<title>
<![CDATA[
Autoantibody landscapes in neurological Long COVID and post-COVID cognitive impairment show heterogeneity without a shared disease signature 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.03.19.26348833v1?rss=1"
</link>
<dc:creator>Chakravarty, D.</dc:creator>
<dc:creator>Dandekar, R.</dc:creator>
<dc:creator>Lashkari, V. D.</dc:creator>
<dc:creator>Tilton, I.</dc:creator>
<dc:creator>McAlpine, L.</dc:creator>
<dc:creator>Chiarella, J.</dc:creator>
<dc:creator>Nelson, A.</dc:creator>
<dc:creator>Ngo, T.</dc:creator>
<dc:creator>Chen, P.</dc:creator>
<dc:creator>Wang, G.</dc:creator>
<dc:creator>Saxena, A.</dc:creator>
<dc:creator>Castillo-Rojas, B.</dc:creator>
<dc:creator>Zorn, K.</dc:creator>
<dc:creator>Tribble, D. R.</dc:creator>
<dc:creator>Burgess, T. H.</dc:creator>
<dc:creator>Rubin, L. H.</dc:creator>
<dc:creator>Richard, S. A.</dc:creator>
<dc:creator>Agan, B. K.</dc:creator>
<dc:creator>Pollett, S. D.</dc:creator>
<dc:creator>Farhadian, S.</dc:creator>
<dc:creator>Spudich, S.</dc:creator>
<dc:creator>Pleasure, S. J.</dc:creator>
<dc:creator>Wilson, M. R.</dc:creator>
<dc:date>2026-03-22</dc:date>
<dc:identifier>doi:10.64898/2026.03.19.26348833</dc:identifier>
<dc:title><![CDATA[Autoantibody landscapes in neurological Long COVID and post-COVID cognitive impairment show heterogeneity without a shared disease signature]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-03-22</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundNeurological Long COVID (n-LC) includes persistent cognitive and autonomic symptoms after SARS-CoV-2 infection. Prior studies of post-COVID conditions have described diverse humoral autoreactivity, but findings are heterogeneous, and it remains unclear whether n-LC is associated with a consistent CNS-directed humoral signature.

MethodsWe performed a cross-cohort case-control analysis to detect autoantibodies in cerebrospinal fluid (CSF) and serum from n-LC participants. In the Yale COVID Mind Study cohort, CSF from n-LC participants and from pre-pandemic and post-COVID asymptomatic controls was assessed by mouse brain immunofluorescence and proteome-wide phage immunoprecipitation sequencing (PhIP-Seq), with candidate reactivities evaluated by orthogonal assays and supervised modeling. In the Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (IDCRP EPICC) cohort, post-COVID sera collected prior to iPhone- or iPad-based cognitive screening were profiled by PhIP-Seq and compared between participants with and without cognitive impairment.

ResultsCSF immunoreactivity on mouse brain tissue was observed in both n-LC and controls, with similar overall frequencies, although n-LC participants more often showed nuclear-predominant staining patterns. PhIP-Seq identified sparse, largely patient-specific peptide reactivities to nuclear and neuronal proteins in CSF and serum. Supervised models provided limited discrimination between cases and controls. Candidate autoantigens had limited disease specificity on orthogonal testing. EPICC serum autoantibody profiling similarly failed to distinguish individuals with and without cognitive impairment.

ConclusionsAcross cohorts and compartments, n-LC did not exhibit a shared autoantibody signature. These findings support the absence of a dominant, common CNS autoantibody-mediated mechanism in n-LC.

FundingGrants HU00012020067, HU00012120103, HU00011920111, R01NS125693, R01MH125737, R01AI157488 from Defense health program and NIH.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.03.18.26348767v1?rss=1">
<title>
<![CDATA[
Prediction of confirmed, hospitalized, and severe COVID-19 cases and mechanistic insights from viral concentrations and variant dynamics in wastewater 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.03.18.26348767v1?rss=1"
</link>
<dc:creator>Murakami, M.</dc:creator>
<dc:creator>Watanabe, R.</dc:creator>
<dc:creator>Iwamoto, R.</dc:creator>
<dc:creator>Chung, U.-i.</dc:creator>
<dc:creator>Kitajima, M.</dc:creator>
<dc:creator>Yoo, B.-K.</dc:creator>
<dc:date>2026-03-20</dc:date>
<dc:identifier>doi:10.64898/2026.03.18.26348767</dc:identifier>
<dc:title><![CDATA[Prediction of confirmed, hospitalized, and severe COVID-19 cases and mechanistic insights from viral concentrations and variant dynamics in wastewater]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-03-20</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
BackgroundFollowing the end of a public health emergency of international concern, divergence emerged between reported coronavirus disease 2019 (COVID-19) cases and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA concentrations in wastewater. Exploring viral, clinical, patient, and surveillance-related factors underlying this divergence, we developed models to predict clinically confirmed infections, hospitalizations, and severe cases.

MethodsIn this observational study, we analyzed [~]2 years of data from January 2022 in Kanagawa Prefecture, Japan, assessing associations between wastewater SARS-CoV-2 RNA concentrations and confirmed, hospitalized, and severe cases, adjusting for wave and variant effects.

FindingsOur models based on wastewater viral RNA concentrations showed high predictive accuracy (R{superscript 2} = 0.8199-0.9961), closely tracking confirmed, hospitalized, and severe cases. Models derived from earlier waves were applied to subsequent waves with residual correction based on prior prediction errors and maintained good predictive performance (root mean square error = 0.0665-0.2065). Divergence between wastewater viral RNA concentrations and reported cases was not explained by changes in viral shedding. Declines in patients healthcare-seeking behavior and testing were associated with trends in confirmed cases, whereas milder clinical presentation was associated with severe case trends. The lineages XBB.1.9.2 and BA.2.86 were identified as candidates associated with reduced virulence.

InterpretationBy incorporating understanding of viral, clinical, and surveillance-related mechanisms, wastewater surveillance may enable prediction of case trends approximately one week earlier than official reporting and inform healthcare capacity planning.
]]></description>
</item>
<item rdf:about="https://www.medrxiv.org/content/10.64898/2026.03.12.26346895v1?rss=1">
<title>
<![CDATA[
Prenatal exposure to SARS-CoV-2, early relational health, and child socio-emotional functioning in the first 6 months 
]]>
</title>
<link>
https://www.medrxiv.org/content/10.64898/2026.03.12.26346895v1?rss=1"
</link>
<dc:creator>Lavallee, A.</dc:creator>
<dc:creator>Warmingham, J. M.</dc:creator>
<dc:creator>Owens, J. B.</dc:creator>
<dc:creator>Xu, R. L.</dc:creator>
<dc:creator>Ahmed, I.</dc:creator>
<dc:creator>Atwood, G. D.</dc:creator>
<dc:creator>Kyle, M. H.</dc:creator>
<dc:creator>Hussain, M.</dc:creator>
<dc:creator>Chaves, V.</dc:creator>
<dc:creator>Arduin, E.</dc:creator>
<dc:creator>Lanoff, M. R.</dc:creator>
<dc:creator>Hyman, S. P.</dc:creator>
<dc:creator>Coskun, L. Z.</dc:creator>
<dc:creator>Shearman, N. D.</dc:creator>
<dc:creator>Russo, J. E.</dc:creator>
<dc:creator>Ettinger, S.</dc:creator>
<dc:creator>Greenman, E. A.</dc:creator>
<dc:creator>Serota, D. E.</dc:creator>
<dc:creator>Bence, M. L.</dc:creator>
<dc:creator>Hott, V.</dc:creator>
<dc:creator>Hu, Y.</dc:creator>
<dc:creator>Kurman, G.</dc:creator>
<dc:creator>Lara, M.</dc:creator>
<dc:creator>Tzul Lopez, H.</dc:creator>
<dc:creator>Mollicone, I.</dc:creator>
<dc:creator>Ravi, R.</dc:creator>
<dc:creator>Rodriguez, C.</dc:creator>
<dc:creator>Smotrich, G. C.</dc:creator>
<dc:creator>Lawless, A.</dc:creator>
<dc:creator>Ontiveros-Angel, P.</dc:creator>
<dc:creator>Curtin, A.</dc:creator>
<dc:creator>Austin, J.</dc:creator>
<dc:creator>Firestein, M. R.</dc:creator>
<dc:creator>Shuffery, L. C.</dc:creator>
<dc:creator>Fernandez, C. R.</dc:creator>
<dc:creator>Battarbee, A. N.</dc:creator>
<dc:creator>Bruno, A.</dc:creator>
<dc:creator>Dawood, F. S.</dc:creator>
<dc:creator>Maniatis, P.</dc:creator>
<dc:creator>Morrill, T. C.</dc:creator>
<dc:creator>Newes-Adeyi, G.</dc:creator>
<dc:creator>Reichle, L.</dc:creator>
<dc:creator>Sem</dc:creator>
<dc:date>2026-03-19</dc:date>
<dc:identifier>doi:10.64898/2026.03.12.26346895</dc:identifier>
<dc:title><![CDATA[Prenatal exposure to SARS-CoV-2, early relational health, and child socio-emotional functioning in the first 6 months]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2026-03-19</prism:publicationDate>
<prism:section></prism:section>
<description><![CDATA[
ImportanceParent/caregiver-infant early relational health (ERH) is known to play a critical role in the promotion of socio-emotional functioning and wellbeing across the life course. The negative impact of the COVID-19 pandemic on maternal mental health and secondarily on ERH and child socio-emotional functioning is clear. However, the direct impact of maternal viral exposure during pregnancy on ERH has not been investigated.

ObjectiveThe goal of this study was to determine the impact of prenatal SARS-CoV-2 exposure on ERH and infant socio-emotional functioning in the first 6 months of life.

DesignMothers with and without SARS-CoV-2 exposure during pregnancy who gave birth from 02/2020 to 09/2021 were enrolled from 05/2020 to 09/2021 in one of two parallel prospective studies (the COVID-19 Mother Baby Outcomes [COMBO] Initiative or the Respiratory Syndrome Coronavirus 2 in Pregnancy and Infancy [ESPI] COMBO sub-study). Mothers reported on their health and the socioemotional functioning of their infant via online surveys (REDCap) at enrollment, 1, 2, 4, and 6 months. At 4 to 6 months, dyads were invited to participate in a video-based, remote assessment of ERH.

Participants884 mother-infant dyads from three U.S. States (Alabama, New York, and Utah).

ExposurePrenatal SARS-CoV-2.

Main Outcomes and MeasuresMaternal-reported ERH (parental stress, parenting confidence and bonding) and observer-based ERH (video-coded quality of maternal caregiving behaviors and mother-infant emotional connection). Infant socio-emotional development assessed using the 6-month Ages and Stages Questionnaire: Socio-Emotional 2nd Edition (ASQ:SE-2).

Results316 (36%) mothers had a positive prenatal SARS-CoV-2 exposure. Prenatal SARS-CoV-2 exposure was associated with an adjusted estimate of [~]5% reduction (incidence rate ratio=0.95, 95% confidence interval [0.90, 1.00], p=0.03) in observed maternal caregiving quality, after accounting for postnatal maternal mental health and sociodemographic factors. We found no evidence of effect on other ERH constructs or infant socio-emotional functioning.

Conclusions and RelevanceIn this large prospective cohort study, prenatal SARS-CoV-2 was associated with a small decrement in caregiving quality, but not other ERH constructs or infant socioemotional functioning. These findings should be interpreted as hypothesis generating and will require replication in independent studies.

Key PointsO_LIQuestion: Is SARS-CoV-2 exposure during pregnancy associated with maternal-reported and observer-based measures of early relational health (ERH) and infant socio-emotional functioning at 4-6 months postpartum?
C_LIO_LIFindings: Prenatal SARS-CoV-2 exposure was associated with a [~]5% reduction in observed quality of maternal caregiving after accounting for postnatal mental health symptomatology and sociodemographic factors.
C_LIO_LIMeaning: A small reduction in maternal caregiving quality, but not other ERH constructs (parental stress, parenting confidence, bonding and emotional connection) or infant socio-emotional functioning, was associated with prenatal SARS-CoV-2 exposure. Results should be interpreted as hypothesis generating and will require replication in independent studies.
C_LI
]]></description>
</item>
</rdf:RDF>
