{"messages":[{"status":"ok","cursor":"20","count":30,"total":31537}], "collection":[{"rel_doi":"10.64898\/2026.05.15.725307","rel_title":"A Structural Domain in the genomic RNA of SARS-CoV-2 Folds into a Compact Granular Structure without the N protein: A Single-Molecule Fluorescence Spectroscopic Investigation","rel_date":"2026-05-15","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.15.725307","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by_nc_nd","type":"new results","category":"biophysics"},{"rel_doi":"10.64898\/2026.05.14.725177","rel_title":"Expansion Revealing of Pathology Resolves Nanostructures Associated with Inflammatory Phenotypes in COVID-19 Decedent Human Brain Tissue","rel_date":"2026-05-15","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.14.725177","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by","type":"new results","category":"neuroscience"},{"rel_doi":"10.64898\/2026.05.12.724509","rel_title":"Pathogen-specific host responses define distinct pneumonia endotypes in the human lung","rel_date":"2026-05-14","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.12.724509","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by_nc_nd","type":"new results","category":"immunology"},{"rel_doi":"10.64898\/2026.05.11.26352906","rel_title":"Transcranial direct current stimulation-augmented cognitive training for post-COVID-19 cognition: A phase IIb randomized controlled trial","rel_date":"2026-05-14","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.11.26352906","rel_abs":"BackgroundCognitive dysfunction is a prevalent and debilitating symptom of post-COVID-19 condition with limited evidence-based interventions. Here, we assessed the efficacy of cognitive training (CT) alone and combined with transcranial direct current stimulation (tDCS) for cognitive enhancement in post-COVID-19 patients.\n\nMethodsNeuromod-COV was a phase IIb, prospective, randomized, open-label, blinded-endpoint trial conducted at University Medicine Greifswald, Germany. The tDCS intervention was evaluated through a double-blind, sham-controlled design. Adults aged 18-60 with confirmed SARS-CoV-2 infection [&ge;] 6 weeks prior and post-infection cognitive complaints were eligible. Participants were randomly assigned (1:1:1) to CT with active tDCS (CT+AtDCS), CT with sham tDCS (CT+StDCS), or progressive muscle relaxation (PMR, non-cognitive control intervention) with sham tDCS. Intervention consisted of nine 20-minute sessions over three weeks of CT (letter updating task) or PMR with 2 mA tDCS (active\/sham) applied over the left dorsolateral prefrontal cortex. The primary outcome was untrained working memory (WM; measured by N-back task accuracy) comparing CT with PMR at post-intervention. Secondary outcomes included trained and untrained WM, visuospatial memory, and self-report measures at post-intervention and 1-month follow-up comparing CT vs. PMR and CT+AtDCS vs. CT+StDCS. The trial was registered at ClinicalTrials.gov (NCT04944147).\n\nResultsBetween October 1, 2021, and August 7, 2024, 60 participants were randomized (76.7% female) to CT+AtDCS (n = 20), CT+StDCS (n = 20), or PMR (n = 20). CT did not improve untrained WM at post-intervention compared with PMR (primary outcome: {beta} = 1.59, 95% CI - 1.30 to 4.48, p = 0.278; 1-back: {beta} = 2.52, 95% CI -1.27 to 6.31, p = 0.191; 2-back: {beta} = 0.66, 95% CI -3.12 to 4.44, p = 0.732). However, CT+AtDCS enhanced untrained WM at post-intervention and follow-up, and visuospatial memory at post-intervention compared with CT+StDCS (secondary outcomes). No intervention improved self-report outcomes. No serious adverse events occurred and incidence rate ratios were similar between groups.\n\nConclusionCT alone did not improve untrained WM performance. However, CT with tDCS enhanced untrained WM and visuospatial memory, suggesting potential benefits of combined neuromodulation approaches for cognitive enhancement in post-COVID-19 patients.","rel_num_authors":9,"rel_authors":[{"author_name":"Catalina Trujillo Llano","author_inst":"University Medicine Greifswald"},{"author_name":"Anna Elisabeth Fromm","author_inst":"University Medicine Greifswald"},{"author_name":"Lydia Lingemann","author_inst":"University Medicine Greifswald"},{"author_name":"Ulrike Grittner","author_inst":"Charite University Medicine"},{"author_name":"Marcus F Meinzer","author_inst":"University Medicine Greifswald"},{"author_name":"Robert Fleischmann","author_inst":"University Medicine Greifswald"},{"author_name":"Eva-Lotta Brakemeier","author_inst":"University of Greifswald"},{"author_name":"Daria F Antonenko","author_inst":"University Medicine Greifswald"},{"author_name":"Agnes Floeel","author_inst":"University Medicine Greifswald"}],"version":"1","license":"cc_no","type":"PUBLISHAHEADOFPRINT","category":"neurology"},{"rel_doi":"10.64898\/2026.05.07.723210","rel_title":"Temperature-Dependent Replication and Sensitivity to Innate Immunity of Human Coronavirus HKU1","rel_date":"2026-05-12","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.07.723210","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by_nc_nd","type":"new results","category":"microbiology"},{"rel_doi":"10.64898\/2026.05.07.723385","rel_title":"Crude Fucus vesiculosus fucoidan demonstrates superior SARS-CoV-2 antiviral activity compared to its pure form: binding kinetics and functional studies","rel_date":"2026-05-12","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.07.723385","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by_nc","type":"new results","category":"biochemistry"},{"rel_doi":"10.64898\/2026.05.08.723928","rel_title":"AI-discovered protein fragments as generalizable regulators of biomolecular condensates","rel_date":"2026-05-12","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.08.723928","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by_nc_nd","type":"new results","category":"biophysics"},{"rel_doi":"10.64898\/2026.05.08.26352776","rel_title":"Monocyte Oxidative Stress Underlies Persistent Immune Activation in Long-COVID Postural Orthostatic Tachycardia Syndrome","rel_date":"2026-05-12","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.08.26352776","rel_abs":"BackgroundLong COVID postural orthostatic tachycardia syndrome (LCPOTS) is characterized by persistent orthostatic tachycardia and multiple constitutional symptoms, many of which suggest persistent inflammation. We sought to define mechanisms responsible for ongoing immune activation in LCPOTs and to determine if this is related to autonomic dysregulation.\n\nMethodsWe performed a case-control study of 25 patients with LCPOTS and 15 controls who recovered from COVID-19 without persistent autonomic sequelae. Peripheral blood mononuclear cells were analyzed by flow cytometry to quantify circulating CD3CD14 T cell-monocyte doublets, cytokine production, memory phenotype, mitochondrial ROS, and isolevuglandin (IsoLG)-adduct formation. Forster resonance energy transfer was used to assess T-cell receptor-HLA interactions within doublets. Single-cell RNA sequencing (scRNA-seq) was performed on a subset of participants, and autonomic phenotyping included orthostatic heart rate responses, heart rate variability, baroreflex sensitivity, and blood volume measurements.\n\nResultsLCPOTS was linked to impaired cardiovagal function and greater autonomic symptom burden. It was also associated with roughly a threefold rise in circulating CD3CD14 doublets and enhanced T cell-monocyte interactions. These complexes demonstrated signs of genuine immune synapse formation and were enriched with effector-memory and TEMRA T-cell types. T cells in doublets produced higher levels of IFN-{gamma} and IL-17A, and the proportion of cytokine-producing doublets correlated with the severity of orthostatic tachycardia and total COMPASS-31 score. Monocytes from LCPOTS showed increased mitochondrial content, superoxide generation, and IsoLG-adduct accumulation, along with decreased expression of antioxidant genes, including those related to NFE2L2.\n\nConclusionsOur findings suggest that ongoing immune activation contributes to LCPOTS pathogenesis. We propose that impaired cardiovagal regulation stimulates monocyte ROS production, promotes neoantigen formation, and T cell activation. This persistent immune response, together with disrupted mitochondrial function, likely contributes to the diverse symptoms linked to LCPOTS.\n\nNovelty and SignificanceO_ST_ABSWhat Is Known?C_ST_ABSO_LILong COVID postural orthostatic tachycardia syndrome is associated with persistent orthostatic tachycardia and disabling orthostatic intolerance symptoms after SARS-CoV-2 infection.\nC_LIO_LIImmune dysregulation and oxidative stress have been implicated in long COVID, but the cellular mechanisms linking inflammation to autonomic dysfunction are not well defined.\nC_LIO_LICirculating T cell: monocyte doublets are a recently recognized marker of ongoing immune activation.\nC_LI\n\nWhat New Information Does This Article Contribute?O_LIPatients with LCPOTS exhibit a marked increase in circulating CD3CD14 T cell-monocyte doublets.\nC_LIO_LIDoublet-associated T cells are enriched for inflammatory effector-memory\/TEMRA phenotypes and produce IFN-{gamma} and IL-17A in proportion to orthostatic tachycardia and autonomic symptoms severity.\nC_LIO_LIImpaired cardiovagal activity, monocyte mitochondrial ROS, IsoLG-adduct formation, and suppression of antioxidant pathways identify a mechanistic axis linking oxidative injury to persistent immune activation in LCPOTS.\nC_LI\n\nSummary of Novelty and SignificanceThis study identifies a mechanistic link between impaired cardiovagal function, mitochondrial oxidative stress, and persistent immune activation in LCPOTS. We show that circulating CD3CD14 T cell-monocyte doublets are expanded in LCPOTS and form true immune synapses, as demonstrated by T-cell receptor-HLA proximity. These are enriched in inflammatory effector-memory\/TEMRA T cells and are associated with increased IFN-{gamma} and IL-17A production that correlate with orthostatic tachycardia severity and symptom burden. We further identified increased mitochondrial ROS, accumulation of IsoLG adducts, and reduced antioxidant gene expression in monocytes, suggesting that oxidation-induced neoantigen formation sustains pathogenic T-cell engagement. Together, these findings move LCPOTS beyond a descriptive post-viral syndrome and define a biologically plausible immune mechanism with diagnostic and therapeutic implications.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC=\"FIGDIR\/small\/26352776v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (68K):\norg.highwire.dtl.DTLVardef@19db16dorg.highwire.dtl.DTLVardef@1eb6cf5org.highwire.dtl.DTLVardef@13e7d19org.highwire.dtl.DTLVardef@18716cc_HPS_FORMAT_FIGEXP  M_FIG C_FIG","rel_num_authors":14,"rel_authors":[{"author_name":"Marwa Ahmed Mohamed","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Meenakshi Golchha","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Yullya A. Vance","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Sachin Y. Paranjape","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Celestine Wanjalla","author_inst":"Vanderbilt Health Services LLC"},{"author_name":"Kuniko C Hunter","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Sergey Dikalov","author_inst":"Vanderbilt University School of Medicine"},{"author_name":"Andr\u00e9 Diedrich","author_inst":"Vanderbilt University"},{"author_name":"Surat Kulapatana","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Pouya E Mehr","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Tatoama X Solis Montegegro","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Joshua D Simmons","author_inst":"Vanderbilt University Medical Center"},{"author_name":"David G. Harrison","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Cyndya A Shibao","author_inst":"Vanderbilt University Medical Center"}],"version":"1","license":"cc_no","type":"PUBLISHAHEADOFPRINT","category":"cardiovascular medicine"},{"rel_doi":"10.64898\/2026.05.08.26352754","rel_title":"Independent Validation of Test-Adjusted COVID-19 Incidence Estimates Using Wastewater Surveillance Data in Ontario, Canada","rel_date":"2026-05-12","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.08.26352754","rel_abs":"BackgroundCase-based infectious disease surveillance is subject to ascertainment bias when testing intensity varies across time and population subgroups. We previously developed a regression-based test adjustment methodology using Standardized Testing Ratios (STRs) to correct for differential testing patterns in COVID-19 surveillance data. Wastewater-based surveillance (WWS) measures viral burden in the community independently of diagnostic testing behavior, making it a valuable external validation tool for test-adjusted case estimates.\n\nMethodsWe analyzed 111 weeks of paired wastewater and case surveillance data from Ontario, Canada (July 19, 2020 to August 28, 2022). Wastewater SARS-CoV-2 signals from 107 sewersheds across 34 public health units were normalized within sewersheds and aggregated using population-weighted averages. We compared wastewater correlations with crude reported and test-adjusted case counts using Spearman rank correlations, linear regression, and negative binomial distributed lag nonlinear models (DLNM), stratified by epidemic period.\n\nResultsTest-adjusted cases correlated substantially more strongly with wastewater signals than crude reported cases overall (Spearman {rho} = 0.849 vs. 0.679; linear R{superscript 2} = 0.609 vs. 0.191). The advantage of test adjustment was greatest during the Omicron wave, when population-level diagnostic testing contracted sharply following PCR eligibility restrictions ({rho} = 0.924 vs. 0.604; R{superscript 2} = 0.815 vs. 0.470). DLNM incorporating the wastewater signal explained substantially more variance in test-adjusted than crude reported cases (McFadden pseudo-R{superscript 2} 0.898 vs. 0.776), despite similar lag-response structure for both outcomes.\n\nConclusionsWastewater surveillance provides compelling independent validation of a previously described test adjustment methodology for COVID-19 case surveillance. The agreement between wastewater signals and test-adjusted cases was strongest precisely when testing scarcity was most severe, supporting the use of test adjustment to recover accurate infection dynamics from case surveillance data during periods of changing testing access and policy.","rel_num_authors":4,"rel_authors":[{"author_name":"David Fisman","author_inst":"University of Toronto"},{"author_name":"Natalie Wilson","author_inst":"University of Toronto"},{"author_name":"Clara Eunyoung Lee","author_inst":"University of Toronto"},{"author_name":"Ashleigh Tuite","author_inst":"Public Health Agency of Canada"}],"version":"1","license":"cc_by_nc_nd","type":"PUBLISHAHEADOFPRINT","category":"infectious diseases"},{"rel_doi":"10.64898\/2026.05.12.724615","rel_title":"Recovery of proofreading-impaired SARS-CoV-2 reveals a mutator phenotype and an ExoN activity threshold for viability","rel_date":"2026-05-12","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.12.724615","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by_nc_nd","type":"new results","category":"microbiology"},{"rel_doi":"10.64898\/2026.05.07.26352639","rel_title":"SARS CoV 2 Associated Shifts in the Upper Respiratory Tract Mycobiome in Non Hospitalized Cases","rel_date":"2026-05-10","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.07.26352639","rel_abs":"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.","rel_num_authors":2,"rel_authors":[{"author_name":"Siddharth Singh Tomar","author_inst":"CSIR-NEERI"},{"author_name":"Krishna Khairnar","author_inst":"CSIR-NEERI"}],"version":"1","license":"cc_by_nc_nd","type":"PUBLISHAHEADOFPRINT","category":"epidemiology"},{"rel_doi":"10.64898\/2026.05.06.723370","rel_title":"vartracker: an end-to-end tool for pathogen longitudinal variant analysis and visualisation","rel_date":"2026-05-08","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.06.723370","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by","type":"new results","category":"bioinformatics"},{"rel_doi":"10.64898\/2026.05.06.723221","rel_title":"Helminth-remodeled microbial indole-3-lactic acid drives AhR-dependent disease tolerance","rel_date":"2026-05-08","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.06.723221","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_no","type":"new results","category":"immunology"},{"rel_doi":"10.64898\/2026.05.07.723425","rel_title":"Site-Specific Entry Factors Define Cellular Susceptibility to SARS-CoV-2 in Human Tissues","rel_date":"2026-05-08","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.07.723425","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by_nc_nd","type":"new results","category":"microbiology"},{"rel_doi":"10.64898\/2026.05.06.723356","rel_title":"The Effect of Vaccination on the Evolution of the SARS-CoV-2 B.1.351 Variant","rel_date":"2026-05-08","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.06.723356","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by","type":"confirmatory results","category":"molecular biology"},{"rel_doi":"10.64898\/2026.05.08.26352596","rel_title":"Safety first: should the high tolerability of intramuscular anti-spike COVID-19 monoclonal antibody change our expectations of vaccine safety?","rel_date":"2026-05-08","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.08.26352596","rel_abs":"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.\n\nMethodsExpanding 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.\n\nResultsEVADE 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.\n\nConclusionsIncreased 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.","rel_num_authors":7,"rel_authors":[{"author_name":"David Putrino","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Allison Curtis","author_inst":"Invivyd, Inc."},{"author_name":"Meredith Leston","author_inst":"Invivyd, Inc."},{"author_name":"Ilker Yalcin","author_inst":"Invivyd, Inc."},{"author_name":"Rachael Gerlach","author_inst":"Invivyd, Inc."},{"author_name":"Marc Elia","author_inst":"Invivyd, Inc."},{"author_name":"Michael Mina","author_inst":"Invivyd, Inc."}],"version":"1","license":"cc_by","type":"PUBLISHAHEADOFPRINT","category":"infectious diseases"},{"rel_doi":"10.64898\/2026.05.06.26352506","rel_title":"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","rel_date":"2026-05-08","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.06.26352506","rel_abs":"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.\n\nObjectiveTo 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.\n\nMethodsThe 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.\n\nResultsDuring 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.\n\nConclusionsCOCOAs 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.","rel_num_authors":3,"rel_authors":[{"author_name":"Shinichi Nakagawa","author_inst":"Research Institute of Info-Commiunication Medicine"},{"author_name":"Seiji Kumagai","author_inst":"Research Institute of Info-Communication Medicine"},{"author_name":"Akira Yamamoto","author_inst":"Faculty of Human Data Science, Juntendo University"}],"version":"1","license":"cc_by","type":"PUBLISHAHEADOFPRINT","category":"health informatics"},{"rel_doi":"10.64898\/2026.05.07.26352649","rel_title":"Delayed humoral kinetics but stabilization of IgG responses in common variable immunodeficiency after SARS-CoV-2 mRNA booster vaccination","rel_date":"2026-05-08","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.07.26352649","rel_abs":"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.\n\nMethodsWe 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.\n\nResultsThe 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.\n\nConclusionVaccine-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.","rel_num_authors":18,"rel_authors":[{"author_name":"Lorenzo Federico","author_inst":"University of Oslo"},{"author_name":"Ragnhild Oeye Loeken","author_inst":"Oslo University Hospital"},{"author_name":"Khang Le Quy","author_inst":"University of Oslo"},{"author_name":"Julie Roekke Osen","author_inst":"University of Oslo"},{"author_name":"Viktoriia Chaban","author_inst":"University of Oslo"},{"author_name":"Ingvild Nordoey","author_inst":"Oslo University Hospital"},{"author_name":"Tonje Skarpengland","author_inst":"Oslo University Hospital"},{"author_name":"Knut Erik Lundin","author_inst":"Oslo University Hospital"},{"author_name":"Silje Fjellgaard Joergensen","author_inst":"Oslo University Hospital"},{"author_name":"Mai Sasaki Aanensen Fraz","author_inst":"Oslo University Hospital"},{"author_name":"Paal Aukrust","author_inst":"Oslo University Hospital"},{"author_name":"Katrine Persgaard Lund","author_inst":"Oslo University Hospital"},{"author_name":"Trung The Tran","author_inst":"University of Oslo"},{"author_name":"Liv Toril Nygaard Osnes","author_inst":"University of Oslo"},{"author_name":"Fridtjof Lund-Johansen","author_inst":"University of Oslo"},{"author_name":"Hassen Kared","author_inst":"University of Oslo"},{"author_name":"Boerre Fevang","author_inst":"Oslo University Hospital"},{"author_name":"Ludvig Andre Munthe","author_inst":"University of Oslo"}],"version":"1","license":"cc_by_nc_nd","type":"PUBLISHAHEADOFPRINT","category":"infectious diseases"},{"rel_doi":"10.64898\/2026.05.06.723222","rel_title":"SARS-CoV-2 Nsp2 reprograms host immunity to drive pathogenic inflammation","rel_date":"2026-05-07","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.06.723222","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_no","type":"new results","category":"microbiology"},{"rel_doi":"10.64898\/2026.05.06.26352509","rel_title":"Determinants and long-term outcomes of COVID-19 undervaccination: a cohort study of 6.8 million individuals in Lombardy, Italy","rel_date":"2026-05-07","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.06.26352509","rel_abs":"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.\n\nMethodsWe 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.\n\nResultsOn 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.\n\nConclusionAbout 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.","rel_num_authors":4,"rel_authors":[{"author_name":"Andrea Corbetta","author_inst":"Human Technopole"},{"author_name":"Katherine Marie Logan","author_inst":"Human Technopole"},{"author_name":"Francesca Ieva","author_inst":"Politecnico di Milano"},{"author_name":"Emanuele Di Angelantonio","author_inst":"Human Technopole"}],"version":"1","license":"cc_by_nc_nd","type":"PUBLISHAHEADOFPRINT","category":"epidemiology"},{"rel_doi":"10.64898\/2026.05.04.722688","rel_title":"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","rel_date":"2026-05-07","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.04.722688","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by_nc","type":"new results","category":"microbiology"},{"rel_doi":"10.64898\/2026.05.06.723231","rel_title":"Functional Landscape of Motifs within the Sarbecovirus Spike Cytoplasmic Tail","rel_date":"2026-05-07","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.06.723231","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_no","type":"new results","category":"microbiology"},{"rel_doi":"10.64898\/2026.05.05.26352439","rel_title":"Identifying the determinants of health protective behaviors during the COVID-19 pandemic using machine learning: an analysis of six countries","rel_date":"2026-05-06","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.05.26352439","rel_abs":"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.","rel_num_authors":14,"rel_authors":[{"author_name":"Joshua M Chevalier","author_inst":"University Medical Center Utrecht"},{"author_name":"Leonard M Stellbrink","author_inst":"University of Luebeck"},{"author_name":"Lisanne Steijvers","author_inst":"Maastricht University"},{"author_name":"Senne Wijnen","author_inst":"Maastricht University"},{"author_name":"Florian van Daalen","author_inst":"Maastricht University"},{"author_name":"Lilian Kojan","author_inst":"University of Luebeck"},{"author_name":"Nannan Li","author_inst":"Maastricht University"},{"author_name":"Beate Jahn","author_inst":"UMIT TIROL-University for Health Sciences and Health Technology"},{"author_name":"Uwe Siebert","author_inst":"UMIT TIROL-University for Health Sciences and Health Technology"},{"author_name":"Andre Calero Valdez","author_inst":"University of Luebeck"},{"author_name":"Mickael Hiligsmann","author_inst":"Maastricht University"},{"author_name":"Rik Crutzen","author_inst":"UM FHML: Universiteit Maastricht Faculty of Health Medicine and Life Sciences"},{"author_name":"Nicole HTM Dukers-Muijrers","author_inst":"Maastricht University\/Public Health Service"},{"author_name":"Mirjam E Kretzschmar","author_inst":"University Medical Center Utrecht"}],"version":"1","license":"cc_by","type":"PUBLISHAHEADOFPRINT","category":"epidemiology"},{"rel_doi":"10.64898\/2026.04.30.26352025","rel_title":"Inequalities in early childhood developmental concerns before, during and after the COVID-19 pandemic in Scotland: a retrospective cohort study","rel_date":"2026-05-06","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.04.30.26352025","rel_abs":"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.\n\nStudy 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.\n\nFindingsThe 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.\n\nConclusionsDevelopmental 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.","rel_num_authors":10,"rel_authors":[{"author_name":"Iain Hardie","author_inst":"University of Edinburgh"},{"author_name":"Louise Marryat","author_inst":"University of Glasgow"},{"author_name":"Aja Murray","author_inst":"University of Edinburgh"},{"author_name":"Josiah King","author_inst":"University of Edinburgh"},{"author_name":"Kenneth Okelo","author_inst":"University of Edinburgh"},{"author_name":"Lynda Fenton","author_inst":"Public Health Scotland"},{"author_name":"James P Boardman","author_inst":"University of Edinburgh"},{"author_name":"Philip Wilson","author_inst":"University of Copenhagen"},{"author_name":"Rachael P Wood","author_inst":"Public Health Scotland"},{"author_name":"Bonnie Auyeung","author_inst":"University of Edinburgh"}],"version":"1","license":"cc_no","type":"PUBLISHAHEADOFPRINT","category":"health policy"},{"rel_doi":"10.64898\/2026.04.30.721843","rel_title":"The redesign of the molecular scaffold of viral ion channel blockers","rel_date":"2026-05-06","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.04.30.721843","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_no","type":"new results","category":"pharmacology and toxicology"},{"rel_doi":"10.64898\/2026.05.04.722452","rel_title":"Longitudinal analysis reveals myeloid cell contributions to neuroPASC pathogenesis","rel_date":"2026-05-06","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.04.722452","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by_nc_nd","type":"new results","category":"immunology"},{"rel_doi":"10.64898\/2026.05.05.723025","rel_title":"Tocilizumab induces significant changes in longitudinal proteomes of blood serum from patients with severe COVID-19 pneumonia","rel_date":"2026-05-06","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.05.723025","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_no","type":"new results","category":"pharmacology and toxicology"},{"rel_doi":"10.64898\/2026.05.03.26351251","rel_title":"Ethnic Inequalities in COVID-19 Vaccination Uptake Among Older Adults in Australia: A Nationwide Linked Data Study","rel_date":"2026-05-05","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.03.26351251","rel_abs":"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.\n\nMethodsWe 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.\n\nResultsIn 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.\n\nConclusionsSubstantial 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.","rel_num_authors":13,"rel_authors":[{"author_name":"Peiyao Xu","author_inst":"The University of Sydney"},{"author_name":"Saman Khalatbari-Soltani","author_inst":"The University of Sydney"},{"author_name":"Meru Sheel","author_inst":"The University of Sydney"},{"author_name":"Maarit A. Laaksonen","author_inst":"The University of Sydney"},{"author_name":"Lin Zhu","author_inst":"The University of Sydney"},{"author_name":"Yiyi Lin","author_inst":"The University of Sydney"},{"author_name":"Christina Abdel Shaheed","author_inst":"The University of Sydney"},{"author_name":"Mouna Sawan","author_inst":"The University of Sydney"},{"author_name":"Assel Mussagulova","author_inst":"The University of Sydney"},{"author_name":"Danijela Gnjidic","author_inst":"The University of Sydney"},{"author_name":"Pani Patu","author_inst":"The University of Sydney"},{"author_name":"Bette Liu","author_inst":"National Centre for Immunisation Research and Surveillance"},{"author_name":"Fiona F Stanaway","author_inst":"The University of Sydney"}],"version":"1","license":"cc_by_nc_nd","type":"PUBLISHAHEADOFPRINT","category":"public and global health"},{"rel_doi":"10.64898\/2026.05.05.722935","rel_title":"Targeted metagenomic recovery of coronaviruses from wildlife samples","rel_date":"2026-05-05","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.05.05.722935","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by_nc_nd","type":"new results","category":"microbiology"},{"rel_doi":"10.64898\/2026.04.30.721889","rel_title":"Single-cell atlas of transcript usage remodelling in antiviral immune responses across human populations","rel_date":"2026-05-04","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.04.30.721889","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by","type":"new results","category":"immunology"}]}