{"messages":[{"status":"ok","cursor":0,"count":30,"total":31358}], "collection":[{"rel_doi":"10.64898\/2026.03.06.710084","rel_title":"Molecular Characterization of SARS-CoV-2 N Protein Interfaces: Implications for Oligomerization, RNA Binding, and Phase Separation","rel_date":"2026-03-06","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.03.06.710084","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by_nc_nd","type":"new results","category":"biophysics"},{"rel_doi":"10.64898\/2026.03.04.709710","rel_title":"Investigating the use of human COVID-19 rapid assays to detect antibody and antigen in domesticated dogs (Canis lupus familiaris) and cats (Felis catus)","rel_date":"2026-03-05","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.03.04.709710","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by","type":"new results","category":"zoology"},{"rel_doi":"10.64898\/2026.03.04.703990","rel_title":"A macrocyclic peptide-based fusion inhibitor targeting SARS-CoV-2 Spike S2 subunit","rel_date":"2026-03-05","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.03.04.703990","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_no","type":"new results","category":"microbiology"},{"rel_doi":"10.64898\/2026.03.03.709384","rel_title":"Exposure route drives SARS-CoV-2 infection patterns in non-human primates","rel_date":"2026-03-04","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.03.03.709384","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by_nc","type":"new results","category":"microbiology"},{"rel_doi":"10.64898\/2026.03.04.709525","rel_title":"Fluorinated RNA origami enables serum-stable nanodevices for sensing and targeting","rel_date":"2026-03-04","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.03.04.709525","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by_nc","type":"new results","category":"biochemistry"},{"rel_doi":"10.64898\/2026.03.03.709398","rel_title":"Defining the Antigenic Topology and Prospective Binding Breadth of Vaccination-induced SARS-CoV-2 Neutralizing Antibodies","rel_date":"2026-03-04","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.03.03.709398","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by","type":"new results","category":"immunology"},{"rel_doi":"10.64898\/2026.03.02.708985","rel_title":"Microfilaremic loiasis is associated with T cell hyporesponsiveness against SARS CoV-2","rel_date":"2026-03-04","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.03.02.708985","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by","type":"new results","category":"immunology"},{"rel_doi":"10.64898\/2026.02.27.708290","rel_title":"A stable subgenomic reporter coronavirus enables transcriptional profiling of bystander cells.","rel_date":"2026-03-03","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.02.27.708290","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by","type":"new results","category":"microbiology"},{"rel_doi":"10.64898\/2026.03.02.709067","rel_title":"An Integrated Computational Antigen Discovery Pipeline with Hierarchical Filtering for Emerging Viral Variants","rel_date":"2026-03-03","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.03.02.709067","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by_nc_nd","type":"new results","category":"bioinformatics"},{"rel_doi":"10.64898\/2026.03.02.709177","rel_title":"A new mRNA antigen vaccine induces potent B and T cell responses and in vivo protection against SARS-CoV-2","rel_date":"2026-03-03","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.03.02.709177","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by_nc_nd","type":"new results","category":"immunology"},{"rel_doi":"10.64898\/2026.02.28.26347308","rel_title":"Admission Predictors of In-Hospital Mortality and the Combined Outcome of Death or Invasive Mechanical Ventilation in Patients with COVID-19 During the Pre-Vaccination Era: A Retrospective Cohort Study","rel_date":"2026-03-03","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.02.28.26347308","rel_abs":"BackgroundReliable identification of early predictors of adverse outcomes was essential during the pre-vaccination phase of the COVID-19 pandemic. Few studies have comprehensively integrated clinical presentation, laboratory parameters including arterial blood gas analysis, and chest computed tomography (CT) findings within a single well-characterized cohort, particularly in underrepresented regions of Brazil.\n\nMethodsThis retrospective cohort study included 482 consecutive adults (median age 61 years [IQR 49-73]; 64.3% men) with RT-PCR-confirmed SARS-CoV-2 infection hospitalized at a tertiary cardiac center in Central-West Brazil between March 2020 and January 2021. Demographic, clinical, laboratory (including arterial blood gas analysis), and chest CT data obtained within 48 hours of admission were analyzed. Univariable logistic regression was performed for 76 variables. Multivariable models were constructed using an a priori variable selection strategy based on clinical relevance, representation of distinct pathophysiological domains, and adherence to events-per-variable principles. Complete-case analyses were performed without imputation.\n\nResultsIn-hospital mortality was 9.3% (45\/482). Invasive mechanical ventilation was required in 74 patients (15.4%), with a mortality rate of 58.1% among those ventilated. In univariable analysis, 42 variables were associated with mortality (p < 0.05). In multivariable analysis (n = 438), five independent predictors of death were identified: age (adjusted OR 1.66 per 10 years; 95% CI 1.19-2.32; p = 0.003), arterial pH (adjusted OR 0.47 per 0.1-unit increase; 95% CI 0.25-0.89; p = 0.021), neutrophil-to-lymphocyte ratio (adjusted OR 1.30; 95% CI 1.18-1.44; p < 0.001), number of comorbidities (adjusted OR 1.59; 95% CI 1.25-2.02; p < 0.001), and serum creatinine (adjusted OR 1.37; 95% CI 1.05-1.77; p = 0.019). The model demonstrated good calibration (Hosmer-Lemeshow p > 0.05) and moderate-to-high explanatory power (Nagelkerke R{superscript 2} = 0.43). For the composite outcome of death or invasive mechanical ventilation (74 events; 15.4%), four predictors remained independently associated; serum creatinine showed a non-significant trend (p = 0.069). On chest CT (n = 424), analyzed descriptively and in univariable models only, pulmonary involvement > 50% was associated with increased odds of death (OR 2.87; 95% CI 1.42-5.79; p = 0.003).\n\nConclusionsFive admission variables representing distinct pathophysiological domains--age, arterial pH, neutrophil-to-lymphocyte ratio, comorbidity burden, and serum creatinine--were independently associated with in-hospital mortality in this pre-vaccination cohort. Arterial pH provided independent prognostic information beyond inflammatory and renal markers. These findings support early risk stratification using routinely available clinical data.","rel_num_authors":14,"rel_authors":[{"author_name":"Anis Rassi Jr.","author_inst":"Hospital do Coracao"},{"author_name":"Vanessa  Mahamed Rassi","author_inst":"Hospital do Coracao"},{"author_name":"Jos\u00e9 Vitor  Rassi Garcia","author_inst":"Hospital do Coracao"},{"author_name":"H\u00e9lvio  Martins Gerv\u00e1sio","author_inst":"Hospital do Coracao"},{"author_name":"Christiane  Reis Kobal","author_inst":"Hospital do Coracao"},{"author_name":"Fabiano  Macedo de Souza","author_inst":"Hospital do Coracao"},{"author_name":"Gabriela  Ferreira de Oliveira Butrico","author_inst":"Federal University of Goias: Universidade Federal de Goias"},{"author_name":"Eddy  Patr\u00edcia Sanchez","author_inst":"Hospital do Coracao"},{"author_name":"F\u00e1bio  Mahamed Rassi","author_inst":"Hospital do Coracao"},{"author_name":"Germana  Peres Canedo","author_inst":"Hospital do Coracao"},{"author_name":"Ver\u00f4nica  Raquel Pinto Cunha","author_inst":"Hospital do Coracao"},{"author_name":"Raimundo Nonato  Diniz Rodrigues-Filho","author_inst":"Hospital do Coracao"},{"author_name":"Antonio  Fernando Carneiro","author_inst":"Hospital do Coracao"},{"author_name":"Gustavo  Gabriel Rassi","author_inst":"Hospital do Coracao"}],"version":"1","license":"cc_by","type":"PUBLISHAHEADOFPRINT","category":"infectious diseases"},{"rel_doi":"10.64898\/2026.02.28.708602","rel_title":"Microbiota-derived extracellular vesicles link intestinal dysbiosis to neuroimmune activation in long COVID","rel_date":"2026-03-02","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.02.28.708602","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by_nc_nd","type":"new results","category":"microbiology"},{"rel_doi":"10.64898\/2026.02.27.26347213","rel_title":"Interplay of Immunity, Climate, and Viral Evolution Explains Semiannual SARS-CoV-2 Dynamics with Implications for Control","rel_date":"2026-03-02","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.02.27.26347213","rel_abs":"In the three years since Omicron emergence, SARS-CoV-2 dynamics have exhibited persistent twice-yearly waves in the United States, peaking in late summer and winter, with heterogeneity in timing and intensity across states. This semiannual pattern sharply contrasts with typical annual respiratory pathogen dynamics in the US, yet their underlying mechanisms and whether this pattern will persist remain poorly understood. Here, we tested several hypothesized mechanisms and found that a combination of waning immunity, climatic factors of relative humidity and temperature, variant activity, and vaccination captured divergent patterns in COVID-19 hospitalization incidence across 10 US states, from January 2022-November 2024. Applying a compartmental disease model, we identified that waning infection-derived immunity was the dominant driver of semiannual SARS-CoV-2 dynamics, with climate factors shaping the timing and magnitude of seasonal waves across US states. Scenario analyses indicated that if infection-derived immunity remains short in duration, semiannual dynamics influenced by climate are likely to persist, with attenuation in severe disease over time. In contrast, more durable infection-derived immunity, or a slower rate of immune-evading viral evolution, could lead to an epidemiologic transition to annual dynamics. In some states, summer waves approached the magnitude of winter waves, likely reflecting local climatic influences on transmission, suggesting that optimal vaccination strategies may vary by state. These findings have broad implications for understanding epidemic dynamics and informing vaccine policy, including seasonal timing and two-dose vaccine schedules for high-risk persons.","rel_num_authors":7,"rel_authors":[{"author_name":"Samantha J. Bents","author_inst":"Stanford University"},{"author_name":"Kate M. Bubar","author_inst":"Stanford University"},{"author_name":"Hailey J. Park","author_inst":"Stanford University"},{"author_name":"Sophia T. Tan","author_inst":"Stanford University"},{"author_name":"Rachel Baker","author_inst":"Brown University"},{"author_name":"Erin A. Mordecai","author_inst":"Stanford University"},{"author_name":"Nathan C. Lo","author_inst":"Stanford University"}],"version":"1","license":"cc_no","type":"PUBLISHAHEADOFPRINT","category":"epidemiology"},{"rel_doi":"10.64898\/2026.02.27.26347274","rel_title":"IL-6 Receptor Antagonists and Severe Post-COVID-19 Outcomes: An Emulated Target Trial","rel_date":"2026-03-02","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.02.27.26347274","rel_abs":"BackgroundInterleukin-6 (IL-6) is a cytokine that plays a key role in systemic hyperinflammation and may mediate the relationship between acute COVID-19 and severe long-term outcomes such as Long COVID or death. IL-6 modulating drugs may reduce patients risk of severe post-COVID-19 outcomes.\n\nMethodsWe conducted an emulated target trial in a retrospective cohort of patients with moderate-to-severe rheumatoid arthritis who were prescribed IL-6 receptor antagonists (sarilumab or tocilizumab, pooled treatment) or other biologic agents (anakinra or baricitinib, pooled comparator) in 2022. We compared the 12-month cumulative incidence of mortality and Long COVID (diagnosed and probable) between groups using Super Learner and targeted maximum likelihood estimation, adjusting for covariates of interest.\n\nResultsIn our cohort of 3,553 patients, we found that prescription of IL-6 receptor antagonists was associated with a lower 12-month cumulative mortality (adjusted relative risk (aRR) 0.40, 95% CI 0.27, 0.59), diagnosed Long COVID aRR 0.42, 95% CI 0.23, 0.78), and probable Long COVID (aRR 0.71, 95% CI 0.61, 0.83), compared to prescription of other biologic agents, among rheumatoid arthritis patients.\n\nConclusionsIL-6 receptor antagonists may prevent the incidence of severe post-COVID-19 outcomes, such as Long COVID or mortality. This supports the hypothesis that IL-6 may be a mechanistic biomarker of COVID-19 sequelae and that acute COVID-19 severity may mediate this relationship.","rel_num_authors":11,"rel_authors":[{"author_name":"Zachary Butzin-Dozier","author_inst":"School of Public Health, University of California, Berkeley, Berkeley, CA USA"},{"author_name":"Manav Kumar","author_inst":"School of Public Health, University of California, Berkeley, Berkeley, CA USA"},{"author_name":"Yunwen Ji","author_inst":"School of Public Health, University of California, Berkeley, Berkeley, CA USA"},{"author_name":"Lin-Chiun Wang","author_inst":"School of Public Health, University of California, Berkeley, Berkeley, CA USA"},{"author_name":"A. Jerrod Anzalone","author_inst":"University of Nebraska Medical Center, Omaha, NE, USA"},{"author_name":"Eric Hurwitz","author_inst":"University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"},{"author_name":"Rena C. Patel","author_inst":"University of Alabama at Birmingham, Birmingham, AL, USA"},{"author_name":"Rachel Wong","author_inst":"Renaissance School of Medicine, Stony Brook University, New York, NY, USA"},{"author_name":"Carolyn Bramante","author_inst":"University of Minnesota, Minneapolis, MN, USA"},{"author_name":"Benjamin Sines","author_inst":"University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"},{"author_name":"- on behalf of the National Clinical Cohort Collaborative","author_inst":"-"}],"version":"1","license":"cc_by","type":"PUBLISHAHEADOFPRINT","category":"epidemiology"},{"rel_doi":"10.64898\/2026.02.26.26343835","rel_title":"Diagnostic Accuracy of an Immunoassay Using Avidity-Enhanced Polymeric Peptides for SARS-CoV-2 Antibody Detection","rel_date":"2026-03-02","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.02.26.26343835","rel_abs":"BackgroundThere is a need for synthetic peptide-based serologic assays that exploit avidity to replace whole antigens while enabling low-cost diagnostics in resource-limited settings.\n\nObjectiveTo evaluate the diagnostic accuracy of a polymeric peptide-based ELISA leveraging avidity to enhance signal.\n\nMethodA 15-member SARS-CoV-2 peptide library corresponding to multiple epitope clusters and proteins was screened by indirect ELISA using pooled sera from RT-PCR-confirmed COVID-19 patients to identify peptides with possible diagnostic utility. The identified lead candidate, S559, possessed terminal cysteine-substitution to allow disulfide polymerization, and the resulting avidity gain was evaluated by comparing the apparent dissociation constant (KDapp) before and after depolymerization with N-acetylcysteine. The performance of an optimized ELISA using S559 was evaluated on 1,222 prospectively collected COVID-19 serum samples and 218 biobanked pre-COVID control serum samples.\n\nResultsPolymeric S559 with a KDapp of 29.26 nM-1was demonstrated to have a 218% avidity gain relative to the completely depolymerized form. At pre-defined thresholds, the optimized S559 ELISA has a sensitivity and specificity of 83.39% (95%CI: 81.18% and 85.43%) and 96.79% (95%CI: 93.50% and 98.70%), respectively. At post hoc thresholds determined by Youden index, sensitivity and specificity reached 95.01 (95% CI: 93.63% - 96.16%) and 100.00% (95% CI: 98.32% - 100.00%), respectively.\n\nConclusionHomomultivalent epitope presentation using polymeric S559 allows a highly specific immunoassay using human sera that may have important value in detecting antibodies, whether for diagnosing infection, confirming vaccination status or conducting surveillance.","rel_num_authors":6,"rel_authors":[{"author_name":"Brian Andrich La Valle Pollo","author_inst":"University of the Philippines Manila"},{"author_name":"Danica Ching","author_inst":"National Institutes of Health"},{"author_name":"Maria Isabel Idolor","author_inst":"University of the Philippines Manila"},{"author_name":"Ruby Anne King","author_inst":"University of the Philippines Manila"},{"author_name":"Fresthel Monica Climacosa","author_inst":"University of the Philippines Manila"},{"author_name":"Salvador Eugenio Caoili","author_inst":"University of the Philippines Manila"}],"version":"1","license":"cc_by","type":"PUBLISHAHEADOFPRINT","category":"infectious diseases"},{"rel_doi":"10.64898\/2026.02.26.706090","rel_title":"Transition from infectivity and immune escape to pure escape as an evolutionary strategy during the COVID-19 pandemic.","rel_date":"2026-02-27","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.02.26.706090","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc0_ng","type":"new results","category":"evolutionary biology"},{"rel_doi":"10.64898\/2026.02.25.26347112","rel_title":"Temporary Shock or Lasting Scar? Life Expectancy Trajectories Since COVID-19","rel_date":"2026-02-27","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.02.25.26347112","rel_abs":"The COVID-19 pandemic led to substantial life expectancy losses globally. Historically, life expectancy reversals have been followed by rapid returns to previous trajectories, but whether this is true for the COVID-19 pandemic is still unknown. We update life expectancy estimates through 2024 for 34 high-income countries and quantify annual and cumulative life expectancy \"deficits\" by comparing observed life expectancy with counterfactuals based on pre-pandemic trends. Five years after the pandemics onset, recovery remains incomplete in most countries. In 2024, 31 out of 34 countries still had lower life expectancy than expected. Across 2020-2024, cumulative deficits were statistically significant in nearly all countries. We identify four distinct life expectancy trajectories: (a) first wave peak (largest deficits in 2020 with gradual recovery); (b) second wave peak (largest deficits in 2021 with a sharper rebound); (c) late peak (minimal early impact followed by smaller deficits from 2022 onward); (d) prolonged depression (smaller but persistent deficits without a sharp peak). In general, countries with severe second-wave peaks (such as the USA and Bulgaria) had the largest cumulative deficits. In contrast, countries that delayed widespread infection (e.g., Norway, Japan) saw later deficits that persisted through 2024, but with lower cumulative mortality. Our findings suggest that COVID-19 was not a uniform, short-lived mortality shock. Instead, most high-income countries experienced multi-year disruptions to life expectancy trajectories, with variable patterns of recovery that continue to shape population health five years on.","rel_num_authors":7,"rel_authors":[{"author_name":"Jennifer B. Dowd","author_inst":"University of Oxford"},{"author_name":"Jonas Sch\u00f6ley","author_inst":"Max Planck Institute for Demographic Research"},{"author_name":"Antonino Polizzi","author_inst":"Max Planck Institute for Demographic Research"},{"author_name":"Jos\u00e9 Manuel Aburto","author_inst":"London School of Hygiene and Tropical Medicine"},{"author_name":"Hannaliis Jaadla","author_inst":"University of Cambridge"},{"author_name":"Haohao Lei","author_inst":"University of Oxford"},{"author_name":"Ridhi Kashyap","author_inst":"University of Oxford"}],"version":"1","license":"cc_by","type":"PUBLISHAHEADOFPRINT","category":"public and global health"},{"rel_doi":"10.64898\/2026.02.26.26347164","rel_title":"Characterising associations between mental distress, mobility, and COVID-19 restrictions: a U.S. study","rel_date":"2026-02-27","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.02.26.26347164","rel_abs":"Large-scale epidemics are consistently associated with increased psychological distress and substantial changes in human mobility, yet the relationship between mental health responses and effective population mobility remains overlooked. During the COVID-19 pandemic, non-pharmaceutical interventions (NPIs) such as lockdowns and travel restrictions altered daily movement patterns while simultaneously affecting psychological well-being. Importantly, formal policy stringency alone does not fully capture realized mobility behavior, which also reflects spontaneous adaptation and adherence fatigue over time. In this study, we examine the association between self-reported mental distress and mobility recovery across the United States during the first wave of the COVID-19 pandemic. We combine state-level human mobility data derived from anonymized mobile phone records with large-scale survey data on self-reported anxiety and depression. Our analysis focuses on the U.S. states and territories from April 1 to September 1, 2020. Using fixed-effects regression models, we assess how variations in mental distress relate to deviations from pre-pandemic mobility levels, while controlling for reported COVID-19 mortality and the stringency of NPIs. We find a negative and statistically significant association between mental distress and mobility recovery: higher levels of self-reported anxiety and depression are associated with lower recovery of pre-pandemic mobility. These results indicate that psychological distress is associated with population mobility beyond what is explained by formal restrictions alone. Our findings highlight the relevance of mental health as a factor linked to behavioral responses during public health crises. Incorporating psychological well-being into the evaluation of mobility dynamics may inform more balanced public health strategies in future emergencies.\n\nAuthor summaryDuring the COVID-19 pandemic, governments introduced restrictions on movement, such as stay-at-home orders and travel limits, to slow the spread of the virus. At the same time, many people experienced increased anxiety and depression. In this study, we ask whether changes in mental well-being were linked to how quickly people returned to their usual patterns of movement. Here, we focus on the first wave of the pandemic in the United States and combine mobility data and large-scale digital survey data to study the association between self-reported mental health indicators and effective mobility at the population level. By comparing states over time, we explore whether changes in mental distress were associated with changes in mobility, beyond what can be explained by public restrictions or reported deaths alone. We find that states with higher levels of reported anxiety and depression tended to show slower recovery toward normal mobility levels. This suggests that psychological well-being played an important role in shaping individual and collective responses to the pandemic, with implications for the design of future public health interventions.","rel_num_authors":13,"rel_authors":[{"author_name":"Stefania Fiandrino","author_inst":"Department of Computer, Control, and Management Engineering Antonio Ruberti, Sapienza University of Rome, Rome, Italy; ISI Foundation, Turin, Italy"},{"author_name":"Saumitra Kulkarni","author_inst":"ISI Foundation, Turin, Italy; Network Science Institute, Northeastern University, Boston, USA"},{"author_name":"Paolo Cornale","author_inst":"ISI Foundation, Turin, Italy"},{"author_name":"Sara Ghivarello","author_inst":"ISI Foundation, Turin, Italy; Grupo Interdisciplinar de Sistemas Complejos (GISC), Departamento de Matematicas, Universidad Carlos III de Madrid, Leganes, Spain"},{"author_name":"Piero Birello","author_inst":"Department of Network and Data Science, Central European University, Vienna, Austria"},{"author_name":"Simone Maria Parazzoli","author_inst":"ISI Foundation, Turin, Italy"},{"author_name":"Federico Moss","author_inst":"ISI Foundation, Turin, Italy"},{"author_name":"Alessandro De Gaetano","author_inst":"ISI Foundation, Turin, Italy"},{"author_name":"Daniele Liberatore","author_inst":"ISI Foundation, Turin, Italy"},{"author_name":"Jacopo D'Ignazi","author_inst":"ISI Foundation, Turin, Italy; UPF, Barcelona, Spain"},{"author_name":"Kyriaki Kalimeri","author_inst":"ISI Foundation, Turin, Italy"},{"author_name":"Michele Tizzani","author_inst":"ISI Foundation, Turin, Italy; DTU, Copenhagen, Denmark"},{"author_name":"Mattia Mazzoli","author_inst":"ISI Foundation"}],"version":"1","license":"cc_by","type":"PUBLISHAHEADOFPRINT","category":"public and global health"},{"rel_doi":"10.64898\/2026.02.27.708159","rel_title":"Antigenic landscape of a highly mutated SARS-CoV-2 Spike in ongoing viral evolution","rel_date":"2026-02-27","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.02.27.708159","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by_nc_nd","type":"new results","category":"immunology"},{"rel_doi":"10.64898\/2026.02.24.26347039","rel_title":"A longitudinal study of anxiety and depression in Belgium during and after the COVID-19 pandemic","rel_date":"2026-02-26","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.02.24.26347039","rel_abs":"BackgroundThe COVID-19 pandemic, coupled with concurrent social instabilities, has raised concerns about the long-term impact on the population mental health. While existing studies have primarily focused on the acute phase, less is known about how anxiety and depression symptoms have evolved throughout prolonged societal disruption. This study aimed to identify distinct anxiety and depression symptom trajectories and to determine the individual, relational, and societal protective and risk factors that influence anxiety and depression scores among Belgian adults from 2020 to 2024.\n\nMethodsWe used longitudinal data from five waves of the COVID-19 Health Surveys and the BELHEALTH study (n = 10,063) among Belgian adults, collected between April 2020 and June 2024. Anxiety and depression were assessed using the Generalized Anxiety Disorder-7 and the Patient Health Questionnaire-9, respectively. Covariates were selected based on the social-ecological framework and included both time-invariant and time-dependent variables. Latent class linear mixed models identified subgroups with distinct trajectories. Multilevel linear mixed effects models examined associations between symptom severity and predictors across individual, relationship, and societal levels. The final model, selected based on the lowest AIC (Akaike Information Criterion), included the full set of covariates.\n\nResultsFour depression and five anxiety trajectories were identified. While most participants maintained stable mild symptoms, 11.3% experienced increasing depression and 8.4% showed increasing anxiety over time. Financial difficulty, female gender, and younger age were overrepresented in moderate and severe symptom trajectories. Protective factors such as social support, satisfying social contact, and life satisfaction were associated with lower symptom severity. Over time, life satisfaction demonstrated an increasing protective effect, while the influence of social contact on reducing symptoms weakened progressively. Risk factors included financial and job-loss worry, loneliness, psychotropic medication use, and high mental health stigma.\n\nConclusionsOur results demonstrate persistent heterogeneity in mental health responses, with a substantial share of the population experiencing worsening symptoms years after the pandemic began. Public mental health strategies must therefore go beyond short-term crisis response, address long-term risks such as financial insecurity, social isolation, and stigma, while fostering individual and collective resilience.","rel_num_authors":5,"rel_authors":[{"author_name":"Thuy Bui","author_inst":"VinUniversity"},{"author_name":"Stefaan Demarest","author_inst":"Sciensano, Belgium"},{"author_name":"Camille Duveau","author_inst":"Sciensano, Belgium"},{"author_name":"Lize Hermans","author_inst":"Sciensano, Belgium"},{"author_name":"Guido Van Hal","author_inst":"University of Antwerp"}],"version":"1","license":"cc_by","type":"PUBLISHAHEADOFPRINT","category":"psychiatry and clinical psychology"},{"rel_doi":"10.64898\/2026.02.24.26346985","rel_title":"Progressively Widening Healthcare Costs in Long COVID Over Five Years","rel_date":"2026-02-26","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.02.24.26346985","rel_abs":"BackgroundLong COVID affects millions worldwide, yet the long-term trajectory of healthcare costs remains poorly characterized. Prior studies with limited follow-up have documented elevated but stable excess costs, leaving uncertainty about whether the economic burden attenuates or persists over time.\n\nMethodsWe conducted a retrospective cohort study using electronic health record data from 12 hospitals and 20 community health centers (January 2018 through December 2024). Adults with documented SARS-CoV-2 infection were classified as having Long COVID using a validated precision phenotyping algorithm or as controls without Long COVID. We used two-part generalized estimating equation models to estimate adjusted quarterly healthcare costs over 20 quarters, decomposed costs into visit frequency and cost-per-visit components, and conducted subgroup and sensitivity analyses accounting for differential mortality.\n\nResultsAmong 143,544 adults (27,986 with Long COVID; 115,558 controls), the adjusted excess quarterly cost for Long COVID widened progressively rather than attenuating, increasing from $79 (95% CI, $48-$118) at baseline to $236 (95% CI, $176-$287) at quarter 19 - a threefold increase in the cost differential. Long COVID was associated with 20% higher odds of any healthcare utilization (OR, 1.20; 95% CI, 1.18-1.23) and 30% higher costs when care was accessed (cost ratio, 1.30; 95% CI, 1.25-1.35). Visit frequency diverged over time, reaching 44% higher utilization by quarter 19, while cost-per-visit premiums remained stable. Excess costs concentrated in the upper distribution tail (99th percentile difference: $8,482). The widening trajectory was consistent across subgroups defined by hospitalization status, sex, and comorbidity burden. Cumulative 5-year excess costs were $7,124 per Long COVID patient after mortality adjustment.\n\nConclusionsContrary to assumptions of post-acute recovery, Long COVID is associated with progressively widening healthcare costs over five years, driven primarily by increasing utilization rather than care intensity, suggesting an evolving chronic disease burden with substantial and growing economic implications.","rel_num_authors":6,"rel_authors":[{"author_name":"Jingya Cheng","author_inst":"Massachusetts General Hospital"},{"author_name":"Alaleh Azhir","author_inst":"Massachusetts General Hospital, Brigham and Women's Hospital"},{"author_name":"Jiazi Tian","author_inst":"Massachusetts General Hospital"},{"author_name":"Jeffrey G. Klann","author_inst":"Massachusetts General Hospital"},{"author_name":"Shawn N. Murphy","author_inst":"Massachusetts General Hospital"},{"author_name":"Hossein Estiri","author_inst":"Massachusetts General Hospital"}],"version":"1","license":"cc_by_nc","type":"PUBLISHAHEADOFPRINT","category":"public and global health"},{"rel_doi":"10.64898\/2026.02.24.26346954","rel_title":"Immunogenicity and safety of LP.8.1 variant-containing mRNA COVID-19 vaccines","rel_date":"2026-02-26","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.02.24.26346954","rel_abs":"BackgroundThe SARS-CoV-2 LP.8.1 subvariant was incorporated into the 2025-2026 U.S. COVID-19 vaccines (mRNA-1273.251 and mRNA-1283.251). We evaluated immunogenicity and safety of these vaccines against vaccine-matched and emerging variants in individuals aged [&ge;]65 and those aged 12-64 years at high-risk of severe COVID-19.\n\nMethodsData were generated from: (1) two independent, ongoing, phase 3b\/4, open-label, single-arm studies in which participants received a single dose of 50-{micro}g mRNA-1273.251 (n=103; median age, 64.0 years) or 10-{micro}g mRNA-1283.251 (n=172, median age, 59.0 years) and followed through Day 29 post-vaccination; neutralizing antibodies (nAb) were measured at baseline (Day 1) and Day 29 using a pseudovirus neutralization assay against the vaccine-matched LP.8.1 variant; (2) Day 29 immunogenicity against circulating variants (BA.3.2.2, XFG, and NB.1.8.1) was assessed in a randomly selected subset; and (3) immune-escape potential was estimated using predictive modeling. Unsolicited adverse events (AEs), including serious AEs, leading to study withdrawal, and those of special interest, were monitored.\n\nResultsBoth vaccines elicited robust nAbs at Day 29 against LP.8.1 (geometric mean fold-rise from baseline: 12-64 years, mRNA-1273.251, 26.3; mRNA-1283.251, 53.0; [&ge;]65 years, mRNA-1273.251, 15.4; mRNA-1283.251, 36.7) and circulating variants. Model-based estimates with mRNA-1273.251 were consistent with clinical data and indicated the highest responses against LP.8.1 and lower responses against BA.3.2.2. No vaccine-related AEs were reported in either study.\n\nConclusionsmRNA-1273.251 and mRNA-1283.251 were well tolerated through Day 29 and elicited robust nAbs against vaccine-matched and circulating variants. In predictive models, BA.3.2.2 had the highest relative risk of immune escape following mRNA-1273.251 vaccination.\n\nSUMMARYLP.8.1-containing mRNA-1273.251 and mRNA-1283.251 vaccines given as a single dose were well tolerated and induced robust Day 29 neutralizing antibodies against LP.8.1 and circulating variants.","rel_num_authors":13,"rel_authors":[{"author_name":"Amparo Figueroa","author_inst":"Moderna, Inc."},{"author_name":"Kimball Johnson","author_inst":"CenExel"},{"author_name":"Robert Springer","author_inst":"DelRicht Research, Springer Wellness and Restorative Health"},{"author_name":"Jarrett Lowe","author_inst":"Moderna, Inc."},{"author_name":"Ann Cripple","author_inst":"Moderna, Inc."},{"author_name":"Darin K Edwards","author_inst":"Moderna, Inc."},{"author_name":"Wenqin Xu","author_inst":"Moderna, Inc."},{"author_name":"Xin Cao","author_inst":"Moderna, Inc."},{"author_name":"Veronica Urdaneta","author_inst":"Moderna, Inc."},{"author_name":"Bethany Girard","author_inst":"Moderna, Inc."},{"author_name":"Arshan Nasir","author_inst":"Moderna, Inc."},{"author_name":"David C. Montefiori","author_inst":"Duke University Medical Center"},{"author_name":"Spyros Chalkias","author_inst":"Moderna, Inc."}],"version":"1","license":"cc_by","type":"PUBLISHAHEADOFPRINT","category":"infectious diseases"},{"rel_doi":"10.64898\/2026.02.24.26346989","rel_title":"The age paradox in post-infectious sequelae: physiological reserve outweighs chronological age in Long COVID susceptibility","rel_date":"2026-02-26","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.02.24.26346989","rel_abs":"BackgroundOlder age is widely considered a risk factor for post-acute sequelae of SARS-CoV-2 infection (PASC), typically attributed to immunosenescence and inflammaging. However, whether this association reflects intrinsic biological ageing or accumulated comorbidity burden remains unclear, with implications for clinical risk stratification.\n\nMethodsWe conducted a retrospective cohort study using the Precision PASC Research Cohort (P2RC) from Mass General Brigham, comprising 133,792 COVID-19 patients from 12 hospitals and 20 community health centres in Massachusetts (March 2020-May 2024). PASC was ascertained using a validated computational phenotyping algorithm. We used generalised estimating equations with cluster-robust variance to model PASC risk, causal mediation analysis to decompose age effects through comorbidity burden and acute severity, and specification curve analysis across 768 analytical specifications to assess robustness.\n\nFindingsAfter adjustment for comorbidity burden, each decade of age was associated with 6% lower odds of PASC (OR 0.94; 95% CI 0.93-0.95). Causal mediation analysis revealed that comorbidities accounted for 145% of the total age effect, indicating inconsistent mediation wherein ages direct protective effect was masked by its indirect harm through chronic disease accumulation. This protection was age-dependent: adults younger than 65 years retained robust resilience independent of comorbidities (ADE:-0.0042, p<0.001), whereas adults 65 years and older showed complete loss of this protection (ADE: +0.0020, p=0.14).\n\nInterpretationLong COVID susceptibility is driven by physiological reserve rather than chronological age until approximately age 65, beyond which age-related protective mechanisms become exhausted. Risk stratification should prioritise comorbidity burden over birth year in younger adults.\n\nFundingNational Institute of Allergy and Infectious Diseases (NIAID).","rel_num_authors":8,"rel_authors":[{"author_name":"Alaleh Azhir","author_inst":"Massachusetts General Hospital, Brigham and Women's Hospital"},{"author_name":"Jingya Cheng","author_inst":"Massachusetts General Hospital"},{"author_name":"Jiazi Tian","author_inst":"Massachusetts General Hospital"},{"author_name":"Ingrid V. Bassett","author_inst":"Massachusetts General Hospital"},{"author_name":"Chirag J. Patel","author_inst":"Harvard Medical School"},{"author_name":"Jeffrey G. Klann","author_inst":"Massachusetts General Hospital"},{"author_name":"Shawn N. Murphy","author_inst":"Massachusetts General Hospital"},{"author_name":"Hossein Estiri","author_inst":"Massachusetts General Hospital"}],"version":"1","license":"cc_by_nc","type":"PUBLISHAHEADOFPRINT","category":"public and global health"},{"rel_doi":"10.64898\/2026.02.26.708234","rel_title":"Identifying severe COVID-19 risk variants modulating enhancer reporter activity in lung cells","rel_date":"2026-02-26","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.02.26.708234","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by_nc_nd","type":"new results","category":"molecular biology"},{"rel_doi":"10.64898\/2026.02.25.707691","rel_title":"Identification of MED13 and DDX60 as critical host factors for SARS-CoV-2 infections","rel_date":"2026-02-25","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.02.25.707691","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by","type":"new results","category":"microbiology"},{"rel_doi":"10.64898\/2026.02.24.707668","rel_title":"Circadian immunometabolic states impart a temporal response to SARS-CoV-2 spike proteins in mammalian macrophages","rel_date":"2026-02-25","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.02.24.707668","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc0","type":"new results","category":"molecular biology"},{"rel_doi":"10.64898\/2026.02.19.26346546","rel_title":"Associations between SARS-CoV-2 Infection and Multidimensional Sleep Health","rel_date":"2026-02-25","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.02.19.26346546","rel_abs":"PuhrposeTo evaluate the short- and long-term cross-sectional associations between COVID-19 infection and multidimensional sleep health.\n\nMethodsData from the COVID-19 Outbreak Public Evaluation (COPE) initiative were used to examine the association between a novel multidimensional sleep health measure (COPE Multidimensional Sleep Health Scale, CMSHS) modeled from the RuSATED instrument and (1) COVID-19 infection and (2) post-acute sequelae of SARS-CoV-2 infection (PASC).\n\nResultsData from 11,326 respondents were used for this study. The cohort was comprised of 51% women, 61% non-Hispanic White, and 17% Hispanic adults. COVID-19 infection was more prevalent among participants who had not received a booster vaccination (55.4% vs. 30.2%, p<0.001); the number of comorbid conditions was higher among those who had been infected (2.2% vs. 1.7%, p<0.001). Participants with COVID-19 infection had significantly lower CMSHS scores indicative of worse sleep health compared with uninfected participants (3.52 {+\/-} 1.37 vs. 3.78 {+\/-} 1.30; p < 0.001). Participants with PASC had lower CMSHS scores in comparison to those without PASC (2.72 {+\/-} 1.30 vs. 3.82 {+\/-} 1.28, p<0.001). In adjusted models, a progressive decline in CMSHS scores was observed over 12 months following infection (3.52 {+\/-} 0.05 vs. 2.98 {+\/-} 0.04; p < 0.001 for <1 month vs. 6-12 months).\n\nConclusionCompared with uninfected individuals, multidimensional sleep health was worse among persons who had a COVID-19 infection. Individuals with PASC had greater and persistent reductions in sleep health for up to 12 months post-infection.\n\nBrief summaryO_LISeveral studies have examined the negative effects of COVID-19 on sleep, however the effects of COVID-19 infection on multidimensional sleep health remain poorly understood as do these associations over time. Using a large, population-based cohort, this study evaluates short- and long-term effects of Covid-19 infection on overall sleep health.\nC_LIO_LIThe study provides evidence that COVID-19 infection is associated with impairments in overall sleep health, with effects persisting up to 12 months post-infection. The findings in this study demonstrate that poor sleep health is an important long-term consequence of COVID-19 infection and emphasizes the need for sleep assessment among patients affected by COVID-19.\nC_LI","rel_num_authors":12,"rel_authors":[{"author_name":"Salma Batool-anwar","author_inst":"Brigham and Women's Hospital"},{"author_name":"Matthew Weaver","author_inst":"Brigham and Women's Hospital"},{"author_name":"Mark Czeisler","author_inst":"Brigham and Women's Hospital"},{"author_name":"Lauren Booker","author_inst":"Austin Health, Heidelberg, Victoria, Australia"},{"author_name":"Mark Howard","author_inst":"Austin Health"},{"author_name":"Melinda Jackson","author_inst":"Monash University"},{"author_name":"Christine McDonald","author_inst":"Austin Health, Heidelberg, Victoria, Australia"},{"author_name":"Rebecca Robbins","author_inst":"Brigham and Women's Hospital"},{"author_name":"Prerna Verma","author_inst":"Monash University"},{"author_name":"Shantha Rajaratnam","author_inst":"Monash University"},{"author_name":"Charles Czeisler","author_inst":"Brigham and Women's Hospital"},{"author_name":"Stuart F. Quan","author_inst":"Brigham and Women's Hospital"}],"version":"1","license":"cc_no","type":"PUBLISHAHEADOFPRINT","category":"infectious diseases"},{"rel_doi":"10.64898\/2026.02.23.707522","rel_title":"Genetic Evidence Indicates the Evolutionary Importance of the SARS-CoV-2 ORF9b protein","rel_date":"2026-02-24","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.02.23.707522","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by_nd","type":"new results","category":"microbiology"},{"rel_doi":"10.64898\/2026.02.23.707600","rel_title":"AVE0991, a Mas receptor agonist, increases influenza and COVID-19 severity in vivo.","rel_date":"2026-02-24","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.02.23.707600","rel_num_authors":0,"rel_authors":null,"version":"1","license":"cc_by","type":"new results","category":"microbiology"},{"rel_doi":"10.64898\/2026.02.22.26346850","rel_title":"Automated Model Discovery Based on COVID-19 Epidemiologic Data","rel_date":"2026-02-24","rel_site":"medRxiv","rel_link":"https:\/\/medrxiv.org\/cgi\/content\/short\/10.64898\/2026.02.22.26346850","rel_abs":"The COVID-19 pandemic has presented severe challenges in understanding and predicting the spread of infectious diseases, necessitating innovative approaches beyond traditional epidemiological models. This study introduces an advanced method for automated model discovery using the Sparse Identification of Nonlinear Dynamics (SINDy) algorithm, leveraging a dataset from the COVID-19 outbreak in Thuringia, Germany, encompassing over 400,000 patient records and vaccination data. By analysing this dataset, we develop a flexible, data-driven model that captures many aspects of the complex dynamics of the pandemics spread. Our approach incorporates external factors and interventions into the mathematical framework, leading to more accurate modelling of the pandemics behaviour. The fixed coefficient values of the differential equation as globally determined by the SINDy were not found to be accurate for locally modelling the measured data. We therefore refined our technique based on the differential equations as found by SINDy, by investigating three modifications that account for recent local data. In a first approach, we re-optimized the coefficient values using seven days of past data, without changing the globally determined differential equation. In a second approach, we allowed a temporal dependence of the coefficient values fitted using all previous data in combination with regularization. As a last method, we kept the coefficients fixed to the original values but augmented the differential equation with a small neural network, locally optimized to the data of the past week. Our findings reveal the critical role of vaccination and public health measures in the pandemics trajectory. The proposed model offers a robust tool for policymakers and health professionals to mitigate future outbreaks, providing insights into the efficacy of intervention strategies and vaccination campaigns. This study advances the understanding of COVID-19 dynamics and lays the groundwork for future research in epidemic modelling, emphasising the importance of adaptive, data-informed approaches in public health planning.","rel_num_authors":6,"rel_authors":[{"author_name":"Morteza Babazadeh Shareh","author_inst":"Leibniz Institute of Photonic Technology: Leibniz-Institut fur Photonische Technologien"},{"author_name":"Florian Kleiner","author_inst":"Leibniz Institute of Photonic Technology: Leibniz-Institut fur Photonische Technologien"},{"author_name":"Michael B\u00f6hme","author_inst":"Leibniz Institute of Photonic Technology: Leibniz-Institut fur Photonische Technologien"},{"author_name":"Corinna H\u00e4gele","author_inst":"Leibniz Institute of Photonic Technology: Leibniz-Institut fur Photonische Technologien"},{"author_name":"Petra Dickmann","author_inst":"Universit\u00e4tsklinikum Jena: Universitatsklinikum Jena"},{"author_name":"Rainer Heintzmann","author_inst":"Friedrich-Schiller-Universitat Jena"}],"version":"1","license":"cc_by","type":"PUBLISHAHEADOFPRINT","category":"epidemiology"}]}



