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Rxivist combines biology preprints from bioRxiv and medRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 137,145 papers from 584,398 authors.

Most downloaded biology preprints, since beginning of last month

133,648 results found. For more information, click each entry to expand.

41: The World Mortality Dataset: Tracking excess mortality across countries during the COVID-19 pandemic
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Posted 29 Jan 2021

The World Mortality Dataset: Tracking excess mortality across countries during the COVID-19 pandemic
5,609 downloads medRxiv epidemiology

Ariel Karlinsky, Dmitry Kobak

Comparing the impact of the COVID-19 pandemic between countries or across time is difficult because the reported numbers of cases and deaths can be strongly affected by testing capacity and reporting policy. Excess mortality, defined as the increase in all-cause mortality relative to the recent average, is widely considered as a more objective indicator of the COVID-19 death toll. However, there has been no central, frequently-updated repository of the all-cause mortality data across countries. To fill this gap, we have collected weekly, monthly, or quarterly all-cause mortality data from 77 countries, openly available as the regularly-updated World Mortality Dataset. We used this dataset to compute the excess mortality in each country during the COVID-19 pandemic. We found that in the worst-affected countries the annual mortality increased by over 50%, while in several other countries it decreased by over 5%, presumably due to lockdown measures decreasing the non-COVID mortality. Moreover, we found that while some countries have been reporting the COVID-19 deaths very accurately, many countries have been underreporting their COVID-19 deaths by an order of magnitude or more. Averaging across the entire dataset suggests that the world's COVID-19 death toll may be at least 1.6 times higher than the reported number of confirmed deaths.

42: A prefusion SARS-CoV-2 spike RNA vaccine is highly immunogenic and prevents lung infection in non-human primates
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Posted 08 Sep 2020

A prefusion SARS-CoV-2 spike RNA vaccine is highly immunogenic and prevents lung infection in non-human primates
5,571 downloads bioRxiv immunology

Annette B. Vogel, Isis Kanevsky, Ye Che, Kena A. Swanson, Alexander Muik, Mathias Vormehr, Lena M Kranz, Kerstin C. Walzer, Stephanie Hein, Alptekin Güler, Jakob Loschko, Mohan S. Maddur, Kristin Tompkins, Journey Cole, Bonny G. Lui, Thomas Ziegenhals, Arianne Plaschke, David Eisel, Sarah C. Dany, Stephanie Fesser, Stephanie Erbar, Ferdia Bates, Diana Schneider, Bernadette Jesionek, Bianca Sänger, Ann-Kathrin Wallisch, Yvonne Feuchter, Hanna Junginger, Stefanie A. Krumm, André P. Heinen, Petra Adams-Quack, Julia Schlereth, Christoph Kröner, Shannan Hall-Ursone, Kathleen Brasky, Matthew C. Griffor, Seungil Han, Joshua A. Lees, Ellene H. Mashalidis, Parag V. Sahasrabudhe, Charles Y. Tan, Danka Pavliakova, Guy Singh, Camila Fontes-Garfias, Michael Pride, Ingrid L. Scully, Tara Ciolino, Jennifer Obregon, Michal Gazi, Ricardo Carrion, Kendra J. Alfson, Warren V. Kalina, Deepak Kaushal, Pei-Yong Shi, Thorsten Klamp, Corinna Rosenbaum, Andreas N. Kuhn, Özlem Türeci, Philip R. Dormitzer, Kathrin U. Jansen, Ugur Sahin

To contain the coronavirus disease 2019 (COVID-19) pandemic, a safe and effective vaccine against the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is urgently needed in quantities sufficient to immunise large populations. In this study, we report the design, preclinical development, immunogenicity and anti-viral protective effect in rhesus macaques of the BNT162b2 vaccine candidate. BNT162b2 contains an LNP-formulated nucleoside-modified mRNA that encodes the spike glycoprotein captured in its prefusion conformation. After expression of the BNT162b2 coding sequence in cells, approximately 20% of the spike molecules are in the one-RBD ‘up’, two-RBD ‘down’ state. Immunisation of mice with a single dose of BNT162b2 induced dose level-dependent increases in pseudovirus neutralisation titers. Prime-boost vaccination of rhesus macaques elicited authentic SARS-CoV-2 neutralising geometric mean titers 10.2 to 18.0 times that of a SARS-CoV-2 convalescent human serum panel. BNT162b2 generated strong TH1 type CD4+ and IFNγ+ CD8+ T-cell responses in mice and rhesus macaques. The BNT162b2 vaccine candidate fully protected the lungs of immunised rhesus macaques from infectious SARS-CoV-2 challenge. BNT162b2 is currently being evaluated in a global, pivotal Phase 2/3 trial ([NCT04368728][1]). ### Competing Interest Statement U.S. and O.T. are management board members and employees at BioNTech SE (Mainz, Germany); K.C.W., B.G.L., D.S., B.J., T.K. and C.R. are employees at BioNTech SE; A.B.V., A.M., M.V., L.M.K., S.He., A.G., T.Z., A.P., D.E., S.C.D., S.F., S.E., F.B., B.S., A.W., Y.F., H.J., S.A.K., A.P.H., P.A., J.S., C.K., and A.N.K. are employees at BioNTech RNA Pharmaceuticals GmbH (Mainz, Germany); A.B.V., A.M., K.C.W., A.G., S.F., A.N.K and U.S. are inventors on patents and patent applications related to RNA technology and COVID-19 vaccine; A.B.V., A.M., M.V., L.M.K., K.C.W., S.He., B.G.L., A.P., D.E., S.C.D., S.F., S.E., D.S., B.J., B.S., A.P.H., P.A., J.S., C.K., T.K., C.R., A.N.K., O.T. and U.S. have securities from BioNTech SE; I.K., Y.C., K.A.S., J.L., M.M., K.T., M.C.G., S.H., J.A.L.,E.H.M., P.V.S., C.Y.T., D.P., G.S., M.P., I.L.S., T.C., J.O., W.V.K., P.R.D. and K.U.J. are employees of Pfizer and may hold stock options; C.F.-G. and P.-Y.S. received compensation from Pfizer to perform neutralisation assays; J.C., S.H.-U, K.B., R.C., jr., K.J.A. and D.K., are employees of Southwest National Primate Research Center, which received compensation from Pfizer to conduct the animal challenge work; no other relationships or activities that could appear to have influenced the submitted work. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04368728&atom=%2Fbiorxiv%2Fearly%2F2020%2F09%2F08%2F2020.09.08.280818.atom

43: Genome-wide molecular recording using Live-seq
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Posted 24 Mar 2021

Genome-wide molecular recording using Live-seq
5,527 downloads bioRxiv molecular biology

Wanze Chen, Orane Guillaume-Gentil, Riccardo Dainese, Pernille Yde Rainer, Magda Zachara, Christoph G. Gabelein, Julia A. Vorholt, Bart Deplancke

Single-cell transcriptomics (scRNA-seq) has greatly advanced our ability to characterize cellular heterogeneity in health and disease. However, scRNA-seq requires lysing cells, which makes it impossible to link the individual cells to downstream molecular and phenotypic states. Here, we established Live-seq, an approach for single-cell transcriptome profiling that preserves cell viability during RNA extraction using fluidic force microscopy. Based on cell division, functional responses and whole-cell transcriptome read-outs, we show that Live-seq does not induce major cellular perturbations and therefore can function as a transcriptomic recorder. We demonstrate this recording capacity by preregistering the transcriptomes of individual macrophage-like RAW 264.7 cells that were subsequently subjected to time-lapse imaging after lipopolysaccharide (LPS) exposure. This enabled the unsupervised, genome-wide ranking of genes based on their ability to impact macrophage LPS response heterogeneity, revealing basal NFKBIA expression level and cell cycle state as major phenotypic determinants. Furthermore, we show that Live-seq can be used to sequentially profile the transcriptomes of individual macrophages before and after stimulation with LPS, thus enabling the direct mapping of a cell's trajectory. Live-seq can address a broad range of biological questions by transforming scRNA-seq from an end-point to a temporal analysis approach.

44: Epidemiological description and analysis of RdRp, E and N genes dynamic by RT-PCR of SARS-CoV-2 in Moroccan population: Experience of the National Reference Laboratory (LNR)-UM6SS
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Posted 20 Jun 2020

Epidemiological description and analysis of RdRp, E and N genes dynamic by RT-PCR of SARS-CoV-2 in Moroccan population: Experience of the National Reference Laboratory (LNR)-UM6SS
5,428 downloads medRxiv infectious diseases

Houda Benrahma, Idrissa Diawara, Imane Smyej, Jalila Rahoui, Nida Meskaouni, Rachid Benmessaoud, Khadija Arouro, Khadija Jaras, Zahra Adam, Salma Nahir, Zineb Aouzal, Hajar Elguazzar, Leila Jeddane, Fadwa Ousti, Jalila Elbakkouri, Chakib Nejjari

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new infectious disease that first emerged in Hubei province, China, in December 2019. On 2 March 2020, the Moroccan Ministry of Health confirmed the first COVID-19 case in Morocco. The new virus SARS-CoV-2 was identified in the sample of a Moroccan expatriate residing in Italy. Without a therapeutic vaccine or specific antiviral drugs, early detection and isolation become essential against novel Coronavirus. This study aims to analyze the epidemiological profile of the SARS-CoV-2 in Moroccan cases and to investigate the dynamic of RdRp gene, N gene, and E gene in patients from diagnosis until the recovery. Among 859 Covid-19 RT-PCR tests realized for 285 patients, 133 cases had positive results Covid-19. 9 % of these cases present the 3 genes RdRp, N, and E, 47% only the RdRp gene, 2% with RdRp and N gene, 26% cases are positives with N gene, and 16 % with N and E gene. The analysis of the Covid-19 genes (RdRp, N, and E) dynamic reveal that more than 6% stay positive with detection of the N and E gene, and 14% with the N gene after 12 days of treatment. The median period from positive to the first negative Covid-19 RT-PCR tests was 6.8{+/-}2.24 days for 44% cases, 14.31 {+/-} 2.4 days for 30%, and 22.67 {+/-} 1.21 days for 4%. This a first description of the Moroccan COVID-19 cases and the analysis of the dynamic of the 3 genes RdRp, N, and E. The analysis of our population can help to involved in the care of patients.

45: Characteristics of Long Covid: findings from a social media survey
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Posted 26 Mar 2021

Characteristics of Long Covid: findings from a social media survey
5,284 downloads medRxiv epidemiology

Nida Ziauddeen, Deepti Gurdasani, Margaret E O'Hara, Claire Hastie, Paul Roderick, Guiqing Yao, Nisreen A Alwan

Many people are not recovering for months after being infected with SARS-CoV-2. Long Covid has emerged as a major public health concern that needs defining, quantifying, and describing. We aimed to explore the initial and ongoing symptoms of Long Covid following SARS-CoV-2 infection and describe its impact on daily life in people who were not admitted to hospital during the first two weeks of the illness. We co-produced a survey with people living with Long Covid. We collected the data through an online survey using convenience non-probability sampling, with the survey posted both specifically on Long Covid support groups and generally on social media. The criteria for inclusion were adults with lab-confirmed (PCR or antibody) or suspected COVID-19 managed in the community (non-hospitalised) in the first two weeks of illness. We used agglomerative hierarchical clustering to identify specific symptom clusters, and their demographic and functional correlates. We analysed data from 2550 participants with a median duration of illness of 7.7 months (interquartile range (IQR) 7.4-8.0). The mean age was 46.5 years (standard deviation 11 years) with 82.8% females and 79.9% of participants based in the UK. 89.5% described their health as good, very good or excellent before COVID-19. The most common initial symptoms that persisted were exhaustion, chest pressure/tightness, shortness of breath and headache. Cough, fever, and chills were common initial symptoms that became less prevalent later in the illness, whereas cognitive dysfunction and palpitations became more prevalent later in the illness. 26.5% reported lab-confirmation of infection. The biggest difference in ongoing symptoms between those who reported testing positive and those who did not was loss of smell/taste. Ongoing symptoms affected at least 3 organ systems in 83.5% of participants. Most participants described fluctuating (57.7%) or relapsing symptoms (17.6%). Physical activity, stress and sleep disturbance commonly triggered symptoms. A third (32%) reported they were unable to live alone without any assistance at six weeks from start of illness. 16.9% reported being unable to work solely due to COVID-19 illness. 66.4% reported taking time off sick (median of 60 days, IQR 20, 129). 37.0% reported loss of income due to illness, and 64.4% said they were unable to perform usual activities/duties. Acute systems clustered broadly into two groups: a majority cluster (n=2235, 88%) with cardiopulmonary predominant symptoms, and a minority cluster (n=305, 12%) with multisystem symptoms. Similarly, ongoing symptoms broadly clustered in two groups; a majority cluster (n=2243, 88.8%) exhibiting mainly cardiopulmonary, cognitive symptoms and exhaustion, and a minority cluster (n=283, 11.2%) exhibited more multisystem symptoms. Belonging to the more severe multisystem cluster was associated with more severe functional impact, lower income, younger age, being female, worse baseline health, and inadequate rest in the first two weeks of the illness, with no major differences in the cluster patterns when restricting analysis to the lab-confirmed subgroup. This is an exploratory survey of Long Covid characteristics. Whilst it is important to acknowledge that it is a non-representative population sample, it highlights the heterogeneity of persistent symptoms, and the significant functional impact of prolonged illness following confirmed or suspected SARS-CoV-2 infection. To study prevalence, predictors and prognosis, research is needed in a representative population sample using standardised case definitions (to include those not lab-confirmed in the first pandemic wave).

46: Newborn antibodies to SARS-CoV-2 detected in cord blood after maternal vaccination
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Posted 05 Feb 2021

Newborn antibodies to SARS-CoV-2 detected in cord blood after maternal vaccination
5,144 downloads medRxiv pediatrics

Paul D Gilbert, Chad A Rudnick

Background: Maternal vaccination for Influenza and TDaP have been well studied in terms of safety and efficacy for protection of the newborn by placental passage of antibodies. Similar newborn protection would be expected after maternal vaccination against SARS-CoV-2 (the virus responsible for COVID-19). There is a significant and urgent need for research regarding safety and efficacy of vaccination against SARS-CoV-2 during pregnancy. Here, we report the first known case of an infant with SARS-CoV-2 IgG antibodies detectable in cord blood after maternal vaccination. Case presentation: A vigorous, healthy, full-term female was born to a COVID-19 naive mother who had received a single dose of mRNA vaccine for SARS-CoV-2 three weeks prior to delivery. Cord blood antibodies (IgG) were detected to the S-protein of SARS-CoV-2 at time of delivery. Conclusion: Here, we report the first known case of an infant with SARS-CoV-2 IgG antibodies detectable in cord blood after maternal vaccination.

47: Memory B cell repertoire for recognition of evolving SARS-CoV-2 spike
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Posted 10 Mar 2021

Memory B cell repertoire for recognition of evolving SARS-CoV-2 spike
5,114 downloads bioRxiv immunology

Pei Tong, Avneesh Gautam, Ian Windsor, Meghan Travers, Yuezhou Chen, Nicholas Garcia, Noah Whiteman, Lindsay McKay, Felipe J.N. Lelis, Shaghayegh Habibi, Yongfei Cai, Linda J Rennick, W. Paul Duprex, Kevin McCarthy, Christy L. Lavine, Teng Zuo, Junrui Lin, Adam Zuiani, Jared Feldman, Elizabeth A. MacDonald, Blake M. Hauser, Anthony Griffths, Michael S. Seaman, Aaron G. Schmidt, Bing Chen, Donna Neuberg, Goran Bajic, Stephen C. Harrison, Duane Wesemann

Memory B cell reserves can generate protective antibodies against repeated SARS-CoV-2 infections, but with an unknown reach from original infection to antigenically drifted variants. We charted memory B cell receptor-encoded monoclonal antibodies (mAbs) from 19 COVID-19 convalescent subjects against SARS-CoV-2 spike (S) and found 7 major mAb competition groups against epitopes recurrently targeted across individuals. Inclusion of published and newly determined structures of mAb-S complexes identified corresponding epitopic regions. Group assignment correlated with cross-CoV-reactivity breadth, neutralization potency, and convergent antibody signatures. mAbs that competed for binding the original S isolate bound differentially to S variants, suggesting the protective importance of otherwise-redundant recognition. The results furnish a global atlas of the S-specific memory B cell repertoire and illustrate properties conferring robustness against emerging SARS-CoV-2 variants.

48: Neutralization of UK-variant VUI-202012/01 with COVAXIN vaccinated human serum
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Posted 26 Jan 2021

Neutralization of UK-variant VUI-202012/01 with COVAXIN vaccinated human serum
4,884 downloads bioRxiv molecular biology

Gajanan N Sapkal, Pragya Yadav, Raches Ella, Gururaj Deshpande, Rima Sahay, Nivedita Gupta, V Krishna Mohan, Priya Abraham, Samiran Panda, Balram Bhargava

We performed the plaque reduction neutralization test (PRNT50) using sera collected from the 26 recipients of BBV152/COVAXINTM against hCoV-19/India/20203522 (UK-variant) and hCoV27 19/India/2020Q111 (heterologous strain). A comparable neutralization activity of sera of the vaccinated individuals showed against UK-variant and the heterologous strain with similar efficiency, dispel the uncertainty of possible neutralization escape.

49: Sudden rise in COVID-19 case fatality among young and middle-aged adults in the south of Brazil after identification of the novel B. (P.1) SARS-CoV-2 strain: analysis of data from the state of Parana
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Posted 26 Mar 2021

Sudden rise in COVID-19 case fatality among young and middle-aged adults in the south of Brazil after identification of the novel B. (P.1) SARS-CoV-2 strain: analysis of data from the state of Parana
4,879 downloads medRxiv infectious diseases

Maria Helena Santos de Oliveira, Giuseppe Lippi, Brandon Michael Henry

Brazil is currently suffering a deadly surge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, which has been attributed to the spread of a new strain known as P.1 (B. In this investigation, we analyzed coronavirus disease 2019 (COVID-19) public health data from Parana, the largest state in southern half of Brazil, between September 1, 2020 and March 17, 2021, to evaluate recent trends in case fatality rates in different age groups. A total of 553,518 cases of SARS-CoV-2, 8,853 currently registered as fatal, were finally included in our analysis. All age groups showed either decline or stabilization of the case fatality rates (CFRs) between September 2020 and January 2021. In February 2021, an increase in CFR for almost all age groups could be instead observed. All groups above 20 years of age showed statistically significant increases in CFR when diagnosed in February 2021 as opposed to January 2021. Patients aged 20-29 years experienced a tripling of their CFR, from 0.04% to 0.13%, while those aged 30-39, 40-49, 50-59 experienced approximate CFR doubling. Individuals between 20 and 29 years of age whose diagnosis was made in February 2021 had an over 3-fold higher risk of death compared to those diagnosed in January 2021 (Risk Ratio (RR): 3.15 [95%CI: 1.52-6.53], p<0.01), while those aged 30-39, 40-49, 50-59 years experienced 93% (1.93 [95%CI:1.31-2.85], p<0.01), 110% (RR: 2.10 [95%CI:1.62-2.72], p<0.01), and 80% (RR: 1.80 [95%CI:1.50-2.16], p<0.01) increases in risk of death, respectively. Notably, the observed CFR increase coincided with the second consecutive month of declining number of diagnosed SARS-CoV-2 cases. Taken together, these preliminary findings suggest significant increases in CFR in young and middle-aged adults after identification of a novel SARS-CoV-2 strain circulating in Brazil, and this should raise public health alarms, including the need for more aggressive local and regional public health interventions and faster vaccination.

50: SARS-CoV-2 infection risk among unvaccinated is negatively associated with community-level vaccination rates
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Posted 29 Mar 2021

SARS-CoV-2 infection risk among unvaccinated is negatively associated with community-level vaccination rates
4,672 downloads medRxiv infectious diseases

Oren Milman, Idan Yelin, Noga Aharony, Rachel Katz, Esma Herzel, Amir Ben-Tov, Jacob Kuint, Sivan Gazit, Gabriel Chodick, Tal Patalon, Roy Kishony

Mass vaccination has the potential to curb the current COVID-19 pandemic by protecting vaccinees from the disease and possibly lowering the chance of transmission to unvaccinated individuals. The high effectiveness of the widely-administered BNT162b vaccine in preventing not only the disease but also infection suggests a potential for a population-level effect, critical for disease eradication. However, this putative effect is difficult to observe, especially in light of highly fluctuating spatio-temporal epidemic dynamics. Here, analyzing vaccination records and test results collected during a rapid vaccine rollout for a large population from 223 geographically defined communities, we find that the rates of vaccination in each community are highly correlated with a later decline in infections among a cohort of under 16 years old which are unvaccinated. These results provide observational evidence that vaccination not only protects individual vaccinees but also provides cross-protection to unvaccinated individuals in the community.

51: Dramatic drop of new SARS-CoV-2 infections among health care workers after the first dose of the BNT162b2 mRNA Covid-19 Vaccine
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Posted 26 Mar 2021

Dramatic drop of new SARS-CoV-2 infections among health care workers after the first dose of the BNT162b2 mRNA Covid-19 Vaccine
4,643 downloads medRxiv infectious diseases

Carlos Guijarro, Isabel Maria Galan, Elia Perez-Fernandez, Diana Cecily Martinez-Ponce, Maria J Goyanes, Virgilio Castilla, Maria Velasco

Objectives. To evaluate the effect of mRNA SARS-Cov-2 vaccination on the incidence of new SARS-CoV-2 infections in health care workers (HCW). Methods. The evolution of the incident rate of SARS-CoV-2 infection in a cohort of 2590 HCW after a mRNA SARS-CoV-2 vaccination, as compared to the rate in the community (n=170513). SARS-CoV-2 infections were microbiologically confirmed by an antigen, a CRP positive test, or both. Results. A total of 1820 HCW (70,3% of total) received the first dose of the vaccine between January 10-16, 2021), and 296 (11,4%) the following week. All of them completed vaccination 3 weeks later. New SARS-COV-2 infections in HCW declined by 62% at 2-4 weeks after the first dose of mRNA SARS-CoV-2 vaccination and virtually disappeared after the second dose of the vaccine. Vaccination rate was negligible for this time period in the community (<5%). The decline in the incident rate of SARS-COoV-2 new infection in HCW shortly after the administration of the first dose of the vaccine was strikingly higher than the reduction observed in the general population (p<0.001and became even more pronounced after the second dose of the vaccine (p<0.001). Conclusions. mRNA SARS-CoV-2 vaccination is associated with a dramatic decline in new SARS-CoV-2 infection among HCW, even before the administration of the second dose of the vaccine.

52: FDA-authorized COVID-19 vaccines are effective per real-world evidence synthesized across a multi-state health system
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Posted 18 Feb 2021

FDA-authorized COVID-19 vaccines are effective per real-world evidence synthesized across a multi-state health system
4,541 downloads medRxiv infectious diseases

Colin Pawlowski, Patrick J Lenehan, Arjun Puranik, Vineet Agarwal, AJ Venkatakrishnan, Michiel J.M. Niesen, John C. O Horo, Andrew D Badley, John Halamka, Venky Soundararajan

Large Phase 3 clinical trials of the two FDA-authorized COVID-19 vaccines, mRNA-1273 (Moderna) and BNT162b2 (Pfizer/BioNTech), have demonstrated efficacies of 94.1% (n = 30,420, 95% CI: 89.3-96.8) and 95% (n = 43,448, 95% CI: 90.3-97.6) in preventing symptomatic COVID-19, respectively. Given the ongoing vaccine rollout to healthcare personnel and residents of long-term care facilities, here we provide a preliminary assessment of real-world vaccination efficacy in 62,138 individuals from the Mayo Clinic and associated health system (Arizona, Florida, Minnesota, Wisconsin) between December 1st 2020 and February 8th 2021. Our retrospective analysis contrasts 31,069 individuals receiving at least one dose of either vaccine with 31,069 unvaccinated individuals who are propensity-matched based on demographics, location (zip code), and number of prior SARS-CoV-2 PCR tests. 8,041 individuals received two doses of a COVID-19 vaccine and were at risk for infection at least 36 days after their first dose. Administration of two COVID-19 vaccine doses was 88.7% effective in preventing SARS-CoV-2 infection (95% CI: 68.4-97.1%) with onset at least 36 days after the first dose. Furthermore, vaccinated patients who were subsequently diagnosed with COVID-19 had significantly lower 14-day hospital admission rates than propensity-matched unvaccinated COVID-19 patients (3.7% vs. 9.2%; Relative Risk: 0.4; p-value: 0.007). Building upon the previous randomized trials of these vaccines, this study demonstrates their real-world effectiveness in reducing the rates of SARS-CoV-2 infection and COVID-19 severity among individuals at highest risk for infection.

53: Inhaled budesonide in the treatment of early COVID-19 illness: a randomised controlled trial
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Posted 08 Feb 2021

Inhaled budesonide in the treatment of early COVID-19 illness: a randomised controlled trial
4,430 downloads medRxiv primary care research

Sanjay Ramakrishnan, Dan V Nicolau, Beverly Langford, Mahdi Mahdi, Helen Jeffers, Christine Mwasuku, Karolina Krassowska, Robin Fox, Ian Binnian, Victoria Glover, Stephen Bright, Christopher Butler, Jennifer L Cane, Andreas Halner, Philippa C Matthews, Louise E Donnelly, Jodie L Simpson, Jonathan R Baker, Nabil T Fadai, Stefan Peterson, Thomas Bengtsson, Peter J Barnes, Richard E K Russell, Mona Bafadhel

Background Multiple early hospital cohorts of coronavirus disease 2019 (COVID-19) showed that patients with chronic respiratory disease were significantly under-represented. We hypothesised that the widespread use of inhaled glucocorticoids was responsible for this finding and tested if inhaled glucorticoids would be an effective treatment for early COVID-19 illness. Methods We conducted a randomised, open label trial of inhaled budesonide, compared to usual care, in adults within 7 days of the onset of mild Covid-19 symptoms. The primary end point was COVID-19-related urgent care visit, emergency department assessment or hospitalisation. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment. Results 146 patients underwent randomisation. For the per protocol population (n=139), the primary outcome occurred in 10 participants and 1 participant in the usual care and budesonide arms respectively (difference in proportion 0.131, p=0.004). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was 8. Clinical recovery was 1 day shorter in the budesonide arm compared to the usual care arm (median of 7 days versus 8 days respectively, logrank test p=0.007). Proportion of days with a fever and proportion of participants with at least 1 day of fever was lower in the budesonide arm. Fewer participants randomised to budesonide had persistent symptoms at day 14 and day 28 compared to participants receiving usual care. Conclusion Early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery following early COVID-19 infection.

54: Are vaccines safe in patients with Long COVID? A prospective observational study.
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Posted 12 Mar 2021

Are vaccines safe in patients with Long COVID? A prospective observational study.
4,364 downloads medRxiv infectious diseases

David T Arnold, Alice Milne, Emma Samms, Louise Stadon, Nick A Maskell, Fergus W Hamilton

Introduction: Although the efficacy of SARS-CoV-2 vaccination to prevent symptomatic COVID-19 is well established, there are no published studies on the impact on symptoms in patients with Long Covid. Anecdotal reports have suggested both a potential benefit and worsening of symptoms post vaccination with the uncertainty leading to some vaccine hesitancy amongst affected individuals. Methods: Patients initially hospitalised with COVID-19 were prospectively recruited to an observational study with clinical follow-up at 3 months (June-July 2020) and 8 months (Dec 2020-Jan 2021) post-admission. Participants who received the Pfizer-BioNTech (BNT162b2) or Oxford-AstraZeneca (ChAdOx1 nCoV-19) vaccine between January to February 2021 were identified and matched 2:1 (in terms of 8-month symptoms) with participants from the same cohort who were unvaccinated. All were re-assessed at 1 month post vaccination (or matched timepoint for unvaccinated cohort). Validated quality of life (SF-36), mental wellbeing (WEMWBS) and ongoing symptoms were assessed at all timepoints. Formal statistical analysis compared the effect of vaccination on recent quality of life using baseline symptoms, age, and gender in linear regression. Results: Forty-four vaccinated participants were assessed at a median of 32 days (IQR 20-41) post vaccination with 22 matched unvaccinated participants. Most were highly symptomatic of Long Covid at 8 months (82% in both groups had at least 1 persistent symptom), with fatigue (61%), breathlessness (50%) and insomnia (38%) predominating. There was no significant worsening in quality-of-life or mental wellbeing metrics pre versus post vaccination. Nearly two-thirds (n=27) reported transient (<72hr duration) systemic effects (including fever, myalgia and headache). When compared to matched unvaccinated participants from the same cohort, those who had receive a vaccine had a small overall improvement in Long Covid symptoms, with a decrease in worsening symptoms (5.6% vaccinated vs 14.2% unvaccinated) and increase in symptom resolution (23.2% vaccinated vs 15.4% unvaccinated) (p=0.035). No difference in response was identified between Pfizer-BioNTech or Oxford-AstraZeneca vaccines. Conclusions: Receipt of vaccination with either an mRNA or adenoviral vector vaccine was not associated with a worsening of Long Covid symptoms, quality of life, or mental wellbeing. Individuals with prolonged COVID-19 symptoms should receive vaccinations as suggested by national guidance.

55: Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19
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Posted 29 Jun 2020

Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19
4,351 downloads bioRxiv immunology

Takuya Sekine, André Perez-Potti, Olga Rivera-Ballesteros, Kristoffer Stralin, Jean-Baptiste Gorin, Annika Olsson, Sian Llewellyn-Lacey, Habiba Kamal, Gordana Bogdanovic, Sandra Muschiol, David J. Wullimann, Tobias Kammann, Johanna Emgård, Tiphaine Parrot, Elin Folkesson, Olav Rooyackers, Lars I Eriksson, Anders Sönnerborg, Tobias Allander, Jan Albert, Morten Nielsen, Jonas Klingström, Sara Gredmark-Russ, Niklas K Björkström, Johan K. Sandberg, David A. Price, Hans-Gustaf Ljunggren, Soo Aleman, Marcus Buggert, Karolinska COVID-19 Study Group

SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. We systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in a large cohort of unexposed individuals as well as exposed family members and individuals with acute or convalescent COVID-19. Acute phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative family members and individuals with a history of asymptomatic or mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits robust memory T cell responses akin to those observed in the context of successful vaccines, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19 also in seronegative individuals. ### Competing Interest Statement The authors have declared no competing interest.

56: Household COVID-19 risk and in-person schooling
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Posted 01 Mar 2021

Household COVID-19 risk and in-person schooling
4,327 downloads medRxiv epidemiology

Justin Lessler, M. Kate Grabowski, Kyra H Grantz, Elena Badillo-Goicoechea, C. Jessica E. Metcalf, Carly Lupton-Smith, Andrew S Azman, Elizabeth A Stuart

In-person schooling has proved contentious and difficult to study throughout the SARS-CoV-2 pandemic. Data from a massive online survey in the United States indicates an increased risk of COVID-19-related outcomes among respondents living with a child attending school in-person. School-based mitigation measures are associated with significant reductions in risk, particularly daily symptoms screens, teacher masking, and closure of extra-curricular activities. With seven or more mitigation measures, the association between in-person schooling and COVID-19-related outcomes all but disappears. Teachers working outside the home were more likely to report COVID-19-related outcomes, but this association is similar to other occupations (e.g., healthcare, office work). In-person schooling is associated with household COVID-19 risk, but this risk can likely be controlled with properly implemented school-based mitigation measures. One sentence summaryLiving with children attending in-person school is linked to a higher risk of COVID-19 outcomes, which school-based interventions can mitigate.

57: Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity
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Posted 18 Feb 2021

Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity
4,295 downloads medRxiv infectious diseases

Wilfredo F Garcia-Beltran, Evan C. Lam, Kerri St. Denis, Adam D. Nitido, Zeidy H. Garcia, Blake M. Hauser, Jared Feldman, Maia N. Pavlovic, David J. Gregory, Mark C Poznansky, Alex Sigal, Aaron G. Schmidt, A. John Iafrate, Vivek Naranbhai, Alejandro Benjamin Balazs

Vaccination elicits immune responses capable of potently neutralizing SARS-CoV-2. However, ongoing surveillance has revealed the emergence of variants harboring mutations in spike, the main target of neutralizing antibodies. To understand the impact of these variants, we evaluated the neutralization potency of 99 individuals that received one or two doses of either BNT162b2 or mRNA-1273 vaccines against pseudoviruses representing 10 globally circulating strains of SARS-CoV-2. Five of the 10 pseudoviruses, harboring receptor-binding domain mutations, including K417N/T, E484K, and N501Y, were highly resistant to neutralization. Cross- neutralization of B.1.351 variants was comparable to SARS-CoV and bat-derived WIV1-CoV, suggesting that a relatively small number of mutations can mediate potent escape from vaccine responses. While the clinical impact of neutralization resistance remains uncertain, these results highlight the potential for variants to escape from neutralizing humoral immunity and emphasize the need to develop broadly protective interventions against the evolving pandemic.

58: SARS-CoV-2 lineage B.1.526 emerging in the New York region detected by software utility created to query the spike mutational landscape
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Posted 15 Feb 2021

SARS-CoV-2 lineage B.1.526 emerging in the New York region detected by software utility created to query the spike mutational landscape
4,229 downloads bioRxiv bioinformatics

Anthony P. West, Christopher O Barnes, Zhi Yang, Pamela Bjorkman

Wide-scale SARS-CoV-2 genome sequencing is critical to monitoring and understanding viral evolution during the ongoing pandemic. Variants first detected in the United Kingdom, South Africa, and Brazil have spread to multiple countries. We have developed a software tool, Variant Database (VDB), for quickly examining the changing landscape of spike mutations. Using this tool, we detected an emerging lineage of viral isolates in the New York region that shares mutations with previously reported variants. The most common sets of spike mutations in this lineage (now designated as B.1.526) are L5F, T95I, D253G, E484K or S477N, D614G, and A701V. This lineage appeared in late November 2020, and isolates from this lineage account for ~25% of coronavirus genomes sequenced and deposited from New York during February 2021.

59: Physical, cognitive and mental health impacts of COVID-19 following hospitalisation: a multi-centre prospective cohort study
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Posted 24 Mar 2021

Physical, cognitive and mental health impacts of COVID-19 following hospitalisation: a multi-centre prospective cohort study
4,226 downloads medRxiv infectious diseases

Rachael Andrea Evans, Hamish McAuley, Ewen M Harrison, Aarti Shikotra, Amisha Singapuri, Marco Sereno, Omer Elneima, Annemarie B Docherty, Nazir I Lone, Olivia C Leavy, Luke Daines, J Kenneth Baillie, Jeremy S Brown, Trudie Chalder, Anthony De Soyza, Nawar Diar Bakerly, Nicholas Easom, John R Geddes, Neil J Greening, Nick Hart, Liam G Heaney, Simon Heller, Luke Howard, Joseph Jacob, Gisli Jenkins, Caroline Jolley, Steven Kerr, Onn M Kon, Keir Lewis, Janet M Lord, Gerry P McCann, Stefan Neubauer, Peter J. M. Openshaw, Paul Pfeffer, Matthew Rowland, Malcolm Gracie Semple, Sally J Singh, Aziz Sheikh, David Thomas, Mark Toshner, James D Chalmers, Ling-Pei Ho, Alex Horsley, Michael Marks, Krisnah Poinasamy, Louise V Wain, Christopher E Brightling

BackgroundThe impact of COVID-19 on physical and mental health, and employment following hospitalisation is poorly understood. MethodsPHOSP-COVID is a multi-centre, UK, observational study of adults discharged from hospital with a clinical diagnosis of COVID-19 involving an assessment between two- and seven-months later including detailed symptom, physiological and biochemical testing. Multivariable logistic regression was performed for patient-perceived recovery with age, sex, ethnicity, body mass index (BMI), co-morbidities, and severity of acute illness as co-variates. Cluster analysis was performed using outcomes for breathlessness, fatigue, mental health, cognition and physical function. FindingsWe report findings of 1077 patients discharged in 2020, from the assessment undertaken a median 5 [IQR4 to 6] months later: 36% female, mean age 58 [SD 13] years, 69% white ethnicity, 27% mechanical ventilation, and 50% had at least two co-morbidities. At follow-up only 29% felt fully recovered, 20% had a new disability, and 19% experienced a health-related change in occupation. Factors associated with failure to recover were female, middle-age, white ethnicity, two or more co-morbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial and weakly related to acute severity. Four clusters were identified with different severities of mental and physical health impairment: 1) Very severe (17%), 2) Severe (21%), 3) Moderate with cognitive impairment (17%), 4) Mild (46%), with 3%, 7%, 36% and 43% feeling fully recovered, respectively. Persistent systemic inflammation determined by C-reactive protein was related to cluster severity, but not acute illness severity. InterpretationWe identified factors related to recovery from a hospital admission with COVID-19 and four different phenotypes relating to the severity of physical, mental, and cognitive health five months later. The implications for clinical care include the potential to stratify care and the need for a pro-active approach with wide-access to COVID-19 holistic clinical services. Funding: UKRI and NIHR

60: COVID Symptoms, Symptom Clusters, and Predictors for Becoming a Long-Hauler:Looking for Clarity in the Haze of the Pandemic
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Posted 05 Mar 2021

COVID Symptoms, Symptom Clusters, and Predictors for Becoming a Long-Hauler:Looking for Clarity in the Haze of the Pandemic
4,180 downloads medRxiv infectious diseases

Yong Huang, Melissa D. Pinto, Jessica L. Borelli, Milad Asgari Mehrabadi, Heather Abrihim, Nikil Dutt, Natalie Lambert, Erika L. Nurmi, Rana Chakraborty, Amir M. Rahmani, Charles A. Downs

Emerging data suggest that the effects of infection with SARS-CoV-2 are far reaching extending beyond those with severe acute disease. Specifically, the presence of persistent symptoms after apparent resolution from COVID-19 have frequently been reported throughout the pandemic by individuals labeled as "long-haulers". The purpose of this study was to assess for symptoms at days 0-10 and 61+ among subjects with PCR-confirmed SARS-CoV-2 infection. The University of California COvid Research Data Set (UC CORDS) was used to identify 1407 records that met inclusion criteria. Symptoms attributable to COVID-19 were extracted from the electronic health record. Symptoms reported over the previous year prior to COVID-19 were excluded, using nonnegative matrix factorization (NMF) followed by graph lasso to assess relationships between symptoms. A model was developed predictive for becoming a long-hauler based on symptoms. 27% reported persistent symptoms after 60 days. Women were more likely to become long-haulers, and all age groups were represented with those aged 50 {+/-} 20 years comprising 72% of cases. Presenting symptoms included palpitations, chronic rhinitis, dysgeusia, chills, insomnia, hyperhidrosis, anxiety, sore throat, and headache among others. We identified 5 symptom clusters at day 61+: chest pain-cough, dyspnea-cough, anxiety-tachycardia, abdominal pain-nausea, and low back pain-joint pain. Long-haulers represent a very significant public health concern, and there are no guidelines to address their diagnosis and management. Additional studies are urgently needed that focus on the physical, mental, and emotional impact of long-term COVID-19 survivors who become long-haulers.

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