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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 140,607 papers from 597,880 authors.

Most downloaded biology preprints, since beginning of last month

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21: Before the Surge: Molecular Evidence of SARS-CoV-2 in New York City Prior to the First Report
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Posted 11 Feb 2021

Before the Surge: Molecular Evidence of SARS-CoV-2 in New York City Prior to the First Report
9,108 downloads medRxiv infectious diseases

Matthew M. Hernandez, Ana S. Gonzalez-Reiche, Hala Alshammary, Shelcie Fabre, Zenab Khan, Adriana van De Guchte, Ajay Obla, Ethan Ellis, Mitchell J. Sullivan, Jessica Tan, Bremy Alburquerque, Juan Soto, Ching-Yi Wang, Shwetha Hara Sridhar, Ying-Chih Wang, Melissa Smith, Robert Sebra, Alberto E. Paniz-Mondolfi, Melissa R. Gitman, Michael D. Nowak, Carlos Cordon-Cardo, Marta Luksza, Florian Krammer, Harm van Bakel, Viviana Simon, Emilia Mia Sordillo

New York City (NYC) emerged as a coronavirus disease 2019 (COVID-19) epicenter in March 2020, but there is limited information regarding potentially unrecognized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections before the first reported case. We utilized a sample pooling strategy to screen for SARS-CoV-2 RNA in de-identified, respiratory pathogen-negative nasopharyngeal specimens from 3,040 patients across our NYC health system who were evaluated for respiratory symptoms or influenza-like illness during the first 10 weeks of 2020. We obtained complete SARS-CoV-2 genome sequences from samples collected between late February and early March. Additionally, we detected SARS-CoV-2 RNA in pooled specimens collected in the week ending 25 January 2020, indicating that SARS-CoV-2 caused sporadic infections in NYC a full month before the first officially documented case.

22: B.1.526 SARS-CoV-2 variants identified in New York City are neutralized by vaccine-elicited and therapeutic monoclonal antibodies
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Posted 24 Mar 2021

B.1.526 SARS-CoV-2 variants identified in New York City are neutralized by vaccine-elicited and therapeutic monoclonal antibodies
9,071 downloads bioRxiv immunology

Hao Zhou, Belinda M. Dcosta, Marie I. Samanovic, Mark J Mulligan, Nathaniel R Landau, Takuya Tada

DNA sequence analysis recently identified the novel SARS-CoV-2 variant B.1.526 that is spreading at an alarming rate in the New York City area. Two versions of the variant were identified, both with the prevalent D614G mutation in the spike protein together with four novel point mutations and with an E484K or S477N mutation in the receptor binding domain, raising concerns of possible resistance to vaccine-elicited and therapeutic antibodies. We report that convalescent sera and vaccine-elicited antibodies retain full neutralizing titer against the S477N B.1.526 variant and neutralize the E484K version with a modest 3.5-fold decrease in titer as compared to D614G. The E484K version was neutralized with a 12-fold decrease in titer by the REGN10933 monoclonal antibody but the combination cocktail with REGN10987 was fully active. The findings suggest that current vaccines and therapeutic monoclonal antibodies will remain protective against the B.1.526 variants. The findings further support the value of wide-spread vaccination.

23: Aerosol and surface stability of HCoV-19 (SARS-CoV-2) compared to SARS-CoV-1
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Posted 10 Mar 2020

Aerosol and surface stability of HCoV-19 (SARS-CoV-2) compared to SARS-CoV-1
8,348 downloads medRxiv infectious diseases

Neeltje van Doremalen, Trenton Bushmaker, Dylan H. Morris, Myndi G Holbrook, Amandine Gamble, Brandi N. Williamson, Azaibi Tamin, Jennifer L. Harcourt, Natalie J. Thornburg, Susan I. Gerber, James O. Lloyd-Smith, Emmie de Wit, Vincent Munster

To the EditorA novel human coronavirus, now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, referred to as HCoV-19 here) that emerged in Wuhan, China in late 2019 is now causing a pandemic1. Here, we analyze the aerosol and surface stability of HCoV-19 and compare it with SARS-CoV-1, the most closely related human coronavirus.2 We evaluated the stability of HCoV-19 and SARS-CoV-1 in aerosols and on different surfaces and estimated their decay rates using a Bayesian regression model (see Supplementary Appendix). All experimental measurements are reported as mean across 3 replicates.

24: Estimating the effective reproduction number of the 2019-nCoV in China
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Posted 29 Jan 2020

Estimating the effective reproduction number of the 2019-nCoV in China
8,174 downloads medRxiv infectious diseases

Zhidong Cao, Qingpeng Zhang, Xin Lu, Dirk Pfeiffer, Zhongwei Jia, Hongbing Song, Dajun Zeng

We estimate the effective reproduction number for 2019-nCoV based on the daily reported cases from China CDC. The results indicate that 2019-nCoV has a higher effective reproduction number than SARS with a comparable fatality rate. Article Summary LineThis modeling study indicates that 2019-nCoV has a higher effective reproduction number than SARS with a comparable fatality rate.

25: Impact of vaccination on SARS-CoV-2 cases in the community: a population-based study using the UK COVID-19 Infection Survey
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Posted 23 Apr 2021

Impact of vaccination on SARS-CoV-2 cases in the community: a population-based study using the UK COVID-19 Infection Survey
8,065 downloads medRxiv infectious diseases

Emma Pritchard, Philippa Matthews, Nicole Stoesser, David Eyre, Owen Gethings, Karina-Doris Vitha, Joel Jones, Thomas House, Harper VanSteenhouse, Iain Bell, John Bell, John Newton, Jeremy Farrar, Ian Diamond, Emma Rourke, Ruth Studley, Derrick W Crook, tim E peto, Ann Sarah Walker, Koen B Pouwels, Coronavirus Infection Survey team

Objectives: To assess the effectiveness of COVID-19 vaccination in preventing SARS-CoV-2 infection in the community. Design: Prospective cohort study. Setting: The UK population-representative longitudinal COVID-19 Infection Survey. Participants: 373,402 participants aged [&ge;]16 years contributing 1,610,562 RT-PCR results from nose and throat swabs between 1 December 2020 and 3 April 2021. Main outcome measures: New RT-PCR-positive episodes for SARS-CoV-2 overall, by self-reported symptoms, by cycle threshold (Ct) value (<30 versus [&ge;]30), and by gene positivity (compatible with the B.1.1.7 variant versus not). Results: Odds of new SARS-CoV-2 infection were reduced 65% (95% CI 60 to 70%; P<0.001) in those [&ge;]21 days since first vaccination with no second dose versus unvaccinated individuals without evidence of prior infection (RT-PCR or antibody). In those vaccinated, the largest reduction in odds was seen post second dose (70%, 95% CI 62 to 77%; P<0.001).There was no evidence that these benefits varied between Oxford-AstraZeneca and Pfizer-BioNTech vaccines (P>0.9).There was no evidence of a difference in odds of new SARS-CoV-2 infection for individuals having received two vaccine doses and with evidence of prior infection but not vaccinated (P=0.89). Vaccination had a greater impact on reducing SARS-CoV-2 infections with evidence of high viral shedding Ct<30 (88% reduction after two doses; 95% CI 80 to 93%; P<0.001) and with self-reported symptoms (90% reduction after two doses; 95% CI 82 to 94%; P<0.001); effects were similar for different gene positivity patterns. Conclusion: Vaccination with a single dose of Oxford-AstraZeneca or Pfizer-BioNTech vaccines, or two doses of Pfizer-BioNTech, significantly reduced new SARS-CoV-2 infections in this large community surveillance study. Greater reductions in symptomatic infections and/or infections with a higher viral burden are reflected in reduced rates of hospitalisations/deaths, but highlight the potential for limited ongoing transmission from asymptomatic infections in vaccinated individuals. Registration: The study is registered with the ISRCTN Registry, ISRCTN21086382.

26: Antibody evasion by the Brazilian P.1 strain of SARS-CoV-2
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Posted 15 Mar 2021

Antibody evasion by the Brazilian P.1 strain of SARS-CoV-2
7,834 downloads bioRxiv microbiology

Wanwisa - Dejnirattisai, Daming - Zhou, Piyada - Supasa, Chang - Liu, Alexander J Mentzer, Helen M Ginn, Yuguang - Zhao, Helen M E Duyvesteyn, Aekkachai Tuekprakhon, Rungtiwa Nutalai, Beibei - Wang, Guido C. Paesen, Cesar - Lopez-Camacho, Jose - Slon-Campos, Thomas Walter, Donal Skelly, Sue Ann Costa Clemens, Felipe Gomes Naveca, Valdinete - Nascimento, Fernanda - Nascimento, Cristiano Fernandes da Costa, Paola Cristina Resende, Alex Pauvolid-Correa, Marilda M Siqueira, Christina Dold, Robert - Levin, Tao - Dong, Andrew J. Pollard, Julian C Knight, Derrick Crook, Teresa Lambe, Elizabeth Clutterbuck, Sagida Bibi, Amy Flaxman, Mustapha Bittaye, Sandra Belij-rammerstorfer, Sarah Gilbert, Miles W Carroll, Paul - Klenerman, Eleanor - Barnes, Susanna J. Dunachie, Neil G Paterson, Mark A. Williams, David R. Hall, Rubin Hulswit, Thomas A. Bowden, Elizabeth E Fry, Juthathip Mongkolsapaya, Jingshan Ren, David I. Stuart, Gavin R Screaton

Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations: P.1 from Brazil, B.1.351 from South Africa and B.1.1.7 from the UK (12, 10 and 9 changes in the spike respectively). All have mutations in the ACE2 binding site with P.1 and B.1.351 having a virtually identical triplet: E484K, K417N/T and N501Y, which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine induced antibody responses than B.1.351 suggesting that changes outside the RBD impact neutralisation. Monoclonal antibody 222 neutralises all three variants despite interacting with two of the ACE2 binding site mutations, we explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies.

27: Protection of previous SARS-CoV-2 infection is similar to that of BNT162b2 vaccine protection: A three-month nationwide experience from Israel
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Posted 24 Apr 2021

Protection of previous SARS-CoV-2 infection is similar to that of BNT162b2 vaccine protection: A three-month nationwide experience from Israel
7,776 downloads medRxiv epidemiology

Yair Goldberg, Micha Mandel, Yonatan Woodbridge, Ronen Fluss, Ilya Novikov, Rami Yaari, Arnona Ziv, Laurence Freedman, Amit Huppert

Worldwide shortage of vaccination against SARS-CoV-2 infection while the pandemic is still uncontrolled leads many states to the dilemma whether or not to vaccinate previously infected persons. Understanding the level of protection of previous infection compared to that of vaccination is critical for policy making. We analyze an updated individual-level database of the entire population of Israel to assess the protection efficacy of both prior infection and vaccination in preventing subsequent SARS-CoV-2 infection, hospitalization with COVID-19, severe disease, and death due to COVID-19. Vaccination was highly effective with overall estimated efficacy for documented infection of 92.8% (CI: [92.6, 93.0]); hospitalization 94.2% (CI: [93.6, 94.7]); severe illness 94.4% (CI: [93.6, 95.0]); and death 93.7% (CI: [92.5, 94.7]). Similarly, the overall estimated level of protection from prior SARS-CoV-2 infection for documented infection is 94.8% (CI: [94.4, 95.1]); hospitalization 94.1% (CI: [91.9, 95.7]); and severe illness 96.4% (CI: [92.5, 98.3]). Our results question the need to vaccinate previously-infected individuals.

28: Model-based estimation of transmissibility and reinfection of SARS-CoV-2 P.1 variant
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Posted 05 Mar 2021

Model-based estimation of transmissibility and reinfection of SARS-CoV-2 P.1 variant
7,571 downloads medRxiv infectious diseases

Renato M. Coutinho, Flavia Maria Darci Marquitti, Leonardo Souto Ferreira, Marcelo Eduardo Borges, Rafael Lopes Paixao da Silva, Otavio Canton, Tatiana P. Portella, Silas Poloni Lyra, Caroline Franco, Mateusz M. Plucinski, Fernanda C. Lessa, Antonio D Silva, Roberto A. Kraenkel, Maria Amelia S M Veras, Paulo Inacio Prado

The variant of concern (VOC) P.1 emerged in the Amazonas state (Brazil) in November-2020. It contains a constellation of mutations, ten of them in the spike protein. Consequences of these specific mutations at the population level have been little studied so far, despite the detection of P.1 variant in 26 countries, with local transmission in at least four other countries in the Americas and Europe. Here, we estimate P.1's transmissibility and reinfection using a model-based approach, by fitting data from the Brazilian national health surveillance of hospitalized individuals and frequency of the P.1 variant in Manaus from December 2020 to February 2021, when the city was devastated by four times more cases than in the previous peak (April 2020). The new variant was found to be about 2.6 times more transmissible (95\% Confidence Interval (CI): 2.4--2.8) than previous circulating variant(s). The city already had a high prevalence of individuals previously affected by the SARS-CoV-2 virus (estimated as 78\%, CI:73--83\%), and the fitted model attributed 28\% of the cases during the period to reinfections by the variant P.1. Our estimates rank P.1 as the most transmissible among the current identified SARS-CoV-2 VOCs, posing a serious threat and requiring urgent measures to control its global spread.

29: Designing a high-resolution, LEGO-based microscope for an educational setting
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Posted 11 Apr 2021

Designing a high-resolution, LEGO-based microscope for an educational setting
7,407 downloads bioRxiv scientific communication and education

Bart Eduard Vos, Emil Betz Blesa, Timo Betz

Microscopy is an essential tool in many fields of science. However, due to their costs and fragility, the usage of microscopes is limited in classroom settings and nearly absent at home. In this article we present the construction of a microscope using LEGO bricks and low-cost, easily available lenses. We demonstrate that the obtained magnification and resolution are sufficient to resolve micrometer-sized objects and propose a series of experiments that explore various biophysical principles. Finally, a study with students in the age range of 9 to 13 shows that the understanding of microscopy increases significantly after working with the LEGO microscope.

30: Neutralization of spike 69/70 deletion, E484K, and N501Y SARS-CoV-2 by BNT162b2 vaccine-elicited sera
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Posted 27 Jan 2021

Neutralization of spike 69/70 deletion, E484K, and N501Y SARS-CoV-2 by BNT162b2 vaccine-elicited sera
7,360 downloads bioRxiv microbiology

Xuping Xie, Yang Liu, Jianying Liu, Xianwen Zhang, Jing Zou, Camila R. Fontes-Garfias, Hongjie Xia, Kena A. Swanson, Mark Cutler, David Cooper, Vineet D Menachery, Scott Weaver, Philip Dormitzer, Pei-Yong Shi

We engineered three SARS-CoV-2 viruses containing key spike mutations from the newly emerged United Kingdom (UK) and South African (SA) variants: N501Y from UK and SA; 69/70-deletion+N501Y+D614G from UK; and E484K+N501Y+D614G from SA. Neutralization geometric mean titers (GMTs) of twenty BTN162b2 vaccine-elicited human sera against the three mutant viruses were 0.81- to 1.46-fold of the GMTs against parental virus, indicating small effects of these mutations on neutralization by sera elicited by two BNT162b2 doses.

31: Indoor transmission of SARS-CoV-2
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Posted 07 Apr 2020

Indoor transmission of SARS-CoV-2
7,292 downloads medRxiv infectious diseases

Hua Qian, Te Miao, Li Liu, Xiaohong Zheng, Danting Luo, Yuguo Li

BackgroundBy early April 2020, the COVID-19 pandemic had infected nearly one million people and had spread to nearly all countries worldwide. It is essential to understand where and how SARS-CoV-2 is transmitted. MethodsCase reports were extracted from the local Municipal Health Commissions of 320 prefectural cities (municipalities) in China, not including Hubei province, between 4 January and 11 February 2020. We identified all outbreaks involving three or more cases and reviewed the major characteristics of the enclosed spaces in which the outbreaks were reported and associated indoor environmental issues. ResultsThree hundred and eighteen outbreaks with three or more cases were identified, involving 1245 confirmed cases in 120 prefectural cities. We divided the venues in which the outbreaks occurred into six categories: homes, transport, food, entertainment, shopping, and miscellaneous. Among the identified outbreaks, 53{middle dot}8% involved three cases, 26{middle dot}4% involved four cases, and only 1{middle dot}6% involved ten or more cases. Home outbreaks were the dominant category (254 of 318 outbreaks; 79{middle dot}9%), followed by transport (108; 34{middle dot}0%; note that many outbreaks involved more than one venue category). Most home outbreaks involved three to five cases. We identified only a single outbreak in an outdoor environment, which involved two cases. ConclusionsAll identified outbreaks of three or more cases occurred in an indoor environment, which confirms that sharing indoor space is a major SARS-CoV-2 infection risk. FundingThe work was supported by the Research Grants Council of Hong (no 17202719, C7025-16G), and National Natural Science Foundation of China (no 41977370).

32: The infection fatality rate of COVID-19 inferred from seroprevalence data
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Posted 19 May 2020

The infection fatality rate of COVID-19 inferred from seroprevalence data
7,173 downloads medRxiv infectious diseases

John Ioannidis

Objective To estimate the infection fatality rate of coronavirus disease 2019 (COVID-19) from data of seroprevalence studies. Methods Population studies with sample size of at least 500 and published as peer-reviewed papers or preprints as of July 11, 2020 were retrieved from PubMed, preprint servers, and communications with experts. Studies on blood donors were included, but studies on healthcare workers were excluded. The studies were assessed for design features and seroprevalence estimates. Infection fatality rate was estimated from each study dividing the number of COVID-19 deaths at a relevant time point by the number of estimated people infected in each relevant region. Correction was also attempted accounting for the types of antibodies assessed. Secondarily, results from national studies were also examined from preliminary press releases and reports whenever a country had no other data presented in full papers of preprints. Results 36 studies (43 estimates) were identified with usable data to enter into calculations and another 7 preliminary national estimates were also considered for a total of 50 estimates. Seroprevalence estimates ranged from 0.222% to 47%. Infection fatality rates ranged from 0.00% to 1.63% and corrected values ranged from 0.00% to 1.31%. Across 32 different locations, the median infection fatality rate was 0.27% (corrected 0.24%). Most studies were done in pandemic epicenters with high death tolls. Median corrected IFR was 0.10% in locations with COVID-19 population mortality rate less than the global average (<73 deaths per million as of July 12, 2020), 0.27% in locations with 73-500 COVID-19 deaths per million, and 0.90% in locations exceeding 500 COVID-19 deaths per million. Among people <70 years old, infection fatality rates ranged from 0.00% to 0.57% with median of 0.05% across the different locations (corrected median of 0.04%). Conclusions The infection fatality rate of COVID-19 can vary substantially across different locations and this may reflect differences in population age structure and case-mix of infected and deceased patients as well as multiple other factors. Estimates of infection fatality rates inferred from seroprevalence studies tend to be much lower than original speculations made in the early days of the pandemic.

33: Inhaled budesonide for COVID-19 in people at higher risk of adverse outcomes in the community: interim analyses from the PRINCIPLE trial
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Posted 12 Apr 2021

Inhaled budesonide for COVID-19 in people at higher risk of adverse outcomes in the community: interim analyses from the PRINCIPLE trial
6,721 downloads medRxiv primary care research

The PRINCIPLE Trial Collaborative Group, Ly-Mee Yu, Mona Bafadhel, Jienchi Dorward, Gail Hayward, Benjamin R Saville, Oghenekome Gbinigie, Oliver van Hecke, Emma Ogburn, Philip H Evans, Nicholas PB Thomas, Mahendra G Patel, Nicholas Berry, Michelle A. Detry, Christina T. Saunders, Mark Fitzgerald, Victoria Harris, Simon de Lusignan, Monique I Andersson, Peter J Barnes, Richard EK Russell, Dan V Nicolau, Sanjay Ramakrishnan, FD Richard Hobbs, Christopher C Butler

BACKGROUND Inhaled budesonide has shown efficacy for treating COVID-19 in the community but has not yet been tested in effectiveness trials. METHODS We performed a multicenter, open-label, multi-arm, adaptive platform randomized controlled trial involving people aged [&ge;]65 years, or [&ge;]50 years with comorbidities, and unwell [&le;]14 days with suspected COVID-19 in the community (PRINCIPLE). Participants were randomized to usual care, usual care plus inhaled budesonide (800g twice daily for 14 days), or usual care plus other interventions. The co-primary endpoints are time to first self-reported recovery, and hospitalization/death related to COVID-19, both measured over 28 days from randomisation and analysed using Bayesian models. RESULTS The trial opened on April 2, 2020. Randomization to inhaled budesonide began on November 27, 2020 and was stopped on March 31, 2021 based on an interim analysis using data from March 4, 2021. Here, we report updated interim analysis data from March 25, 2021, at which point the trial had randomized 4663 participants with suspected COVID-19. Of these, 2617 (56.1%) tested SARS-CoV-2 positive and contributed data to this interim budesonide primary analysis; 751 budesonide, 1028 usual care and 643 to other interventions. Time to first self-reported recovery was shorter in the budesonide group compared to usual care (hazard ratio 1.208 [95% BCI 1.076 - 1.356], probability of superiority 0.999, estimated benefit [95% BCI] of 3.011 [1.134 - 5.41] days). Among those in the interim budesonide primary analysis who had the opportunity to contribute data for 28 days follow up, there were 59/692 (8.5%) COVID-19 related hospitalizations/deaths in the budesonide group vs 100/968 (10.3%) in the usual care group (estimated percentage benefit, 2.1% [95% BCI -0.7% - 4.8%], probability of superiority 0.928). CONCLUSIONS In this updated interim analysis, inhaled budesonide reduced time to recovery by a median of 3 days in people with COVID-19 with risk factors for adverse outcomes. Once 28 day follow up is complete for all participants randomized to budesonide, final analyses of time to recovery and hospitalization/death will be published. (Funded by the National Institute of Health Research/ United Kingdom Research Innovation [MC_PC_19079]; PRINCIPLE ISRCTN number, ISRCTN86534580.)

34: Characterizing Long COVID in an International Cohort: 7 Months of Symptoms and Their Impact
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Posted 26 Dec 2020

Characterizing Long COVID in an International Cohort: 7 Months of Symptoms and Their Impact
6,563 downloads medRxiv infectious diseases

Hannah E Davis, Gina S. Assaf, Lisa McCorkell, Hannah Wei, Ryan J Low, Yochai Reem, Signe Redfield, Jared P Austin, Athena Akrami

Objective. To characterize the symptom profile and time course in patients with Long COVID, along with the impact on daily life, work, and return to baseline health. Design. International web-based survey of suspected and confirmed COVID-19 cases with illness lasting over 28 days and onset prior to June 2020. Setting. Survey distribution via online COVID-19 support groups and social media Participants. 3,762 respondents from 56 countries completed the survey. 1166 (33.7%) were 40-49 years old, 937 (27.1%) were 50-59 years old, and 905 (26.1%) were 30-39 years old. 2961 (78.9%) were women, 718 (19.1%) were men, and 63 (1.7%) were nonbinary. 8.4% reported being hospitalized. 27% reported receiving a laboratory-confirmed diagnosis of COVID-19. 96% reported symptoms beyond 90 days. Results. Prevalence of 205 symptoms in 10 organ systems was estimated in this cohort, with 66 symptoms traced over seven months. Respondents experienced symptoms in an average of 9.08 (95% confidence interval 9.04 to 9.13) organ systems. The most frequent symptoms reported after month 6 were: fatigue (77.7%, 74.9% to 80.3%), post-exertional malaise (72.2%, 69.3% to 75.0%), and cognitive dysfunction (55.4%, 52.4% to 58.8%). These three symptoms were also the three most commonly reported overall. In those who recovered in less than 90 days, the average number of symptoms peaked at week 2 (11.4, 9.4 to 13.6), and in those who did not recover in 90 days, the average number of symptoms peaked at month 2 (17.2, 16.5 to 17.8). Respondents with symptoms over 6 months experienced an average of 13.8 (12.7 to 14.9) symptoms in month 7. 94.9% (94.1% to 95.6%) experienced relapses, with exercise, physical or mental activity, and stress as the main triggers. 86.7% (85.6% to 92.5%) of unrecovered respondents were experiencing fatigue at the time of survey, compared to 44.7% (38.5% to 50.5%) of recovered respondents. 45.2% (42.9% to 47.2%) reported requiring a reduced work schedule compared to pre-illness and 22.3% (20.5% to 24.3%) were not working at the time of survey due to their health conditions. Conclusions. Patients with Long COVID report prolonged multisystem involvement and significant disability. Most had not returned to previous levels of work by 6 months. Many patients are not recovered by 7 months, and continue to experience significant symptom burden. Significance Statement. Results from our international online survey of 3,762 individuals with suspected or confirmed COVID-19 illness suggest that Long COVID is composed of heterogeneous post-acute infection sequelae that often affect multiple organ systems, with impact on functioning and quality of life ranging from mild to severe. This study represents the largest collection of symptoms identified in the Long COVID population to date, and is the first to quantify individual symptom trajectory over time, for 7 months. Three clusters of symptoms were quantified, each with different morphologies over time. The clusters of symptoms that persist longest include a combination of the neurological/cognitive and systemic symptoms. The reduced work capacity because of cognitive dysfunction, in addition to other debilitating symptoms, translated into the loss of hours, jobs, and ability to work relative to pre-illness levels.

35: Anti-Spike protein assays to determine post-vaccination antibody levels: a head-to-head comparison of five quantitative assays
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Posted 08 Mar 2021

Anti-Spike protein assays to determine post-vaccination antibody levels: a head-to-head comparison of five quantitative assays
6,556 downloads medRxiv infectious diseases

Thomas Perkmann, Nicole Perkmann-Nagele, Thomas Koller, Patrick Mucher, Astrid Radakovics, Rodrig Marculescu, Michael Wolzt, Oswald F Wagner, Christoph J Binder, Helmuth Haslacher

Background Reliable quantification of the antibody response to SARS-CoV-2 vaccination is highly relevant for identifying possible vaccine failure and estimating the time of protection. Therefore, we aimed to evaluate the performance of five different Anti-SARS-CoV-2 antibody assays regarding the quantification of anti-spike (S) antibodies induced after a single dose of BNT162b2. Methods Sera of n=69 SARS-CoV-2 naive individuals 21+/-1 days after vaccination with BNT162b2 (Pfizer/BioNTech) were tested using the following quantitative SARS-CoV-2 antibody assays: Roche S total antibody, DiaSorin trimeric spike IgG, DiaSorin S1/S2 IgG, Abbott II IgG, and Serion/Virion IgG. Test agreement was assessed by Passing-Bablok regression. Results were further compared to the percent inhibition calculated from a surrogate virus neutralization test (sVNT) by correlation and ROC (receiver-operating-characteristics) analysis. Results Individual values were distributed over several orders of magnitude for all assays evaluated. Although the assays were in good overall agreement (rho=0.80-0.94), Passing-Bablok regression revealed systematic and proportional differences, which could not be eliminated by converting the results to BAU/mL as suggested by the manufacturers. 7 (10%) individuals had a negative sVNT results (i.e. <30% inhibition). These samples were reliably identified by most assays and yielded low binding antibody levels (ROC-AUCs 0.84-0.93). Conclusions Although all assays evaluated showed good correlation, readings from different assays were not interchangeable, even when converted to BAU/mL using the WHO international standard for SARS-CoV-2 immunoglobulin. This highlights the need for further standardization of SARS-CoV-2 serology.

36: Glucocorticoids and B Cell Depleting Agents Substantially Impair Immunogenicity of mRNA Vaccines to SARS-CoV-2
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Posted 07 Apr 2021

Glucocorticoids and B Cell Depleting Agents Substantially Impair Immunogenicity of mRNA Vaccines to SARS-CoV-2
6,482 downloads medRxiv infectious diseases

Parakkal Deepak, Wooseob Kim, Michael A Paley, Monica Yang, Alexander B Carvidi, Alia A El-Qunni, Alem Haile, Katherine Huang, Baylee Kinnett, Mariel J. Liebeskind, Zhuoming Liu, Lily E McMorrow, Diane Paez, Dana C Perantie, Rebecca E Schriefer, Shannon Sides, Mahima Thapa, Mate Gergely, Suha Abushamma, Micahel Kelbert, Lynne Mitchell, Billy Nix, Jonathan D Graf, Kimberly E Taylor, Salim Chahin, Matthew A Ciorba, Patricia A Katz, Mehrdad Matloubian, Jane A O'Halloran, Rachel M Presti, Gregory F Wu, Sean P. J. Whelan, William J Buchser, Lianne S Gensler, Mary C Nakamura, Ali H. Ellebedy, Alfred HJ Kim

BackgroundIndividuals with chronic inflammatory diseases (CID) are frequently treated with immunosuppressive medications that can increase their risk of severe COVID-19. While novel mRNA-based SARS-CoV-2 vaccination platforms provide robust protection in immunocompetent individuals, the immunogenicity in CID patients on immunosuppression is not well established. Therefore, determining the effectiveness of SARS-CoV-2 vaccines in the setting of immunosuppression is essential to risk-stratify CID patients with impaired protection and provide clinical guidance regarding medication management. MethodsWe conducted a prospective assessment of mRNA-based vaccine immunogenicity in 133 adults with CIDs and 53 immunocompetent controls. Blood from participants over 18 years of age was collected before initial immunization and 1-2 weeks after the second immunization. Serum anti-SARS-CoV-2 spike (S) IgG+ binding, neutralizing antibody titers, and circulating S-specific plasmablasts were quantified to assess the magnitude and quality of the humoral response following vaccination. ResultsCompared to immunocompetent controls, a three-fold reduction in anti-S IgG titers (P=0.009) and SARS-CoV-2 neutralization (p<0.0001) were observed in CID patients. B cell depletion and glucocorticoids exerted the strongest effect with a 36- and 10-fold reduction in humoral responses, respectively (p<0.0001). Janus kinase inhibitors and antimetabolites, including methotrexate, also blunted antibody titers in multivariate regression analysis (P<0.0001, P=0.0023, respectively). Other targeted therapies, such as TNF inhibitors, IL-12/23 inhibitors, and integrin inhibitors, had only modest impacts on antibody formation and neutralization. ConclusionsCID patients treated with immunosuppressive therapies exhibit impaired SARS-CoV-2 vaccine-induced immunity, with glucocorticoids and B cell depletion therapy more severely impeding optimal responses.

37: Uncanny similarity of unique inserts in the 2019-nCoV spike protein to HIV-1 gp120 and Gag
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Posted 31 Jan 2020

Uncanny similarity of unique inserts in the 2019-nCoV spike protein to HIV-1 gp120 and Gag
6,061 downloads bioRxiv evolutionary biology

Prashant Pradhan, Ashutosh Kumar Pandey, Akhilesh Mishra, Parul Gupta, Praveen Kumar Tripathi, Manoj Balakrishnan Menon, James Gomes, Perumal Vivekanandan, Bishwajit Kundu

This paper has been withdrawn by its authors. They intend to revise it in response to comments received from the research community on their technical approach and their interpretation of the results. If you have any questions, please contact the corresponding author.

38: Negligible impact of SARS-CoV-2 variants on CD4+ and CD8+ T cell reactivity in COVID-19 exposed donors and vaccinees.
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Posted 01 Mar 2021

Negligible impact of SARS-CoV-2 variants on CD4+ and CD8+ T cell reactivity in COVID-19 exposed donors and vaccinees.
5,961 downloads bioRxiv immunology

Alison Tarke, John Sidney, Nils Methot, Jennifer M. Dan, Benjamin Goodwin, Paul Rubiro, Aaron Sutherland, Ricardo da Silva Antunes, April Frazier, Stephen A Rawlings, Davey M Smith, Bjoern Peters, Richard H. Scheuermann, Daniela Weiskopf, Shane Crotty, Alba Grifoni, Alessandro Sette

The emergence of SARS-CoV-2 variants highlighted the need to better understand adaptive immune responses to this virus. It is important to address whether also CD4+ and CD8+ T cell responses are affected, because of the role they play in disease resolution and modulation of COVID-19 disease severity. Here we performed a comprehensive analysis of SARS-CoV-2-specific CD4+ and CD8+ T cell responses from COVID-19 convalescent subjects recognizing the ancestral strain, compared to variant lineages B.1.1.7, B.1.351, P.1, and CAL.20C as well as recipients of the Moderna (mRNA-1273) or Pfizer/BioNTech (BNT162b2) COVID-19 vaccines. Similarly, we demonstrate that the sequences of the vast majority of SARS-CoV-2 T cell epitopes are not affected by the mutations found in the variants analyzed. Overall, the results demonstrate that CD4+ and CD8+ T cell responses in convalescent COVID-19 subjects or COVID-19 mRNA vaccinees are not substantially affected by mutations found in the SARS-CoV-2 variants.

39: Anti-SARS-CoV-2 activity of Andrographis paniculata extract and its major component Andrographolide in human lung epithelial cells and cytotoxicity evaluation in major organ cell representatives
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Posted 08 Dec 2020

Anti-SARS-CoV-2 activity of Andrographis paniculata extract and its major component Andrographolide in human lung epithelial cells and cytotoxicity evaluation in major organ cell representatives
5,903 downloads bioRxiv microbiology

Khanit Sa-ngiamsuntorn, Ampa Suksatu, Yongyut Pewkliang, Piyanoot Thongsri, Phongthon Kanjanasirirat, Suwimon Manopwisedjaroen, Sitthivut Charoensutthivarakul, Patompon Wongtrakoongate, Supaporn Pitiporn, Phisit Khemawoot, Somchai Chutipongtanate, Suparerk Borwornpinyo, Arunee Thitithanyanont, Suradej Hongeng

The coronavirus disease 2019 (COVID-19) caused by a novel coronavirus (SARS-CoV-2) has become a major health problem affecting more than fifty million cases with over one million deaths globally. The effective antivirals are still lacking. Here, we optimized a high-content imaging platform and the plaque assay for viral output study using the legitimate model of human lung epithelial cells, Calu-3, to determine anti-SARS-CoV-2 activity of Andrographis paniculata extract and its major component andrographolide. SARS-CoV-2 at 25TCID50 was able to reach the maximal infectivity of 95% in Calu-3 cells. Post-infection treatment of A. paniculata and andrographolide in SARS-CoV-2 infected Calu-3 cells significantly inhibited the production of infectious virions with the IC50 of 0.036 g/mL and 0.034 M, respectively, as determined by plaque assay. The cytotoxicity profile developed over the cell line representatives of major organs, including liver (HepG2 and imHC), kidney (HK-2), intestine (Caco-2), lung (Calu-3), and brain (SH-SY5Y), showed the CC50 of >100 g/mL for A. paniculata extract and 13.2-81.5 M for andrographolide, respectively, corresponding to the selectivity index over 380. In conclusion, this study provided experimental evidence in favor of A. paniculata and andrographolide for further development as a monotherapy or in combination with other effective drugs against SARS-CoV-2 infection.

40: Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): preliminary results of a randomised, controlled, open-label, platform trial
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Posted 11 Feb 2021

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): preliminary results of a randomised, controlled, open-label, platform trial
5,667 downloads medRxiv infectious diseases

Peter Horby, Mark Campbell, Natalie Staplin, Enti Spata, Jonathan R Emberson, Guilherme Pessoa-Amorim, Leon Peto, Christopher E Brightling, Rahuldeb Sarkar, Koshy Thomas, Vandana Jeebun, Abdul Ashish, Redmond Tully, David Chadwick, Muhammad Sharafat, Richard Stewart, Banu Rudran, J. Kenneth Baillie, Maya H Buch, Lucy C Chappell, Jeremy N Day, Saul N Faust, Thomas Jaki, Katie Jeffery, Edmund Juszczak, Wei Shen Lim, Alan Montgomery, Andrew Mumford, Kathryn Rowan, Guy Thwaites, Marion Mafham, Richard Haynes, Martin J Landray

Findings: Between 23 April 2020 and 25 January 2021, 4116 adults were included in the assessment of tocilizumab, including 562 (14%) patients receiving invasive mechanical ventilation, 1686 (41%) receiving non-invasive respiratory support, and. 1868 (45%) receiving no respiratory support other than oxygen. Median CRP was 143 [IQR 107-205] mg/L and 3385 (82%) patients were receiving systemic corticosteroids at randomisation. Overall, 596 (29%) of the 2022 patients allocated tocilizumab and 694 (33%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0.86; 95% confidence interval [CI] 0.77-0.96; p=0.007). Consistent results were seen in all pre-specified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital alive within 28 days (54% vs. 47%; rate ratio 1.23; 95% CI 1.12-1.34; p<0.0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (33% vs. 38%; risk ratio 0.85; 95% CI 0.78-0.93; p=0.0005). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes regardless of the level of respiratory support received and in addition to the use of systemic corticosteroids.

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