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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 136,092 papers from 580,432 authors.

Most downloaded biology preprints, since beginning of last month

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1: More than 50 Long-term effects of COVID-19: a systematic review and meta-analysis
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Posted 29 Jan 2021

More than 50 Long-term effects of COVID-19: a systematic review and meta-analysis
24,114 downloads medRxiv infectious diseases

Sandra Lopez-Leon, Talia Wegman-Ostrosky, Carol Perelman, Rosalinda Sepulveda, Paulina A Rebolledo, Angelica Cuapio, Sonia Villapol

COVID-19, caused by SARS-CoV-2, can involve sequelae and other medical complications that last weeks to months after initial recovery, which has come to be called Long-COVID or COVID long-haulers. This systematic review and meta-analysis aims to identify studies assessing long-term effects of COVID-19 and estimates the prevalence of each symptom, sign, or laboratory parameter of patients at a post-COVID-19 stage. LitCOVID (PubMed and Medline) and Embase were searched by two independent researchers. All articles with original data for detecting long-term COVID-19 published before 1st of January 2021 and with a minimum of 100 patients were included. For effects reported in two or more studies, meta-analyses using a random-effects model were performed using the MetaXL software to estimate the pooled prevalence with 95% CI. Heterogeneity was assessed using I2 statistics. The Preferred Reporting Items for Systematic Reviewers and Meta-analysis (PRISMA) reporting guideline was followed. A total of 18,251 publications were identified, of which 15 met the inclusion criteria. The prevalence of 55 long-term effects was estimated, 21 meta-analyses were performed, and 47,910 patients were included. The follow-up time ranged from 15 to 110 days post-viral infection. The age of the study participants ranged between 17 and 87 years. It was estimated that 80% (95% CI 65-92) of the patients that were infected with SARS-CoV-2 developed one or more long-term symptoms. The five most common symptoms were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%). All meta-analyses showed medium (n=2) to high heterogeneity (n=13). In order to have a better understanding, future studies need to stratify by sex, age, previous comorbidities, severity of COVID-19 (ranging from asymptomatic to severe), and duration of each symptom. From the clinical perspective, multi-disciplinary teams are crucial to developing preventive measures, rehabilitation techniques, and clinical management strategies with whole-patient perspectives designed to address long COVID-19 care.

2: 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
18,927 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.

3: SARS-CoV-2 antibodies detected in human breast milk post-vaccination
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Posted 02 Mar 2021

SARS-CoV-2 antibodies detected in human breast milk post-vaccination
17,922 downloads medRxiv infectious diseases

Jill K. Baird, Shawn M. Jensen, Walter J. Urba, Bernard A. Fox, Jason R. Baird

Importance: The SARS-CoV-2 pandemic has infected over a hundred million people worldwide, with almost 2.5 million deaths at the date of this publication. In the United States, Pfizer-BioNTech and Moderna vaccines were first administered to the public starting in December 2020, and no lactating women were included in the initial trials of safety/efficacy. Research on SARS-CoV-2 vaccination in lactating women and the potential transmission of passive immunity to the infant through breast milk is needed to guide patients, clinicians and policy makers during the worldwide effort to curb the spread of this virus. Objective: To determine whether SARS-CoV-2 specific immunoglobins are found in breast milk post-vaccination, and to characterize the time course and types of immunoglobulins present. Design:.Prospective cohort study Setting: Providence Portland Medical Center, Oregon, USA Participants: Six lactating women who planned to receive both doses of the Pfizer-BioNTech or Moderna vaccine between December 2020 and January 2021. Breast milk samples were collected pre-vaccination and at 11 additional timepoints, with last sample at 14 days post 2nd dose of vaccine. Exposure: Two doses of Pfizer-BioNTech or Moderna SARS-CoV-2 vaccine. Main Outcome(s) and Measure(s): Levels of SARS-CoV-2 specific IgA and IgG immunoglobulins in breast milk. Results: In this cohort of 6 lactating women who received 2 doses of SARS-CoV-2 vaccine, we observed significantly elevated levels of SARS-CoV-2 specific IgG and IgA antibodies in breast milk beginning at Day 7 after the initial vaccine dose, with an IgG-dominant response. Conclusions and Relevance: We are the first to show that maternal vaccination results in SARS-CoV-2 specific immunoglobulins in breast milk that may be protective for infants.

4: What level of neutralising antibody protects from COVID-19? .
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Posted 11 Mar 2021

What level of neutralising antibody protects from COVID-19? .
15,225 downloads medRxiv infectious diseases

David S. Khoury, Deborah Cromer, Arnold Reynaldi, Timothy E Schlub, Adam K Wheatley, Jennifer A Juno, Kanta Subbarao, Stephen J Kent, James A Triccas, Miles P Davenport

Both previous infection and vaccination have been shown to provide potent protection from COVID-19. However, there are concerns that waning immunity and viral variation may lead to a loss of protection over time. Predictive models of immune protection are urgently needed to identify immune correlates of protection to assist in the future deployment of vaccines. To address this, we modelled the relationship between in vitro neutralisation levels and observed protection from SARS-CoV-2 infection using data from seven current vaccines as well as convalescent cohorts. Here we show that neutralisation level is highly predictive of immune protection. The 50% protective neutralisation level was estimated to be approximately 20% of the average convalescent level (95% CI = 14-28%). The estimated neutralisation level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level (CI = 0.7-13%, p = 0.0004). Given the relationship between in vitro neutralization titer and protection, we then used this to investigate how waning immunity and antigenic variation might affect vaccine efficacy. We found that the decay of neutralising titre in vaccinated subjects over the first 3-4 months after vaccination was at least as rapid as the decay observed in convalescent subjects. Modelling the decay of neutralisation titre over the first 250 days after immunisation predicts a significant loss in protection from SARS-CoV-2 infection will occur, although protection from severe disease should be largely retained. Neutralisation titres against some SARS-CoV-2 variants of concern are reduced compared to the vaccine strain and our model predicts the relationship between neutralisation and efficacy against viral variants. Our analyses provide an evidence-based prediction of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic.

5: 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.
14,274 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.

6: Decreased SARS-CoV-2 viral load following vaccination
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Posted 08 Feb 2021

Decreased SARS-CoV-2 viral load following vaccination
13,719 downloads medRxiv infectious diseases

Matan Levine-Tiefenbrun, Idan Yelin, Rachel Katz, Esma Herzel, Ziv Golan, Licita Schreiber, Tamar Wolf, Varda Nadler, Amir Ben-Tov, Jacob Kuint, Sivan Gazit, Tal Patalon, Gabriel Chodick, Roy Kishony

Beyond their substantial protection of individual vaccinees, it is hoped that the COVID-19 vaccines would reduce viral load in breakthrough infections thereby further suppress onward transmission. Here, analyzing positive SARS-CoV-2 test results following inoculation with the BNT162b2 mRNA vaccine, we find that the viral load is reduced 4-fold for infections occurring 12-28 days after the first dose of vaccine. These reduced viral loads hint to lower infectiousness, further contributing to vaccine impact on virus spread.

7: Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine
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Posted 01 Feb 2021

Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine
13,496 downloads medRxiv allergy and immunology

Florian Krammer, Komal Srivastava, PARIS team, Viviana Simon

As COVID-19 vaccines are getting rolled out, an important question is arising: Should individuals who already had a SARS-CoV-2 infection receive one or two shots of the currently authorized mRNA vaccines. In this short report, we are providing evidence that the antibody response to the first vaccine dose in individuals with pre-existing immunity is equal to or even exceeds the titers found in naive individuals after the second dose. We also show that the reactogenicity is significantly higher in individuals who already have been infected with SARS-CoV-2 in the past. Changing the policy to give these individuals only one dose of vaccine would not negatively impact on their antibody titers, spare them from unnecessary pain and free up many urgently needed vaccine doses.

8: Obesity may hamper SARS-CoV-2 vaccine immunogenicity
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Posted 26 Feb 2021

Obesity may hamper SARS-CoV-2 vaccine immunogenicity
12,583 downloads medRxiv allergy and immunology

Raul Pellini, Aldo Venuti, Fulvia Pimpinelli, Elva Abril, Giovanni Blandino, Flaminia Campo, Laura Conti, Armando De Virgilio, Federico De Marco, Enea Gino Di Domenico, Ornella Di Bella, Simona Di Martino, Fabrizio Ensoli, Diana Giannarelli, Chiara Mandoj, Valentina Manciocco, Paolo Marchesi, Francesco Mazzola, Silvia Moretto, Gerardo Petruzzi, Fabrizio Petrone, Barbara Pichi, Martina Pontone, Jacopo Zocchi, Antonello Vidiri, Branka Vujovic, Giulia Piaggio, Aldo Morrone, Gennaro Ciliberto

BackgroundThe first goal of the study was to analyse the antibody titre 7 days after the second dose of BNT162b2 vaccine in a group of 248 healthcare workers (HCW). The second goal was to analyse how the antibody titre changes in correlation with age, gender and BMI. MethodsParticipants were assigned to receive the priming dose at baseline and booster dose at day 21. Blood and nasopharyngeal swabs were collected at baseline and 7 days after second dose of vaccine. Findings248 HWCs were analysed, 158 women (63.7%) and 90 men (36.3%). After the second dose of BNT162b2 vaccine, 99.5% of participants developed a humoral immune response. The geometric mean concentration of antibodies among the vaccinated subjects after booster dose (285.9 AU/mL 95% CI: 249.5-327.7); was higher than that of human convalescent sera (39.4 AU/mL, 95% CI: 33.1-46.9), with p<0.0001. The antibody titre was found to be higher in young and female participants. A strong correlation of BMI classes with antibody titres was noticed: humoral response was more efficient in the group with under- and normal-weight vs the group with pre- and obesity participants (p<0.0001 at T1). InterpretationThese findings imply that females, lean and young people have an increased capacity to mount humoral immune responses compared to males, overweight and the older population. Although further studies are needed, this data may have important implications for the development of vaccination strategies for COVID-19, particularly in obese people. FundingNone

9: Barriers to online learning in the time of COVID-19: A national survey of medical students in the Philippines
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Posted 18 Jul 2020

Barriers to online learning in the time of COVID-19: A national survey of medical students in the Philippines
12,243 downloads medRxiv medical education

Ronnie E Baticulon, Nicole Rose I Alberto, Maria Beatriz C Baron, Robert Earl C Mabulay, Lloyd Gabriel T Rizada, Jinno Jenkin Sy, Christl Jan S Tiu, Charlie A Clarion, John Carlo B Reyes

INTRODUCTION: In March 2020, the coronavirus disease 2019 (COVID-19) pandemic forced medical schools in the Philippines to stop face-to-face learning activities and abruptly shift to an online curriculum. This study aimed to identify barriers to online learning from the perspective of medical students in a developing country. METHOD: The authors sent out an electronic survey to medical students in the Philippines from 11 to 24 May 2020. Using a combination of multiple choice, Likert scale, and open-ended questions, the following data were obtained: demographics, medical school information, access to technological resources, study habits, living conditions, self-assessment of capacity for and perceived barriers to online learning, and proposed interventions. Descriptive statistics were calculated. Responses were compared between student subgroups using nonparametric tests. RESULTS: Among 3,670 medical students, 3,421 (93%) owned a smartphone and 3,043 (83%) had a laptop or desktop computer. To access online resources, 2,916 (79%) had a postpaid internet subscription while 696 (19%) used prepaid mobile data. Under prevailing conditions, only 1,505 students (41%) considered themselves physically and mentally capable of engaging in online learning. Barriers were classified under five categories: technological, individual, domestic, institutional, and community barriers. Most frequently encountered were difficulty adjusting learning styles, having to perform responsibilities at home, and poor communication between educators and learners. CONCLUSION: Medical students in the Philippines confronted several interrelated barriers as they tried to adapt to online learning. By implementing student-centered interventions, medical schools and educators play a significant role in addressing these challenges during the COVID-19 pandemic and beyond.

10: Vaccine effectiveness after 1st and 2nd dose of the BNT162b2 mRNA Covid-19 Vaccine in long-term care facility residents and healthcare workers - a Danish cohort study
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Posted 09 Mar 2021

Vaccine effectiveness after 1st and 2nd dose of the BNT162b2 mRNA Covid-19 Vaccine in long-term care facility residents and healthcare workers - a Danish cohort study
10,247 downloads medRxiv epidemiology

Ida Rask Moustsen-Helms, Hanne-Dorthe Emborg, Jens Nielsen, Katrine Finderup Nielsen, Tyra Grove Krause, Kaare Molbak, Karina Lauenborg Moeller, Ann-Sofie Nicole Berthelsen, Palle Valentiner-Branth

Abstract Background At the end of 2020, Denmark launched an immunization program against SARS-CoV-2. The Danish health authorities prioritized persons currently living in long-term care facilities (LTCF residents) and frontline healthcare workers (HCW) as the first receivers of vaccination. Here we present preliminary population based vaccine effectiveness (VE) estimates in these two target groups. Methods The study was designed as a retrospective registry- and population-based observational cohort study including all LTCF residents and all HWC. The outcome was a polymerase chain reaction confirmed SARS-CoV-2, and VE was estimated for different periods following first and second dose. We used Poisson and Cox regressions to estimate respectively crude and calendar time-adjusted VE for the BNT162b2 mRNA Covid-19 Vaccine from Pfizer/BioNTech with 95% confidence intervals (CI) for vaccinated versus unvaccinated. Results A total of 39,040 LTCF residents (median age at first dose; 84 years, Interquartile range (IQR): 77-90) and 331,039 HCW (median age at first dose; 47 years, IQR: 36-57) were included. Among LTCF residents, 95.2% and 86.0% received first and second dose from 27 December 2020 until 18 February 2021, for HWC the proportion was 27.8% and 24.4%. During a median follow-up of 53 days , there were 488 and 5,663 confirmed SARS-CoV-2 cases in the unvaccinated groups, whereas there were 57 and 52 in LTCF residents and HCW within the first 7 days after the second dose and 27 and 10 cases beyond seven days of second dose. No protective effect was observed for LTCF residents after first dose. In HCW, VE was 17% (95% CI; 4-28) in the > 14 days after first dose (before second dose). Furthermore, the VE in LTCF residents at day 0-7 of second dose was 52% (95% CI; 27-69) and 46% (95% CI; 28-59) in HCW. Beyond seven days of second dose, VE increased to 64% (95% CI; 14-84) and 90% (95% CI; 82-95) in the two groups, respectively. Conclusion The results were promising regarding the VE both within and beyond seven days of second vaccination with the BNT162b2 mRNA Covid-19 Vaccine currently used in many countries to help mitigate the global SARS-CoV-2 pandemic. Impact of the research: So far, observational studies of the real-word effectiveness of the mRNA Vaccine BNT162b2 has been limited to the period after the administration of the first dose. This is the first report to date to present vaccine effectiveness (VE) estimates after the second BNT162b2 mRNA Covid-19 Vaccine. We estimated a VE of 52% and 46% in LTCF residents and HCW within seven days, which increased to 64% and 90% in the two groups respectively beyond seven days of immunization. These findings supports maintaining a two-dose schedule of the BNT162b2 mRNA Covid-19 Vaccine.

11: 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
9,925 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.

12: The B1.351 and P.1 variants extend SARS-CoV-2 host range to mice
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Posted 18 Mar 2021

The B1.351 and P.1 variants extend SARS-CoV-2 host range to mice
9,813 downloads bioRxiv microbiology

Xavier Montagutelli, Matthieu Prot, Laurine Levillayer, Eduard Baquero Salazar, Gregory Jouvion, Laurine Conquet, Flora Donati, Melanie Albert, Fabiana Gambaro, Sylvie Behillil, Vincent Enouf, Dominique Rousset, Jean Jaubert, Felix A Rey, Sylvie van der Werf, Etienne Simon-Loriere

Receptor recognition is a major determinant of viral host range, as well as infectivity and pathogenesis. Emergences have been associated with serendipitous events of adaptation upon encounters with a novel host, and the high mutation rate of RNA viruses has been proposed to explain their frequent host shifts. SARS-CoV-2 extensive circulation in humans has been associated with the emergence of variants, including variants of concern (VOCs) with diverse mutations in the spike and increased transmissibility or immune escape. Here we show that unlike the initial virus, VOCs are able to infect common laboratory mice, replicating to high titers in the lungs. This host range expansion is explained in part by the acquisition of changes at key positions of the receptor binding domain that enable binding to the mouse angiotensin-converting enzyme 2 (ACE2) cellular receptor, although differences between viral lineages suggest that other factors are involved in the capacity of SARS-CoV-2 VOCs to infect mice. This abrogation of the species barrier raises the possibility of wild rodent secondary reservoirs and provides new experimental models to study disease pathophysiology and countermeasures.

13: SARS-CoV-2 RNA reverse-transcribed and integrated into the human genome
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Posted 13 Dec 2020

SARS-CoV-2 RNA reverse-transcribed and integrated into the human genome
9,701 downloads bioRxiv genomics

Liguo Zhang, Alexsia Richards, Andrew Khalil, Emile Wogram, Haiting Ma, Richard A. Young, Rudolf Jaenisch

Prolonged SARS-CoV-2 RNA shedding and recurrence of PCR-positive tests have been widely reported in patients after recovery, yet these patients most commonly are non-infectious. Here we investigated the possibility that SARS-CoV-2 RNAs can be reverse-transcribed and integrated into the human genome and that transcription of the integrated sequences might account for PCR-positive tests. In support of this hypothesis, we found chimeric transcripts consisting of viral fused to cellular sequences in published data sets of SARS-CoV-2 infected cultured cells and primary cells of patients, consistent with the transcription of viral sequences integrated into the genome. To experimentally corroborate the possibility of viral retro-integration, we describe evidence that SARS-CoV-2 RNAs can be reverse transcribed in human cells by reverse transcriptase (RT) from LINE-1 elements or by HIV-1 RT, and that these DNA sequences can be integrated into the cell genome and subsequently be transcribed. Human endogenous LINE-1 expression was induced upon SARS-CoV-2 infection or by cytokine exposure in cultured cells, suggesting a molecular mechanism for SARS-CoV-2 retro-integration in patients. This novel feature of SARS-CoV-2 infection may explain why patients can continue to produce viral RNA after recovery and suggests a new aspect of RNA virus replication.

14: The impact of high frequency rapid viral antigen screening on COVID-19 spread and outcomes: a validation and modeling study
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Posted 03 Sep 2020

The impact of high frequency rapid viral antigen screening on COVID-19 spread and outcomes: a validation and modeling study
8,768 downloads medRxiv epidemiology

Beatrice Nash, Anthony Badea, Ankita Reddy, Miguel Bosch, Nol Salcedo, Adam R. Gomez, Alice Versiani, Gislaine Celestino Dutra, Thayza Maria Izabel Lopes dos Santos, Bruno H. G. A. Milhim, Marilia M Moraes, Guilherme Rodrigues Fernandes Campos, Flávia Quieroz, Andreia Francesli Negri Reis, Mauricio L Nogueira, Elena N. Naumova, Irene Bosch, Bobby Brooke Herrera

High frequency screening of populations has been proposed as a strategy in facilitating control of the COVID-19 pandemic. We use computational modeling, coupled with clinical data from rapid antigen tests, to predict the impact of frequent viral antigen rapid testing on COVID-19 spread and outcomes. Using patient nasal or nasopharyngeal swab specimens, we demonstrate that the sensitivity/specificity of two rapid antigen tests compared to quantitative real-time polymerase chain reaction (qRT-PCR) are 82.0%/100% and 84.7%/85.7%, respectively; moreover, sensitivity correlates directly with viral load. Based on COVID-19 data from three regions in the United States and Sao Jose do Rio Preto, Brazil, we show that high frequency, strategic population-wide rapid testing, even at varied accuracy levels, diminishes COVID-19 infections, hospitalizations, and deaths at a fraction of the cost of nucleic acid detection via qRT-PCR. We propose large-scale antigen-based surveillance as a viable strategy to control SARS-CoV-2 spread and to enable societal re-opening.

15: COVID-19 in India: State-wise Analysis and Prediction
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Posted 29 Apr 2020

COVID-19 in India: State-wise Analysis and Prediction
8,595 downloads medRxiv public and global health

Palash Ghosh, Rik Ghosh, Bibhas Chakraborty

Coronavirus disease 2019 (COVID-19), a highly infectious disease, was first detected in Wuhan, China, in December 2019. The disease has spread to 212 countries and territories around the world and infected (confirmed) more than three million people. In India, the disease was first detected on 30 January 2020 in Kerala in a student who returned from Wuhan. The total (cumulative) number of confirmed infected people is more than 37000 till now across India (3 May 2020). Most of the research and newspaper articles focus on the number of infected people in the entire country. However, given the size and diversity of India, it may be a good idea to look at the spread of the disease in each state separately, along with the entire country. For example, currently, Maharashtra has more than 10000 confirmed cumulative infected cases, whereas West Bengal has less than 800 confirmed infected cases (1 May 2020). The approaches to address the pandemic in the two states must be different due to limited resources. In this article, we will focus the infected people in each state (restricting to only those states with enough data for prediction) and build three growth models to predict infected people for that state in the next 30 days. The impact of preventive measures on daily infected-rate is discussed for each state.

16: 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
8,542 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.

17: Understanding the effectiveness of government interventions in Europe's second wave of COVID-19
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Posted 26 Mar 2021

Understanding the effectiveness of government interventions in Europe's second wave of COVID-19
8,269 downloads medRxiv epidemiology

Mrinank Sharma, Sören Mindermann, Charlie Rogers-Smith, Gavin Leech, Benedict Snodin, Janvi Ahuja, Jonas B. Sandbrink, Joshua Teperowski Monrad, George Altman, Gurpreet Dhaliwal, Lukas Finnveden, Alexander John Norman, Sebastian B. Oehm, Julia Fabienne Sandkühler, Thomas Mellan, Jan Kulveit, Leonid Chindelevitch, Seth Flaxman, Yarin Gal, Swapnil Mishra, Jan Markus Brauner, Samir Bhatt

As European governments face resurging waves of COVID-19, non-pharmaceutical interventions (NPIs) continue to be the primary tool for infection control. However, updated estimates of their relative effectiveness have been absent for Europe's second wave, largely due to a lack of collated data that considers the increased subnational variation and diversity of NPIs. We collect the largest dataset of NPI implementation dates in Europe, spanning 114 subnational areas in 7 countries, with a systematic categorisation of interventions tailored to the second wave. Using a hierarchical Bayesian transmission model, we estimate the effectiveness of 17 NPIs from local case and death data. We manually validate the data, address limitations in modelling from previous studies, and extensively test the robustness of our estimates. The combined effect of all NPIs was smaller relative to estimates from the first half of 2020, indicating the strong influence of safety measures and individual protective behaviours--such as distancing--that persisted after the first wave. Closing specific businesses was highly effective. Gathering restrictions were highly effective but only for the strictest limits. We find smaller effects for closing educational institutions compared to the first wave, suggesting that safer operation of schools was possible with a set of stringent safety measures including testing and tracing, preventing mixing, and smaller classes. These results underscore that effectiveness estimates from the early stage of an epidemic are measured relative to pre-pandemic behaviour. Updated estimates are required to inform policy in an ongoing pandemic.

18: Myocarditis in naturally infected pets with the British variant of COVID-19
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Posted 18 Mar 2021

Myocarditis in naturally infected pets with the British variant of COVID-19
8,076 downloads bioRxiv microbiology

Luca Ferasin, Matthieu Fritz, Heidi Ferasin, Pierre Becquart, Vincent Legros, Eric M. Leroy

Domestic pets can contract SARS-CoV-2 infection but, based on the limited information available to date, it is unknown whether the new British B.1.1.7 variant can more easily infect certain animal species or increase the possibility of human-to-animal transmission. In this study, we report the first cases of infection of domestic cats and dogs by the British B.1.1.7 variant of SARS-CoV-2 diagnosed at a specialist veterinary hospital in the South-East of England. Furthermore, we discovered that many owners and handlers of these pets had developed Covid-19 respiratory symptoms 3-6 weeks before their pets became ill and had also tested PCR positive for Covid-19. Interestingly, all these B.1.1.7 infected pets developed atypical clinical manifestations, including severe cardiac abnormalities secondary to myocarditis and a profound impairment of the general health status of the patient but without any primary respiratory signs. Together, our findings demonstrate for the first time the ability for companion animals to be infected by the B.1.1.7 variant of SARS-CoV-2 and raise questions regarding its pathogenicity in these animals. Moreover, given the enhanced infectivity and transmissibility of B.1.1.7 variant for humans, these findings also highlights more than ever the risk that companion animals may potentially play a significant role in SARS-CoV-2 outbreak dynamics than previously appreciated.

19: Case fatality risk of the SARS-CoV-2 variant of concern B.1.1.7 in England
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Posted 08 Mar 2021

Case fatality risk of the SARS-CoV-2 variant of concern B.1.1.7 in England
8,046 downloads medRxiv infectious diseases

Daniel J Grint, Kevin Wing, Elizabeth Williamson, Helen I McDonald, Krishnan Bhaskaran, David Evans, Stephen JW Evans, Alex J Walker, George Hickman, Emily Nightingale, Anna Schultze, Christopher T Rentsch, Christopher Bates, Jonathan Cockburn, Helen J Curtis, Caroline E Morton, Sebastian CJ Bacon, Simon Davy, Angel YS Wong, Amir Mehrkar, Laurie Tomlinson, Ian J Douglas, Rohini Mathur, Paula Blomquist, Brian MacKenna, Peter Ingelsby, Richard Croker, John Parry, Frank Hester, Sam Harper, Nicolas J DeVito, Will Hulme, John Tazare, Ben Goldacre, Liam Smeeth, Rosalind M Eggo

The B.1.1.7 variant of concern (VOC) is increasing in prevalence across Europe. Accurate estimation of disease severity associated with this VOC is critical for pandemic planning. We found increased risk of death for VOC compared with non-VOC cases in England (HR: 1.67 (95% CI: 1.34 - 2.09; P<.0001). Absolute risk of death by 28-days increased with age and comorbidities. VOC has potential to spread faster with higher mortality than the pandemic to date.

20: Early effectiveness of COVID-19 vaccination with BNT162b2 mRNA vaccine and ChAdOx1 adenovirus vector vaccine on symptomatic disease, hospitalisations and mortality in older adults in England
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Posted 02 Mar 2021

Early effectiveness of COVID-19 vaccination with BNT162b2 mRNA vaccine and ChAdOx1 adenovirus vector vaccine on symptomatic disease, hospitalisations and mortality in older adults in England
7,893 downloads medRxiv infectious diseases

Jamie Lopez Bernal, Nick Andrews, Charlotte Gower, Julia Stowe, Chris Robertson, Elise Tessier, Ruth Simmons, Simon Cottrell, Richard Roberts, Mark O’Doherty, Kevin Brown, Claire Cameron, Diane Stockton, Jim McMenamin, Mary Ramsay

ObjectivesTo estimate the real-world effectiveness of the Pfizer/BioNTech BNT162b2 vaccine and Astrazeneca ChAdOx1 vaccine against Confirmed COVID-19, hospitalisations and deaths. To estimate effectiveness on the UK variant of concern. DesignTest negative case control design SettingCommunity COVID-19 PCR testing in England ParticipantsAll adults in England aged 70 years and older (over 7.5 million). All COVID-19 testing in the community among eligible individuals who reported symptoms between 8th December 2020 and 19th February 2021 was included in the analysis. InterventionsOne and two doses of BNT162b2 vaccine. One dose of ChAdOx1 vaccine. Main outcome measuresSymptomatic PCR confirmed SARS-CoV-2 infection, hospitalisations and deaths with COVID-19. ResultsIndividuals aged >=80 years vaccinated with BNT162b2 prior to 4th January, had a higher odds of testing positive in the first 9 days after vaccination (odds ratio up to 1.48, 95%CI 1.23-1.77), indicating that those initially targeted had a higher underlying risk of infection. Vaccine effectiveness was therefore estimated relative to the baseline post-vaccination period. Vaccine effects were noted from 10-13 days after vaccination, reaching an effectiveness of 70% (95% CI 59-78%) from 28-34 days, then plateauing. From 14 days after the second dose a vaccine effectiveness of 89% (95%CI: 85-93%) was seen. Individuals aged >=70 years vaccinated from 4th January had a similar underlying risk of COVID-19 to unvaccinated individuals. With BNT162b2, vaccine effectiveness reached 61% (95%CI 51-69%) from 28-34 days after vaccination then plateaued. With the ChAdOx1 vaccine, vaccine effects were seen from 14-20 days after vaccination reaching an effectiveness of 60% (95%CI 41-73%) from 28-34 days and further increasing to 73% (95%CI 27-90%) from day 35 onwards. On top of the protection against symptomatic disease, cases who had been vaccinated with one dose of BNT162b2 had an additional 43% (95%CI 33-52%) lower risk of emergency hospitalisation and an additional 51% (95%CI 37-62%) lower risk of death. Cases who had been vaccinated with one dose of ChAdOx1 had an additional 37% (95% CI 3-59%) lower risk of emergency hospitalisation. There was insufficient follow-up to assess the effect of ChAdOx1 on mortality due to the later rollout of this vaccine. Combined with the effect against symptomatic disease, this indicates that a single dose of either vaccine is approximately 80% effective at preventing hospitalisation and a single dose of BNT162b2 is 85% effective at preventing death with COVID-19. ConclusionVaccination with either a single dose of BNT162b2 or ChAdOx1 COVID-19 vaccination was associated with a significant reduction in symptomatic SARS-CoV2 positive cases in older adults with even greater protection against severe disease. Both vaccines show similar effects. Protection was maintained for the duration of follow-up (>6 weeks). A second dose of BNT162b2 provides further protection against symptomatic disease but second doses of ChAdOx1 have not yet been rolled out in England. There is a clear effect of the vaccines against the UK variant of concern.

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