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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 131,285 papers from 561,734 authors.

Most downloaded biology preprints, since beginning of last month

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1: 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
41,534 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.

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

Decreased SARS-CoV-2 viral load following vaccination
28,738 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.

3: 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
22,395 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.

4: Single Dose Vaccination in Healthcare Workers Previously Infected with SARS-CoV-2
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Posted 01 Feb 2021

Single Dose Vaccination in Healthcare Workers Previously Infected with SARS-CoV-2
15,613 downloads medRxiv infectious diseases

Saman Saadat, Zahra Rikhtegaran-Tehrani, James Logue, Michelle Newman, Matthew B Frieman, Anthony D. Harris, Mohammad M. Sajadi

Coronavirus disease 2019 (COVID-19) vaccine shortages have led some experts and countries to consider untested dosing regimens. We studied antibody responses to a single dose of the Pfizer-BioNTech or Moderna vaccines in healthcare workers (HCW) with laboratory-confirmed COVID-19 infection and compared to them to antibody responses of HCW who were IgG negative to SARS-CoV-2 spike protein. HCW with prior COVID-19 showed clear secondary antibody responses to vaccination with IgG spike binding titers rapidly increasing by 7 days and peaking by days 10 and 14 post-vaccination. At all time points tested, HCW with prior COVID-19 infection showed statistically significant higher antibody titers of binding and functional antibody compared to HCW without prior COVID-19 infection (p<.0001for each of the time points tested). In times of vaccine shortage, and until correlates of protection are identified, our findings preliminarily suggest the following strategy as more evidence-based: a) a single dose of vaccine for patients already having had laboratory-confirmed COVID-19; and b) patients who have had laboratory-confirmed COVID-19 can be placed lower on the vaccination priority list.

5: 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
15,354 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.

6: 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
15,167 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.

7: 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
14,887 downloads bioRxiv bioinformatics

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

8: mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants
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Posted 19 Jan 2021

mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants
13,818 downloads bioRxiv immunology

Zijun Wang, Fabian Schmidt, Yiska Weisblum, Frauke Muecksch, Christopher O. Barnes, Shlomo Finkin, Dennis Schaefer-Babajew, Melissa Cipolla, Christian Gaebler, Jenna A Lieberman, Thiago Y. Oliveira, Zhi Yang, Morgan E. Abernathy, Kathryn E. Huey-Tubman, Arlene Hurley, Martina Turroja, Kamille A West, Kristie Gordon, Katrina G Millard, Victor Ramos, Justin Da Silva, Jianliang Xu, Robert A Colbert, Roshni Patel, Juan P. Dizon, Cecille Unson-O'Brien, Irina Shimeliovich, Anna Gazumyan, Marina Caskey, Pamela J Bjorkman, Rafael Casellas, Theodora Hatziioannou, Paul D. Bieniasz, Michel C. Nussenzweig

To date severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected nearly 100 million individuals resulting in over two million deaths. Many vaccines are being deployed to prevent coronavirus disease-2019 (COVID-19) including two novel mRNA-based vaccines. These vaccines elicit neutralizing antibodies and appear to be safe and effective, but the precise nature of the elicited antibodies is not known. Here we report on the antibody and memory B cell responses in a cohort of 20 volunteers who received either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines. Consistent with prior reports, 8 weeks after the second vaccine injection volunteers showed high levels of IgM, and IgG anti-SARS-CoV-2 spike protein (S), receptor binding domain (RBD) binding titers. Moreover, the plasma neutralizing activity, and the relative numbers of RBD-specific memory B cells were equivalent to individuals who recovered from natural infection. However, activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. Consistent with these findings, vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes epitopes in common with mAbs isolated from infected donors. Structural analyses of mAbs complexed with S trimer suggest that vaccine- and virus-encoded S adopts similar conformations to induce equivalent anti-RBD antibodies. However, neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations. Notably, the same mutations were selected when recombinant vesicular stomatitis virus (rVSV)/SARS-CoV-2 S was cultured in the presence of the vaccine elicited mAbs. Taken together the results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy.

9: The effectiveness of the first dose of BNT162 b 2 vaccine in reducing SARS-CoV-2 infection 13-24 days after immunization: real-world evidence
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Posted 29 Jan 2021

The effectiveness of the first dose of BNT162 b 2 vaccine in reducing SARS-CoV-2 infection 13-24 days after immunization: real-world evidence
12,750 downloads medRxiv infectious diseases

Gabriel Chodcik, Lilac Tene, Tal Patalon, Sivan Gazit, Amir Ben-Tov, Dani Cohen, Khitam Muhsen

Background BNT162b2 vaccines showed high efficacy against COVID-19 in a randomized controlled phase-III trial. A vaccine effectiveness evaluation in real life settings is urgently needed, especially given the global disease surge. Hence, we assessed the short-term effectiveness of the first dose of BNT162b2-vaccine against SARS-CoV-2 infection. Given the BNT162b2 Phase-III results, we hypothesized that the cumulative incidence of SARS-CoV-2 infection among vaccinees will decline after 12 days following immunization compared to the incidence during the preceding days. Methods We conducted a retrospective cohort study using data from 2.6 million-member state-mandated health provider in Israel. Study population consisted of all members aged 16 or above years who were vaccinated with BNT162b2-vaccine between December/19/2020 and January/15/2021. We collected information regarding medical history and positive SARS-CoV-2 polymerase chain reaction test from days after first dose to January/17/2021. Daily and cumulative infection rates in days 13-24 were compared to days 1-12 after first dose using Kaplan-Meier survival analysis and generalized linear models. Findings Data of 503,875 individuals (mean age 59.7 years SD=14.7, 47.8% males) were analyzed, of whom 351,897 had 13-24 days of follow-up. The cumulative incidence of SARS-CoV-2 infection was 0.57% (n=2484) during days 1-12 and 0.27% (n=614) in days 13-24. A 51.4% relative risk reduction (RRR) was calculated in weighted-average daily incidence of SARS-CoV-2 infection from 43.41-per-100,000(SE=12.07) in days 1-12 to 21.08-per-100,000(SE=6.16) in days 13-24 following immunization. The decrement in incidence was evident from day 18 after first dose. Similar RRRs were calculated in individuals aged 60 or above (44.5%), younger individuals (50.2%), females (50.0%) and males (52.1%). Findings were similar in sub-populations and patients with various comorbidities. Conclusions We demonstrated an effectiveness of 51% of BNT162b2 vaccine against SARS-CoV-2 infection 13-24 days after immunization with the first dose. Immunization with the second dose should be continued to attain the anticipated protection.

10: Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7
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Posted 26 Jan 2021

Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7
11,736 downloads bioRxiv immunology

Pengfei Wang, Manoj S. Nair, Lihong Liu, Sho Iketani, Yang Luo, Yicheng Guo, Maple Wang, Jian Yu, Baoshan Zhang, Peter D. Kwong, Barney Graham, John R. Mascola, Jennifer Y Chang, Michael T. Yin, Magdalena E Sobieszczyk, Christos A Kyratsous, Lawrence Shapiro, Zizhang Sheng, Yaoxing Huang, David D Ho

The COVID-19 pandemic has ravaged the globe, and its causative agent, SARS-CoV-2, continues to rage. Prospects of ending this pandemic rest on the development of effective interventions. Single and combination monoclonal antibody (mAb) therapeutics have received emergency use authorization, with more in the pipeline. Furthermore, multiple vaccine constructs have shown promise, including two with ~95% protective efficacy against COVID-19. However, these interventions were directed toward the initial SARS-CoV-2 that emerged in 2019. The recent emergence of new SARS-CoV-2 variants B.1.1.7 in the UK and B.1.351 in South Africa is of concern because of their purported ease of transmission and extensive mutations in the spike protein. We now report that B.1.1.7 is refractory to neutralization by most mAbs to the N-terminal domain (NTD) of spike and relatively resistant to a few mAbs to the receptor-binding domain (RBD). It is not more resistant to convalescent plasma or vaccinee sera. Findings on B.1.351 are more worrisome in that this variant is not only refractory to neutralization by most NTD mAbs but also by multiple individual mAbs to the receptor-binding motif on RBD, largely due to an E484K mutation. Moreover, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4 fold) and vaccinee sera (10.3-12.4 fold). B.1.351 and emergent variants with similar spike mutations present new challenges for mAb therapy and threaten the protective efficacy of current vaccines.

11: 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
11,428 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 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.

12: Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States
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Posted 07 Feb 2021

Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States
11,213 downloads medRxiv infectious diseases

Nicole L. Washington, Karthik Gangavarapu, Mark Zeller, Alexandre Bolze, Elizabeth T. Cirulli, Kelly M Schiabor Barrett, Brendan B Larsen, Catelyn Anderson, Simon White, Tyler Cassens, Sharoni Jacobs, Geraint Levan, Jason Nguyen, Jimmy M Ramirez, Charlotte Rivera-Garcia, Efren Sandoval, Xueqing Wang, David Wong, Emily Spencer, Refugio Robles-Sikisaka, Ezra Kurzban, Laura D. Hughes, Xianding Deng, Candace Wang, Venice Servellita, Holly Valentine, Peter De Hoff, Phoebe Seaver, Shashank Sathe, Kimberly Gietzen, Brad Sickler, Jay Antico, Kelly Hoon, Jingtao Liu, Aaron Harding, Omid Bakhtar, Tracy Basler, Brett Austin, Magnus Isaksson, Phil Febbo, David Becker, Marc Laurent, Eric McDonald, Gene W Yeo, Rob Knight, Louise C. Laurent, Eileen de Feo, Michael Worobey, Charles Chiu, Marc A Suchard, James T. Lu, William Lee, Kristian G. Andersen

As of January of 2021, the highly transmissible B.1.1.7 variant of SARS-CoV-2, which was first identified in the United Kingdom (U.K.), has gained a strong foothold across the world. Because of the sudden and rapid rise of B.1.1.7, we investigated the prevalence and growth dynamics of this variant in the United States (U.S.), tracking it back to its early emergence and onward local transmission. We found that the RT-qPCR testing anomaly of S gene target failure (SGTF), first observed in the U.K., was a reliable proxy for B.1.1.7 detection. We sequenced 212 B.1.1.7 SARS-CoV-2 genomes collected from testing facilities in the U.S. from December 2020 to January 2021. We found that while the fraction of B.1.1.7 among SGTF samples varied by state, detection of the variant increased at a logistic rate similar to those observed elsewhere, with a doubling rate of a little over a week and an increased transmission rate of 35-45%. By performing time-aware Bayesian phylodynamic analyses, we revealed several independent introductions of B.1.1.7 into the U.S. as early as late November 2020, with onward community transmission enabling the variant to spread to at least 30 states as of January 2021. Our study shows that the U.S. is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.

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

Obesity may hamper SARS-CoV-2 vaccine immunogenicity
11,094 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

14: Efficacy of Colchicine in Non-Hospitalized Patients with COVID-19
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Posted 27 Jan 2021

Efficacy of Colchicine in Non-Hospitalized Patients with COVID-19
10,589 downloads medRxiv infectious diseases

Jean-Claude Tardif, Nadia Bouabdallaoui, Philippe L L'Allier, Daniel Gaudet, Binita Shah, Michael H Pillinger, Jose Lopez-Sendon, Protasio da Luz, Lucie Verret, Sylvia Audet, Jocelyn Dupuis, Andre Y Denault, Martin Pelletier, Philippe A Tessier, Sarah Samson, Denis Fortin, Jean-Daniel Tardif, David Busseuil, Elisabeth Goulet, Chantal Lacoste, Anick Dubois, Avni Y Joshi, David D Waters, Priscilla Hsue, Norman E Lepor, Frederic Lesage, Nicolas Sainturet, Eve Roy-Clavel, Zohar Bassevitch, Andreas Orfanos, Jean C Gregoire, Lambert Busque, Christian Lavallee, Pierre-Olivier Hetu, Jean-Sebastien Paquette, Sylvie Levesque, Marieve Cossette, Anna Nozza, Malorie Chabot-Blanchet, Marie-Pierre Dubé, Marie-Claude Guertin, Guy Boivin

Background Evidence suggests the role of an inflammatory storm in COVID-19 complications. Colchicine is an orally administered, anti-inflammatory medication beneficial in gout, pericarditis and coronary disease. Methods We performed a randomized, double-blind trial involving non-hospitalized patients with COVID-19 diagnosed by polymerase chain reaction (PCR) testing or clinical criteria. The patients were randomly assigned to receive colchicine (0.5 mg twice daily for 3 days and once daily thereafter) or placebo for 30 days. The primary efficacy endpoint was the composite of death or hospitalization for COVID-19. Results A total of 4488 patients were enrolled. The primary endpoint occurred in 4.7% of the patients in the colchicine group and 5.8% of those in the placebo group (odds ratio, 0.79; 95.1% confidence interval (CI), 0.61 to 1.03; P=0.08). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 4.6% and 6.0% of patients in the colchicine and placebo groups, respectively (odds ratio, 0.75; 95% CI, 0.57 to 0.99; P=0.04). In these patients with PCR-confirmed COVID-19, the odds ratios were 0.75 (95% CI, 0.57 to 0.99) for hospitalization due to COVID-19, 0.50 (95% CI, 0.23 to 1.07) for mechanical ventilation, and 0.56 (95% CI, 0.19 to 1.66) for death. Serious adverse events were reported in 4.9% and 6.3% in the colchicine and placebo groups (P=0.05); pneumonia occurred in 2.9% and 4.1% of patients (P=0.02). Diarrhea was reported in 13.7% and 7.3% in the colchicine and placebo groups (P<0.0001). Conclusion Among non-hospitalized patients with COVID-19, colchicine reduces the composite rate of death or hospitalization. (COLCORONA ClinicalTrials.gov number: NCT04322682)

15: 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
9,947 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.

16: 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
9,810 downloads medRxiv infectious diseases

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

ImportanceThe 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. ObjectiveTo 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. DesignProspective cohort study SettingProvidence Portland Medical Center, Oregon, USA ParticipantsSix 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. ExposureTwo 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. ResultsIn 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 RelevanceWe are the first to show that maternal vaccination results in SARS-CoV-2 specific immunoglobulins in breast milk that may be protective for infants.

17: 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
9,397 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.

18: 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
9,198 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.

19: Antibodies elicited by SARS-CoV-2 infection and boosted by vaccination neutralize an emerging variant and SARS-CoV-1
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Posted 08 Feb 2021

Antibodies elicited by SARS-CoV-2 infection and boosted by vaccination neutralize an emerging variant and SARS-CoV-1
9,184 downloads medRxiv infectious diseases

Leonidas Stamatatos, Julie Czartoski, Yu-Hsin Wan, Leah Homad, Vanessa Rubin, Hayley Glantz, Moni Neradilek, Emilie Seydoux, Madeleine F Jennewein, Anna MacCamy, Junli Feng, Greogry Mize, Stephen C De Rosa, Andres Finzi, Maria Lemos, Kristen W Cohen, Zoe Moodie, M. Juliana McElrath, Andrew McGuire

The emergence of SARS-CoV-2 variants raises concerns about their resistance to neutralizing antibodies elicited from previous infection, or from vaccination. Here we examined whether sera and monoclonal antibodies from convalescent donors, prior to and following a single immunization with the Pfizer or Moderna mRNA vaccines, neutralize the Wuhan-Hu-1 strain and a variant, B.1.351 from South Africa. Pre-vaccination sera weakly neutralized Wuhan-Hu-1 and sporadically neutralized B.1.351. Immunization with either vaccine generated anamnestic B and CD4+ T cell responses and a 1000-fold increase in neutralizing antibody titers against both strains and SARS-CoV-1. Neutralization was likely due to anti-RBD and anti-S2 antibodies. Our study highlights the importance of vaccination of both uninfected and of previously infected subjects, as the elicited immune response will neutralize distinct viral strains.

20: Preliminary Evidence on Long COVID in children
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Posted 26 Jan 2021

Preliminary Evidence on Long COVID in children
9,154 downloads medRxiv pediatrics

danilo buonsenso, Daniel Munblit, Cristina De Rose, Dario Sinatti, Antonia Ricchiuto, Angelo Carfi, Piero Valentini

There is increasing evidence that adult patients diagnosed with acute COVID-19 suffer from Long COVID initially described in Italy. To date, data on Long COVID in children are lacking. We assessed persistent symptoms in pediatric patients previously diagnosed with COVID-19. More than a half reported at least one persisting symptom even after 120 days since COVID-19, with 42.6% being impaired by these symptoms during daily activities. Symptoms like fatigue, muscle and joint pain, headache , insomnia, respiratory problems and palpitations were particularly frequent, as also described in adults. The evidence that COVID-19 can have long-term impact children as well, including those with asymptomatic/paucisymptomatic COVID-19, highlight the need for pediatricians, mental health experts and policy makers of implementing measures to reduce impact of the pandemic on child s health.

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