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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 128,741 papers from 551,614 authors.

Most downloaded biology preprints, since beginning of last month

122,684 results found. For more information, click each entry to expand.

81: Inward and outward effectiveness of cloth masks, a surgical mask, and a face shield
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Posted 20 Nov 2020

Inward and outward effectiveness of cloth masks, a surgical mask, and a face shield
5,261 downloads medRxiv public and global health

Jin Pan, Charbel Harb, Weinan Leng, Linsey C. Marr

We evaluated the effectiveness of 11 face coverings for material filtration efficiency, inward protection efficiency on a manikin, and outward protection efficiency on a manikin. At the most penetrating particle size, the vacuum bag, microfiber cloth, and surgical mask had material filtration efficiencies >50%, while the other materials had much lower filtration efficiencies. However, these efficiencies increased rapidly with particle size, and many materials had efficiencies >50% at 2 m and >75% at 5 m. The vacuum bag performed best, with efficiencies of 54-96% for all three metrics, depending on particle size. The thin acrylic and face shield performed worst. Inward protection efficiency and outward protection efficiency were similar for many masks; the two efficiencies diverged for stiffer materials and those worn more loosely (e.g., bandana) or more tightly (e.g., wrapped around the head) compared to a standard earloop mask. Discrepancies between material filtration efficiency and inward/outward protection efficiency indicated that the fit of the mask was important. We calculated that the particle size most likely to deposit in the respiratory tract when wearing a mask is [~]2 m. Based on these findings, we recommend a three-layer mask consisting of outer layers of a flexible, tightly woven fabric and an inner layer consisting of a material designed to filter out particles. This combination should produce an overall efficiency of >70% at the most penetrating particle size and >90% for particles 1 m and larger if the mask fits well.

82: Emergence of an early SARS-CoV-2 epidemic in the United States
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Posted 08 Feb 2021

Emergence of an early SARS-CoV-2 epidemic in the United States
5,176 downloads medRxiv epidemiology

Mark Zeller, Karthik Gangavarapu, Catelyn Anderson, Allison R. Smither, John A. Vanchiere, Rebecca Rose, Gytis Dudas, Daniel J. Snyder, Alexander Watts, Nathaniel L Matteson, Refugio Robles-Sikisaka, Maximilian Marshall, Amy K Feehan, Gilberto Sabino-Santos, Antoinette Bell-Kareem, Laura D. Hughes, Manar Alkuzweny, Patricia Snarski, Julia Garcia-Diaz, Rona S. Scott, Lilia I. Melnik, Raphaelle Klitting, Michelle McGraw, Pedro Belda-Ferre, Peter DeHoff, Shashank Sathe, Clarisse Marotz, Nathan Grubaugh, David J Nolan, Arnaud C. Drouin, Kaylynn J. Genemaras, Karissa Chao, Sarah Topol, Emily Spencer, Laura Nicholson, Stefan Aigner, Gene W Yeo, Lauge Farnaes, Charlotte A. Hobbs, Louise C. Laurent, Rob Knight, Emma B. Hodcroft, Kamran Khan, Dahlene N. Fusco, Vaughn S Cooper, Phillipe Lemey, Lauren Gardner, Susanna L Lamers, Jeremy P. Kamil, Robert F Garry, Marc A Suchard, Kristian G. Andersen

The emergence of the early COVID-19 epidemic in the United States (U.S.) went largely undetected, due to a lack of adequate testing and mitigation efforts. The city of New Orleans, Louisiana experienced one of the earliest and fastest accelerating outbreaks, coinciding with the annual Mardi Gras festival, which went ahead without precautions. To gain insight into the emergence of SARS-CoV-2 in the U.S. and how large, crowded events may have accelerated early transmission, we sequenced SARS-CoV-2 genomes during the first wave of the COVID-19 epidemic in Louisiana. We show that SARS-CoV-2 in Louisiana initially had limited sequence diversity compared to other U.S. states, and that one successful introduction of SARS-CoV-2 led to almost all of the early SARS-CoV-2 transmission in Louisiana. By analyzing mobility and genomic data, we show that SARS-CoV-2 was already present in New Orleans before Mardi Gras and that the festival dramatically accelerated transmission, eventually leading to secondary localized COVID-19 epidemics throughout the Southern U.S.. Our study provides an understanding of how superspreading during large-scale events played a key role during the early outbreak in the U.S. and can greatly accelerate COVID-19 epidemics on a local and regional scale.

83: COVID-19: Rapid Antigen detection for SARS-CoV-2 by lateral flow assay: a national systematic evaluation for mass-testing
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Posted 15 Jan 2021

COVID-19: Rapid Antigen detection for SARS-CoV-2 by lateral flow assay: a national systematic evaluation for mass-testing
5,150 downloads medRxiv infectious diseases

UK COVID-19 Lateral Flow Oversight Team, Tim Peto

Lateral flow device (LFD) viral antigen immunoassays have been developed around the world as diagnostic tests for SARS-CoV-2 infection. They have been proposed to deliver an infrastructure-light, cost-economical solution giving results within half an hour. Here we report on standardised laboratory evaluations of LFDs, and for those that met the published criteria, field testing in the Falcon-C19 research study and UK pilots (UK COVID-19 testing centres, hospital, schools, armed forces). 4/64 LFDs so far have desirable performance characteristics (Orient Gene, Deepblue, Abbott and Innova SARS-CoV-2 Antigen Rapid Qualitative Test). All these LFDs have a viral antigen detection of >90% at 100,000 RNA copies/ml. 8951 Innova LFD tests were performed with a kit failure rate of 5.6% (502/8951, 95% CI: 5.1-6.1), false positive rate of 0.32% (22/6954, 95% CI: 0.20-0.48). Viral antigen detection/sensitivity across the sampling cohort when performed by laboratory scientists (156/198, 95% CI 72.4-84.3) was 78.8%. Our results suggest LFDs have promising performance characteristics for mass population testing and can be used to identify infectious positive individuals. The Innova LFD shows good viral antigen detection/sensitivity with excellent specificity, although kit failure rates and the impact of training are potential issues. These results support the expanded evaluation of LFDs, and assessment of greater access to testing on COVID-19 transmission. Funding: Department of Health and Social Care. University of Oxford. Public Health England Porton Down, Manchester University NHS Foundation Trust, National Institute of Health Research.

84: BNT162b2 induces SARS-CoV-2-neutralising antibodies and T cells in humans
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Posted 11 Dec 2020

BNT162b2 induces SARS-CoV-2-neutralising antibodies and T cells in humans
5,136 downloads medRxiv infectious diseases

Ugur Sahin, Alexander Muik, Isabel Vogler, Evelyna Derhovanessian, Lena M Kranz, Mathias Vormehr, Jasmin Quandt, Nicole Bidmon, Alexander Ulges, Alina Baum, Kristen Pascal, Daniel Maurus, Sebastian Brachtendorf, Verena L Loerks, Julian Sikorski, Peter Koch, Rolf Hilker, Dirk Becker, Ann-Kathrin Eller, Jan Gruetzner, Manuel Tonigold, Carsten Boesler, Corinna Rosenbaum, Ludwig Heesen, Marie-Cristine Kuehnle, Asaf Poran, Jesse Z Dong, Ulrich Luxemburger, Alexandra Kemmer-Brueck, David Langer, Martin Bexon, Stefanie Bolte, Tania Palanche, Armin Schultz, Sybille Baumann, Azita J Mahiny, Gabor Boros, Jonas Reinholz, Gabor T Szabo, Katalin Kariko, Pei-Yong Shi, Camila Fontes-Garfias, John L Perez, Mark Cutler, David Cooper, Christos A Kyratsous, Philip R. Dormitzer, Kathrin U. Jansen, Oezlem Tuereci

BNT162b2, a lipid nanoparticle (LNP) formulated nucleoside-modified messenger RNA (mRNA) encoding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) stabilized in the prefusion conformation, has demonstrated 95% efficacy to prevent coronavirus disease 2019 (COVID-19). Recently, we reported preliminary BNT162b2 safety and antibody response data from an ongoing placebo-controlled, observer-blinded phase 1/2 vaccine trial. We present here antibody and T cell responses from a second, non-randomized open-label phase 1/2 trial in healthy adults, 19-55 years of age, after BNT162b2 prime/boost vaccination at 1 to 30 g dose levels. BNT162b2 elicited strong antibody responses, with S-binding IgG concentrations above those in a COVID-19 human convalescent sample (HCS) panel. Day 29 (7 days post-boost) SARS-CoV-2 serum 50% neutralising geometric mean titers were 0.3-fold (1 g) to 3.3-fold (30 g) those of the HCS panel. The BNT162b2-elicited sera neutralised pseudoviruses with diverse SARS-CoV-2 S variants. Concurrently, in most participants, S-specific CD8+ and T helper type 1 (TH1) CD4+ T cells had expanded, with a high fraction producing interferon-{gamma} (IFN{gamma}). Using peptide MHC multimers, the epitopes recognised by several BNT162b2-induced CD8+ T cells when presented on frequent MHC alleles were identified. CD8+ T cells were shown to be of the early-differentiated effector-memory phenotype, with single specificities reaching 0.01-3% of circulating CD8+ T cells. In summary, vaccination with BNT162b2 at well tolerated doses elicits a combined adaptive humoral and cellular immune response, which together may contribute to protection against COVID-19.

85: Lockdown Effects on Sars-CoV-2 Transmission - The evidence from Northern Jutland
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Posted 04 Jan 2021

Lockdown Effects on Sars-CoV-2 Transmission - The evidence from Northern Jutland
5,108 downloads medRxiv epidemiology

Kasper Planeta Kepp, Christian Bjørnskov

The exact impact of lockdowns and other NPIs on Sars-CoV-2 transmission remain a matter of debate as early models assumed 100% susceptible homogenously transmitting populations, an assumption known to overestimate counterfactual transmission, and since most real epidemiological data are subject to massive confounding variables. Here, we analyse the unique case-controlled epidemiological dataset arising from the selective lockdown of parts of Northern Denmark, but not others, as a consequence of the spread of mink-related mutations in November 2020. Our analysis shows that while infection levels decreased, they did so before lockdown was effective, and infection numbers also decreased in neighbour municipalities without mandates. Direct spill-over to neighbour municipalities or the simultaneous mass testing do not explain this. Instead, control of infection pockets possibly together with voluntary social behaviour was apparently effective before the mandate, explaining why the infection decline occurred before and in both the mandated and non-mandated areas. The data suggest that efficient infection surveillance and voluntary compliance make full lockdowns unnecessary at least in some circumstances.

86: Large field of view-spatially resolved transcriptomics at nanoscale resolution
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Posted 19 Jan 2021

Large field of view-spatially resolved transcriptomics at nanoscale resolution
5,059 downloads bioRxiv cell biology

Ao Chen, Sha Liao, Mengnan Cheng, Kailong Ma, Liang Wu, Yiwei Lai, Jin Yang, Wenjiao Li, Jiangshan Xu, Shijie Hao, Huifang Lu, Xi Chen, Xing Liu, Xin Huang, Feng Lin, Xiaoxuan Tang, Zhao Li, Yan Hong, Defeng Fu, Yujia Jiang, Jian Peng, Shuai Liu, Mengzhe Shen, Chuanyu Liu, Quanshui Li, Zhifeng Wang, Zhaohui Wang, Yue Yuan, Giacomo Volpe, Carl Ward, Pura Munoz-Canoves, Jean Paul Thiery, Fuxiang Zhao, Mei Li, Haoyan Kuang, Ou Wang, Haorong Lu, Bo Wang, Ming Ni, Wenwei Zhang, Feng Mu, Ye Yin, Huanming Yang, Michael Lisby, Richard J Cornall, Mathias Uhlen, Miguel A. Esteban, Yuxiang Li, Longqi Liu, Xun Xu, Jian Wang

High-throughput profiling of in situ gene expression represents a major advance towards the systematic understanding of tissue complexity. Applied with enough capture area and high sample throughput it will help to define the spatio-temporal dynamics of gene expression in tissues and organisms. Yet, current technologies have considerable bottlenecks that limit widespread application. Here, we have combined DNA nanoball (DNB) patterned array chips and in situ RNA capture to develop Stereo-seq (Spatio-Temporal Enhanced REsolution Omics-sequencing). This approach allows high sample throughput transcriptomic profiling of histological sections at unprecedented (nanoscale) resolution with areas expandable to centimeter scale, high sensitivity and homogenous capture rate. As proof of principle, we applied Stereo-seq to the adult mouse brain and sagittal sections of E11.5 and E16.5 mouse embryos. Thanks to its unique features and amenability to additional modifications, Stereo-seq can pave the way for the systematic spatially resolved-omics characterization of tissues and organisms.

87: Design of Specific Primer Set for Detection of B.1.1.7 SARS-CoV-2 Variant using Deep Learning
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Posted 29 Dec 2020

Design of Specific Primer Set for Detection of B.1.1.7 SARS-CoV-2 Variant using Deep Learning
4,986 downloads bioRxiv bioinformatics

Alejandro Lopez-Rincon, Carmina Perez-Romero, Alberto Tonda, Lucero Mendoza-Maldonado, Eric Claassen, Johan Garssen, Aletta D Kraneveld

The SARS-CoV-2 variant B.1.1.7 lineage, also known as clade GR from Global Initiative on Sharing All Influenza Data (GISAID), Nextstrain clade 20B, or Variant Under Investigation in December 2020 (VUI - 202012/01), appears to have an increased transmissability in comparison to other variants. Thus, to contain and study this variant of the SARS-CoV-2 virus, it is necessary to develop a specific molecular test to uniquely identify it. Using a completely automated pipeline involving deep learning techniques, we designed a primer set which is specific to SARS-CoV-2 variant B.1.1.7 with >99% accuracy, starting from 8,923 sequences from GISAID. The resulting primer set is in the region of the synonymous mutation C16176T in the ORF1ab gene, using the canonical sequence of the variant B.1.1.7 as a reference. Further in-silico testing shows that the primer sets sequences do not appear in different viruses, using 20,571 virus samples from the National Center for Biotechnology Information (NCBI), nor in other coronaviruses, using 487 samples from National Genomics Data Center (NGDC). In conclusion, the presented primer set can be exploited as part of a multiplexed approach in the initial diagnosis of Covid-19 patients, or used as a second step of diagnosis in cases already positive to Covid-19, to identify individuals carrying the B.1.1.7 variant.

88: N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2
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Posted 14 Jan 2021

N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2
4,615 downloads bioRxiv immunology

Matthew McCallum, Anna De Marco, Florian Lempp, M. Alejandra Tortorici, Dora Pinto, Alexandra C. Walls, Martina Beltramello, Alex Chen, Zhuoming Liu, Fabrizia Zatta, Samantha Zepeda, Julia di Iulio, John E Bowen, Martin Montiel-Ruiz, Jiayi Zhou, Laura Rosen, Siro Bianchi, Barbara Guarino, Chiara Silacci Fregni, Rana Abdelnabi, Shi-Yan Caroline Foo, Paul W Rothlauf, Louis-Marie Bloyet, Fabio Benigni, Elisabetta Cameroni, Johan Neyts, Agostino Riva, Gyorgy Snell, Amalio Telenti, Sean P.J. Whelan, Herbert W. Virgin, Davide Corti, Matteo Samuele Pizzuto, David Veesler

SARS-CoV-2 entry into host cells is orchestrated by the spike (S) glycoprotein that contains an immunodominant receptor-binding domain (RBD) targeted by the largest fraction of neutralizing antibodies (Abs) in COVID-19 patient plasma. Little is known about neutralizing Abs binding to epitopes outside the RBD and their contribution to protection. Here, we describe 41 human monoclonal Abs (mAbs) derived from memory B cells, which recognize the SARS-CoV-2 S N-terminal domain (NTD) and show that a subset of them neutralize SARS-CoV-2 ultrapotently. We define an antigenic map of the SARS-CoV-2 NTD and identify a supersite recognized by all known NTD-specific neutralizing mAbs. These mAbs inhibit cell-to-cell fusion, activate effector functions, and protect Syrian hamsters from SARS-CoV-2 challenge. SARS-CoV-2 variants, including the 501Y.V2 and B.1.1.7 lineages, harbor frequent mutations localized in the NTD supersite suggesting ongoing selective pressure and the importance of NTD-specific neutralizing mAbs to protective immunity.

89: Diverse Functional Autoantibodies in Patients with COVID-19
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Posted 11 Dec 2020

Diverse Functional Autoantibodies in Patients with COVID-19
4,582 downloads medRxiv infectious diseases

Eric Y. Wang, Tianyang Mao, Jon Klein, Yile Dai, John D. Huck, Feimei Liu, Neil S. Zheng, Ting Zhou, Benjamin Israelow, Patrick Wong, Carolina Lucas, Julio Silva, Ji Eun Oh, Eric Song, Emily S. Perotti, Suzanne Fischer, Melissa Campbell, John B. Fournier, Anne L Wyllie, Chantal B. F. Vogels, Isabel M. Ott, Chaney C. Kalinich, Mary E. Petrone, Anne E Watkins, Yale IMPACT Team, Charles Dela Cruz, Shelli F. Farhadian, Wade L. Schulz, Nathan D. Grubaugh, Albert I. Ko, Akiko Iwasaki, Aaron M. Ring

COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses. While pathological innate immune activation is well documented in severe disease, the impact of autoantibodies on disease progression is less defined. Here, we used a high-throughput autoantibody discovery technique called Rapid Extracellular Antigen Profiling (REAP) to screen a cohort of 194 SARS-CoV-2 infected COVID-19 patients and healthcare workers for autoantibodies against 2,770 extracellular and secreted proteins (the "exoproteome"). We found that COVID-19 patients exhibit dramatic increases in autoantibody reactivities compared to uninfected controls, with a high prevalence of autoantibodies against immunomodulatory proteins including cytokines, chemokines, complement components, and cell surface proteins. We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signaling and by altering peripheral immune cell composition, and found that murine surrogates of these autoantibodies exacerbate disease severity in a mouse model of SARS-CoV-2 infection. Analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics and disease severity. In summary, these findings implicate a pathological role for exoproteome-directed autoantibodies in COVID-19 with diverse impacts on immune functionality and associations with clinical outcomes.

90: Dynamics of ORF1ab and N Gene among hospitalized COVID-19 positive cohorts: A hospital based retrospective study
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Posted 23 Nov 2020

Dynamics of ORF1ab and N Gene among hospitalized COVID-19 positive cohorts: A hospital based retrospective study
4,458 downloads medRxiv infectious diseases

Pojul Loying, Vaishali Sarma, Suranjana C. Hazarika, Monjuri Kataki, Dina Raja, Divyashree Medhi, Ridip Dutta, Achu Chena, Divya Daimary, Aakangkhita Choudhury, Lahari Saikia

1.ObjectiveThe present study hospital based retrospective study aimed at investigating the dynamics of ORF1ab and N gene from hospitalized COVID-19 positive cohorts considering the Ct values of both genes. Study design and MethodologyRetrospective analyses of Ct values were done from 115 hospitalized COVID-19 positive patients in different time interval. Patients were admitted to the hospital either by RAT or/and RT-PCR and first RT-PCR testing were made after 9 days of incubation followed by testing in every 3 days of interval till negative, subsequently release of the patients. ResultsWe have looked into the dynamics of ORF1ab and N gene and found that N gene require longer duration of days with 12.68 (S.D.{+/-}3.24) to become negative than ORF1ab with 12.09 (S.D.{+/-}2.88) days and it differs significantly (p=0.012; p<0.05). The persistent of N gene found in 46 patients out of 115 (39.65%) to the succeeding reading after 3 days. We have also looked into the mean differences in the between N and ORF1ab genes every readings separately and found that there were no significant differences between the mean Ct value of ORF1ab and N gene except in the day 3 (p=0.015; p<0.05). Further, we have looked into the relationship of age and gender of patients with the duration of positivity; however we did not find any significant role. ConclusionIn COVID-19 hospital positive cohorts, the persistent of positivity of N gene is significantly for more duration than ORF1ab. As the SARS-CoV-2 is a new virus and study on it is evolving, so, exhaustive study is required on the dynamic of N gene positivity persistent in relation to the other pathophysiological parameters for the management and control of COVID-19.

91: Outcomes of Ivermectin in the treatment of COVID-19: a systematic review and meta-analysis
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Posted 27 Jan 2021

Outcomes of Ivermectin in the treatment of COVID-19: a systematic review and meta-analysis
4,380 downloads medRxiv infectious diseases

Alex Castaneda-Sabogal, Diego Chambergo-Michilot, Carlos J. Toro-Huamanchumo, Christian Silva-Rengifo, Jose Gonzales-Zamora, Joshuan J. Barboza

Background: To assess the outcomes of ivermectin in ambulatory and hospitalized patients with COVID-19. Methods: Five databases and websites for preprints were searched until January 2021 for randomized controlled trials (RCTs) and retrospective cohorts assessing ivermectin versus control in ambulatorys or hospitalized participants. The primary outcome was overall mortality. Secondary outcome was the recovered patients. For meta-analysis, random-effects and inverse variance meta-analyses with logarithmic transformation were performed. ROBINS-I for cohort studies, and the Cochrane Risk of Bias 2.0 tool for trials were used. The strength of evidence was assessed using GRADE. Results. After the selection, twelve studies (five retrospective cohort studies, six randomized clinical trials and one case series), were included. In total, 7412 participants were reported, the mean age was 47.5 (SD 9.5) years, and 4283 (58%) were male. Ivermectin is not associated with reduced mortality (logRR: 0.89, 95% CI 0.09 to 1.70, p = 0.04, I2= 84.7%), and it was not associated with reduced patient recovery (logRR 5.52 , 95% CI -24.36 to 35.4, p = 0.51, I2 = 92.6%). All studies had a high risk of bias, and showed a very low certainty of the evidence. Conclusions: There insufficient certainty and quality of evidence to recommend the use of ivermectin to prevent or treat ambulatory or hospitalized patients with COVID-19.

92: SARS-CoV-2 neutralizing antibodies; longevity, breadth, and evasion by emerging viral variants
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Posted 22 Dec 2020

SARS-CoV-2 neutralizing antibodies; longevity, breadth, and evasion by emerging viral variants
4,363 downloads medRxiv infectious diseases

Fiona Tea, Alberto Ospina Stella, Anupriya Aggarwal, David Ross Darley, Deepti Pilli, Daniele Vitale, Vera Merheb, Fiona X. Z. Lee, Philip Cunningham, Gregory J Walker, David A Brown, William D Rawlinson, Sonia R Isaacs, Vennila Mathivanan, Markus Hoffman, Stefan Poehlmann, Dominic E Dwyer, Rebecca Rockett, Vitali Sintchenko, Veronica C Hoad, David O Irving, Gregory J. Dore, Iain B Gosbell, Anthony D Kelleher, Gail V. Matthews, Fabienne Brilot, Stuart G Turville

The SARS-CoV-2 antibody neutralization response and its evasion by emerging viral variants are unknown. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus-cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 RT-PCR-confirmed COVID-19 individuals with detailed demographics and followed up to seven months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization were associated with COVID-19 severity. A subgroup of high responders maintained high neutralizing responses over time, representing ideal convalescent plasma therapy donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal plasma donors and vaccine monitoring and design.

93: Cognitive deficits in people who have recovered from COVID-19 relative to controls: An N=84,285 online study
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Posted 21 Oct 2020

Cognitive deficits in people who have recovered from COVID-19 relative to controls: An N=84,285 online study
4,350 downloads medRxiv psychiatry and clinical psychology

Adam Hampshire, William Trender, Samuel R Chamberlain, Amy Jolly, Jon E. Grant, Fiona Patrick, Ndaba Mazibuko, Steve Williams, Joseph M Barnby, Peter Hellyer, Mitul A Mehta

Case studies have revealed neurological problems in severely affected COVID-19 patients. However, there is little information regarding the nature and broader prevalence of cognitive problems post-infection or across the full spread of severity. We analysed cognitive test data from 84,285 Great British Intelligence Test participants who completed a questionnaire regarding suspected and biologically confirmed COVID-19 infection. People who had recovered, including those no longer reporting symptoms, exhibited significant cognitive deficits when controlling for age, gender, education level, income, racial-ethnic group and pre-existing medical disorders. They were of substantial effect size for people who had been hospitalised, but also for mild but biologically confirmed cases who reported no breathing difficulty. Finer grained analyses of performance support the hypothesis that COVID-19 has a multi-system impact on human cognition. Significance statementThere is evidence that COVID-19 may cause long term health changes past acute symptoms, termed long COVID. Our analyses of detailed cognitive assessment and questionnaire data from tens thousands of datasets, collected in collaboration with BBC2 Horizon, align with the view that there are chronic cognitive consequences of having COVID-19. Individuals who recovered from suspected or confirmed COVID-19 perform worse on cognitive tests in multiple domains than would be expected given their detailed age and demographic profiles. This deficit scales with symptom severity and is evident amongst those without hospital treatment. These results should act as a clarion call for more detailed research investigating the basis of cognitive deficits in people who have survived SARS-COV-2 infection.

94: SARS-CoV-2 reinfection in a cohort of 43,000 antibody-positive individuals followed for up to 35 weeks
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Posted 15 Jan 2021

SARS-CoV-2 reinfection in a cohort of 43,000 antibody-positive individuals followed for up to 35 weeks
4,305 downloads medRxiv epidemiology

Laith J Abu-Raddad, Hiam Chemaitelly, Peter Coyle, Joel A Malek, Ayeda A Ahmed, Yasmin A. Mohamoud, Shameem Younuskunju, Houssein H. Ayoub, Zaina Al Kanaani, Einas Al Kuwari, Adeel A Butt, Andrew Jeremijenko, Anvar Hassan Kaleeckal, Ali Nizar Latif, Riyazuddin Mohammad Shaik, Hanan F. Abdul Rahim, Gheyath K. Nasrallah, Hadi M. Yassine, Mohamed G. Al Kuwari, Hamad Eid Al Romaihi, Mohamed H. Al-Thani, Abdullatif Al Khal, Roberto Bertollini

Background: Reinfection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been documented, raising public health concerns. Risk and incidence rate of SARS-CoV-2 reinfection were assessed in a large cohort of antibody-positive persons in Qatar. Methods: All SARS-CoV-2 antibody-positive persons with a PCR-positive swab [&ge;]14 days after the first-positive antibody test were individually investigated for evidence of reinfection. Viral genome sequencing was conducted for paired viral specimens to confirm reinfection. Incidence of reinfection was compared to incidence of infection in the complement cohort of those antibody-negative. Results: Among 43,044 anti-SARS-CoV-2 positive persons who were followed for a median of 16.3 weeks (range: 0-34.6), 314 individuals (0.7%) had at least one PCR positive swab [&ge;]14 days after the first-positive antibody test. Of these individuals, 129 (41.1%) had supporting epidemiological evidence for reinfection. Reinfection was next investigated using viral genome sequencing. Applying the viral-genome-sequencing confirmation rate, the risk of reinfection was estimated at 0.10% (95% CI: 0.08-0.11%). The incidence rate of reinfection was estimated at 0.66 per 10,000 person-weeks (95% CI: 0.56-0.78). Incidence rate of reinfection versus month of follow-up did not show any evidence of waning of immunity for over seven months of follow-up. Meanwhile, in the complement cohort of 149,923 antibody-negative persons followed for a median of 17.0 weeks (range: 0-45.6), risk of infection was estimated at 2.15% (95% CI: 2.08-2.22%) and incidence rate of infection was estimated at 13.69 per 10,000 person-weeks (95% CI: 13.22-14.14). Efficacy of natural infection against reinfection was estimated at 95.2% (95% CI: 94.1-96.0%). Reinfections were less severe than primary infections. Only one reinfection was severe, two were moderate, and none were critical or fatal. Most reinfections (66.7%) were diagnosed incidentally through random or routine testing, or through contact tracing. Conclusions: Reinfection is rare. Natural infection appears to elicit strong protection against reinfection with an efficacy ~95% for at least seven months.

95: Modeling the spread of Covid-19 under active management
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Posted 23 Nov 2020

Modeling the spread of Covid-19 under active management
4,285 downloads medRxiv epidemiology

Ivan Cherednik

Classical approaches to modeling the spread of epidemics are based on two assumptions: the exponential growth of the total number of infections and the saturation due to the herd immunity. With Covid-19, the growth is essentially power-type, especially during the middle stages, and the saturation is currently mostly due to the protective measures. Focusing on these features and the role of epidemic management, we obtain differential equations for the total number of detected cases of Covid-19, which describe the actual curves in many countries almost with the accuracy of physics laws. The two-phase solution we propose works very well almost for the whole periods of the spread practically in all countries we analyzed that reached the saturation during the first waves. Bessel functions play the key role in our approach. Due to a very small number of parameters, namely, the initial transmission rate and the intensity of the hard and soft measures, we obtain a convincing explanation of the surprising uniformity of the curves of the total numbers of detected infections in many different areas. This theory can serve as a tool for forecasting the epidemic spread and evaluating the efficiency of the protective measures, which is very much needed for epidemics. As its practical application, the computer programs aimed at providing projections for late stages of Covid-19 proved to be remarkably stable in many countries, including Western Europe, the USA and some in Asia. We provide a projection for the saturation of the 3rd wave in the USA: the corresponding number of total, detected or not, cases can presumably reach then the herd immunity levels (G-strains). This can be used to analyze the efficiency of the vaccinations.

96: Molecular dynamic simulation reveals E484K mutation enhances spike RBD-ACE2 affinity and the combination of E484K, K417N and N501Y mutations (501Y.V2 variant) induces conformational change greater than N501Y mutant alone, potentially resulting in an escape mutant
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Posted 13 Jan 2021

Molecular dynamic simulation reveals E484K mutation enhances spike RBD-ACE2 affinity and the combination of E484K, K417N and N501Y mutations (501Y.V2 variant) induces conformational change greater than N501Y mutant alone, potentially resulting in an escape mutant
4,228 downloads bioRxiv biophysics

Gard Nelson, Oleksandr Buzko, Patricia R Spilman, Kayvan Niazi, Shahrooz Rabizadeh, Patrick R Soon-Shiong

Rapidly spreading SARS-CoV-2 variants present not only an increased threat to human health due to the confirmed greater transmissibility of several of these new strains but, due to conformational changes induced by the mutations, may render first-wave SARS-CoV-2 convalescent sera, vaccine-induced antibodies, or recombinant neutralizing antibodies (nAbs)ineffective. To be able to assess the risk of viral escape from neutralization by first-wave antibodies, we leveraged our capability for Molecular Dynamic (MD) simulation of the spike receptor binding domain (S RBD)and its binding to human angiotensin-converting enzyme 2 (hACE2) to predict alterations in molecular interactions resulting from the presence of the E484K, K417N, and N501Y variants found in the South African 501Y.V2 strain - alone and in combination. We report here the combination of E484K, K417N, and N501Y results in the highest degree of conformational alterations of S RBD when bound to hACE2, compared to either E484K or N501Y alone. Both E484K and N501Y increase affinity of S RBD for hACE2 and E484K in particular switched the charge on the flexible loop region of S RBD which leads to the formation of novel favorable contacts. Enhanced affinity of S RBD for hACE2 very likely underpins the greater transmissibility conferred by the presence of either E484K or N501Y; while the induction of conformational changes may provide an explanation for evidence that the 501Y.V2 variant, distinguished from the B.1.1.7 UK variant by the presence of E484K, is able to escape neutralization by existing first-wave anti-SARS-CoV-2 antibodies and re-infect COVID-19 convalescent individuals.

97: Safety and Efficacy of the combined use of ivermectin, dexamethasone, enoxaparin and aspirin against COVID-19
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Posted 15 Sep 2020

Safety and Efficacy of the combined use of ivermectin, dexamethasone, enoxaparin and aspirin against COVID-19
4,114 downloads medRxiv infectious diseases

Hector Eduardo Carvallo, Roberto Raul Hirsch, Maria Eugenia Farinella

From the first outbreak in Wuhan (China) in December 2019, until today the number of deaths worldwide due to the coronavirus pandemic exceeds eight hundred thousand people and the number of infected people arises to more than 25 million. No treatment tested worldwide has shown unquestionable efficacy in the fight against COVID 19, according to NICE reports. We have designed an experimental treatment called IDEA based on four affordable drugs already available on the market in Argentina, based on the following rationale: -Ivermectin solution at a relatively high dose to lower the viral load in all stages of COVID 19 -Dexamethasone 4-mg injection, as anti-inflammatory drug to treat hyperinflammatory reaction to COVID-infection -Enoxaparin injection as anticoagulant to treat hypercoagulation in severe cases. -Aspirin 250-mg tablets to prevent hypercoagulation in mild and moderate cases Except for Ivermection oral solution, which was used in a higher dose than approved for parasitosis, all other drugs were used in the already approved dose and indication. Regarding Ivermectin safety, several oral studies have shown it to be safe even when used at daily doses much higher than those approved already. A clinical study has been conducted on COVID-19 patients at Eurnekian Hospital in the Province of Buenos Aires, Argentina. The study protocol and its final outcomes are described in this article. Results were compared with published data and data from patients admitted to the hospital receiving other treatments. None of the patient presenting mild symptoms needed to be hospitalized. Only one patient died (0.59 % of all included patients vs. 2.1 % overall mortality for the disease in Argentina today; 3.1 % of hospitalized patients vs. 26.8 % mortality in published data). IDEA protocol appears to be a useful alternative to prevent disease progression of COVID-19 when applied to mild cases and to decrease mortality in patients at all stages of the disease with a favorable risk-benefit ratio.

98: Controlled randomized clinical trial on using Ivermectin with Doxycycline for treating COVID-19 patients in Baghdad, Iraq
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Posted 27 Oct 2020

Controlled randomized clinical trial on using Ivermectin with Doxycycline for treating COVID-19 patients in Baghdad, Iraq
4,088 downloads medRxiv infectious diseases

Hashim A. Hashim, Mohammed F. Maulood, Anwar M. Rasheed, Dhurgham F. Fatak, Khulood K Kabah, Ahmed S. Abdulamir

ObjectivesCOVID-19 patients suffer from the lack of curative therapy. Hence, there is an urgent need to try repurposed old drugs on COVID-19. MethodsRandomized controlled study on 70 COVID-19 patients (48 mild-moderate, 11 severe, and 11 critical patients) treated with 200ug/kg PO of Ivermectin per day for 2-3 days along with 100mg PO doxycycline twice per day for 5-10 days plus standard therapy; the second arm is 70 COVID-19 patients (48 mild-moderate and 22 severe and zero critical patients) on standard therapy. The time to recovery, the progression of the disease, and the mortality rate were the outcome-assessing parameters. Resultsamong all patients and among severe patients, 3/70 (4.28%) and 1/11 (9%), respectively progressed to a more advanced stage of the disease in the Ivermectin-Doxycycline group versus 7/70 (10%) and 7/22 (31.81%), respectively in the control group (P>0.05). The mortality rate was 0/48 (0%), 0/11 (0%), and 2/11 (18.2%) in mild-moderate, severe, and critical COVID-19 patients, respectively in Ivermectin-Doxycycline group versus 0/48 (0%), and 6/22 (27.27%) in mild-moderate and severe COVID-19 patients, respectively in standard therapy group (p=0.052). Moreover, the mean time to recovery was 6.34, 20.27, and 24.13 days in mild-moderate, severe, and critical COVID-19 patients, respectively in Ivermectin-Doxycycline group versus 13.66 and 24.25 days in mild-moderate and severe COVID-19 patients, respectively in standard therapy group (P<0.01). ConclusionsIvermectin with doxycycline reduced the time to recovery and the percentage of patients who progress to more advanced stage of disease; in addition, Ivermectin with doxycycline reduced mortality rate in severe patients from 22.72% to 0%; however, 18.2% of critically ill patients died with Ivermectin and doxycycline therapy. Taken together, the earlier administered Ivermectin with doxycycline, the higher rate of successful therapy.

99: Low-Cost Enhancement of Facial Mask Filtration to Prevent Transmission of COVID-19
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Posted 04 Aug 2020

Low-Cost Enhancement of Facial Mask Filtration to Prevent Transmission of COVID-19
4,042 downloads medRxiv public and global health

Hari Bhimaraju, Nitish Nag, Ramesh Jain

The use of face masks is recommended worldwide to reduce the spread of COVID-19. A plethora of facial coverings and respirators, both commercial and homemade, pervade the market, but the true filtration capabilities of many homemade measures against the virus are unclear and continue to be unexplored. In this work, we compare the efficacy of the following masks in keeping out particulate matter below 2.5 microns: N95 respirators, surgical masks, cloth masks, cloth masks with activated carbon air filters, cloth masks with HVAC air filters, lightly starch-enhanced cloth masks, and heavily-starched cloth masks. The experiments utilize an inhalation system and aerosol chamber to simulate a masked individual respiring aerosolized air. COVID-19 disproportionately affects people in low-income communities, who often lack the resources to acquire appropriate personal protective equipment and tend to lack the flexibility to shelter in place due to their public-facing occupations. This work tests low-cost enhancements to homemade masks to assist these communities in making better masks to reduce viral transmission. Experimental results demonstrate that the filtration efficacy of cloth masks with either a light or heavy starch can approach the performance of much costlier masks. This discovery supports the idea of low-cost enhancements to reduce transmission and protect individuals from contracting COVID-19.

100: Repurposed antiviral drugs for COVID-19; interim WHO SOLIDARITY trial results
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Posted 15 Oct 2020

Repurposed antiviral drugs for COVID-19; interim WHO SOLIDARITY trial results
4,015 downloads medRxiv infectious diseases

WHO Solidarity trial consortium, Hongchao Pan, Richard Peto, Quarraisha Abdool Karim, Marissa Alejandria, Ana-Maria Henao Restrepo, César Hernández García, Marie-Paule Kieny, Reza Malekzadeh, Srinivas Murthy, Marie-Pierre Preziosi, Srinath Reddy, Mirta Roses Periago, Vasee Sathiyamoorthy, John-Arne Røttingen, Soumya Swaminathan, as the members of the Writing Committee, assume responsibility for the content and integrity of this article

BACKGROUNDWHO expert groups recommended mortality trials in hospitalized COVID-19 of four re-purposed antiviral drugs. METHODSStudy drugs were Remdesivir, Hydroxychloroquine, Lopinavir (fixed-dose combination with Ritonavir) and Interferon-{beta}1a (mainly subcutaneous; initially with Lopinavir, later not). COVID-19 inpatients were randomized equally between whichever study drugs were locally available and open control (up to 5 options: 4 active and local standard-of-care). The intent-to-treat primary analyses are of in-hospital mortality in the 4 pairwise comparisons of each study drug vs its controls (concurrently allocated the same management without that drug, despite availability). Kaplan-Meier 28-day risks are unstratified; log-rank death rate ratios (RRs) are stratified for age and ventilation at entry. RESULTSIn 405 hospitals in 30 countries 11,266 adults were randomized, with 2750 allocated Remdesivir, 954 Hydroxychloroquine, 1411 Lopinavir, 651 Interferon plus Lopinavir, 1412 only Interferon, and 4088 no study drug. Compliance was 94-96% midway through treatment, with 2-6% crossover. 1253 deaths were reported (at median day 8, IQR 4-14). Kaplan-Meier 28-day mortality was 12% (39% if already ventilated at randomization, 10% otherwise). Death rate ratios (with 95% CIs and numbers dead/randomized, each drug vs its control) were: Remdesivir RR=0.95 (0.81-1.11, p=0.50; 301/2743 active vs 303/2708 control), Hydroxychloroquine RR=1.19 (0.89-1.59, p=0.23; 104/947 vs 84/906), Lopinavir RR=1.00 (0.79-1.25, p=0.97; 148/1399 vs 146/1372) and Interferon RR=1.16 (0.96-1.39, p=0.11; 243/2050 vs 216/2050). No study drug definitely reduced mortality (in unventilated patients or any other subgroup of entry characteristics), initiation of ventilation or hospitalisation duration. CONCLUSIONSThese Remdesivir, Hydroxychloroquine, Lopinavir and Interferon regimens appeared to have little or no effect on hospitalized COVID-19, as indicated by overall mortality, initiation of ventilation and duration of hospital stay. The mortality findings contain most of the randomized evidence on Remdesivir and Interferon, and are consistent with meta-analyses of mortality in all major trials. (Funding: WHO. Registration: ISRCTN83971151, NCT04315948)

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