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Rxivist combines biology preprints from bioRxiv and medRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 140,676 papers from 598,159 authors.

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135,938 results found. For more information, click each entry to expand.

81: Knowledge, attitudes and perceptions towards COVID-19 vaccinations: a cross-sectional community survey in Bangladesh
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Posted 19 Feb 2021

Knowledge, attitudes and perceptions towards COVID-19 vaccinations: a cross-sectional community survey in Bangladesh
2,854 downloads medRxiv public and global health

Md. Saiful Islam, Abu Bakkar Siddique, Rejina Akter, Rafia Tasnim, Md. Safaet Hossain Sujan, Paul R Ward, Md. Tajuddin Sikder

BackgroundSeveral vaccines have been approved against coronavirus disease (COVID-19) and distributed globally in different regions. However, general community knowledge, attitudes and perceptions towards COVID-19 vaccinations are poorly understood. Thus, the study aimed to investigate community knowledge, attitudes and perceptions towards COVID-19 vaccinations in Bangladesh. MethodsAn exploratory and anonymous population-based e-survey was conducted among 1658 general individuals (55.6% male; mean age=23.17{+/-}6.05 years; age range=18-65 years). The survey was conducted using a semi-structured and self-reported questionnaire containing informed consent along with four sections (i.e., socio-demographics, knowledge, attitudes, and perceptions). Multiple linear regression was performed to determine the variables predicting knowledge, and attitudes towards COVID-19 vaccinations. ResultsThe mean scores of knowledge and attitudes were 2.83{+/-}1.48 (out of 5) and 9.34{+/-}2.39 (out of 12) respectively. About a quarter of participants thought that the COVID-19 vaccination available in Bangladesh is safe, only 60% will have the vaccination and about two-thirds will recommend it to family and friends. In the multiple regression model, higher SES, having university/ higher levels of education, holding nuclear families and having previous history of essential vaccines uptake were associated with knowledge; whilst attitudes were significantly associated with being female and having previous history of essential vaccines uptake. Just over half of the participants thought that everyone should be vaccinated and 61% responded that health workers should be vaccinated first on priority basis. 95% vaccine should be administered free of charge in Bangladesh and almost 90% believed that the COVID-19 vaccine used in Bangladesh may have side effects. ConclusionsThe findings reflect inadequate knowledge but more positive attitudes towards COVID-19 vaccine among the general population in Bangladesh. In order to improve knowledge, immediate health education programs need to be initiated before mass vaccination schedule.

82: 3D Flexible Refinement: Structure and Motion of Flexible Proteins from Cryo-EM
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Posted 22 Apr 2021

3D Flexible Refinement: Structure and Motion of Flexible Proteins from Cryo-EM
2,849 downloads bioRxiv biophysics

Ali Punjani, David J. Fleet

Single particle cryo-EM excels in determining static structures of biological macromolecules such as proteins. However, many proteins are dynamic, with their motion inherently linked to their function. Recovering the continuous motion and detailed 3D structure of flexible proteins from cryo-EM data has remained an open challenge. We introduce 3D Flexible Refinement (3DFlex), a motion-based deep neural network model of continuous heterogeneity. 3DFlex directly exploits the knowledge that conformational variability of a protein is often the result of physical processes that transport density over space and tend to conserve mass and preserve local geometry. From 2D image data, the 3DFlex model jointly learns a single canonical 3D map, latent coordinate vectors that specify positions on the protein's conformational landscape, and a flow generator that, given a latent position as input, outputs a 3D deformation field. This deformation field convects the canonical map into appropriate conformations to explain experimental images. Applied to experimental data, 3DFlex learns non-rigid motion spanning several orders of magnitude while preserving high-resolution details of secondary structure elements. Further, 3DFlex resolves canonical maps that are improved relative to conventional refinement methods because particle images contribute to the maps coherently regardless of the conformation of the protein in the image. Together, the ability to obtain insight into motion in macromolecules, as well as the ability to resolve features that are usually lost in cryo-EM of flexible specimens, will provide new insight and allow new avenues of investigation into biomolecular structure and function.

83: Analysis of SARS-CoV-2 spike glycosylation reveals shedding of a vaccine candidate
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Posted 16 Nov 2020

Analysis of SARS-CoV-2 spike glycosylation reveals shedding of a vaccine candidate
2,841 downloads bioRxiv biochemistry

Juliane Brun, Snezana Vasiljevic, Bevin Gangadharan, Mario Hensen, Anu V. Chandran, Michelle L. Hill, J.L. Kiappes, Raymond A. Dwek, Dominic S. Alonzi, Weston B. Struwe, Nicole Zitzmann

Severe acute respiratory syndrome coronavirus 2 is the causative pathogen of the COVID-19 pandemic which as of Nov 15, 2020 has claimed 1,319,946 lives worldwide. Vaccine development focuses on the viral trimeric spike glycoprotein as the main target of the humoral immune response. Viral spikes carry glycans that facilitate immune evasion by shielding specific protein epitopes from antibody neutralisation. Immunogen integrity is therefore important for glycoprotein-based vaccine candidates. Here we show how site-specific glycosylation differs between virus-derived spikes and spike proteins derived from a viral vectored SARS-CoV-2 vaccine candidate. We show that their cellular secretion pathways are unique, resulting in different protein glycosylation and secretion, which may have implications for the resulting immune response and future vaccine design. ### Competing Interest Statement W.B.S. is a shareholder and consultant to Refeyn Ltd. All other authors declare no conflict of interest.

84: Efficacy of a nasal spray containing Iota-Carrageenan in the prophylaxis of COVID-19 in hospital personnel dedicated to patients care with COVID-19 disease. A pragmatic multicenter, randomized, double-blind, placebo-controlled trial (CARR-COV-02)
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Posted 15 Apr 2021

Efficacy of a nasal spray containing Iota-Carrageenan in the prophylaxis of COVID-19 in hospital personnel dedicated to patients care with COVID-19 disease. A pragmatic multicenter, randomized, double-blind, placebo-controlled trial (CARR-COV-02)
2,818 downloads medRxiv infectious diseases

Juan Manuel Figueroa, Monica Lombardo, Ariel Dogliotti, Luis Flynn, Robert P. Giugliano, Guido Simonelli, Ricardo Valentini, Agnel Ramos, Pablo Romano, Marcelo Marcote, Alicia Michelini, Alejandro Salvado, Emilio Sykora, Cecilia Kniz, Marcelo Kobelinsky, David Salzberg, Diana Jerusalinsky, Osvaldo Uchitel, CARR-COV2 Trial Group

Background Iota-Carrageenan (I-C) is a sulfate polysaccharide synthesized by red algae, with demonstrated antiviral activity and clinical efficacy as nasal spray in the treatment of common cold. In vitro, I-C inhibits SARS-CoV-2 infection in cell culture. Methods This is a pragmatic multicenter, randomized, double-blind, placebo-controlled trial assessing the use of a nasal spray containing I-C in the prophylaxis of COVID-19 in hospital personnel dedicated to care of COVID-19 patients. Clinically healthy physicians, nurses, kinesiologists and others medical providers were assigned in a 1:1 ratio to receive four daily doses of I-C spray or placebo for 21 days. The primary end point was clinical COVID-19, as confirmed by reverse-transcriptase-polymerase-chain-reaction testing, over a period of 21 days. The trial is registered at ClinicalTrials.gov (NCT04521322). Findings A total of 394 individuals were randomly assigned to receive I-C or placebo. Both treatment groups had similar baseline characteristics. The incidence of COVID-19 was significantly lower in the I-C group compared to placebo (1.0% vs 5.0%) (Odds Ratio 0.19 (95% confidence interval 0.05 to 0.77; p= 0.03). Workday loss in placebo group compared to I-C were 1.6% days / person (95% CI, 1.0 to 2.2); p <0.0001 There were no differences in the incidence of adverse events across the two groups (17.3% in the I-C group and 15.2% in the placebo group, p= 0.5). Interpretation I-C showed significant efficacy in preventing SARS-CoV-2 infection in hospital personnel dedicated to care patients with COVID-19 disease.

85: COVID-19 Antibody Seroprevalence in Santa Clara County, California
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Posted 17 Apr 2020

COVID-19 Antibody Seroprevalence in Santa Clara County, California
2,804 downloads medRxiv epidemiology

Eran Bendavid, Bianca Mulaney, Neeraj Sood, Soleil Shah, Emilia Ling, Rebecca Bromley-Dulfano, Cara Lai, Zoe Weissberg, Rodrigo Saavedra-Walker, James Tedrow, Dona Tversky, Andrew Bogan, Thomas Kupiec, Daniel Eichner, Ribhav Gupta, John Ioannidis, Jay Bhattacharya

Background Addressing COVID-19 is a pressing health and social concern. To date, many epidemic projections and policies addressing COVID-19 have been designed without seroprevalence data to inform epidemic parameters. We measured the seroprevalence of antibodies to SARS-CoV-2 in a community sample drawn from Santa Clara County. Methods On April 3-4, 2020, we tested county residents for antibodies to SARS-CoV-2 using a lateral flow immunoassay. Participants were recruited using Facebook ads targeting a sample of individuals living within the county by demographic and geographic characteristics. We estimate weights to adjust our sample to match the zip code, sex, and race/ethnicity distribution within the county. We report both the weighted and unweighted prevalence of antibodies to SARS-CoV-2. We also adjust for test performance characteristics by combining data from 16 independent samples obtained from manufacturer's data, regulatory submissions, and independent evaluations: 13 samples for specificity (3,324 specimens) and 3 samples for sensitivity (157 specimens). Results The raw prevalence of antibodies to SARS-CoV-2 in our sample was 1.5% (exact binomial 95CI 1.1-2.0%). Test performance specificity in our data was 99.5% (95CI 99.2-99.7%) and sensitivity was 82.8% (95CI 76.0-88.4%). The unweighted prevalence adjusted for test performance characteristics was 1.2% (95CI 0.7-1.8%). After weighting for population demographics of Santa Clara County, the prevalence was 2.8% (95CI 1.3-4.7%), using bootstrap to estimate confidence bounds. These prevalence point estimates imply that 54,000 (95CI 25,000 to 91,000 using weighted prevalence; 23,000 with 95CI 14,000-35,000 using unweighted prevalence) people were infected in Santa Clara County by early April, many more than the approximately 1,000 confirmed cases at the time of the survey. Conclusions The estimated population prevalence of SARS-CoV-2 antibodies in Santa Clara County implies that the infection may be much more widespread than indicated by the number of confirmed cases. More studies are needed to improve precision of prevalence estimates. Locally-derived population prevalence estimates should be used to calibrate epidemic and mortality projections.

86: Initial real world evidence for lower viral load of individuals who have been vaccinated by BNT162b2
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Posted 08 Feb 2021

Initial real world evidence for lower viral load of individuals who have been vaccinated by BNT162b2
2,732 downloads medRxiv epidemiology

Ella Petter, Orna Mor, Neta Zuckerman, Danit Oz-Levi, Asaf Younger, Dvir Aran, Yaniv Erlich

One of the key questions regarding COVID19 vaccines is whether they can reduce viral shedding. To date, Israel vaccinated substantial parts of the adult population, which enables extracting real world signals. The vaccination rollout started on Dec 20th 2020, utilized mainly the BNT162b2 vaccine, and focused on individuals who are 60 years or older. By now, more than 75% of the individuals of this age group have been at least 14 days after the first dose, compared to 25% of the individuals between ages 40-60 years old. Here, we traced the Ct value distribution of 16,297 positive qPCR tests in our lab between Dec 1st to Jan 31st that came from these two age groups. As we do not have access to the vaccine status of each test, our hypothesis was that if vaccines reduce viral load, we should see a difference in the Ct values between these two age groups in late January but not before. Consistent with this hypothesis, until Jan 15th, we did not find any statistically significant differences in the average Ct value between the groups. In stark contrast, our results in the last two weeks of January show a significant weakening in the average Ct value of 60+ individuals to the 40-60 group. To further corroborate these results, we also used a series nested linear models to explain the Ct values of the positive tests. This analysis favored a model that included an interaction between age and the late January time period, consistent with the effect of vaccination. We then used demographic data and the daily vaccination rates to estimate the effect of vaccination on viral load reduction. Our estimate suggests that vaccination reduces the viral load by 1.6x to 20x in individuals who are positive for SARS-CoV-2. This estimate might improve after more individuals receive the second dose. Taken together, our findings indicate vaccination is not only important for individual's protection but can reduce transmission.

87: Increased Resistance of SARS-CoV-2 Variant P.1 to Antibody Neutralization
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Posted 02 Mar 2021

Increased Resistance of SARS-CoV-2 Variant P.1 to Antibody Neutralization
2,719 downloads bioRxiv microbiology

Pengfei Wang, Ryan G. Casner, Manoj S. Nair, Maple Wang, Jian Yu, Gabriele Cerutti, Lihong Liu, Peter D. Kwong, Yaoxing Huang, Lawrence Shapiro, David D Ho

The relative resistance of SARS-CoV-2 variants B.1.1.7 and B.1.351 to antibody neutralization has been described recently. We now report that another emergent variant from Brazil, P.1, is not only refractory to multiple neutralizing monoclonal antibodies, but also more resistant to neutralization by convalescent plasma (3.4 fold) and vaccinee sera (3.8-4.8 fold). The cryo-electron microscopy structure of a soluble prefusion-stabilized spike reveals the P.1 trimer to adopt exclusively a conformation in which one of the receptor-binding domains is in the "up" position, with the functional impact of mutations appearing to arise from local changes instead of global conformational alterations. The P.1 variant threatens current antibody therapies but less so the protective efficacy of our vaccines.

88: Nonlinear control of transcription through enhancer-promoter interactions
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Posted 22 Apr 2021

Nonlinear control of transcription through enhancer-promoter interactions
2,709 downloads bioRxiv molecular biology

Jessica Zuin, Gregory Roth, Yinxiu Zhan, Julie Cramard, Josef Redolfi, Ewa Piskadlo, Pia Mach, Mariya Kryzhanovska, Gergely Tihanyi, Hubertus Kohler, Peter Meister, Sebastien Smallwood, Luca Giorgetti

Chromosome structure in mammals is thought to regulate transcription by modulating the three-dimensional interactions between enhancers and promoters, notably through CTCF-mediated interactions and topologically associating domains (TADs). However, how chromosome interactions are actually translated into transcriptional outputs remains unclear. To address this question we use a novel assay to position an enhancer at a large number of densely spaced chromosomal locations relative to a fixed promoter, and measure promoter output and interactions within a genomic region with minimal regulatory and structural complexity. Quantitative analysis of hundreds of cell lines reveal that the transcriptional effect of an enhancer depends on its contact probabilities with the promoter through a non-linear relationship. Mathematical modeling and validation against experimental data further provide evidence that nonlinearity arises from transient enhancer-promoter interactions being memorized into longer-lived promoter states in individual cells, thus uncoupling the temporal dynamics of interactions from those of transcription. This uncovers a potential mechanism for how enhancers control transcription across large genomic distances despite rarely meeting their target promoters, and for how TAD boundaries can block distal enhancers. We finally show that enhancer strength additionally determines not only absolute transcription levels, but also the sensitivity of a promoter to CTCF-mediated functional insulation. Our unbiased, systematic and quantitative measurements establish general principles for the context-dependent role of chromosome structure in long-range transcriptional regulation.

89: Predicting the Trajectory of Any COVID19 Epidemic From the Best Straight Line
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Posted 28 Jun 2020

Predicting the Trajectory of Any COVID19 Epidemic From the Best Straight Line
2,680 downloads medRxiv epidemiology

Michael Levitt, Andrea Scaiewicz, Francesco Zonta

A pipeline involving data acquisition, curation, carefully chosen graphs and mathematical models, allows analysis of COVID-19 outbreaks at 3,546 locations world-wide (all countries plus smaller administrative divisions with data available). Comparison of locations with over 50 deaths shows all outbreaks have a common feature: H(t) defined as loge(X(t)/X(t 1)) decreases linearly on a log scale, where X(t) is the total number of Cases or Deaths on day, t (we use ln for loge). The downward slopes vary by about a factor of three with time constants (1/slope) of between 1 and 3 weeks; this suggests it may be possible to predict when an outbreak will end. Is it possible to go beyond this and perform early prediction of the outcome in terms of the eventual plateau number of total confirmed cases or deaths? We test this hypothesis by showing that the trajectory of cases or deaths in any outbreak can be converted into a straight line. Specifically , is a straight line for the correct plateau value N, which is determined by a new method, Best-Line Fitting (BLF). BLF involves a straight-line facilitation extrapolation needed for prediction; it is blindingly fast and amenable to optimization. We find that in some locations that entire trajectory can be predicted early, whereas others take longer to follow this simple functional form. Fortunately, BLF distinguishes predictions that are likely to be correct in that they show a stable plateau of total cases or death (N value). We apply BLF to locations that seem close to a stable predicted N value and then forecast the outcome at some locations that are still growing wildly. Our accompanying web-site will be updated frequently and provide all graphs and data described here.

90: Assessment of Fabric Masks as Alternatives to Standard Surgical Masks in Terms of Particle Filtration Efficiency
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Posted 22 Apr 2020

Assessment of Fabric Masks as Alternatives to Standard Surgical Masks in Terms of Particle Filtration Efficiency
2,664 downloads medRxiv occupational and environmental health

Amy V Mueller, Matthew J. Eden, Jessica J. Oakes, Chiara Bellini, Loretta A Fernandez

In response to the COVID-19 pandemic, cloth masks are being used to control the spread of virus, but the efficacy of these loose-fitting masks is not well known. Here, tools and methods typically used to assess tight-fitting respirators were modified to quantify the efficacy of community- and commercially-produced fabric masks as PPE. Two particle counters concurrently sample ambient air and air inside the masks; mask performance is evaluated by mean particle removal efficiency and statistical variability when worn as designed and with a nylon overlayer, to independently assess fit and material. Worn as designed both commercial surgical masks and cloth masks had widely varying effectiveness (53-75% and 28-90% filtration efficiency, respectively). Most surgical-style masks improved with the nylon overlayer, indicating poor fit. This rapid testing method uses widely available hardware, requires only a few calculations from collected data, and provides both a holistic and aspect-wise evaluation of mask performance.

91: A sensitive and affordable multiplex RT-qPCR assay for SARS-CoV-2 detection
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Posted 16 Jul 2020

A sensitive and affordable multiplex RT-qPCR assay for SARS-CoV-2 detection
2,662 downloads medRxiv infectious diseases

Martin A.M. Reijns, Louise Thompson, Juan Carlos Acosta, Holly A Black, Francisco J. Sanchez-Luque, Austin Diamond, David A. Parry, Alison Daniels, Marie O’Shea, Carolina Uggenti, Maria C. Sanchez, Alan O’Callaghan, Michelle L.L. McNab, Martyna Adamowicz, Elias T Friman, Toby Hurd, Edward J. Jarman, Frederic Li Mow Chee, Jacqueline K. Rainger, Marion Walker, Camilla Drake, Dasa Longman, Christine Mordstein, Sophie J. Warlow, Stewart McKay, Louise Slater, Morad Ansari, Ian PM Tomlinson, David Moore, Nadine Wilkinson, Jill Shepherd, Kate Templeton, Ingolfur Johannessen, Christine Tait-Burkard, Jürgen G. Haas, Nick Gilbert, Ian R. Adams, Andrew P. Jackson

With the ongoing COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, there is need for sensitive, specific and affordable diagnostic tests to identify infected individuals, not all of whom are symptomatic. The most sensitive test involves the detection of viral RNA using RT-qPCR, with many commercial kits now available for this purpose. However, these are expensive and supply of such kits in sufficient numbers cannot always be guaranteed. We therefore developed a multiplex assay using well-established SARS-CoV-2 targets alongside a human cellular control (RPP30) and a viral spike-in control (PhHV-1), which monitor sample quality and nucleic acid extraction efficiency respectively. Here, we establish that this test performs as well as widely used commercial assays, but at substantially reduced cost. Furthermore, we demonstrate >1,000-fold variability in material routinely collected by nose-and-throat swabbing, and establish a statistically significant correlation between the detected level of human and SARS-CoV-2 nucleic acids. The inclusion of the human control probe in our assay therefore provides a quantitative measure of sample quality that could help reduce false negative rates. We demonstrate feasibility of establishing a robust RT-qPCR assay at [~]10% of the cost of equivalent commercial assays, which could benefit low resource environments and make high volume testing more affordable.

92: 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
2,647 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.

93: 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
2,643 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.

94: Duration of Oxygen Requirement and Predictors in Severe COVID-19 Patients in Ethiopia: A Survival Analysis
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Posted 13 Oct 2020

Duration of Oxygen Requirement and Predictors in Severe COVID-19 Patients in Ethiopia: A Survival Analysis
2,626 downloads medRxiv infectious diseases

Tigist W. Leulseged, Ishmael S. Hassen, Mesay G. Edo, Daniel S. Abebe, Endalkachew H. Maru, Wuletaw C. Zewde, Nigat W. Chamesew, Tariku B. Jagema

AimTo estimate time to getting off supplemental oxygen therapy and identify predictors among COVID-19 patients admitted to Millennium COVID-19 Care Center in Addis Ababa, Ethiopia. MethodsA prospective observational study was conducted among 244 consecutively admitted COVID-19 patients from July to September, 2020. Frequency tables, KM plots, median survival times and Log-rank test were used to describe the data and compare survival distribution between groups. Cox proportional hazard survival model was used to assess the presence of a statistically significant association between time to getting off supplemental oxygen therapy and the independent variables, where hazard ratio, P-value and 95% CI for hazard ratio were used for testing significance and interpretation of results. ResultsMedian time to getting off supplemental oxygen therapy among the studied population was 6 days. Factors that affect time to getting off supplemental oxygen therapy were age group (HR= 0.522, 95% CI= 0.323, 0.844, p-value=0.008 for [&ge;] 70 years) and shortness of breath (HR= 0.705, 95% CI= 0.519, 0.959, p-value=0.026). ConclusionsAverage duration of supplemental oxygen therapy requirement among COVID-19 patients was 6 days and being 70 years and older and having shortness of breath were found to be associated with prolonged duration of supplemental oxygen therapy requirement. This result can be used as a guide in planning institutional resource allocation and patient management to provide a well equipped care to prevent complications and death from the disease.

95: Why most Principal Component Analyses (PCA) in population genetic studies are wrong
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Posted 12 Apr 2021

Why most Principal Component Analyses (PCA) in population genetic studies are wrong
2,611 downloads bioRxiv genetics

Eran Elhaik

Principal Component Analysis (PCA) is a multivariate analysis that allows reduction of the complexity of datasets while preserving data's covariance and visualizing the information on colorful scatterplots, ideally with only a minimal loss of information. PCA applications are extensively used as the foremost analyses in population genetics and related fields (e.g., animal and plant or medical genetics), implemented in well-cited packages like EIGENSOFT and PLINK. PCA outcomes are used to shape study design, identify and characterize individuals and populations, and draw historical and ethnobiological conclusions on origins, evolution, whereabouts, and relatedness. The replicability crisis in science has prompted us to evaluate whether PCA results are reliable, robust, and replicable. We employed an intuitive color-based model alongside human population data for eleven common test cases. We demonstrate that PCA results are artifacts of the data and that they can be easily manipulated to generate desired outcomes. PCA results may not be reliable, robust, or replicable as the field assumes. Our findings raise concerns on the validity of results reported in the literature of population genetics and related fields that place a disproportionate reliance upon PCA outcomes and the insights derived from them. We conclude that PCA may have a biasing role in genetic investigations. An alternative mixed-admixture population genetic model is discussed.

96: Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications
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Posted 06 Apr 2020

Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications
2,604 downloads medRxiv infectious diseases

Fan Wu, Aojie Wang, Mei Liu, Qimin Wang, Jun Chen, Shuai Xia, Yun Ling, Yuling Zhang, Jingna Xun, Lu Lu, Shibo Jiang, Hongzhou Lu, Yumei Wen, Jinghe Huang

BackgroundThe COVID-19 pandemic caused by SARS-CoV-2 coronavirus threatens global public health. Currently, neutralizing antibodies (NAbs) versus this virus are expected to correlate with recovery and protection of this disease. However, the characteristics of these antibodies have not been well studied in association with the clinical manifestations in patients. MethodsPlasma collected from 175 COVID-19 recovered patients with mild symptoms were screened using a safe and sensitive pseudotyped-lentiviral-vector-based neutralization assay. Spike-binding antibody in plasma were determined by ELISA using RBD, S1, and S2 proteins of SARS-CoV-2. The levels and the time course of SARS-CoV-2-specific NAbs and the spike-binding antibodies were monitored at the same time. FindingsSARS-CoV-2 NAbs were unable to cross-reactive with SARS-CoV virus. SARS-CoV-2-specific NAbs were detected in patients from day 10-15 after the onset of the disease and remained thereafter. The titers of NAb among these patients correlated with the spike-binding antibodies targeting S1, RBD, and S2 regions. The titers of NAbs were variable in different patients. Elderly and middle-age patients had significantly higher plasma NAb titers (P<0.0001) and spike-binding antibodies (P=0.0003) than young patients. Notably, among these patients, there were ten patients whose NAb titers were under the detectable level of our assay (ID50: < 40); while in contrast, two patients, showed very high titers of NAb, with ID50 :15989 and 21567 respectively. The NAb titers were positive correlated with plasma CRP levels but negative correlated with the lymphocyte counts of patients at the time of admission, indicating an association between humoral response and cellular immune response. InterpretationThe variations of SARS-CoV-2 specific NAbs in recovered COVID-19 patients may raise the concern about the role of NAbs on disease progression. The correlation of NAb titers with age, lymphocyte counts, and blood CRP levels suggested that the interplay between virus and host immune response in coronavirus infections should be further explored for the development of effective vaccine against SARS-CoV-2 virus. Furthermore, titration of NAb is helpful prior to the use of convalescent plasma for prevention or treatment. FundingMinistry of Science and Technology of China, National Natural Science Foundation of China, Shanghai Municipal Health Commission, and Chinese Academy of Medical Sciences

97: Comprehensive mapping of mutations to the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human serum antibodies
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Posted 04 Jan 2021

Comprehensive mapping of mutations to the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human serum antibodies
2,592 downloads bioRxiv microbiology

Allison J Greaney, Andrea N Loes, Katharine HD Crawford, Tyler N Starr, Keara D Malone, Helen Y Chu, Jesse D Bloom

The evolution of SARS-CoV-2 could impair recognition of the virus by human antibody-mediated immunity. To facilitate prospective surveillance for such evolution, we map how convalescent serum antibodies are impacted by all mutations to the spikes receptor-binding domain (RBD), the main target of serum neutralizing activity. Binding by polyclonal serum antibodies is affected by mutations in three main epitopes in the RBD, but there is substantial variation in the impact of mutations both among individuals and within the same individual over time. Despite this inter- and intra-person heterogeneity, the mutations that most reduce antibody binding usually occur at just a few sites in the RBDs receptor binding motif. The most important site is E484, where neutralization by some sera is reduced >10-fold by several mutations, including one in emerging viral lineages in South Africa and Brazil. Going forward, these serum escape maps can inform surveillance of SARS-CoV-2 evolution.

98: Magnitude and Dynamics of the T-Cell Response to SARS-CoV-2 Infection at Both Individual and Population Levels
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Posted 04 Aug 2020

Magnitude and Dynamics of the T-Cell Response to SARS-CoV-2 Infection at Both Individual and Population Levels
2,569 downloads medRxiv infectious diseases

Thomas M Snyder, Rachel M Gittelman, Mark Klinger, Damon H May, Edward J Osborne, Ruth Taniguchi, H Jabran Zahid, Ian M Kaplan, Jennifer N Dines, Matthew N Noakes, Ravi Pandya, Xiaoyu Chen, Summer Elasady, Emily Svejnoha, Peter Ebert, Mitchell W. Pesesky, Patricia De Almeida, Hope O'Donnell, Quinn DeGottardi, Gladys Keitany, Jennifer Lu, Allen Vong, Rebecca Elyanow, Paul Fields, Julia Greissl, Lance Baldo, Simona Semprini, Claudio Cerchione, Fabio Nicolini, Massimiliano Mazza, Ottavia M Delmonte, Kerry Dobbs, Rocio Laguna-Goya, Gonzalo Carreño-Tarragona, Santiago Barrio, Luisa Imberti, Alessandra Sottini, Eugenia Quiros-Roldan, Camillo Rossi, Andrea Biondi, Laura Rachele Bettini, Mariella D'Angio, Paolo Bonfanti, Miranda F Tompkins, Camille Alba, Clifton Dalgard, Vittorio Sambri, Giovanni Martinelli, Jason D. Goldman, James R. Heath, Helen C. Su, Luigi D Notarangelo, Estela Paz-Artal, Joaquin Martinez-Lopez, Jonathan M. Carlson, Harlan S Robins

T cells are involved in the early identification and clearance of viral infections and also support the development of antibodies by B cells. This central role for T cells makes them a desirable target for assessing the immune response to SARS-CoV-2 infection. Here, we combined two high-throughput immune profiling methods to create a quantitative picture of the T-cell response to SARS-CoV-2. First, at the individual level, we deeply characterized 3 acutely infected and 58 recovered COVID-19 subjects by experimentally mapping their CD8 T-cell response through antigen stimulation to 545 Human Leukocyte Antigen (HLA) class I presented viral peptides (class II data in a forthcoming study). Then, at the population level, we performed T-cell repertoire sequencing on 1,815 samples (from 1,521 COVID-19 subjects) as well as 3,500 controls to identify shared "public" T-cell receptors (TCRs) associated with SARS-CoV-2 infection from both CD8 and CD4 T cells. Collectively, our data reveal that CD8 T-cell responses are often driven by a few immunodominant, HLA-restricted epitopes. As expected, the T-cell response to SARS-CoV-2 peaks about one to two weeks after infection and is detectable for at least several months after recovery. As an application of these data, we trained a classifier to diagnose SARS-CoV-2 infection based solely on TCR sequencing from blood samples, and observed, at 99.8% specificity, high early sensitivity soon after diagnosis (Day 3-7 = 85.1% [95% CI = 79.9-89.7]; Day 8-14 = 94.8% [90.7-98.4]) as well as lasting sensitivity after recovery (Day 29+/convalescent = 95.4% [92.1-98.3]). These results demonstrate an approach to reliably assess the adaptive immune response both soon after viral antigenic exposure (before antibodies are typically detectable) as well as at later time points. This blood-based molecular approach to characterizing the cellular immune response has applications in clinical diagnostics as well as in vaccine development and monitoring.

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

FDA-authorized COVID-19 vaccines are effective per real-world evidence synthesized across a multi-state health system
2,513 downloads medRxiv infectious diseases

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

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

100: Discrete immune response signature to SARS-CoV-2 mRNA vaccination versus infection
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Posted 21 Apr 2021

Discrete immune response signature to SARS-CoV-2 mRNA vaccination versus infection
2,508 downloads medRxiv infectious diseases

Ellie N Ivanova, Joseph C Devlin, Terild B Buus, Akiko Koide, Amber Cornelius, Marie I. Samanovic, Alberto Herrera, Chenzhen Zhang, Ludovic Desvignes, Niels Odum, Robert Ulrich, Mark J Mulligan, Shohei Koide, Kelly V Ruggle, Ramin Herati, Sergei Koralov

Both SARS-CoV-2 infection and vaccination elicit potent immune responses. A number of studies have described immune responses to SARS-CoV-2 infection. However, beyond antibody production, immune responses to COVID-19 vaccines remain largely uncharacterized. Here, we performed multimodal single-cell sequencing on peripheral blood of patients with acute COVID- 19 and healthy volunteers before and after receiving the SARS-CoV-2 BNT162b2 mRNA vaccine to compare the immune responses elicited by the virus and by this vaccine. Phenotypic and transcriptional profiling of immune cells, coupled with reconstruction of the B and T cell antigen receptor rearrangement of individual lymphocytes, enabled us to characterize and compare the host responses to the virus and to defined viral antigens. While both infection and vaccination induced robust innate and adaptive immune responses, our analysis revealed significant qualitative differences between the two types of immune challenges. In COVID-19 patients, immune responses were characterized by a highly augmented interferon response which was largely absent in vaccine recipients. Increased interferon signaling likely contributed to the observed dramatic upregulation of cytotoxic genes in the peripheral T cells and innate-like lymphocytes in patients but not in immunized subjects. Analysis of B and T cell receptor repertoires revealed that while the majority of clonal B and T cells in COVID-19 patients were effector cells, in vaccine recipients clonally expanded cells were primarily circulating memory cells. Importantly, the divergence in immune subsets engaged, the transcriptional differences in key immune populations, and the differences in maturation of adaptive immune cells revealed by our analysis have far-ranging implications for immunity to this novel pathogen.

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