Most downloaded biology preprints, since beginning of last month
122,650 results found. For more information, click each entry to expand.
6,488 downloads medRxiv infectious diseases
Edward E. Walsh, Robert Frenck, Ann R Falsey, Nicholas Kitchin, Judith Absalon, Alejandra Gurtman, Stephen Lockhart, Kathleen Neuzil, Mark J Mulligan, Ruth Bailey, Kena A. Swanson, Ping Li, Kenneth Koury, Warren Kalina, David Cooper, Camila Fontes-Garfias, Pei-Yong Shi, Özlem Türeci, Kristin R Thompkins, Kirsten E. Lyke, Vanessa Raabe, Philip R. Dormitzer, Kathrin U. Jansen, Uğur Sahin, William C. Gruber
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of people globally. Multiple vaccine candidates are under development, but no vaccine is currently available. Methods: Healthy adults 18-55 and 65-85 years of age were randomized in an ongoing, placebo-controlled, observer-blinded dose-escalation study to receive 2 doses at 21-day intervals of placebo or either of 2 lipid nanoparticle-formulated, nucleoside-modified RNA vaccine candidates: BNT162b1, which encodes a secreted trimerized SARS-CoV-2 receptor-binding domain, or BNT162b2, which encodes a prefusion stabilized membrane-anchored SARS-CoV-2 full-length spike. In each of 13 groups of 15 participants, 12 received vaccine and 3 received placebo. Groups were distinguished by vaccine candidate, age of participant, and vaccine dose level. Interim safety and immunogenicity data of BNT162b1 in younger adults have been reported previously from US and German trials. We now present additional safety and immunogenicity data from the US Phase 1 trial that supported selection of the vaccine candidate advanced to a pivotal Phase 2/3 safety and efficacy evaluation. Results: In both younger and older adults, the 2 vaccine candidates elicited similar dose-dependent SARS-CoV-2-neutralizing geometric mean titers (GMTs), comparable to or higher than the GMT of a panel of SARS-CoV-2 convalescent sera. BNT162b2 was associated with less systemic reactogenicity, particularly in older adults. Conclusion: These results support selection of the BNT162b2 vaccine candidate for Phase 2/3 large-scale safety and efficacy evaluation, currently underway.
6,465 downloads medRxiv health policy
Andrea Dennis, Malgorzata Wamil, Sandeep Kapur, Johann Alberts, Andrew D Badley, Gustav Anton Decker, Stacey A. Rizza, Rajarshi Banerjee, Amitava Banerjee, On behalf of the COVERSCAN study investigators
BackgroundSevere acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection has disproportionately affected older individuals and those with underlying medical conditions. Research has focused on short-term outcomes in hospital, and single organ involvement. Consequently, impact of long COVID (persistent symptoms three months post-infection) across multiple organs in low-risk individuals is yet to be assessed. MethodsAn ongoing prospective, longitudinal, two-centre, observational study was performed in individuals symptomatic after recovery from acute SARS-CoV-2 infection. Symptoms and organ function (heart, lungs, kidneys, liver, pancreas, spleen) were assessed by standardised questionnaires (EQ-5D-5L, Dyspnoea-12), blood investigations and quantitative magnetic resonance imaging, defining single and multi-organ impairment by consensus definitions. FindingsBetween April and September 2020, 201 individuals (mean age 44 (SD 11.0) years, 70% female, 87% white, 31% healthcare workers) completed assessments following SARS-CoV-2 infection (median 140, IQR 105-160 days after initial symptoms). The prevalence of pre-existing conditions (obesity: 20%, hypertension: 6%; diabetes: 2%; heart disease: 4%) was low, and only 18% of individuals had been hospitalised with COVID-19. Fatigue (98%), muscle aches (88%), breathlessness (87%), and headaches (83%) were the most frequently reported symptoms. Ongoing cardiorespiratory (92%) and gastrointestinal (73%) symptoms were common, and 42% of individuals had ten or more symptoms. There was evidence of mild organ impairment in heart (32%), lungs (33%), kidneys (12%), liver (10%), pancreas (17%), and spleen (6%). Single (66%) and multi-organ (25%) impairment was observed, and was significantly associated with risk of prior COVID-19 hospitalisation (p<0.05). InterpretationIn a young, low-risk population with ongoing symptoms, almost 70% of individuals have impairment in one or more organs four months after initial symptoms of SARS-CoV-2 infection. There are implications not only for burden of long COVID but also public health approaches which have assumed low risk in young people with no comorbidities. FundingThis work was supported by the UKs National Consortium of Intelligent Medical Imaging through the Industry Strategy Challenge Fund, Innovate UK Grant 104688, and also through the European Unions Horizon 2020 research and innovation programme under grant agreement No 719445.
6,386 downloads medRxiv infectious diseases
Structured AbstractO_ST_ABSObjectiveC_ST_ABSDetermine age-specific infection fatality rates for COVID-19 to inform public health policies and communications that help protect vulnerable age groups. MethodsStudies of COVID-19 prevalence were collected by conducting an online search of published articles, preprints, and government reports that were publicly disseminated prior to 18 September 2020. The systematic review encompassed 113 studies, of which 27 studies (covering 34 geographical locations) satisfied the inclusion criteria and were included in the meta-analysis. Age-specific IFRs were computed using the prevalence data in conjunction with reported fatalities four weeks after the midpoint date of the study, reflecting typical lags in fatalities and reporting. Meta-regression procedures in Stata were used to analyze the infection fatality rate (IFR) by age. ResultsOur analysis finds a exponential relationship between age and IFR for COVID-19. The estimated age-specific IFR is very low for children and younger adults (e.g., 0.002% at age 10 and 0.01% at age 25) but increases progressively to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75, and 15% at age 85. Moreover, our results indicate that about 90% of the variation in population IFR across geographical locations reflects differences in the age composition of the population and the extent to which relatively vulnerable age groups were exposed to the virus. DiscussionThese results indicate that COVID-19 is hazardous not only for the elderly but also for middle-aged adults, for whom the infection fatality rate is two orders of magnitude greater than the annualized risk of a fatal automobile accident and far more dangerous than seasonal influenza. Moreover, the overall IFR for COVID-19 should not be viewed as a fixed parameter but as intrinsically linked to the age-specific pattern of infections. Consequently, public health measures to mitigate infections in older adults could substantially decrease total deaths.
5,974 downloads medRxiv infectious diseases
Jerry Sadoff, Mathieu Le Gars, Georgi Shukarev, Dirk Heerwegh, Carla Truyers, Anna Marit de Groot, Jeroen Stoop, Sarah Tete, Wim Van Damme, Isabel Leroux-Roels, Pieter-Jan Berghmans, Murray Kimmel, Pierre Van Damme, Jan De Hoon, William Smith, Kathryn Stephenson, Dan Barouch, Stephen De Rosa, Kristen Cohen, Juliana McElrath, Emmanuel Cormier, Gert Scheper, Jenny Hendriks, Frank Struyf, Macaya Douoguih, Johan Van Hoof, Hanneke Schuitemaker
BACKGROUND The ongoing coronavirus disease (COVID)-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be controlled by an efficacious vaccine. Multiple vaccines are in development, but no efficacious vaccine is currently available. METHODS We designed a multi-center phase 1/2a randomized, double-blinded, placebo-controlled clinical study to assesses the safety, reactogenicity and immunogenicity of Ad26.COV2.S, a non-replicating adenovirus 26 based vector expressing the stabilized pre-fusion spike (S) protein of SARS-CoV-2. Ad26.COV2.S was administered at a dose level of 5x1010 or 1x1011 viral particles (vp) per vaccination, either as a single dose or as a two-dose schedule spaced by 56 days in healthy adults (18-55 years old; cohort 1a & 1b; n= 402 and healthy elderly >65 years old; cohort 3; n=394). Vaccine elicited S specific antibody levels were measured by ELISA and neutralizing titers were measured in a wild-type virus neutralization assay (wtVNA). CD4+ T-helper (Th)1 and Th2, and CD8+ immune responses were assessed by intracellular cytokine staining (ICS). RESULTS We here report interim analyses after the first dose of blinded safety data from cohorts 1a, 1b and 3 and group unblinded immunogenicity data from cohort 1a and 3. In cohorts 1 and 3 solicited local adverse events were observed in 58% and 27% of participants, respectively. Solicited systemic adverse events were reported in 64% and 36% of participants, respectively. Fevers occurred in both cohorts 1 and 3 in 19% (5% grade 3) and 4% (0% grade 3), respectively, were mostly mild or moderate, and resolved within 1 to 2 days after vaccination. The most frequent local adverse event (AE) was injection site pain and the most frequent solicited AEs were fatigue, headache and myalgia. After only a single dose, seroconversion rate in wtVNA (50% inhibitory concentration - IC50) at day 29 after immunization in cohort 1a already reached 92% with GMTs of 214 (95% CI: 177; 259) and 92% with GMTs of 243 (95% CI: 200; 295) for the 5x1010 and 1x1011vp dose levels, respectively. A similar immunogenicity profile was observed in the first 15 participants in cohort 3, where 100% seroconversion (6/6) (GMTs of 196 [95%CI: 69; 560]) and 83% seroconversion (5/6) (GMTs of 127 [95% CI: <58; 327]) were observed for the 5x1010 or 1x1011 vp dose level, respectively. Seroconversion for S antibodies as measured by ELISA (ELISA Units/mL) was observed in 99% of cohort 1a participants (GMTs of 528 [95% CI: 442; 630) and 695 (95% CI: 596; 810]), for the 5x1010 or 1x1011 vp dose level, respectively, and in 100% (6/6 for both dose levels) of cohort 3 with GMTs of 507 (95% CI: 181; 1418) and 248 (95% CI: 122; 506), respectively. On day 14 post immunization, Th1 cytokine producing S-specific CD4+ T cell responses were measured in 80% and 83% of a subset of participants in cohort 1a and 3, respectively, with no or very low Th2 responses, indicative of a Th1-skewed phenotype in both cohorts. CD8+ T cell responses were also robust in both cohort 1a and 3, for both dose levels. CONCLUSIONS The safety profile and immunogenicity after only a single dose are supportive for further clinical development of Ad26.COV2.S at a dose level of 5x1010 vp, as a potentially protective vaccine against COVID-19. Trial registration number: NCT04436276
5,831 downloads bioRxiv molecular biology
We performed the plaque reduction neutralization test (PRNT50) using sera collected from the 26 recipients of BBV152/COVAXINTM against hCoV-19/India/20203522 (UK-variant) and hCoV27 19/India/2020Q111 (heterologous strain). A comparable neutralization activity of sera of the vaccinated individuals showed against UK-variant and the heterologous strain with similar efficiency, dispel the uncertainty of possible neutralization escape.
5,819 downloads medRxiv health policy
Objective: To compare the inference regarding the effectiveness of the various non-pharmaceutical interventions (NPIs) for COVID-19 obtained from different SIR models. Study design and setting: We explored two models developed by Imperial College that considered only NPIs without accounting for mobility (model 1) or only mobility (model 2), and a model accounting for the combination of mobility and NPIs (model 3). Imperial College applied models 1 and 2 to 11 European countries and to the USA, respectively. We applied these models to 14 European countries (original 11 plus another 3), over two different time horizons. Results: While model 1 found that lockdown was the most effective measure in the original 11 countries, model 2 showed that lockdown had little or no benefit as it was typically introduced at a point when the time-varying reproductive number was already very low. Model 3 found that the simple banning of public events was beneficial, while lockdown had no consistent impact. Based on Bayesian metrics, model 2 was better supported by the data than either model 1 or model 3 for both time horizons. Conclusions: Inferences on effects of NPIs are non-robust and highly sensitive to model specification. Claimed benefits of lockdown appear grossly exaggerated.
5,784 downloads medRxiv infectious diseases
A distinctive feature of the roll out of vaccination against SARS-CoV-2 virus in the UK was the decision to delay the timing of the second injection till 12 weeks after the first. The logic behind this is to protect more people sooner and so reduce the total number of severe infections, hospitalisations, and deaths. This decision caused criticism from some quarters due in part to a belief that a single injection may not give adequate immunity. A recent paper based on Israel s experience of vaccination suggested that a single dose may not provide adequate protection. Here we extract the primary data from the Israeli paper and then estimate the incidence per day for each day after the first injection and also estimate vaccine effectiveness for each day from day 13 to day 24. We used a pooled estimate of the daily incidence rate during days 1 to 12 as the counterfactual estimate of incidence without disease and estimated confidence intervals using Monte Carlo modelling. After initial injection case numbers increased to day 8 before declining to low levels by day 21. Estimated vaccine effectiveness was pretty much 0 at day 14 but then rose to about 90% at day 21 before levelling off. The cause of the initial surge in infection risk is unknown but may be related to people being less cautious about maintaining protective behaviours as soon as they have the injection. What our analysis shows is that a single dose of vaccine is highly protective, although it can take up to 21 days to achieve this. The early results coming from Israel support the UK policy of extending the gap between doses by showing that a single dose can give a high level of protection.
5,750 downloads medRxiv epidemiology
Objective To review the evidence from studies comparing SARS-CoV-2 culture, with the results of reverse transcriptase polymerase chain reaction (RT-PCR). Methods We searched LitCovid, medRxiv, Google Scholar and the WHO Covid-19 database for Covid-19 using the terms viral culture or viral replication and associated synonyms up to 10 September 2020. We carried out citation matching and included studies reporting attempts to culture or observe SARS-CoV-2 matching with cutoffs for RT-PCR positivity. One reviewer extracted data for each study and a second reviewer checked end edited the extraction and summarised the narratively by sample: fecal, respiratory, environment, blood or mixed. Where necessary we wrote to corresponding authors of the included or background papers for additional information. We assessed quality using a modified QUADAS 2 risk of bias tool. This is the fourth version of this review that was first published on the 4th of August and updated on the 21t of August, on the 3rd and 10th of September. Results We included 29 studies reporting culturing or observing tissue invasion by SARS-CoV in sputum, naso or oropharyngeal, urine, stool, blood and environmental samples from patients diagnosed with Covid-19. The data are suggestive of a relation between the time from collection of a specimen to test, cycle threshold and symptom severity. The quality of the studies was moderate with lack of standardised reporting. Twelve studies reported that Ct values were significantly lower and log copies higher in samples producing live virus culture. Five studies reported no growth in samples based on a Ct cut-off value. These values ranged from CT > 24 for no growth to Ct > 34 or more. Two studies report a strong relationship between Ct value and ability to recover infectious virus and that the odds of live virus culture reduced by 33% for every one unit increase in Ct. A cut-off RT-PCR Ct > 30 was associated with non-infectious samples. One study that analysed the NSP, N and E gene fragments of the PCR result reported different cut-off thresholds depending on the gene fragment analysed. The duration of RNA shedding detected by PCR was far longer compared to detection of live culture. Six out of eight studies reported RNA shedding for longer than 14 days. Yet, infectivity declines after day 8 even among cases with ongoing high viral loads. A very small proportion of people re-testing positive after hospital discharge or with high Ct are likely to be infectious. Conclusion Prospective routine testing of reference and culture specimens are necessary for each country involved in the pandemic to establish the usefulness and reliability of PCR for Covid-19 and its relation to patient factors. Infectivity is related to the date of onset of symptoms and cycle threshold level. A binary Yes / No approach to the interpretation RT-PCR unvalidated against viral culture will result in false positives with possible segregation of large numbers of people who are no longer infectious and hence not a threat to public health.
5,749 downloads medRxiv infectious diseases
Emily R Adams, Mark Ainsworth, Rekha Anand, Monique Andersson, Kathryn Auckland, J Kenneth Baillie, Eleanor Barnes, Sally Beer, John Bell, Tamsin Berry, Sagida Bibi, Miles Carroll, Senthil Chinnakannan, Elizabeth Clutterbuck, Richard J Cornall, Derrick Crook, Thushan De Silva, Wanwisa Dejnirattisai, Kate E. Dingle, Christina Dold, Alexis Espinosa, David W Eyre, Helen Farmer, Maria Fernandez Mendoza, Dominique Georgiou, Sarah J Hoosdally, Alistair Hunter, Katie Jeffrey, Paul Klenerman, Julian Knight, Clarice Knowles, Andrew J Kwok, Ullrich Leuschner, Robert Levin, Chang Liu, Cesar Lopez-Camacho, Jose Carlos Martinez Garrido, Philippa C Matthews, Hannah McGivern, Alexander J Mentzer, Jonathan Milton, Juthathip Mongkolsapaya, Shona C. Moore, Marta S Oliveira, Fiona Pereira, Elena Perez Lopez, Timothy Peto, Rutger J Ploeg, Andrew Pollard, Tessa Prince, David J. Roberts, Justine K Rudkin, Veronica Sanchez, Gavin R Screaton, Malcolm G Semple, Donal T. Skelly, Jose Slon-Campos, Elliot Nathan Smith, Alberto Jose Sobrino Diaz, Julie Staves, David Stuart, Piyada Supasa, Tomas Surik, Hannah Thraves, Pat Tsang, Lance Turtle, Ann Sarah Walker, Beibei Wang, Charlotte Washington, Nicholas Watkins, James Whitehouse
ABSTRACT Objectives: The COVID-19 pandemic caused >1 million infections during January-March 2020. There is an urgent need for reliable antibody detection approaches to support diagnosis, vaccine development, safe release of individuals from quarantine, and population lock-down exit strategies. We set out to evaluate the performance of ELISA and lateral flow immunoassay (LFIA) devices. Design: We tested plasma for COVID (SARS-CoV-2) IgM and IgG antibodies by ELISA and using nine different LFIA devices. Setting: We performed laboratory work at the University of Oxford. Participants: We used a panel of plasma samples from individuals who have had confirmed COVID infection based on a PCR result (n=40), and pre-pandemic negative control samples banked in the UK prior to December-2019 (n=142). Main outcome measures: We recorded optical density results from ELISA experiments and positive/negative/invalid results from LFIA devices. Results: ELISA detected IgM or IgG in 34/40 individuals with a confirmed history of COVID infection (sensitivity 85%, 95%CI 70-94%), vs. 0/50 pre-pandemic controls (specificity 100% [95%CI 93-100%]). IgG levels were detected in 31/31 COVID-positive individuals tested [≥]10 days after symptom onset (sensitivity 100%, 95%CI 89-100%). IgG titres rose during the 3 weeks post symptom onset and began to fall by 8 weeks, but remained above the detection threshold. Point estimates for the sensitivity of LFIA devices ranged from 55-70% versus RT-PCR and 65-85% versus ELISA, with specificity 95-100% and 93-100% respectively. Within the limits of the study size, the performance of most LFIA devices was similar. Conclusions: Currently available commercial LFIA devices do not perform sufficiently well for individual patient applications. ELISA can be calibrated to be specific for detecting and quantifying SARS-CoV-2 IgM and IgG and is highly sensitive for IgG from 10 days following first symptoms.
5,741 downloads medRxiv epidemiology
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.
5,738 downloads medRxiv infectious diseases
Objectives Is herd immunity to COVID-19 a realistic outcome of any immunisation programme with the two main vaccines currently licenced in the UK (Pfizer vaccine BNT162b2 and Astra Zeneca/Oxford vaccine ChAdOx1-S)? More formally, can these vaccines achieve a sufficient level of population immunity to reduce R, the reproduction number of the infection, to below one in the absence of any non-pharmaceutical interventions? Design The study uses simple mathematical models of the transmission of COVID-19 infection from primary to secondary cases parameterised using data on virus transmission and vaccine efficacy from the literature and the regulatory approval process for the vaccines. Results In the regulatory approval documents, the efficacy of the Pfizer vaccine is estimated at 0.948 (that for the Moderna vaccine is similar). Efficacy for the Oxford vaccine against primary symptomatic illness is estimated as 0.704, based on pooling of data from two dose regimes. For values of R0 similar to those reported during the first months of the pandemic, the simplest analysis implies that reducing the value of R below 1 would require 69% and 93% of the population to be vaccinated with the Pfizer and Oxford vaccine respectively (or achieve a comparable level of immunity through natural infection). However, the new variant of COVID-19 (Lineage B.1.1.7, named Variant of Concern VOC-202012/01) is reported to have an R-value 1.56 (0.92 to 2.28) times higher than the original strain. Vaccinating the entire population with the Oxford vaccine would only reduce the R value to 1.325 while the Pfizer vaccine would require 82% of the population to be vaccinated to control the spread of the new variant. The Oxford vaccine reduces the incidence of serious illness to a greater extent than it reduces symptomatic illness. But its efficacy against the incidence of asymptomatic infections is lower, reducing its efficacy against all infection from 0.704 to 0.525 for the pooled data. Although asymptomatics are less infectious, including them in our calculations still raises R values by 20% or more, from 1.33 to 1.6 for the new variant with 100% vaccination. Neither vaccine is licenced for use in children, and when this is taken into account, this R value rises by a further 37% to 2.2 if the whole adult population is vaccinated. Even the more effective mRNA vaccines may allow the pandemic to persist via transmission amongst children, as current authorisations only allow their use on adults. In the absence of vaccination, R will reduce to 1 when 89% of the population has acquired immunity as a result of previous infection with COVID-19. Conclusions All currently licensed vaccines provide substantial protection against serious illness to vaccinated individuals themselves. But the Oxford vaccine appears to have relatively low efficacy against asymptomatic infections. Although no comparable data from human trials are available for the mRNA vaccines, non-human primate studies suggest they are better at preventing nasal shedding and so transmission. Herd immunity to COVID-19 will be very difficult to achieve, especially so for the less effective vaccine. The possibility of transmission from vaccinated but infected individuals to vulnerable unvaccinated individuals is of serious concern. There is a strong case for preferring the more effective mRNA vaccines for health and social care workers and those who have contact with large numbers of vulnerable others.
5,664 downloads medRxiv infectious diseases
Katharina Jahn, David Dreifuss, Ivan Topolsky, Anina Kull, Pravin Ganesanandamoorthy, Xavier Fernandez-Cassi, Carola Bänziger, Elyse Stachler, Lara Fuhrmann, Kim Philipp Jablonski, Chaoran Chen, Catharine Aquino, Tanja Stadler, Christoph Ort, Tamar Kohn, Timothy R. Julian, Niko Beerenwinkel
The SARS-CoV-2 lineages B.1.1.7 and 501.V2, which were first detected in the United Kingdom and South Africa, respectively, are spreading rapidly in the human population. Thus, there is an increased need for genomic and epidemiological surveillance in order to detect the strains and estimate their abundances. Here, we report a genomic analysis of SARS-CoV-2 in 48 raw wastewater samples collected from three wastewater treatment plants in Switzerland between July 9 and December 21, 2020. We find evidence for the presence of several mutations that define the B.1.1.7 and 501.V2 lineages in some of the samples, including co-occurrences of up to three B.1.1.7 signature mutations on the same amplicon in four samples from Lausanne and one sample from a Swiss ski resort dated December 9 - 21. These findings suggest that the B.1.1.7 strain could be detected by mid December, two weeks before its first verification in a patient sample from Switzerland. We conclude that sequencing SARS-CoV-2 in community wastewater samples may help detect and monitor the circulation of diverse lineages.
5,653 downloads medRxiv epidemiology
Nicholas G Davies, Sam Abbott, Rosanna C. Barnard, Christopher Jarvis, Adam J. Kucharski, James D Munday, Carl A. B. Pearson, Timothy Russell, Damien Tully, Alex D Washburne, Tom Wenseleers, Amy Gimma, William Waites, Kerry L. M. Wong, Kevin van Zandvoort, Justin D Silverman, CMMID COVID-19 Working Group, Rosalind M Eggo, Sebastian Funk, Mark Jit, Katherine E Atkins, W John Edmunds
A novel SARS-CoV-2 variant, VOC 202012/01, emerged in southeast England in November 2020 and is rapidly spreading towards fixation. Using a variety of statistical and dynamic modelling approaches, we assessed the relative transmissibility of this novel variant. Depending on the analysis, we estimate that VOC 202012/01 is 43-82% (range of 95% credible intervals 38-106%) more transmissible than preexisting variants of SARS-CoV-2. We did not find clear evidence that VOC 202012/01 results in greater or lesser severity of disease than preexisting variants. Nevertheless, the increase in transmissibility is likely to lead to a large increase in incidence. To assess the potential impact of VOC 202012/01, we fitted a two-strain mathematical model of SARS-CoV-2 transmission to observed COVID-19 hospital admissions, hospital and ICU bed occupancy, and deaths; SARS-CoV-2 PCR prevalence and seroprevalence; and the relative frequency of VOC 202012/01. We find that without stringent control measures, COVID-19 hospitalisations and deaths are projected to reach higher levels in 2021 than were observed in 2020. Control measures of a similar stringency to the national lockdown implemented in England in November 2020 are unlikely to reduce the effective reproduction number Rt to less than 1, unless primary schools, secondary schools, and universities are also closed. We project that large resurgences of the virus are likely to occur following easing of control measures. It may be necessary to greatly accelerate vaccine roll-out to have an appreciable impact in suppressing the resulting disease burden.
5,560 downloads medRxiv infectious diseases
The current epidemic of COVID-19 is unparalleled in recent history as are the social distancing interventions that have led to a significant halt on the economic and social life of so many countries. However, there is very little empirical evidence about which social distancing measures have the most impact. We report a quasi-experimental study of the impact of various interventions for control of the outbreak. Data on case numbers and deaths were taken from the daily published figures by the European Centre for Disease Control and dates of initiation of various control strategies from the Institute of Health Metrics and Evaluation website and published sources. Our complementary analyses were modelled in R using Bayesian generalised additive mixed models (GAMM) and in Stata using multi-level mixed effects regression models. From both sets of modelling, we found that closure of education facilities, prohibiting mass gatherings and closure of some non-essential businesses were associated with reduced incidence whereas stay at home orders and closure of all non-businesses was not associated with any independent additional impact. Our results could help inform strategies for coming out of lockdown.
5,487 downloads medRxiv occupational and environmental health
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.
5,465 downloads medRxiv epidemiology
Mark S Graham, Carole H Sudre, Anna May, Michela Antonelli, Benjamin Murray, Thomas Varsavsky, Kerstin Klaser, Liane Dos Santos Canas, Erika Molteni, Marc Modat, David Alden Drew, Long H Nguyen, Lorenzo Polidori, Somesh Selvachandran, Christina Hu, Joan Capdevila Pujol, The COVID-19 Genomics UK (COG-UK) consortium, Alexander Hammers, Andrew T Chan, Jonathan Wolf, Timothy Spector, Claire Steves, Sebastien Ourselin
The new SARS-CoV-2 variant B.1.1.7 was identified in December 2020 in the South-East of England, and rapidly increased in frequency and geographic spread. While there is some evidence for increased transmissibility of this variant, it is not known if the new variant presents with variation in symptoms or disease course, or if previously infected individuals may become reinfected with the new variant. Using longitudinal symptom and test reports of 36,920 users of the Covid Symptom Study app testing positive for COVID-19 between 28 September and 27 December 2020, we examined the association between the regional proportion of B.1.1.7 and reported symptoms, disease course, rates of reinfection, and transmissibility. We found no evidence for changes in reported symptoms, disease severity and disease duration associated with B.1.1.7. We found a likely reinfection rate of around 0.7% (95% CI 0.6-0.8), but no evidence that this was higher compared to older strains. We found an increase in R(t) by a factor of 1.35 (95% CI 1.02-1.69). Despite this, we found that regional and national lockdowns have reduced R(t) below 1 in regions with very high proportions of B.1.1.7.
5,457 downloads bioRxiv cell biology
David W. Sanders, Chanelle C. Jumper, Paul J. Ackerman, Dan Bracha, Anita Donlic, Hahn Kim, Devin Kenney, Ivan Castello-Serrano, Saori Suzuki, Tomokazu Tamura, Alexander H. Tavares, Mohsan Saeed, Alex S Holehouse, Alexander Ploss, Ilya Levental, Florian Douam, Robert F. Padera, Bruce D. Levy, Clifford P. Brangwynne
Many enveloped viruses induce multinucleated cells (syncytia), reflective of membrane fusion events caused by the same machinery that underlies viral entry. These syncytia are thought to facilitate replication and evasion of the host immune response. Here, we report that co-culture of human cells expressing the receptor ACE2 with cells expressing SARS-CoV-2 spike, results in synapse-like intercellular contacts that initiate cell-cell fusion, producing syncytia resembling those we identify in lungs of COVID-19 patients. To assess the mechanism of spike/ACE2-driven membrane fusion, we developed a microscopy-based, cell-cell fusion assay to screen ~6000 drugs and >30 spike variants. Together with cell biological and biophysical approaches, the screen reveals an essential role for membrane cholesterol in spike-mediated fusion, which extends to replication-competent SARS-CoV-2 isolates. Our findings provide a molecular basis for positive outcomes reported in COVID-19 patients taking statins, and suggest new strategies for therapeutics targeting the membrane of SARS-CoV-2 and other fusogenic viruses.
5,385 downloads medRxiv epidemiology
A variant of SARS-CoV-2 emerged in early summer 2020, presumably in Spain, and has since spread to multiple European countries. The variant was first observed in Spain in June and has been at frequencies above 40% since July. Outside of Spain, the frequency of this variant has increased from very low values prior to 15th July to 40-70% in Switzerland, Ireland, and the United Kingdom in September. It is also prevalent in Norway, Latvia, the Netherlands, and France. Little can be said about other European countries because few recent sequences are available. Sequences in this cluster (20A.EU1) differ from ancestral sequences at 6 or more positions, including the mutation A222V in the spike protein and A220V in the nucleoprotein. We show that this variant was exported from Spain to other European countries multiple times and that much of the diversity of this cluster in Spain is observed across Europe. It is currently unclear whether this variant is spreading because of a transmission advantage of the virus or whether high incidence in Spain followed by dissemination through tourists is sufficient to explain the rapid rise in multiple countries. CAVEATSO_LIThis variant rose in frequency in multiple countries, but we have no direct evidence that it spreads faster. The rise in frequency could also be due to epidemiological factors. C_LIO_LIThere are currently no data to evaluate whether this variant affects the severity of the disease. C_LIO_LIWhile dominant in some countries, 20A.EU1 has not taken over everywhere and diverse variants of SARS-CoV-2 continue to circulate across Europe. C_LI
5,288 downloads medRxiv pediatrics
Background: Maternal vaccination for Influenza and TDaP have been well studied in terms of safety and efficacy for protection of the newborn by placental passage of antibodies. Similar newborn protection would be expected after maternal vaccination against SARS-CoV-2 (the virus responsible for COVID-19). There is a significant and urgent need for research regarding safety and efficacy of vaccination against SARS-CoV-2 during pregnancy. Here, we report the first known case of an infant with SARS-CoV-2 IgG antibodies detectable in cord blood after maternal vaccination. Case presentation: A vigorous, healthy, full-term female was born to a COVID-19 naive mother who had received a single dose of mRNA vaccine for SARS-CoV-2 three weeks prior to delivery. Cord blood antibodies (IgG) were detected to the S-protein of SARS-CoV-2 at time of delivery. Conclusion: Here, we report the first known case of an infant with SARS-CoV-2 IgG antibodies detectable in cord blood after maternal vaccination.
5,271 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.
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