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Open accessPosted ContentDOI: 10.1101/2021.03.03.21252856

REACT-1 round 9 final report: Continued but slowing decline of prevalence of SARS-CoV-2 during national lockdown in England in February 2021

04 Mar 2021-medRxiv (Cold Spring Harbor Laboratory Press)-
Abstract: BackgroundEngland will start to exit its third national lockdown in response to the COVID-19 pandemic on 8th March 2021, with safe effective vaccines being rolled out rapidly against a background of emerging transmissible and immunologically novel variants of SARS-CoV-2. A subsequent increase in community prevalence of infection could delay further relaxation of lockdown if vaccine uptake and efficacy are not sufficiently high to prevent increased pressure on healthcare services. MethodsThe PCR self-swab arm of the REal-time Assessment of Community Transmission Study (REACT-1) estimates community prevalence of SARS-CoV-2 infection in England based on random cross-sections of the population ages five and over. Here, we present results from the complete round 9 of REACT-1 comprising round 9a in which swabs were collected from 4th to 12th February 2021 and round 9b from 13th to 23rd February 2021. We also compare the results of REACT-1 round 9 to round 8, in which swabs were collected mainly from 6th January to 22nd January 2021. ResultsOut of 165,456 results for round 9 overall, 689 were positive. Overall weighted prevalence of infection in the community in England was 0.49% (0.44%, 0.55%), representing a fall of over two thirds from round 8. However the rate of decline of the epidemic has slowed from 15 (13, 17) days, estimated for the period from the end of round 8 to the start of round 9, to 31 days estimated using data from round 9 alone (lower confidence limit 17 days). When comparing round 9a to 9b there were apparent falls in four regions, no apparent change in one region and apparent rises in four regions, including London where there was a suggestion of sub-regional heterogeneity in growth and decline. Smoothed prevalence maps suggest large contiguous areas of growth and decline that do not align with administrative regions. Prevalence fell by 50% or more across all age groups in round 9 compared to round 8, with prevalence (round 9) ranging from 0.21% in those aged 65 and over to 0.71% in those aged 13 to 17 years. Round 9 prevalence was highest among Pakistani participants at 2.1% compared to white participants at 0.45% and Black participants at 0.83%. There were higher adjusted odds of infection for healthcare and care home workers, for those working in public transport and those working in education, school, nursery or childcare and lower adjusted odds for those not required to work outside the home. ConclusionsCommunity prevalence of swab-positivity has declined markedly between January and February 2021 during lockdown in England, but remains high; the rate of decline has slowed in the most recent period, with a suggestion of pockets of growth. Continued adherence to social distancing and public health measures is required so that infection rates fall to much lower levels. This will help to ensure that the benefits of the vaccination roll-out programme in England are fully realised.

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Topics: Population (51%)
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Open accessJournal ArticleDOI: 10.1016/S0140-6736(21)00622-X
Deepti Gurdasani1, Nisreen A Alwan2, Trisha Greenhalgh3, Zoë Hyde4  +8 moreInstitutions (10)
27 Mar 2021-The Lancet
Topics: Pandemic (51%)

15 Citations


Open accessJournal ArticleDOI: 10.1136/BMJ.N823
25 Mar 2021-BMJ
Abstract: Rapid antigen (lateral flow) tests are better at identifying covid-19 infection in people with symptoms than in those with none, although the diagnostic accuracy of different brands of tests varies widely, a Cochrane review has found.1 The review’s lead author criticised the UK government for rolling out the lateral flow testing programme in the absence of empirical evidence. The latest report updates previous reviews2 and includes evidence from 64 studies up to November 2020. Most were conducted in Europe and the United States and assessed the accuracy of lateral flow tests in detecting current SARS-CoV-2 infection when compared with the standard laboratory genome testing. The World Health Organization’s performance standards require that tests correctly identify at least 80% of infected people (test sensitivity) and exclude infection in at least 97% of uninfected people (test specificity). The Cochrane analysis found that …

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7 Citations


Open accessJournal ArticleDOI: 10.1098/RSTB.2021.0001
Abstract: Infectious disease modelling has played an integral part of the scientific evidence used to guide the response to the COVID-19 pandemic. In the UK, modelling evidence used for policy is reported to the Scientific Advisory Group for Emergencies (SAGE) modelling subgroup, SPI-M-O (Scientific Pandemic Influenza Group on Modelling-Operational). This Special Issue contains 20 articles detailing evidence that underpinned advice to the UK government during the SARS-CoV-2 pandemic in the UK between January 2020 and July 2020. Here, we introduce the UK scientific advisory system and how it operates in practice, and discuss how infectious disease modelling can be useful in policy making. We examine the drawbacks of current publishing practices and academic credit and highlight the importance of transparency and reproducibility during an epidemic emergency. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.

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Topics: Scientific evidence (55%), Pandemic (51%)

6 Citations


Open accessPosted ContentDOI: 10.1101/2021.05.08.21256867
Oliver Eales1, Andrew J. Page2, Sonja N. Tang1, Caroline E. Walters1  +24 moreInstitutions (5)
07 May 2021-medRxiv
Abstract: Genomic surveillance for SARS-CoV-2 lineages informs our understanding of possible future changes in transmissibility and vaccine efficacy. However, small changes in the frequency of one lineage over another are often difficult to interpret because surveillance samples are obtained from a variety of sources. Here, we describe lineage dynamics and phylogenetic relationships using sequences obtained from a random community sample who provided a throat and nose swab for rt-PCR during the first three months of 2021 as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Overall, diversity decreased during the first quarter of 2021, with the B.1.1.7 lineage (first identified in Kent) predominant, driven by a 0.3 unit higher reproduction number over the prior wild type. During January, positive samples were more likely B.1.1.7 in younger and middle-aged adults (aged 18 to 54) than in other age groups. Although individuals infected with the B.1.1.7 lineage were no more likely to report one or more classic COVID-19 symptoms compared to those infected with wild type, they were more likely to be antibody positive 6 weeks after infection. Viral load was higher in B.1.1.7 infection as measured by cycle threshold (Ct) values, but did not account for the increased rate of testing positive for antibodies. The presence of infections with non-imported B.1.351 lineage (first identified in South Africa) during January, but not during February or March, suggests initial establishment in the community followed by fade-out. However, this occurred during a period of stringent social distancing and targeted public health interventions and does not immediately imply similar lineages could not become established in the future. Sequence data from representative community surveys such as REACT-1 can augment routine genomic surveillance.

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Topics: Lineage (genetic) (51%)

5 Citations


Open accessJournal ArticleDOI: 10.1136/BMJ.N2060
Lynda Fenton, Ciara Gribben, David H Caldwell, Sam Colville  +10 moreInstitutions (3)
02 Sep 2021-BMJ
Abstract: Objective To determine the risk of hospital admission with covid-19 and severe covid-19 among teachers and their household members, overall and compared with healthcare workers and adults of working age in the general population. Design Population based nested case-control study. Setting Scotland, March 2020 to July 2021, during defined periods of school closures and full openings in response to covid-19. Participants All cases of covid-19 in adults aged 21 to 65 (n=132 420) and a random sample of controls matched on age, sex, and general practice (n=1 306 566). Adults were identified as actively teaching in a Scottish school by the General Teaching Council for Scotland, and their household members were identified through the unique property reference number. The comparator groups were adults identified as healthcare workers in Scotland, their household members, and the remaining general population of working age. Main outcome measures The primary outcome was hospital admission with covid-19, defined as having a positive test result for SARS-CoV-2 during hospital admission, being admitted to hospital within 28 days of a positive test result, or receiving a diagnosis of covid-19 on discharge from hospital. Severe covid-19 was defined as being admitted to intensive care or dying within 28 days of a positive test result or assigned covid-19 as a cause of death. Results Most teachers were young (mean age 42), were women (80%), and had no comorbidities (84%). The risk (cumulative incidence) of hospital admission with covid-19 was Conclusion Compared with adults of working age who are otherwise similar, teachers and their household members were not found to be at increased risk of hospital admission with covid-19 and were found to be at lower risk of severe covid-19. These findings should reassure those who are engaged in face-to-face teaching.

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Topics: Intensive care (54%), Population (54%)

4 Citations


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Open accessJournal ArticleDOI: 10.1016/S0140-6736(20)32661-1
Merryn Voysey1, Clemens Sac.1, Shabir A. Madhi, Lily Yin Weckx2  +78 moreInstitutions (30)
09 Jan 2021-The Lancet
Abstract: Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials.

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1,792 Citations


Open accessJournal ArticleDOI: 10.1056/NEJMOA2101765
Noa Dagan1, Noam Barda2, Noam Barda3, Noam Barda1  +12 moreInstitutions (4)
Abstract: Background As mass vaccination campaigns against coronavirus disease 2019 (Covid-19) commence worldwide, vaccine effectiveness needs to be assessed for a range of outcomes across diverse p...

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870 Citations


Journal ArticleDOI: 10.1198/1061860043010
Stefan Lang1, Andreas Brezger1Institutions (1)
Abstract: P-splines are an attractive approach for modeling nonlinear smooth effects of covariates within the additive and varying coefficient models framework. In this article, we first develop a Bayesian version for P-splines and generalize in a second step the approach in various ways. First, the assumption of constant smoothing parameters can be replaced by allowing the smoothing parameters to be locally adaptive. This is particularly useful in situations with changing curvature of the underlying smooth function or with highly oscillating functions. In a second extension, one-dimensional P-splines are generalized to two-dimensional surface fitting for modeling interactions between metrical covariates. In a last step, the approach is extended to situations with spatially correlated responses allowing the estimation of geoadditive models. Inference is fully Bayesian and uses recent MCMC techniques for drawing random samples from the posterior. In a couple of simulation studies the performance of Bayesian P-spline...

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Topics: Smoothing (57%), Bayesian probability (54%)

776 Citations


Open accessPosted ContentDOI: 10.1101/2021.03.01.21252652
02 Mar 2021-medRxiv
Abstract: Objectives To 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. Design Test negative case control design Setting Community COVID-19 PCR testing in England Participants All 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. Interventions One and two doses of BNT162b2 vaccine. One dose of ChAdOx1 vaccine. Main outcome measures Symptomatic PCR confirmed SARS-CoV-2 infection, hospitalisations and deaths with COVID-19. Results Individuals 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. Conclusion Vaccination with either a single dose of BNT162b2 or ChAdOx1 COVID-19 vaccination was associated with a significant reduction in symptomatic SARS-CoV2 positive cases in older adults with even greater protection against severe disease. Both vaccines show similar effects. Protection was maintained for the duration of follow-up (>6 weeks). A second dose of BNT162b2 provides further protection against symptomatic disease but second doses of ChAdOx1 have not yet been rolled out in England. There is a clear effect of the vaccines against the UK variant of concern.

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Topics: Vaccination (59%)

107 Citations


Open accessPosted ContentDOI: 10.1101/2021.02.18.21251973
Steven Riley1, Caroline E. Walters1, Haowei Wang1, Oliver Eales1  +19 moreInstitutions (5)
18 Feb 2021-medRxiv
Abstract: Background and Methods England entered its third national lockdown of the COVID-19 pandemic on 6th January 2021 with the aim of reducing the daily number of deaths and pressure on healthcare services. The real-time assessment of community transmission study (REACT-1) obtains throat and nose swabs from randomly selected people in England in order to describe patterns of SARS-CoV-2 prevalence. Here, we report data from round 9a of REACT-1 for swabs collected between 4th and 13th February 2021. Results Out of 85,473 tested-swabs, 378 were positive. Overall weighted prevalence of infection in the community in England was 0.51%, a fall of more than two thirds since our last report (round 8) in January 2021 when 1.57% of people tested positive. We estimate a halving time of 14.6 days and a reproduction number R of 0.72, based on the difference in prevalence between the end of round 8 and the beginning of round 9. Although prevalence fell in all nine regions of England over the same period, there was greater uncertainty in the trend for North West, North East, and Yorkshire and The Humber. Prevalence fell substantially across all age groups with highest prevalence among 18- to 24-year olds at 0.89% (0.47%, 1.67%) and those aged 5 to12 years at 0.86% (0.60%, 1.24%). Large household size, living in a deprived neighbourhood, and Asian ethnicity were all associated with increased prevalence. Healthcare and care home workers were more likely to test positive compared to other workers. Conclusions There is a strong decline in prevalence of SARS-CoV-2 in England among the general population five to six weeks into lockdown, but prevalence remains high: at levels similar to those observed in late September 2020. Also, the number of COVID-19 cases in hospitals is higher than at the peak of the first wave in April 2020. The effects of easing of social distancing when we transition out of lockdown need to be closely monitored to avoid a resurgence in infections and renewed pressure on health services.

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Topics: Population (52%)

7 Citations