Publications
288 results found
Eales O, de Oliveira Martins L, Page AJ, et al., 2022, The new normal? Dynamics and scale of the SARS-CoV-2 variant Omicron epidemic in England
<jats:title>Summary</jats:title><jats:p>The SARS-CoV-2 pandemic has been characterised by the regular emergence of genomic variants which have led to substantial changes in the epidemiology of the virus. With natural and vaccine-induced population immunity at high levels, evolutionary pressure favours variants better able to evade SARS-CoV-2 neutralising antibodies. The Omicron variant was first detected in late November 2021 and exhibited a high degree of immune evasion, leading to increased infection rates in many countries. However, estimates of the magnitude of the Omicron wave have relied mainly on routine testing data, which are prone to several biases. Here we infer the dynamics of the Omicron wave in England using PCR testing and genomic sequencing obtained by the REal-time Assessment of Community Transmission-1 (REACT-1) study, a series of cross-sectional surveys testing random samples of the population of England. We estimate an initial peak in national Omicron prevalence of 6.89% (5.34%, 10.61%) during January 2022, followed by a resurgence in SARS-CoV-2 infections in England during February-March 2022 as the more transmissible Omicron sub-lineage, BA.2 replaced BA.1 and BA.1.1. Assuming the emergence of further distinct genomic variants, intermittent epidemics of similar magnitude as the Omicron wave may become the ‘new normal’.</jats:p>
Chadeau-Hyam M, Wang H, Eales O, et al., 2022, SARS-CoV-2 infection and vaccine effectiveness in England (REACT-1): a series of cross-sectional random community surveys, The Lancet Respiratory Medicine, Vol: 10, Pages: 355-366, ISSN: 2213-2600
SummaryBackground England has experienced a third wave of the COVID-19 epidemic since the end of May, 2021, coincidingwith the rapid spread of the delta (B.1.617.2) variant, despite high levels of vaccination among adults. Vaccinationrates (single dose) in England are lower among children aged 16–17 years and 12–15 years, whose vaccination inEngland commenced in August and September, 2021, respectively. We aimed to analyse the underlying dynamicsdriving patterns in SARS-CoV-2 prevalence during September, 2021, in England.Methods The REal-time Assessment of Community Transmission-1 (REACT-1) study, which commenced datacollection in May, 2020, involves a series of random cross-sectional surveys in the general population of Englandaged 5 years and older. Using RT-PCR swab positivity data from 100 527 participants with valid throat and noseswabs in round 14 of REACT-1 (Sept 9–27, 2021), we estimated community-based prevalence of SARS-CoV-2 andvaccine effectiveness against infection by combining round 14 data with data from round 13 (June 24 to July 12, 2021;n=172 862).Findings During September, 2021, we estimated a mean RT-PCR positivity rate of 0·83% (95% CrI 0·76–0·89), with areproduction number (R) overall of 1·03 (95% CrI 0·94–1·14). Among the 475 (62·2%) of 764 sequenced positiveswabs, all were of the delta variant; 22 (4·63%; 95% CI 3·07–6·91) included the Tyr145His mutation in the spikeprotein associated with the AY.4 sublineage, and there was one Glu484Lys mutation. Age, region, key worker status,and household size jointly contributed to the risk of swab positivity. The highest weighted prevalence was observedamong children aged 5–12 years, at 2·32% (95% CrI 1·96–2·73) and those aged 13–17 years, at 2·55% (2·11–3·08).The SARS-CoV-2 epidemic grew in those aged 5–11 years, with an R of 1&m
Eales O, Walters CE, Wang H, et al., 2022, Characterising the persistence of RT-PCR positivity and incidence in a community survey of SARS-CoV-2, Wellcome Open Research, Vol: 7, Pages: 102-102, ISSN: 2398-502X
Background: The REal-time Assessment of Community Transmission-1 (REACT-1) study has provided unbiased estimates of swab-positivity in England approximately monthly since May 2020 using RT-PCR testing of self-administered throat and nose swabs. However, estimating infection incidence requires an understanding of the persistence of RT-PCR swab-positivity in the community.Methods: During round 8 of REACT-1 from 6 January to 22 January 2021, we collected up to two additional swabs from 896 initially RT-PCR positive individuals approximately 6 and 9 days after their initial swab.Results: Test sensitivity and duration of positivity were estimated using an exponential decay model, for all participants and for subsets by initial N-gene cycle threshold (Ct) value, symptom status, lineage and age. A P-spline model was used to estimate infection incidence for the entire duration of the REACT-1 study. REACT-1 test sensitivity was estimated at 0.79 (0.77, 0.81) with median duration of positivity at 9.7 (8.9, 10.6) days. We found greater duration of positivity in those exhibiting symptoms, with low N-gene Ct values, or infected with the Alpha variant. Test sensitivity was found to be higher for those who were pre-symptomatic or with low N-gene Ct values. Compared to swab-positivity, our estimates of infection incidence included sharper features with evident transient increases around the time of changes in social distancing measures.Conclusions: These results validate previous efforts to estimate incidence of SARS-CoV-2 from swab-positivity data and provide a reliable means to obtain community infection estimates to inform policy response.
Chadeau-Hyam M, Tang D, Eales O, et al., 2022, The Omicron SARS-CoV-2 epidemic in England during February 2022
Background The third wave of COVID-19 in England peaked in January 2022 resulting fromthe rapid transmission of the Omicron variant. However, rates of hospitalisations and deathswere substantially lower than in the first and second wavesMethods In the REal-time Assessment of Community Transmission-1 (REACT-1) study weobtained data from a random sample of 94,950 participants with valid throat and nose swabresults by RT-PCR during round 18 (8 February to 1 March 2022).Findings We estimated a weighted mean SARS-CoV-2 prevalence of 2.88% (95% credibleinterval [CrI] 2.76–3.00), with a within-round reproduction number (R) overall of 0.94 (0·91–0.96). While within-round weighted prevalence fell among children (aged 5 to 17 years) andadults aged 18 to 54 years, we observed a level or increasing weighted prevalence amongthose aged 55 years and older with an R of 1.04 (1.00–1.09). Among 1,195 positive sampleswith sublineages determined, only one (0.1% [0.0–0.5]) corresponded to AY.39 Deltasublineage and the remainder were Omicron: N=390, 32.7% (30.0–35.4) were BA.1; N=473,39.6% (36.8–42.5) were BA.1.1; and N=331, 27.7% (25.2–30.4) were BA.2. We estimated anR additive advantage for BA.2 (vs BA.1 or BA.1.1) of 0.40 (0.36–0.43). The highest proportionof BA.2 among positives was found in London.Interpretation In February 2022, infection prevalence in England remained high with levelor increasing rates of infection in older people and an uptick in hospitalisations. Ongoingsurveillance of both survey and hospitalisations data is required.Funding Department of Health and Social Care, England.
Ashby D, 2022, Commentary on training and education in medical statistics, in celebration of 40 years of statistics in medicine and 50 years of the MSc medical statistics at LSHTM COMMENT, STATISTICS IN MEDICINE, Vol: 41, Pages: 835-837, ISSN: 0277-6715
Ward H, Whittaker M, Flower B, et al., 2022, Population antibody responses following COVID-19 vaccination in 212,102 individuals, Nature Communications, Vol: 13, ISSN: 2041-1723
Population antibody surveillance helps track immune responses to COVID-19 vaccinations at scale, and identify host factors that may affect antibody production. We analyse data from 212,102 vaccinated individuals within the REACT-2 programme in England, which uses self-administered lateral flow antibody tests in sequential cross-sectional community samples; 71,923 (33.9%) received at least one dose of BNT162b2 vaccine and 139,067 (65.6%) received ChAdOx1. For both vaccines, antibody positivity peaks 4-5 weeks after first dose and then declines. At least 21 days after second dose of BNT162b2, close to 100% of respondents test positive, while for ChAdOx1, this is significantly reduced, particularly in the oldest age groups (72.7% [70.9–74.4] at ages 75 years and above). For both vaccines, antibody positivity decreases with age, and is higher in females and those with previous infection. Antibody positivity is lower in transplant recipients, obese individuals, smokers and those with specific comorbidities. These groups will benefit from additional vaccine doses.
Elliott P, Bodinier B, Eales O, et al., 2022, Rapid increase in Omicron infections in England during December 2021: REACT-1 study., Science, Vol: 375, Pages: eabn8347-eabn8347, ISSN: 0036-8075
The unprecedented rise in SARS-CoV-2 infections during December 2021 was concurrent with rapid spread of the Omicron variant in England and globally. We analyzed prevalence of SARS-CoV-2 and its dynamics in England from end November to mid-December 2021 among almost 100,000 participants from the REACT-1 study. Prevalence was high with rapid growth nationally and particularly in London during December 2021, and an increasing proportion of infections due to Omicron. We observed large falls in swab positivity among mostly vaccinated older children (12-17 years) compared with unvaccinated younger children (5-11 years), and in adults who received a third (booster) vaccine dose vs. two doses. Our results reinforce the importance of vaccination and booster campaigns, although additional measures have been needed to control the rapid growth of the Omicron variant.
Eales O, Ainslie KEC, Walters CE, et al., 2022, Appropriately smoothing prevalence data to inform estimates of growth rate and reproduction number
<jats:title>Abstract</jats:title><jats:p>The time-varying reproduction number (<jats:bold><jats:italic>R</jats:italic></jats:bold><jats:sub><jats:bold><jats:italic>t</jats:italic></jats:bold></jats:sub>) can change rapidly over the course of a pandemic due to changing restrictions, behaviours, and levels of population immunity. Many methods exist that allow the estimation of <jats:bold><jats:italic>R</jats:italic></jats:bold><jats:sub><jats:bold><jats:italic>t</jats:italic></jats:bold></jats:sub> from case data. However, these are not easily adapted to point prevalence data nor can they infer <jats:bold><jats:italic>R</jats:italic></jats:bold><jats:sub><jats:bold><jats:italic>t</jats:italic></jats:bold></jats:sub> across periods of missing data. We developed a Bayesian P-spline model suitable for fitting to a wide range of epidemic time-series, including point-prevalence data. We demonstrate the utility of the model by fitting to periodic daily SARS-CoV-2 swab-positivity data in England from the first 7 rounds (May 2020 – December 2020) of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Estimates of <jats:bold><jats:italic>R</jats:italic></jats:bold><jats:sub><jats:bold><jats:italic>t</jats:italic></jats:bold></jats:sub> over the period of two subsequent rounds (6-8 weeks) and single rounds (2-3 weeks) inferred using the Bayesian P-spline model were broadly consistent with estimates from a simple exponential model, with overlapping credible intervals. However, there were sometimes substantial differences in point estimates. The Bayesian P-spline model was further able to infer changes in <jats:bold><jats:italic>R</jats:italic></jats:bold><jats:sub><jats
Elliott P, Eales O, Bodinier B, et al., 2022, Post-peak dynamics of a national Omicron SARS-CoV-2 epidemic during January 2022
Background: Rapid transmission of the SARS-CoV-2 Omicron variant has led to the highestever recorded case incidence levels in many countries around the world.Methods: The REal-time Assessment of Community Transmission-1 (REACT-1) study hasbeen characterising the transmission of the SARS-CoV-2 virus using RT-PCR test results fromself-administered throat and nose swabs from randomly-selected participants in England atages 5 years and over, approximately monthly since May 2020. Round 17 data were collectedbetween 5 and 20 January 2022 and provide data on the temporal, socio-demographic andgeographical spread of the virus, viral loads and viral genome sequence data for positiveswabs.Results: From 102,174 valid tests in round 17, weighted prevalence of swab positivity was4.41% (95% credible interval [CrI], 4.25% to 4.56%), which is over three-fold higher than inDecember 2021 in England. Of 3,028 sequenced positive swabs, 2,393 lineages weredetermined and 2,374 (99.2%) were Omicron including 19 (0.80% of all Omicron lineages)cases of BA.2 sub-lineage and one BA.3 (0.04% of all Omicron) detected on 17 January 2022,and only 19 (0.79%) were Delta. The growth of the BA.2 Omicron sub-lineage against BA.1and its sub-lineage BA.1.1 indicated a daily growth rate advantage of 0.14 (95% CrI, 0.03,0.28) for BA.2, which corresponds to an additive R advantage of 0.46 (95% CrI, 0.10, 0.92).Within round 17, prevalence was decreasing overall (R=0.95, 95% CrI, 0.93, 0.97) butincreasing in children aged 5 to 17 years (R=1.13, 95% CrI, 1.09, 1.18). Those 75 years andolder had a swab-positivity prevalence of 2.46% (95% CI, 2.16%, 2.80%) reflecting a highlevel of infection among a highly vulnerable group. Among the 3,613 swab-positiveindividuals reporting whether or not they had had previous infection, 2,334 (64.6%)reported previous confirmed COVID-19. Of these, 64.4% reported a positive test from 1 to30 days before their swab date. Risks of infection were increased among essential/keyworkers
Elliott P, Bodinier B, Eales O, et al., 2021, Rapid increase in Omicron infections in England during December 2021: REACT-1 study
Background: The highest-ever recorded numbers of daily severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in England has been observed during December 2021 and have coincided with a rapid rise in the highly transmissible Omicron variant despite high levels of vaccination in the population. Although additional COVID-19 measures have beenintroduced in England and internationally to contain the epidemic, there remains uncertainty about the spread and severity of Omicron infections among the general population.Methods: The REal-time Assessment of Community Transmission–1 (REACT-1) study has been monitoring the prevalence of SARS-CoV-2 infection in England since May 2020.REACT-1 obtains self-administered throat and nose swabs from a random sample of the population of England at ages 5 years and over. Swabs are tested for SARS-CoV-2 infection by reverse transcription polymerase chain reaction (RT-PCR) and samples testing positive are sent for viral genome sequencing. To date 16 rounds have been completed, each including~100,000 or more participants with data collected over a period of 2 to 3 weeks per month.Socio-demographic, lifestyle and clinical information (including previous history of COVID-19 and symptoms prior to swabbing) is collected by online or telephone questionnaire. Here we report results from round 14 (9-27 September 2021), round 15 (19 October - 05 November2021) and round 16 (23 November - 14 December 2021) for a total of 297,728 participants with a valid RT-PCR test result, of whom 259,225 (87.1%) consented for linkage to their NHS records including detailed information on vaccination (vaccination status, date). We usedthese data to estimate community prevalence and trends by age and region, to evaluate vaccine effectiveness against infection in children ages 12 to 17 years, and effect of a third (booster) dose in adults, and to monitor the emergence of the Omicron variant in England.Results: We observed a high overall prevalen
Cann A, Clarke C, Brown J, et al., 2021, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody lateral flow assay for antibody prevalence studies following vaccination: a diagnostic accuracy study, Publisher: Wellcome Open Research
Background: Lateral flow immunoassays (LFIAs) are able to achieve affordable, large scale antibody testing and provide rapid results without the support of central laboratories. As part of the development of the REACT programme extensive evaluation of LFIA performance was undertaken with individuals following natural infection. Here we assess the performance of the selected LFIA to detect antibody responses in individuals who have received at least one dose of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Methods: This was a prospective diagnostic accuracy study. Sampling was carried out at renal outpatient clinic and healthcare worker testing sites at Imperial College London NHS Trust. Two cohorts of patients were recruited; the first was a cohort of 108 renal transplant patients attending clinic following two doses of SARS-CoV-2 vaccine, the second cohort comprised 40 healthcare workers attending for first SARS-CoV-2 vaccination and subsequent follow up. During the participants visit, finger-prick blood samples were analysed on LFIA device, while paired venous sampling was sent for serological assessment of antibodies to the spike protein (anti-S) antibodies. Anti-S IgG was detected using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA. A total of 186 paired samples were collected. The accuracy of Fortress LFIA in detecting IgG antibodies to SARS-CoV-2 compared to anti-spike protein detection on Abbott Assay Results: The LFIA had an estimated sensitivity of 92.0% (114/124; 95% confidence interval [CI] 85.7% to 96.1%) and specificity of 93.6% (58/62; 95% CI 84.3% to 98.2%) using the Abbott assay as reference standard (using the threshold for positivity of 7.10 BAU/ml) Conclusions: Fortress LFIA performs well in the detection of antibody responses for intended purpose of population level surveillance but does not meet criteria for individual testing.
Eales O, Page AJ, de Oliveira Martins L, et al., 2021, SARS-CoV-2 lineage dynamics in England from September to November 2021: high diversity of Delta sub-lineages and increased transmissibility of AY.4.2
<jats:title>Abstract</jats:title><jats:p>Since the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Here we present phylogenetic relationships and lineage dynamics within England (a country with high levels of immunity), as inferred from a random community sample of individuals who provided a self-administered throat and nose swab for rt-PCR testing as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. From 9 to 27 September 2021 (round 14) and 19 October to 5 November 2021 (round 15), all lineages sequenced within REACT-1 were Delta or a Delta sub-lineage with 44 unique lineages identified. The proportion of the original Delta variant (B.1.617.2) was found to be increasing between September and November 2021, which may reflect an increasing number of sub-lineages which have yet to be identified. The proportion of B.1.617.2 was greatest in London, which was further identified as a region with an increased level of genetic diversity. The Delta sub-lineage AY.4.2 was found to be robustly increasing in proportion, with a reproduction number 15% (8%, 23%) greater than its parent and most prevalent lineage, AY.4. Both AY.4.2 and AY.4 were found to be geographically clustered in September but this was no longer the case by late October/early November, with only the lineage AY.6 exhibiting clustering towards the South of England. Though no difference in the viral load based on cycle threshold (Ct) values was identified, a lower proportion of those infected with AY.4.2 had symptoms for which testing is usually recommend (loss or change of sense of taste, loss or change of sense of smell, new persistent cough, fever), compared to AY.4 (p = 0.026). The evolutionary rate of SARS-CoV-2, as measured by the mutation rate, was fou
Redd R, Cooper E, Atchison C, et al., 2021, Behavioural responses to SARS-CoV-2 antibody testing in England: REACT-2 study, Wellcome Open Research, Vol: 6, Pages: 203-203
<ns5:p><ns5:bold>Background: </ns5:bold>This study assesses the behavioural responses to SARS-CoV-2 antibody test results as part of the REal-time Assessment of Community Transmission-2 (REACT-2) research programme, a large community-based surveillance study of antibody prevalence in England.</ns5:p><ns5:p> <ns5:bold>Methods:</ns5:bold> A follow-up survey was conducted six weeks after the SARS-CoV-2 antibody test. The follow-up survey included 4500 people with a positive result and 4039 with a negative result. Reported changes in behaviour were assessed using difference-in-differences models. A nested interview study was conducted with 40 people to explore how they thought through their behavioural decisions.</ns5:p><ns5:p> <ns5:bold>Results:</ns5:bold> While respondents reduced their protective behaviours over the six weeks, we did not find evidence that positive test results changed participant behaviour trajectories in relation to the number of contacts the respondents had, for leaving the house to go to work, or for leaving the house to socialise in a personal place. The qualitative findings supported these results. Most people did not think that they had changed their behaviours because of their test results, however they did allude to some changes in their attitudes and perceptions around risk, susceptibility, and potential severity of symptoms.</ns5:p><ns5:p> <ns5:bold>Conclusions: </ns5:bold>We found limited evidence that knowing your antibody status leads to behaviour change in the context of a research study. While this finding should not be generalised to widespread self-testing in other contexts, it is reassuring given the importance of large prevalence studies, and the practicalities of doing these at scale using self-testing with lateral flow immunoassay (LFIA).</ns5:p>
Chadeau-Hyam M, Eales O, Bodinier B, et al., 2021, REACT-1 round 15 final report: Increased breakthrough SARS-CoV-2 infections among adults who had received two doses of vaccine, but booster doses and first doses in children are providing important protection
Background: It has been nearly a year since the first vaccinations against SARS-CoV-2were delivered in England. The third wave of COVID-19 in England began in May 2021 asthe Delta variant began to outcompete and largely replace other strains. The REal-timeAssessment of Community Transmission-1 (REACT-1) series of community surveys forSARS-CoV-2 infection has provided insights into transmission dynamics since May 2020.Round 15 of the REACT-1 study was carried out from 19 October to 5 November 2021.Methods: We estimated prevalence of SARS-CoV2 infection and used multiple logisticregression to analyse associations between SARS-CoV-2 infection in England anddemographic and other risk factors, based on RT-PCR results from self-administered throatand nose swabs in over 100,000 participants. We estimated (single-dose) vaccineeffectiveness among children aged 12 to 17 years, and among adults comparedswab-positivity in people who had received a third (booster) dose with those who hadreceived two vaccine doses. We used splines to analyse time trends in swab-positivity.Results: During mid-October to early-November 2021, weighted prevalence was 1.57%(1.48%, 1.66%) compared to 0.83% (0.76%, 0.89%) in September 2021 (round 14).Weighted prevalence increased between rounds 14 and 15 across most age groups(including older ages, 65 years and over) and regions, with average reproduction numberacross rounds of R=1.09 (1.08, 1.11). During round 15, there was a fall in prevalence from amaximum around 20-21 October, with an R of 0.76 (0.70, 0.83), reflecting falls in prevalenceat ages 17 years and below and 18 to 54 years. School-aged children had the highestweighted prevalence of infection: 4.95% (4.39%, 5.58%) in those aged 5 to 12 years and5.21% (4.61%, 5.87%) in those aged 13 to 17 years. In multiple logistic regression, age, sex,key worker status and presence of one or more children in the home were associated withswab positivity. There was evidence of heterogeneity between rounds in
Chadeau-Hyam M, Eales O, Bodinier B, et al., 2021, REACT-1 round 15 interim report: Exponential rise in prevalence of SARS-CoV-2 infection in England from end September 2021 followed by dip during October 2021
Background: The third wave of COVID-19 in England coincided with the rapid spread of theDelta variant of SARS-CoV-2 from the end of May 2021. Case incidence data from thenational testing programme (Pillar 2) in England may be affected by changes in testingbehaviour and other biases. Community surveys may provide important contextualinformation to inform policy and the public health response.Methods: We estimated patterns of community prevalence of SARS-CoV-2 infection inEngland using RT-PCR swab-positivity, demographic and other risk factor data from round15 (interim) of the REal-time Assessment of Community Transmission-1 (REACT-1) study(round 15a, carried out from 19 to 29 October 2021). We compared these findings with thosefrom round 14 (9 to 27 September 2021).Results: During mid- to late-October 2021 (round 15a) weighted prevalence was 1.72%(1.61%, 1.84%) compared to 0.83% (0.76%, 0.89%) in September 2021 (round 14). Theoverall reproduction number (R) from round 14 to round 15a was 1.12 (1.11, 1.14) withincreases in prevalence over this period (September to October) across age groups andregions except Yorkshire and The Humber. However, within round 15a (mid- to late-October)there was evidence of a fall in prevalence with R of 0.76 (0.65, 0.88). The highest weightedprevalence was observed among children aged 5 to 12 years at 5.85% (5.10%, 6.70%) and13 to 17 years at 5.75% (5.02%, 6.57%). At regional level, there was an almost four-foldincrease in weighted prevalence in South West from round 14 at 0.59% (0.43%,0.80%) toround 15a at 2.18% (1.84%, 2.58%), with highest smoothed prevalence at subregional levelalso found in South West in round 15a. Age, sex, key worker status, and presence ofchildren in the home jointly contributed to the risk of swab-positivity. Among the 126sequenced positive swabs obtained up until 23 October, all were Delta variant; 13 (10.3%)were identified as the AY.4.2 sub-lineage.Discussion: We observed the highest overall prevalence of swab-p
Elliott P, Haw D, Wang H, et al., 2021, Exponential growth, high prevalence of SARS-CoV-2 and vaccine effectiveness associated with Delta variant, Science, Vol: 374, Pages: 1-11, ISSN: 0036-8075
SARS-CoV-2 infections were rising during early summer 2021 in many countries associated with the Delta variant. We assessed RT-PCR swab-positivity in the REal-time Assessment of Community Transmission-1 (REACT-1) study in England. We observed sustained exponential growth with average doubling time (June-July 2021) of 25 days driven by complete replacement of Alpha variant by Delta, and by high prevalence at younger less-vaccinated ages. Unvaccinated people were three times more likely than double-vaccinated people to test positive. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination.
Hewer SCL, Smyth AR, Brown M, et al., 2021, Intravenous or oral antibiotic treatment in adults and children with cystic fibrosis and <i>Pseudomonas</i> <i>aeruginosa</i> infection: the TORPEDO-CF RCT, HEALTH TECHNOLOGY ASSESSMENT, Vol: 25, Pages: 1-+, ISSN: 1366-5278
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Chadeau-Hyam M, Wang H, Eales O, et al., 2021, REACT-1 study round 14: High and increasing prevalence of SARS-CoV-2 infection among school-aged children during September 2021 and vaccine effectiveness against infection in England
Background: England experienced a third wave of the COVID-19 epidemic from end May2021 coinciding with the rapid spread of Delta variant. Since then, the population eligible forvaccination against COVID-19 has been extended to include all 12-15-year-olds, and abooster programme has been initiated among adults aged 50 years and over, health careand care home workers, and immunocompromised people. Meanwhile, schoolchildren havereturned to school often with few COVID-19-related precautions in place.Methods: In the REal-time Assessment of Community Transmission-1 (REACT-1) study,throat and nose swabs were sent to non-overlapping random samples of the populationaged 5 years and over in England. We analysed prevalence of SARS-CoV-2 using reversetranscription-polymerase chain reaction (RT-PCR) swab-positivity data from REACT-1 round14 (between 9 and 27 September 2021). We combined results for round 14 with round 13(between 24 June and 12 July 2021) and estimated vaccine effectiveness and prevalence ofswab-positivity among double-vaccinated individuals. Unlike all previous rounds, in round 14,we switched from dry swabs transported by courier on a cold chain to wet swabs usingsaline. Also, at random, 50% of swabs (not chilled until they reached the depot) weretransported by courier and 50% were sent through the priority COVID-19 postal service.Results: We observed stable or rising prevalence (with an R of 1.03 (0.94, 1.14) overall)during round 14 with a weighted prevalence of 0.83% (0.76%, 0.89%). The highest weightedprevalence was found in children aged 5 to 12 years at 2.32% (1.96%, 2.73%) and 13 to 17years at 2.55% (2.11%, 3.08%). All positive virus samples analysed correspond to the Deltavariant or sub-lineages of Delta with one instance of the E484K escape mutation detected.The epidemic was growing in those aged 17 years and under with an R of 1.18 (1.03, 1.34),but decreasing in those aged 18 to 54 years with an R of 0.81 (0.68, 0.97). For allparticipants and all vaccin
Davies B, Araghi M, Moshe M, et al., 2021, Acceptability, usability and performance of lateral flow immunoassay tests for SARS-CoV-2 antibodies: REACT-2 study of self-testing in non-healthcare key workers, Open Forum Infectious Diseases, Vol: 8, ISSN: 2328-8957
Background Seroprevalence studies are essential to understand the epidemiology of SARS-CoV-2. Various technologies, including laboratory assays and point-of-care self-tests, are available for antibody testing. The interpretation of seroprevalence studies requires comparative data on the performance of antibody tests. Methods In June 2020, current and former members of the UK Police forces and Fire service performed a self-test lateral flow immunoassay (LFIA), had a nurse-performed LFIA and provided a venous blood sample for ELISA . We present the prevalence of antibodies to SARS-CoV-2; the acceptability and usability of self-test LFIAs; and determine the sensitivity and specificity of LFIAs compared to laboratory ELISA. Results In this cohort of 5189 current and former members of the Police service and 263 members of the Fire service, 7.4% (396/5,348; 95% CI, 6.7-8.1) were antibody positive. Seroprevalence was 8.9% (6.9-11.4) in those under 40 years, 11.5% (8.8-15.0) in those of non-white ethnicity and 7.8% (7.1-8.7) in those currently working. Self-test LFIA had an acceptability of 97.7% and a usability of 90.0%. There was substantial agreement between within-participant LFIA results (kappa 0.80; 0.77-0.83). The LFIAs had a similar performance: compared to ELISA, sensitivity was 82.1% (77.7-86.0) self-test and 76.4% (71.9-80.5) nurse-performed with specificity of 97.8% (97.3-98.2) and 98.5% (98.1-98.8) respectively. Conclusion A greater proportion of this non-healthcare key worker cohort showed evidence of previous infection with SARS-CoV-2 than the general population at 6.0% (5.8-6.1) following the first wave in England. The high acceptability and usability reported by participants and similar performance of self-test and nurse-performed LFIAs indicate that the self-test LFIA is fit for purpose for home-testing in occupational and community prevalence studies.
Eales O, Walters C, Wang H, et al., 2021, Characterising the persistence of RT-PCR positivity and incidence in a community survey of SARS-CoV-2
BackgroundCommunity surveys of SARS-CoV-2 RT-PCR swab-positivity provide prevalence estimates largely unaffected by biases from who presents for routine case testing. The REal-time Assessment of Community Transmission-1 (REACT-1) has estimated swab-positivity approximately monthly since May 2020 in England from RT-PCR testing of self-administeredthroat and nose swabs in random non-overlapping cross-sectional community samples. Estimating infection incidence from swab-positivity requires an understanding of the persistence of RT-PCR swab positivity in the community.MethodsDuring round 8 of REACT-1 from 6 January to 22 January 2021, of the 2,282 participants who tested RT-PCR positive, we recruited 896 (39%) from whom we collected up to two additional swabs for RT-PCR approximately 6 and 9 days after the initial swab. We estimated sensitivity and duration of positivity using an exponential model of positivity decay, for all participants and for subsets by initial N-gene cycle threshold (Ct) value, symptom status, lineage and age. Estimates of infection incidence were obtained for the entire duration of the REACT-1 study using P-splines.ResultsWe estimated the overall sensitivity of REACT-1 to detect virus on a single swab as 0.79 (0.77, 0.81) and median duration of positivity following a positive test as 9.7 (8.9, 10.6) days. We found greater median duration of positivity where there was a low N-gene Ct value, in those exhibiting symptoms, or for infection with the Alpha variant. The estimated proportionof positive individuals detected on first swab, was found to be higher 𝑃 for those with an 0 initially low N-gene Ct value and those who were pre-symptomatic. When compared to swab-positivity, estimates of infection incidence over the duration of REACT-1 included sharper features with evident transient increases around the time of key changes in socialdistancing measures.DiscussionHome self-swabbing for RT-PCR based on a single swab, as implemented in REACT-1, has hig
Redd R, Cooper E, Atchison C, et al., 2021, Behavioural responses to SARS-CoV-2 antibody testing in England: REACT-2 study, Wellcome Open Research, Vol: 6, Pages: 1-10, ISSN: 2398-502X
Background: This study assesses the behavioural responses to SARS-CoV-2 antibody test results as part of the REal-time Assessment of Community Transmission-2 (REACT-2) research programme, a large community-based surveillance study of antibody prevalence in England.Methods: A follow-up survey was conducted six weeks after the SARS-CoV-2 antibody test. The follow-up survey included 4500 people with a positive result and 4039 with a negative result. Reported changes in behaviour were assessed using difference-in-differences models. A nested interview study was conducted with 40 people to explore how they thought through their behavioural decisions.Results: While respondents reduced their protective behaviours over the six weeks, we did not find evidence that positive test results changed participant behaviour trajectories in relation to the number of contacts the respondents had, for leaving the house to go to work, or for leaving the house to socialise in a personal place. The qualitative findings supported these results. Most people did not think that they had changed their behaviours because of their test results, however they did allude to some changes in their attitudes and perceptions around risk, susceptibility, and potential severity of symptoms.Conclusions: We found limited evidence that knowing your antibody status leads to behaviour change in the context of a research study. While this finding should not be generalised to widespread self-testing in other contexts, it is reassuring given the importance of large prevalence studies, and the practicalities of doing these at scale using self-testing with lateral flow immunoassay (LFIA).
Elliott P, Haw D, Wang H, et al., 2021, REACT-1 round 13 final report: exponential growth, high prevalence of SARS-CoV-2 and vaccine effectiveness associated with Delta variant in England during May to July 2021
BackgroundThe prevalence of SARS-CoV-2 infection continues to drive rates of illness andhospitalisations despite high levels of vaccination, with the proportion of cases caused by theDelta lineage increasing in many populations. As vaccination programs roll out globally andsocial distancing is relaxed, future SARS-CoV-2 trends are uncertain.MethodsWe analysed prevalence trends and their drivers using reverse transcription-polymerasechain reaction (RT-PCR) swab-positivity data from round 12 (between 20 May and 7 June2021) and round 13 (between 24 June and 12 July 2021) of the REal-time Assessment ofCommunity Transmission-1 (REACT-1) study, with swabs sent to non-overlapping randomsamples of the population ages 5 years and over in England.ResultsWe observed sustained exponential growth with an average doubling time in round 13 of 25days (lower Credible Interval of 15 days) and an increase in average prevalence from 0.15%(0.12%, 0.18%) in round 12 to 0.63% (0.57%, 0.18%) in round 13. The rapid growth acrossand within rounds appears to have been driven by complete replacement of Alpha variant byDelta, and by the high prevalence in younger less-vaccinated age groups, with a nine-foldincrease between rounds 12 and 13 among those aged 13 to 17 years. Prevalence amongthose who reported being unvaccinated was three-fold higher than those who reported beingfully vaccinated. However, in round 13, 44% of infections occurred in fully vaccinatedindividuals, reflecting imperfect vaccine effectiveness against infection despite high overalllevels of vaccination. Using self-reported vaccination status, we estimated adjusted vaccineeffectiveness against infection in round 13 of 49% (22%, 67%) among participants aged 18to 64 years, which rose to 58% (33%, 73%) when considering only strong positives (Cyclethreshold [Ct] values < 27); also, we estimated adjusted vaccine effectiveness againstsymptomatic infection of 59% (23%, 78%), with any one of three common COVID-19symptoms reported
Ward H, Atchison C, Whitaker M, et al., 2021, Increasing SARS-CoV-2 antibody prevalence in England at the start of the second wave: REACT-2 Round 4 cross-sectional study in 160,000 adults
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>REACT-2 Study 5 is a population survey of the prevalence of SARS-CoV-2 antibodies in the community in England.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We contacted a random sample of the population by sending a letter to named individuals aged 18 or over from the NHS GP registrations list. We then sent respondents a lateral flow immunoassay (LFIA) kit for SARS-CoV-2 antibody self-testing and asked them to perform the test at home and complete a questionnaire, including reporting of their test result. Overall, 161,537 adults completed questionnaires and self-administered LFIA tests for IgG against SARS-CoV-2 between 27 October and 10 November 2020.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The overall adjusted and weighted prevalence was 5.6% (95% CI 5.4-5.7). This was an increase from 4.4% (4.3-4.5) in round 3 (September), a relative increase of 26.9% (24.0-29.9).The largest increase by age was in the 18 to 24 year old age group, which increased (adjusted and weighted) from 6.7% (6.3-7.2) to 9.9% (9.3-10.4), and in students, (adjusted, unweighted) from 5.9% (4.8-7.1) to 12.1% (10.8-13.5). Prevalence increased most in Yorkshire and The Humber, from 3.4% (3.0-3.8) to 6.3% (5.9-6.8) and the North West from 4.5% (4.2-4.9) to 7.7% (7.2-8.1). In contrast, the prevalence in London was stable, at 9.5% (9.0-9.9) and 9.5% (9.1-10.0) in rounds 3 and 4 respectively. We found the highest prevalence in people of Bangladeshi 15.1% (10.9-20.5), Pakistani 13.9% (11.2-17.2) and African 13.5% (10.7-16.8) ethnicity, and lowest in those of white British ethnicity at 4.2% (4.0-4.3).</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>The second wave of infection in England is apparen
Ward H, Whitaker M, Tang SN, et al., 2021, Vaccine uptake and SARS-CoV-2 antibody prevalence among 207,337 adults during May 2021 in England: REACT-2 study
Background The programme to vaccinate adults in England has been rapidly implementedsince it began in December 2020. The community prevalence of SARS-CoV-2 anti-spikeprotein antibodies provides an estimate of total cumulative response to natural infection andvaccination. We describe the distribution of SARS-CoV-2 IgG antibodies in adults inEngland in May 2021 at a time when approximately 7 in 10 adults had received at least onedose of vaccine.Methods Sixth round of REACT-2 (REal-time Assessment of Community Transmission-2),a cross-sectional random community survey of adults in England, from 12 to 25 May 2021;207,337 participants completed questionnaires and self-administered a lateral flowimmunoassay test producing a positive or negative result.Results Vaccine coverage with one or more doses, weighted to the adult population inEngland, was 72.9% (95% confidence interval 72.7-73.0), varying by age from 25.1% (24.5-25.6) of those aged 18 to 24 years, to 99.2% (99.1-99.3) of those 75 years and older. Inadjusted models, odds of vaccination were lower in men (odds ratio [OR] 0.89 [0.85-0.94])than women, and in people of Black (0.41 [0.34-0.49]) compared to white ethnicity. Therewas higher vaccine coverage in the least deprived and highest income households. Peoplewho reported a history of COVID-19 were less likely to be vaccinated (OR 0.61 [0.55-0.67]).There was high coverage among health workers (OR 9.84 [8.79-11.02] and care workers (OR4.17 [3.20-5.43]) compared to non-key workers, but lower in hospitality and retail workers(OR 0.73 [0.64-0.82] and 0.77 [0.70-0.85] respectively) after adjusting for age and keycovariates.
Riley S, Eales O, Haw D, et al., 2021, REACT-1 round 13 interim report: acceleration of SARS-CoV-2 Delta epidemic in the community in England during late June and early July 2021
BackgroundDespite high levels of vaccination in the adult population, cases of COVID-19 have risenexponentially in England since the start of May 2021 driven by the Delta variant. However,with far fewer hospitalisations and deaths per case during the recent growth in casescompared with 2020, it is intended that all remaining social distancing legislation in Englandwill be removed from 19 July 2021.MethodsWe report interim results from round 13 of the REal-time Assessment of CommunityTransmission-1 (REACT-1) study in which a cross-sectional sample of the population ofEngland was asked to provide a throat and nose swab for RT-PCR and to answer aquestionnaire. Data collection for this report (round 13 interim) was from 24 June to 5 July2021.ResultsIn round 13 interim, we found 237 positives from 47,729 swabs giving a weighted prevalenceof 0.59% (0.51%, 0.68%) which was approximately four-fold higher compared with round 12at 0.15% (0.12%, 0.18%). This resulted from continued exponential growth in prevalencewith an average doubling time of 15 (13, 17) days between round 12 and round 13.However, during the recent period of round 13 interim only, we observed a shorter doublingtime of 6.1 (4.0, 12) days with a corresponding R number of 1.87 (1.40, 2.45). There weresubstantial increases in all age groups under the age of 75 years, and especially at youngerages, with the highest prevalence in 13 to 17 year olds at 1.33% (0.97%, 1.82%) and in 18 to24 years olds at 1.40% (0.89%, 2.18%). Infections have increased in all regions with thelargest increase in London where prevalence increased more than eight-fold from 0.13%(0.08%, 0.20%) in round 12 to 1.08% (0.79%, 1.47%) in round 13 interim. Overall,prevalence was over 3 times higher in the unvaccinated compared with those reporting twodoses of vaccine in both round 12 and round 13 interim, although there was a similarproportional increase in prevalence in vaccinated and unvaccinated individuals between thetwo rounds.DiscussionWe
Davies B, Araghi M, Moshe M, et al., 2021, Acceptability, usability and performance of lateral flow immunoassay tests for SARSCoV-2 antibodies: REACT-2 study of self-testing in non-healthcare key workers, Publisher: Cold Spring Harbor Laboratory
BackgroundSeroprevalence studies in key worker populations are essential to understand the epidemiology of SARS-CoV-2. Various technologies, including laboratory assays and pointof-care self-tests, are available for antibody testing. The interpretation of seroprevalence studies requires comparative data on the performance of antibody tests.MethodsIn June 2020, current and former members of the UK Police forces and Fire service performed a self-test lateral flow immunoassay (LFIA) and provided a saliva sample, nasopharyngeal swab, venous blood samples for Abbott ELISA and had a nurse performed LFIA. We present the prevalence of PCR positivity and antibodies to SARS-CoV-2 in this cohort following the first wave of infection in England; the acceptability and usability of selftest LFIAs (defined as use of the LFIA kit and provision of a valid result, respectively); and determine the sensitivity and specificity of LFIAs compared to laboratory ELISAs.ResultsIn this cohort of non-healthcare key workers, 7.4% (396/5,348; 95% CI, 6.7-8.1) were antibody positive. Seroprevalence was 8.9% (6.9-11.4) in those under 40 years, 11.5% (8.8-15.0) in those of non-white British ethnicity and 7.8% (7.1-8.7) in those currently working.The self-test LFIA had an acceptability of 97.7% and a usability of 90.0%. There was substantial agreement between within-participant LFIA results (kappa 0.80; 0.77-0.83). The LFIAs (self-test and nurse-performed) had a similar performance: compared to ELISA, sensitivity was 82.1% (77.7-86.0) self-test and 76.4% (71.9-80.5) nurse-performed with specificity of 97.8% (97.3-98.2) and 98.5% (98.1-98.8) respectively.ConclusionA greater proportion of the non-healthcare key worker cohort showed evidence of previous infection with SARS-CoV-2 than the general population at 6.0% (5.8-6.1) following the first wave in England. The high acceptability and usability reported by participants and the similar performance of self-test and nurse-performed LFIAs indicate that t
Riley S, Wang H, Eales O, et al., 2021, REACT-1 round 12 report: resurgence of SARS-CoV-2 infections in England associated with increased frequency of the Delta variant
BackgroundEngland entered a third national lockdown from 6 January 2021 due to the COVID-19pandemic. Despite a successful vaccine rollout during the first half of 2021, cases andhospitalisations have started to increase since the end of May as the SARS-CoV-2 Delta(B.1.617.2) variant increases in frequency. The final step of relaxation of COVID-19restrictions in England has been delayed from 21 June to 19 July 2021.MethodsThe REal-time Assessment of Community Transmision-1 (REACT-1) study measures theprevalence of swab-positivity among random samples of the population of England. Round12 of REACT-1 obtained self-administered swab collections from participants from 20 May2021 to 7 June 2021; results are compared with those for round 11, in which swabs werecollected from 15 April to 3 May 2021.ResultsBetween rounds 11 and 12, national prevalence increased from 0.10% (0.08%, 0.13%) to0.15% (0.12%, 0.18%). During round 12, we detected exponential growth with a doublingtime of 11 (7.1, 23) days and an R number of 1.44 (1.20, 1.73). The highest prevalence wasfound in the North West at 0.26% (0.16%, 0.41%) compared to 0.05% (0.02%, 0.12%) in theSouth West. In the North West, the locations of positive samples suggested a cluster inGreater Manchester and the east Lancashire area. Prevalence in those aged 5-49 was 2.5times higher at 0.20% (0.16%, 0.26%) compared with those aged 50 years and above at0.08% (0.06%, 0.11%). At the beginning of February 2021, the link between infection ratesand hospitalisations and deaths started to weaken, although in late April 2021, infectionrates and hospital admissions started to reconverge. When split by age, the weakened linkbetween infection rates and hospitalisations at ages 65 years and above was maintained,while the trends converged below the age of 65 years. The majority of the infections in theyounger group occurred in the unvaccinated population or those without a stated vaccinehistory. We observed the rapid replacement of the Alpha (
Riley S, Ainslie KEC, Eales O, et al., 2021, Resurgence of SARS-CoV-2: detection by community viral surveillance, Science, Vol: 372, Pages: 990-995, ISSN: 0036-8075
Surveillance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has mainly relied on case reporting, which is biased by health service performance, test availability, and test-seeking behaviors. We report a community-wide national representative surveillance program in England based on self-administered swab results from ~594,000 individuals tested for SARS-CoV-2, regardless of symptoms, between May and the beginning of September 2020. The epidemic declined between May and July 2020 but then increased gradually from mid-August, accelerating into early September 2020 at the start of the second wave. When compared with cases detected through routine surveillance, we report here a longer period of decline and a younger age distribution. Representative community sampling for SARS-CoV-2 can substantially improve situational awareness and feed into the public health response even at low prevalence.
Riley S, Haw D, Walters C, et al., 2021, REACT-1 round 11 report: low prevalence of SARS-CoV-2 infection in the community prior to the third step of the English roadmap out of lockdown
BackgroundNational epidemic dynamics of SARS-CoV-2 infections are being driven by: the degree of recent indoor mixing (both social and workplace), vaccine coverage, intrinsic properties of the circulating lineages, and prior history of infection (via natural immunity). In England, infections, hospitalisations and deaths fell during the first two steps of the “roadmap” for exiting the third national lockdown. The third step of the roadmap in England takes place on 17 May 2021.MethodsWe report the most recent findings on community infections from the REal-time Assessment of Community Transmission-1 (REACT-1) study in which a swab is obtained from a representative cross-sectional sample of the population in England and tested using PCR. Round 11 of REACT-1 commenced self-administered swab-collection on 15 April 2021 and completed collections on 3 May 2021. We compare the results of REACT-1 round 11 to round 10, in which swabs were collected from 11 to 30 March 2021.ResultsBetween rounds 10 and 11, prevalence of swab-positivity dropped by 50% in England from 0.20% (0.17%, 0.23%) to 0.10% (0.08%, 0.13%), with a corresponding R estimate of 0.90 (0.87, 0.94). Rates of swab-positivity fell in the 55 to 64 year old group from 0.17% (0.12%, 0.25%) in round 10 to 0.06% (0.04%, 0.11%) in round 11. Prevalence in round 11 was higher in the 25 to 34 year old group at 0.21% (0.12%, 0.38%) than in the 55 to 64 year olds and also higher in participants of Asian ethnicity at 0.31% (0.16%, 0.60%) compared with white participants at 0.09% (0.07%, 0.11%). Based on sequence data for positive samples for which a lineage could be identified, we estimate that 92.3% (75.9%, 97.9%, n=24) of infections were from the B.1.1.7 lineage compared to 7.7% (2.1%, 24.1%, n=2) from the B.1.617.2 lineage. Both samples from the B.1.617.2 lineage were detected in London from participants not reporting travel in the previous two weeks. Also, allowing for suitable lag periods, the prior close alig
Eales O, Page AJ, Tang S, et al., 2021, SARS-CoV-2 lineage dynamics in England from January to March 2021 inferred from representative community samples
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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