Design and Implementation of a National SARS-CoV-2 Monitoring Program in England: REACT-1 Study.

Data System. The REal-time Assessment of Community Transmission-1 (REACT-1) Study was funded by the Department of Health and Social Care in England to provide reliable and timely estimates of prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection over time, by person and place. Data Collection/Processing. The study team (researchers from Imperial College London and its logistics partner Ipsos) wrote to named individuals aged 5 years and older in random cross-sections of the population of England, using the National Health Service list of patients registered with a general practitioner (near-universal coverage) as a sampling frame. We collected data over 2 to 3 weeks approximately every month across 19 rounds of data collection from May 1, 2020, to March 31, 2022. Data Analysis/Dissemination. We have disseminated the data and study materials widely via the study Web site, preprints, publications in peer-reviewed journals, and the media. We make available data tabulations, suitably anonymized to protect participant confidentiality, on request to the study's data access committee. Public Health Implications. The study provided inter alia real-time data on SARS-CoV-2 prevalence over time, by area, and by sociodemographic variables; estimates of vaccine effectiveness; and symptom profiles, and detected emergence of new variants based on viral genome sequencing. (Am J Public Health. 2023;113(5):545-554. https://doi.org/10.2105/AJPH.2023.307230).

Variant-specific symptoms of COVID-19 in a study of 1,542,510 adults in England.

Infection with SARS-CoV-2 virus is associated with a wide range of symptoms. The REal-time Assessment of Community Transmission -1 (REACT-1) study monitored the spread and clinical manifestation of SARS-CoV-2 among random samples of the population in England from 1 May 2020 to 31 March 2022. We show changing symptom profiles associated with the different variants over that period, with lower reporting of loss of sense of smell or taste for Omicron compared to previous variants, and higher reporting of cold-like and influenza-like symptoms, controlling for vaccination status. Contrary to the perception that recent variants have become successively milder, Omicron BA.2 was associated with reporting more symptoms, with greater disruption to daily activities, than BA.1. With restrictions lifted and routine testing limited in many countries, monitoring the changing symptom profiles associated with SARS-CoV-2 infection and effects on daily activities will become increasingly important.

Dynamics of a national Omicron SARS-CoV-2 epidemic during January 2022 in England.

Rapid transmission of the SARS-CoV-2 Omicron variant has led to record-breaking case incidence rates around the world. Since May 2020, the REal-time Assessment of Community Transmission-1 (REACT-1) study tracked the spread of SARS-CoV-2 infection in England through RT-PCR of self-administered throat and nose swabs from randomly-selected participants aged 5 years and over. In January 2022, we found an overall weighted prevalence of 4.41% (n = 102,174), three-fold higher than in November to December 2021; we sequenced 2,374 (99.2%) Omicron infections (19 BA.2), and only 19 (0.79%) Delta, with a growth rate advantage for BA.2 compared to BA.1 or BA.1.1. Prevalence was decreasing overall (reproduction number R = 0.95, 95% credible interval [CrI], 0.93, 0.97), but increasing in children aged 5 to 17 years (R = 1.13, 95% CrI, 1.09, 1.18). In England during January 2022, we observed unprecedented levels of SARS-CoV-2 infection, especially among children, driven by almost complete replacement of Delta by Omicron.

Omicron SARS-CoV-2 epidemic in England during February 2022: A series of cross-sectional community surveys.

Background: The Omicron wave of COVID-19 in England peaked in January 2022 resulting from the rapid transmission of the Omicron BA.1 variant. We investigate the spread and dynamics of the SARS-CoV-2 epidemic in the population of England during February 2022, by region, age and main SARS-CoV-2 sub-lineage. Methods: In the REal-time Assessment of Community Transmission-1 (REACT-1) study we obtained data from a random sample of 94,950 participants with valid throat and nose swab results 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% credible interval [CrI] 2.76-3.00), with a within-round effective reproduction number (R) overall of 0.94 (0·91-0.96). While within-round weighted prevalence fell among children (aged 5 to 17 years) and adults aged 18 to 54 years, we observed a level or increasing weighted prevalence among those aged 55 years and older with an R of 1.04 (1.00-1.09). Among 1,616 positive samples with sublineages determined, one (0.1% [0.0-0.3]) corresponded to XE BA.1/BA.2 recombinant and the remainder were Omicron: N=1047, 64.8% (62.4-67.2) were BA.1; N=568, 35.2% (32.8-37.6) were BA.2. We estimated an R additive advantage for BA.2 (vs BA.1) of 0.38 (0.34-0.41). The highest proportion of BA.2 among positives was found in London. Interpretation: In February 2022, infection prevalence in England remained high with level or increasing rates of infection in older people and an uptick in hospitalisations. Ongoing surveillance of both survey and hospitalisations data is required. Funding: Department of Health and Social Care, England.

Twin peaks: The Omicron SARS-CoV-2 BA.1 and BA.2 epidemics in England.

Rapid transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has led to record-breaking incidence rates around the world. The Real-time Assessment of Community Transmission-1 (REACT-1) study has tracked SARS-CoV-2 infection in England using reverse transcription polymerase chain reaction (RT-PCR) results from self-administered throat and nose swabs from randomly selected participants aged 5 years and older approximately monthly from May 2020 to March 2022. Weighted prevalence in March 2022 was the highest recorded in REACT-1 at 6.37% (N = 109,181), with the Omicron BA.2 variant largely replacing the BA.1 variant. Prevalence was increasing overall, with the greatest increase in those aged 65 to 74 years and 75 years and older. This was associated with increased hospitalizations and deaths, but at much lower levels than in previous waves against a backdrop of high levels of vaccination.

Breakthrough SARS-CoV-2 infections in double and triple vaccinated adults and single dose vaccine effectiveness among children in Autumn 2021 in England: REACT-1 study.

Background: Prevalence of SARS-CoV-2 infection with Delta variant was increasing in England in late summer 2021 among children aged 5 to 17 years, and adults who had received two vaccine doses. In September 2021, a third (booster) dose was offered to vaccinated adults aged 50 years and over, vulnerable adults and healthcare/care-home workers, and a single vaccine dose already offered to 16 and 17 year-olds was extended to children aged 12 to 15 years. Methods: SARS-CoV-2 community prevalence in England was available from self-administered throat and nose swabs using reverse transcriptase polymerase chain reaction (RT-PCR) in round 13 (24 June to 12 July 2021, N = 98,233), round 14 (9 to 27 September 2021, N = 100,527) and round 15 (19 October to 5 November 2021, N = 100,112) from the REACT-1 study randomised community surveys. Linking to National Health Service (NHS) vaccination data for consenting participants, we estimated vaccine effectiveness in children aged 12 to 17 years and compared swab-positivity rates in adults who received a third dose with those who received two doses. Findings: Weighted SARS-CoV-2 prevalence was 1.57% (1.48%, 1.66%) in round 15 compared with 0.83% (0.76%, 0.89%) in round 14, and the previously observed link between infections and hospitalisations and deaths had weakened. Vaccine effectiveness against infection in children aged 12 to 17 years was estimated (round 15) at 64.0% (50.9%, 70.6%) and 67.7% (53.8%, 77.5%) for symptomatic infections. Adults who received a third vaccine dose were less likely to test positive compared to those who received two doses, with adjusted OR of 0.36 (0.25, 0.53). Interpretation: Vaccination of children aged 12 to 17 years and third (booster) doses in adults were effective at reducing infection risk. High rates of vaccination, including booster doses, are a key part of the strategy to reduce infection rates in the community. Funding: Department of Health and Social Care, England.

Persistent COVID-19 symptoms in a community study of 606,434 people in England.

Long COVID remains a broadly defined syndrome, with estimates of prevalence and duration varying widely. We use data from rounds 3-5 of the REACT-2 study (n = 508,707; September 2020 - February 2021), a representative community survey of adults in England, and replication data from round 6 (n = 97,717; May 2021) to estimate the prevalence and identify predictors of persistent symptoms lasting 12 weeks or more; and unsupervised learning to cluster individuals by reported symptoms. At 12 weeks in rounds 3-5, 37.7% experienced at least one symptom, falling to 21.6% in round 6. Female sex, increasing age, obesity, smoking, vaping, hospitalisation with COVID-19, deprivation, and being a healthcare worker are associated with higher probability of persistent symptoms in rounds 3-5, and Asian ethnicity with lower probability. Clustering analysis identifies a subset of participants with predominantly respiratory symptoms. Managing the long-term sequelae of COVID-19 will remain a major challenge for affected individuals and their families and for health services.

Rapid increase in Omicron infections in England during December 2021: REACT-1 study.

The unprecedented rise in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during December 2021 was concurrent with rapid spread of the Omicron variant in England and globally. We analyzed the prevalence of SARS-CoV-2 and its dynamics in England from the end of November to mid-December 2021 among almost 100,000 participants in the REACT-1 study. Prevalence was high with rapid growth nationally and particularly in London during December 2021, with an increasing proportion of infections due to Omicron. We observed large decreases in swab positivity among mostly vaccinated older children (12 to 17 years) relative to unvaccinated younger children (5 to 11 years), and in adults who received a third (booster) vaccine dose versus 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.

Predictive symptoms for COVID-19 in the community: REACT-1 study of over 1 million people.

BACKGROUND: Rapid detection, isolation, and contact tracing of community COVID-19 cases are essential measures to limit the community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to identify a parsimonious set of symptoms that jointly predict COVID-19 and investigated whether predictive symptoms differ between the B.1.1.7 (Alpha) lineage (predominating as of April 2021 in the US, UK, and elsewhere) and wild type. METHODS AND FINDINGS: We obtained throat and nose swabs with valid SARS-CoV-2 PCR test results from 1,147,370 volunteers aged 5 years and above (6,450 positive cases) in the REal-time Assessment of Community Transmission-1 (REACT-1) study. This study involved repeated community-based random surveys of prevalence in England (study rounds 2 to 8, June 2020 to January 2021, response rates 22%-27%). Participants were asked about symptoms occurring in the week prior to testing. Viral genome sequencing was carried out for PCR-positive samples with N-gene cycle threshold value < 34 (N = 1,079) in round 8 (January 2021). In univariate analysis, all 26 surveyed symptoms were associated with PCR positivity compared with non-symptomatic people. Stability selection (1,000 penalized logistic regression models with 50% subsampling) among people reporting at least 1 symptom identified 7 symptoms as jointly and positively predictive of PCR positivity in rounds 2-7 (June to December 2020): loss or change of sense of smell, loss or change of sense of taste, fever, new persistent cough, chills, appetite loss, and muscle aches. The resulting model (rounds 2-7) predicted PCR positivity in round 8 with area under the curve (AUC) of 0.77. The same 7 symptoms were selected as jointly predictive of B.1.1.7 infection in round 8, although when comparing B.1.1.7 with wild type, new persistent cough and sore throat were more predictive of B.1.1.7 infection while loss or change of sense of smell was more predictive of the wild type. The main limitations of our study are (i) potential participation bias despite random sampling of named individuals from the National Health Service register and weighting designed to achieve a representative sample of the population of England and (ii) the necessary reliance on self-reported symptoms, which may be prone to recall bias and may therefore lead to biased estimates of symptom prevalence in England. CONCLUSIONS: Where testing capacity is limited, it is important to use tests in the most efficient way possible. We identified a set of 7 symptoms that, when considered together, maximize detection of COVID-19 in the community, including infection with the B.1.1.7 lineage.

Prevalence of antibody positivity to SARS-CoV-2 following the first peak of infection in England: Serial cross-sectional studies of 365,000 adults.

BACKGROUND: The time-concentrated nature of the first wave of the COVID-19 epidemic in England in March and April 2020 provides a natural experiment to measure changes in antibody positivity at the population level before onset of the second wave and initiation of the vaccination programme. METHODS: Three cross-sectional national surveys with non-overlapping random samples of the population in England undertaken between late June and September 2020 (REACT-2 study). 365,104 adults completed questionnaires and self-administered lateral flow immunoassay (LFIA) tests for IgG against SARS-CoV-2. FINDINGS: Overall, 17,576 people had detectable antibodies, a prevalence of 4.9% (95% confidence intervals 4.9, 5.0) when adjusted for test characteristics and weighted to the adult population of England. The prevalence declined from 6.0% (5.8, 6.1), to 4.8% (4.7, 5.0) and 4.4% (4.3, 4.5), over the three rounds of the study a difference of -26.5% (-29.0, -23.8). The highest prevalence and smallest overall decline in positivity was in the youngest age group (18-24 years) at -14.9% (-21.6, -8.1), and lowest prevalence and largest decline in the oldest group (>74 years) at -39.0% (-50.8, -27.2). The decline from June to September 2020 was largest in those who did not report a history of COVID-19 at -64.0% (-75.6, -52.3), compared to -22.3% (-27.0, -17.7) in those with SARS-CoV-2 infection confirmed on PCR. INTERPRETATION: A large proportion of the population remained susceptible to SARS-CoV-2 infection in England based on naturally acquired immunity from the first wave. Widespread vaccination is needed to confer immunity and control the epidemic at population level. FUNDING: This work was funded by the Department of Health and Social Care in England.

COVID-19 mortality in the UK Biobank cohort: revisiting and evaluating risk factors.

Most studies of severe/fatal COVID-19 risk have used routine/hospitalisation data without detailed pre-morbid characterisation. Using the community-based UK Biobank cohort, we investigate risk factors for COVID-19 mortality in comparison with non-COVID-19 mortality. We investigated demographic, social (education, income, housing, employment), lifestyle (smoking, drinking, body mass index), biological (lipids, cystatin C, vitamin D), medical (comorbidities, medications) and environmental (air pollution) data from UK Biobank (N = 473,550) in relation to 459 COVID-19 and 2626 non-COVID-19 deaths to 21 September 2020. We used univariate, multivariable and penalised regression models. Age (OR = 2.76 [2.18-3.49] per S.D. [8.1 years], p = 2.6 × 10-17), male sex (OR = 1.47 [1.26-1.73], p = 1.3 × 10-6) and Black versus White ethnicity (OR = 1.21 [1.12-1.29], p = 3.0 × 10-7) were independently associated with and jointly explanatory of (area under receiver operating characteristic curve, AUC = 0.79) increased risk of COVID-19 mortality. In multivariable regression, alongside demographic covariates, being a healthcare worker, current smoker, having cardiovascular disease, hypertension, diabetes, autoimmune disease, and oral steroid use at enrolment were independently associated with COVID-19 mortality. Penalised regression models selected income, cardiovascular disease, hypertension, diabetes, cystatin C, and oral steroid use as jointly contributing to COVID-19 mortality risk; Black ethnicity, hypertension and oral steroid use contributed to COVID-19 but not non-COVID-19 mortality. Age, male sex and Black ethnicity, as well as comorbidities and oral steroid use at enrolment were associated with increased risk of COVID-19 death. Our results suggest that previously reported associations of COVID-19 mortality with body mass index, low vitamin D, air pollutants, renin-angiotensin-aldosterone system inhibitors may be explained by the aforementioned factors.

SARS-CoV-2 antibody prevalence in England following the first peak of the pandemic.

England has experienced a large outbreak of SARS-CoV-2, disproportionately affecting people from disadvantaged and ethnic minority communities. It is unclear how much of this excess is due to differences in exposure associated with structural inequalities. Here, we report from the REal-time Assessment of Community Transmission-2 (REACT-2) national study of over 100,000 people. After adjusting for test characteristics and re-weighting to the population, overall antibody prevalence is 6.0% (95% CI: 5.8-6.1). An estimated 3.4 million people had developed antibodies to SARS-CoV-2 by mid-July 2020. Prevalence is two- to three-fold higher among health and care workers compared with non-essential workers, and in people of Black or South Asian than white ethnicity, while age- and sex-specific infection fatality ratios are similar across ethnicities. Our results indicate that higher hospitalisation and mortality from COVID-19 in minority ethnic groups may reflect higher rates of infection rather than differential experience of disease or care.

Risk factors for positive and negative COVID-19 tests: a cautious and in-depth analysis of UK biobank data.

BACKGROUND: The recent COVID-19 outbreak has generated an unprecedented public health crisis, with millions of infections and hundreds of thousands of deaths worldwide. Using hospital-based or mortality data, several COVID-19 risk factors have been identified, but these may be confounded or biased. METHODS: Using SARS-CoV-2 infection test data (n = 4509 tests; 1325 positive) from Public Health England, linked to the UK Biobank study, we explored the contribution of demographic, social, health risk, medical and environmental factors to COVID-19 risk. We used multivariable and penalized logistic regression models for the risk of (i) being tested, (ii) testing positive/negative in the study population and, adopting a test negative design, (iii) the risk of testing positive within the tested population. RESULTS: In the fully adjusted model, variables independently associated with the risk of being tested for COVID-19 with odds ratio >1.05 were: male sex; Black ethnicity; social disadvantage (as measured by education, housing and income); occupation (healthcare worker, retired, unemployed); ever smoker; severely obese; comorbidities; and greater exposure to particulate matter (PM) 2.5 absorbance. Of these, only male sex, non-White ethnicity and lower educational attainment, and none of the comorbidities or health risk factors, were associated with testing positive among tested individuals. CONCLUSIONS: We adopted a careful and exhaustive approach within a large population-based cohort, which enabled us to triangulate evidence linking male sex, lower educational attainment and non-White ethnicity with the risk of COVID-19. The elucidation of the joint and independent effects of these factors is a high-priority area for further research to inform on the natural history of COVID-19.