LONG-TERM PHYSICAL AND MENTAL HEALTH IMPACT OF COVID-19 ON ADULTS IN ENGLAND: FOLLOW UP OF A LARGE RANDOM COMMUNITY SAMPLE (preprint)

BackgroundThe COVID-19 pandemic is having a lasting impact on health and well-being. We compare current self-reported health, quality of life and symptom profiles for people with ongoing symptoms following COVID-19 to those who have never had COVID-19 or have recovered. MethodsA cohort study was established with participants from the REACT programme. A sample (N=800,000) of adults were contacted between August and December 2022 to complete a questionnaire about their current health and COVID-19 history. We used logistic regression to identify predictors of persistent symptoms lasting [≥]12 weeks following COVID-19. We fitted Accelerated Failure Time models to assess factors associated with rate of recovery from persistent symptoms. FindingsOverall, 276,840/800,000 (34.6%) of invited participants completed the questionnaire. Median duration of COVID-related symptoms (N=130,251) was 1.3 weeks (inter-quartile range 6 days to 2 weeks), with 7.5% and 5.2% reporting ongoing symptoms [≥]12 weeks and [≥]52 weeks respectively. Female sex, having [≥]1 comorbidity, more severe symptoms at time of COVID-19 and being infected when Wild-type variant was dominant were associated with higher probability of symptoms lasting [≥]12 weeks. Longer time to recovery in those with persistent symptoms was found for females, people with comorbidities, living in more deprived areas, current smokers and for Wild-type compared to later variants. Mental health and health-related quality of life were significantly worse among participants with ongoing persistent COVID-19 symptoms compared with those who had never had COVID-19 or had recovered. InterpretationAlthough COVID-19 is usually of short duration, some adults experience persistent and burdensome illness. FundingThis work is independent research funded by the National Institute for Health and Care Research (NIHR) (REACT Long COVID (REACT-LC) (COV-LT-0040)). This research is part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (UKRI) (MC_PC_20029). The views expressed in this publication are those of the author(s) and not necessarily those of NIHR or UKRI.

Validity of self-testing at home with rapid SARS-CoV-2 antibody detection by lateral flow immunoassay (preprint)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody lateral flow immunoassays (LFIA) can be carried out in the home and have been used as an affordable and practical approach to large-scale antibody prevalence studies. However, assay performance differs from that of high-throughput laboratory-based assays which can be highly sensitive. We explore LFIA performance under field conditions compared to laboratory-based ELISA and assess the potential of LFIAs to identify people who lack functional antibodies following infection or vaccination. Methods: Field evaluation of a self-administered LFIA test (Fortress, NI) among 3758 participants from the REal-time Assessment of Community Transmission-2 (REACT-2) study in England selected based on vaccination history and previous LFIA result to ensure a range of antibody titres. In July 2021, participants performed, at home, a self-administered LFIA on finger-prick blood, reported and submitted a photograph of the result, and provided a self-collected capillary blood sample (Tasso-SST) for serological assessment of IgG antibodies to the spike protein using the Roche Elecsys Anti-SARS-CoV-2 assay. We compared the self-administered and reported LFIA result to the quantitative Roche assay and checked the reading of the LFIA result with an automated image analysis (ALFA). In a subsample of 250 participants, we compared the results to live virus neutralisation. Results: Almost all participants (3593/3758, 95.6%) had been vaccinated or reported prior infection, with most having received one (862, 22.9%) or two (2430, 64.7%) COVID-19 vaccine doses. Overall, 2777/3758 (73.9%) were positive on self-reported LFIA, 2811/3457 (81.3%) positive by LFIA when ALFA-reported, and 3622/3758 (96.4%) positive on Roche anti-S (using the manufacturer reference standard threshold for positivity of 0.8 U ml-1). Live virus neutralisation was detected in 169 of 250 randomly selected samples (67.6%); 133/169 were positive with self-reported LFIA (sensitivity 78.7%; 95% CI 71.8, 84.6), 142/155 (91.6%; 86.1, 95.5) with ALFA, and 169 (100%; 97.8, 100.0) with Roche anti-S. There were 81 samples with no detectable virus neutralisation; 47/81 were negative with self-reported LFIA (specificity 58.0%; 95% CI 46.5, 68.9), 34/75 (45.3%; 33.8, 57.3) with ALFA, and 0/81 (0%; 0.0, 4.5) with Roche anti-S. All 250 samples remained positive with Roche anti-S when the threshold was increased to 1000U ml-1. Conclusions: Self-administered LFIA can provide insights into population patterns of infection and vaccine response, and sensitivity can be improved with automated reading of the result. The LFIA is less sensitive than a quantitative antibody test, but the positivity in LFIA correlates better than the quantitative ELISA with virus neutralisation.

Variant-specific symptoms of COVID-19 among 1,542,510 people in England (preprint)

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 has been monitoring 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 and 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 induced changes in daily activities will become increasingly important.

The Omicron SARS-CoV-2 epidemic in England during February 2022 (preprint)

Background: The third wave of COVID-19 in England peaked in January 2022 resulting from the rapid transmission of the Omicron variant. However, rates of hospitalisations and deaths were substantially lower than in the first and second waves 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 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 1,195 positive samples with sublineages determined, only one (0.1% [0.0-0.5]) corresponded to AY.39 Delta sublineage 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 an R additive advantage for BA.2 (vs BA.1 or BA.1.1) of 0.40 (0.36-0.43). 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.

Post-peak dynamics of a national Omicron SARS-CoV-2 epidemic during January 2022 (preprint)

Background: Rapid transmission of the SARS-CoV-2 Omicron variant has led to the highest ever recorded case incidence levels in many countries around the world. Methods: The REal-time Assessment of Community Transmission-1 (REACT-1) study has been characterising the transmission of the SARS-CoV-2 virus using RT-PCR test results from self-administered throat and nose swabs from randomly-selected participants in England at ages 5 years and over, approximately monthly since May 2020. Round 17 data were collected between 5 and 20 January 2022 and provide data on the temporal, socio-demographic and geographical spread of the virus, viral loads and viral genome sequence data for positive swabs. Results: From 102,174 valid tests in round 17, weighted prevalence of swab positivity was 4.41% (95% credible interval [CrI], 4.25% to 4.56%), which is over three-fold higher than in December 2021 in England. Of 3,028 sequenced positive swabs, 2,393 lineages were determined 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.1 and 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) but increasing in children aged 5 to 17 years (R=1.13, 95% CrI, 1.09, 1.18). Those 75 years and older had a swab-positivity prevalence of 2.46% (95% CI, 2.16%, 2.80%) reflecting a high level of infection among a highly vulnerable group. Among the 3,613 swab-positive individuals 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 to 30 days before their swab date. Risks of infection were increased among essential/key workers (other than healthcare or care home workers) with mutually adjusted Odds Ratio (OR) of 1.15 (95% CI, 1.05, 1.26), people living in large compared to single-person households (6+ household size OR 1.73; 95% CI, 1.44, 2.08), those living in urban vs rural areas (OR 1.24, 95% CI, 1.13, 1.35) and those living in the most vs least deprived areas (OR 1.34, 95% CI, 1.20, 1.49). Conclusions: We observed unprecedented levels of infection with SARS-CoV-2 in England in January 2022, an almost complete replacement of Delta by Omicron, and evidence for a growth advantage for BA.2 compared to BA.1. The increase in the prevalence of infection with Omicron among children (aged 5 to 17 years) during January 2022 could pose a risk to adults, despite the current trend for prevalence in adults to decline. (Funded by the Department of Health and Social Care in England.)

Rapid increase in Omicron infections in England during December 2021: REACT-1 study (preprint)

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 been introduced 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 November 2021) 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 used these 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 prevalence of 1.41% (1.33%, 1.51%) in the community during round 16. We found strong evidence of an increase in prevalence during round 16 with an estimated reproduction number R of 1.13 (1.06, 1.09) for the whole of round 16 and 1.27 (1.14, 1.40) when restricting to observations from 1 December onwards. The reproduction number in those aged 18-54 years was estimated at 1.23 (1.14, 1.33) for the whole of round 16 and 1.41 (1.23, 1.61) from 1 December. Our data also provide strong evidence of a steep increase in prevalence in London with an estimated R of 1.62 (1.34, 1.93) from 1 December onwards and a daily prevalence reaching 6.07% (4.06%, 9.00%) on 14 December 2021. As of 1 to 11 December 2021, of the 275 lineages determined, 11 (4.0%) corresponded to the Omicron variant. The first Omicron infection was detected in London on 3 December, and subsequent infections mostly appeared in the South of England. The 11 Omicron cases were all aged 18 to 54 years, double-vaccinated (reflecting the large numbers of people who have received two doses of vaccine in this age group) but not boosted, 9 were men, 5 lived in London and 7 were symptomatic (5 with classic COVID-19 symptoms: loss or change of sense of smell or taste, fever, persistent cough), 2 were asymptomatic, and symptoms were unknown for 2 cases. The proportion of Omicron (vs Delta or Delta sub-lineages) was found to increase rapidly with a daily increase of 66.0% (32.7%, 127.3%) in the odds of Omicron (vs. Delta) infection, conditional on swab positivity. Highest prevalence of swab positivity by age was observed in (unvaccinated) children aged 5 to 11 years (4.74% [4.15%, 5.40%]) similar to the prevalence observed at these ages in round 15. In contrast, prevalence in children aged 12 to 17 years more than halved from 5.35% (4.78%, 5.99%) in round 15 to 2.31% (1.91%, 2.80%) in round 16. As of 14 December 2021, 76.6% children at ages 12 to 17 years had received at least one vaccine dose; we estimated that vaccine effectiveness against infection was 57.9% (44.1%, 68.3%) in this age group. In addition, the prevalence of swab positivity in adults aged 65 years and over fell by over 40% from 0.84% (0.72%, 0.99%) in round 15 to 0.48% (0.39%,0.59%) in round 16 and for those aged 75 years and over it fell by two-thirds from 0.63% (0.48%,0.82%) to 0.21% (0.13%,0.32%). At these ages a high proportion of participants (>90%) had received a third vaccine dose; we estimated that adults having received a third vaccine dose had a three- to four-fold lower risk of testing positive compared to those who had received two doses. Conclusion A large fall in swab positivity from round 15 to round 16 among 12 to 17 year olds, most of whom have been vaccinated, contrasts with the continuing high prevalence among 5 to 11 year olds who have largely not been vaccinated. Likewise there were large falls in swab positivity among people aged 65 years and over, the vast majority of whom have had a third (booster) vaccine dose; these results reinforce the importance of the vaccine and booster campaign. However, the rapidly increasing prevalence of SARS-CoV-2 infections in England during December 2021, coincident with the rapid rise of Omicron infections, may lead to renewed pressure on health services. Additional measures beyond vaccination may be needed to control the current wave of infections and prevent health services (in England and other countries) from being overwhelmed. Summary The unprecedented rise in SARS-CoV-2 infections is concurrent with rapid spread of the Omicron variant in England and globally. We analysed prevalence of SARS-CoV-2 and its dynamics in England from end of November to mid-December 2021 among almost 100,000 participants from the REACT-1 study. Prevalence was high during December 2021 with rapid growth nationally and in London, and of the proportion of infections due to Omicron. We observed a large fall 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 vs. two doses of vaccine. Our results reiterate the importance of vaccination and booster campaigns; however, additional measures may be needed to control the rapid growth of the Omicron variant.

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 (preprint)

Background It has been nearly a year since the first vaccinations against SARS-CoV-2 were delivered in England. The third wave of COVID-19 in England began in May 2021 as the Delta variant began to outcompete and largely replace other strains. The REal-time Assessment of Community Transmission-1 (REACT-1) series of community surveys for SARS-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 logistic regression to analyse associations between SARS-CoV-2 infection in England and demographic and other risk factors, based on RT-PCR results from self-administered throat and nose swabs in over 100,000 participants. We estimated (single-dose) vaccine effectiveness among children aged 12 to 17 years, and among adults compared swab-positivity in people who had received a third (booster) dose with those who had received 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 number across rounds of R=1.09 (1.08, 1.11). During round 15, there was a fall in prevalence from a maximum around 20-21 October, with an R of 0.76 (0.70, 0.83), reflecting falls in prevalence at ages 17 years and below and 18 to 54 years. School-aged children had the highest weighted prevalence of infection: 4.95% (4.39%, 5.58%) in those aged 5 to 12 years and 5.21% (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 with swab positivity. There was evidence of heterogeneity between rounds in swab positivity rates among vaccinated individuals at ages 18 to 64 years, and differences in key demographic and other variables between vaccinated and unvaccinated adults at these ages. Vaccine effectiveness against infection in children was estimated to be 56.2% (41.3%, 67.4%) in rounds 13, 14 and 15 combined, adjusted for demographic factors, with a similar estimate obtained for round 15 only. Among adults we found that those who received a third dose of vaccine were less likely to test positive compared to those who received only two vaccine doses, with adjusted odds ratio (OR) =0.38 (0.26, 0.55). Discussion Swab-positivity was very high at the start of round 15, reaching a maximum around 20 to 21 October 2021, and then falling through late October with an uncertain trend in the last few days of data collection. The observational nature of survey data and the relatively small proportion of unvaccinated adults call into question the comparability of vaccinated and unvaccinated groups at this relatively late stage in the vaccination programme. However, third vaccine doses for eligible adults and the vaccination of children aged 12 years and over are associated with lower infection risk and, thus, remain a high priority (with possible extension to children aged 5-12 years). These should help reduce SARS-CoV-2 transmission during the winter period when healthcare demands typically rise.

REACT-1 round 15 interim report: High and rising prevalence of SARS-CoV-2 infection in England from end of September 2021 followed by a fall in late October 2021 (preprint)

Background: The third wave of COVID-19 in England coincided with the rapid spread of the Delta variant of SARS-CoV-2 from the end of May 2021. Case incidence data from the national testing programme (Pillar 2) in England may be affected by changes in testing behaviour and other biases. Community surveys may provide important contextual information to inform policy and the public health response. Methods: We estimated patterns of community prevalence of SARS-CoV-2 infection in England using RT-PCR swab-positivity, demographic and other risk factor data from round 15 (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 those from 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). The overall reproduction number (R) from round 14 to round 15a was 1.12 (1.11, 1.14) with increases in prevalence over this period (September to October) across age groups and regions 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 weighted prevalence was observed among children aged 5 to 12 years at 5.85% (5.10%, 6.70%) and 13 to 17 years at 5.75% (5.02%, 6.57%). At regional level, there was an almost four-fold increase in weighted prevalence in South West from round 14 at 0.59% (0.43%,0.80%) to round 15a at 2.18% (1.84%, 2.58%), with highest smoothed prevalence at subregional level also found in South West in round 15a. Age, sex, key worker status, and presence of children in the home jointly contributed to the risk of swab-positivity. Among the 126 sequenced 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-positivity seen in the REACT-1 study in England to date in round 15a (October 2021), with a two-fold rise in swab-positivity from round 14 (September 2021). Despite evidence of a fall in prevalence from mid- to late-October 2021, prevalence remains high, particularly in school-aged children, with evidence also of higher prevalence in households with one or more children. Thus, vaccination of children aged 12 and over remains a high priority (with possible extension to children aged 5-12) to help reduce within-household transmission and disruptions to education, as well as among adults, to lessen the risk of serious disease among those infected.

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 (preprint)

Background: England experienced a third wave of the COVID-19 epidemic from end May 2021 coinciding with the rapid spread of Delta variant. Since then, the population eligible for vaccination against COVID-19 has been extended to include all 12-15-year-olds, and a booster programme has been initiated among adults aged 50 years and over, health care and care home workers, and immunocompromised people. Meanwhile, schoolchildren have returned 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 population aged 5 years and over in England. We analysed prevalence of SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR) swab-positivity data from REACT-1 round 14 (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 of swab-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 using saline. Also, at random, 50% of swabs (not chilled until they reached the depot) were transported 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 weighted prevalence was found in children aged 5 to 12 years at 2.32% (1.96%, 2.73%) and 13 to 17 years at 2.55% (2.11%, 3.08%). All positive virus samples analysed correspond to the Delta variant 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 all participants and all vaccines combined, vaccine effectiveness against infection (rounds 13 and 14 combined) was estimated to be 62.8% (49.3%, 72.7%) after two doses compared to unvaccinated people when adjusted for round, age, sex, index of multiple deprivation, region and ethnicity; the adjusted estimate was 44.8% (22.5%, 60.7%) for AstraZeneca and 71.3% (56.6%, 81.0%) for Pfizer-BioNTech, and for all vaccines combined it was 66.4% (49.6%, 77.6%) against symptomatic infection (one or more of 26 surveyed symptoms in month prior). Across rounds 13 and 14, weighted prevalence of swab-positivity was 0.55% (0.50%, 0.61%) for those who received their second dose 3-6 months before their swab compared to 0.35% (0.31%, 0.40%) for those whose second dose was within 3 months of their swab. However, the prevalence was lower in those with one or two doses of vaccine than in unvaccinated individuals at 1.76% (1.60%, 1.95%). In round 14, age group, region, key worker status, and household size jointly contributed to the risk of higher prevalence of swab-positivity. Discussion: In September 2021 infections were increasing exponentially in the 5-to-17-year age group coinciding with the start of the autumn school term in England. Relatively few schoolchildren aged 5 to 17 years have been vaccinated in the UK though single doses are now being offered to those aged 12 years and over. In adults, the higher prevalence of swab-positivity following two doses of vaccine within 3 to 6 months supports the use of a booster vaccine. It is important that the vaccination programme maintains high coverage and reaches children and unvaccinated or partially vaccinated adults to reduce transmission and associated disruptions to work and education.

Vaccine uptake and SARS-CoV-2 antibody prevalence among 207,337 adults during May 2021 in England: REACT-2 study (preprint)

Background The programme to vaccinate adults in England has been rapidly implemented since it began in December 2020. The community prevalence of SARS-CoV-2 anti-spike protein antibodies provides an estimate of total cumulative response to natural infection and vaccination. We describe the distribution of SARS-CoV-2 IgG antibodies in adults in England in May 2021 at a time when approximately 7 in 10 adults had received at least one dose 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 flow immunoassay test producing a positive or negative result. Results Vaccine coverage with one or more doses, weighted to the adult population in England, 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. In adjusted 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. There was higher vaccine coverage in the least deprived and highest income households. People who 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 (OR 4.17 [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 key covariates. The prevalence of antibodies (weighted to the adult population of England and adjusted for test characteristics) was 61.1% (95% CI 60.9-61.4), up from 6.6% (5.4-5.7) in round 4 (27 October to 10 November 2020) and 13.9% (13.7-14.1) in round 5 (26 January to 8 February 2021). Prevalence (adjusted and weighted) increased with age, from 35.8% (35.1-36.5) in those aged 18 to 24 years, to 95.3% (94.6-95.9) in people 75 and over. Antibodies were 30% less likely to be detected in men than women (adjusted OR 0.69, 0.68-0.70), and were higher in people of Asian (OR 1.67 [1.58-1.77]), Black (1.55 [1.41-1.69]), mixed 1.17 [1.06-1.29] and other (1.37 [1.23-1.51]) ethnicities compared with white ethnicity. Workers in hospitality (OR 0.69 [0.63-0.74]) and retail (0.71 [0.67-0.75]) were less likely to have antibodies. Following two doses of Pfizer-BioNTech vaccine, antibody positivity (adjusted for test performance) was 100% (100-100) at all ages except 80 years and older when it was 97.8% (95.9-99.6). For AstraZeneca positivity was over 90% up to age 69, and then 89.2% (88.5-89.9) in 70-79 year olds and 83.6% (78.5-88.3) in those aged 80 and over. Following a single dose of Pfizer-BioNTech positivity ranged from 100.0% (91.1-100.0) in those aged 18-29 to 32.2% (18.2-51.1) in those aged 70-79 years. For AstraZeneca this was 72.2% (68.5-75.9) in the youngest and 46.2% (40.0-52.7) in the oldest age group. Discussion The successful roll out of the vaccination programme in England has led to a high proportion of individuals having detectable antibodies, particularly in older age groups and those who have had two doses of vaccine. This is likely to be associated with high levels of protection from severe disease, and possibly from infection. Nonetheless, there remain some key groups with a lower prevalence of antibody, notably unvaccinated younger people, certain minority ethnic groups, those living in deprived areas and workers in some public facing employment. Obtaining improved rates of vaccination in these groups is essential to achieving high levels of protection against the virus through population immunity.

Persistent symptoms following SARS-CoV-2 infection in a random community sample of 508,707 people (preprint)

Introduction Long COVID, describing the long-term sequelae after SARS-CoV-2 infection, remains a poorly defined syndrome. There is uncertainty about its predisposing factors and the extent of the resultant public health burden, with estimates of prevalence and duration varying widely. Methods Within rounds 3-5 of the REACT-2 study, 508,707 people in the community in England were asked about a prior history of COVID-19 and the presence and duration of 29 different symptoms. We used uni- and multivariable models to identify predictors of persistence of symptoms (12 weeks or more). We estimated the prevalence of symptom persistence at 12 weeks, and used unsupervised learning to cluster individuals by symptoms experienced. Results Among the 508,707 participants, the weighted prevalence of self-reported COVID-19 was 19.2% (95% CI: 19.1,19.3). 37.7% of 76,155 symptomatic people post COVID-19 experienced at least one symptom, while 14.8% experienced three or more symptoms, lasting 12 weeks or more. This gives a weighted population prevalence of persistent symptoms of 5.75% (5.68, 5.81) for one and 2.22% (2.1, 2.26) for three or more symptoms. Almost a third of people 8,771/28,713 (30.5%) with at least one symptom lasting 12 weeks or more reported having had severe COVID-19 symptoms ('significant effect on my daily life') at the time of their illness, giving a weighted prevalence overall for this group of 1.72% (1.69,1.76). The prevalence of persistent symptoms was higher in women than men (OR: 1.51 [1.46,1.55]) and, conditional on reporting symptoms, risk of persistent symptoms increased linearly with age by 3.5 percentage points per decade of life. Obesity, smoking or vaping, hospitalisation , and deprivation were also associated with a higher probability of persistent symptoms, while Asian ethnicity was associated with a lower probability. Two stable clusters were identified based on symptoms that persisted for 12 weeks or more: in the largest cluster, tiredness predominated, while in the second there was a high prevalence of respiratory and related symptoms. Interpretation A substantial proportion of people with symptomatic COVID-19 go on to have persistent symptoms for 12 weeks or more, which is age-dependent. Clinicians need to be aware of the differing manifestations of Long COVID which may require tailored therapeutic approaches. Managing the long-term sequelae of SARS-CoV-2 infection in the population will remain a major challenge for health services in the next stage of the pandemic.

REACT-2 Round 5: increasing prevalence of SARS-CoV-2 antibodies demonstrate impact of the second wave and of vaccine roll-out in England (preprint)

Abstract Background England has experienced high rates of SARS-CoV-2 infection during the COVID-19 pandemic, affecting in particular minority ethnic groups and more deprived communities. A vaccination programme began in England in December 2020, with priority given to administering the first dose to the largest number of older individuals, healthcare and care home workers. Methods A cross-sectional community survey in England undertaken between 26 January and 8 February 2021 as the fifth round of the REal-time Assessment of Community Transmission-2 (REACT-2) programme. Participants completed questionnaires, including demographic details and clinical and COVID-19 vaccination histories, and self-administered a lateral flow immunoassay (LFIA) test to detect IgG against SARS-CoV-2 spike protein. There were sufficient numbers of participants to analyse antibody positivity after 21 days from vaccination with the PfizerBioNTech but not the AstraZeneca/Oxford vaccine which was introduced slightly later. Results The survey comprised 172,099 people, with valid IgG antibody results from 155,172. The overall prevalence of antibodies (weighted to be representative of the population of England and adjusted for test sensitivity and specificity) in England was 13.9% (95% CI 13.7, 14.1) overall, 37.9% (37.2, 38.7) in vaccinated and 9.8% (9.6, 10.0) in unvaccinated people. The prevalence of antibodies (weighted) in unvaccinated people was highest in London at 16.9% (16.3, 17.5), and higher in people of Black (22.4%, 20.8, 24.1) and Asian (20.0%, 19.0, 21.0) ethnicity compared to white (8.5%, 8.3, 8.7) people. The uptake of vaccination by age was highest in those aged 80 years or older (93.5%). Vaccine confidence was high with 92.0% (91.9, 92.1) of people saying that they had accepted or intended to accept the offer. Vaccine confidence varied by age and ethnicity, with lower confidence in young people and those of Black ethnicity. Particular concerns were identified around pregnancy, fertility and allergies. In 971 individuals who received two doses of the Pfizer-BioNTech vaccine, the proportion testing positive was high across all age groups. Following a single dose of Pfizer-BioNTech vaccine after 21 days or more, 84.1% (82.2, 85.9) of people under 60 years tested positive (unadjusted) with a decreasing trend with increasing age, but high responses to a single dose in those with confirmed or suspected prior COVID at 90.1% (87.2, 92.4) across all age groups. Conclusions There is uneven distribution of SARS-CoV-2 antibodies in the population with a higher burden in key workers and some minority ethnic groups, similar to the pattern in the first wave. Confidence in the vaccine programme is high overall although it was lower in some of the higher prevalence groups which suggests the need for improved communication about specific perceived risks. Two doses of Pfizer-BioNTech vaccine, or a single dose following previous infection, confers high levels of antibody positivity across all ages. Further work is needed to understand the relationship between antibody positivity, clinical outcomes such as hospitalisation, and transmission.

Symptom reporting in over 1 million people: community detection of COVID-19 (preprint)

Summary Control of the SARS-CoV-2 epidemic requires rapid identification and isolation of infected individuals and their contacts. Community testing in England (Pillar 2) by polymerase chain reaction (PCR) is reserved for those reporting at least one of four ‘classic’ COVID-19 symptoms (loss or change of sense of smell, loss or change of sense of taste, fever, new continuous cough). 1 Detection of positive cases in the community might be improved by including additional symptoms and their combinations. We used data from the REal-time Assessment of Community Transmission-1 (REACT-1) study to investigate symptom profiles for PCR positivity at different ages. Among rounds 2–7 (June to December 2020), an age-stratified, variable selection approach stably selected chills (all ages), headache (5–17 years), appetite loss (18–54 and 55+ years) and muscle aches (18–54 years) as jointly and positively predictive of PCR positivity together with the classic four symptoms. Between round 7 (November to December 2020) and round 8 (January 2021) when new variant B.1.1.7 predominated, only loss or change of sense of smell (more predictive in round 7) and (borderline) new persistent cough (more predictive in round 8) differed between cases. At any level of PCR testing, triage based on the symptoms identified here would result in more cases detected than the current approach.

Declining prevalence of antibody positivity to SARS-CoV-2: a community study of 365,000 adults (preprint)

Background The prevalence and persistence of antibodies following a peak SARS-CoV-2 infection provides insights into its spread in the community, the likelihood of reinfection and potential for some level of population immunity. Methods Prevalence of antibody positivity in England, UK (REACT2) with three cross-sectional surveys between late June and September 2020. 365104 adults used a self-administered lateral flow immunoassay (LFIA) test for IgG. A laboratory comparison of LFIA results to neutralization activity in panel of sera was performed. Results There were 17,576 positive tests over the three rounds. Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% [5.8, 6.1], to 4.8% [4.7, 5.0] and 4.4% [4.3, 4.5], a fall of 26.5% [-29.0, -23.8] over the three months of the study. There was a decline between rounds 1 and 3 in all age groups, with the highest prevalence of a positive result and smallest overall decline in positivity in the youngest age group (18-24 years: -14.9% [-21.6, -8.1]), and lowest prevalence and largest decline in the oldest group (75+ years: -39.0% [-50.8, -27.2]); there was no change in antibody positivity between rounds 1 and 3 in healthcare workers (+3.45% [-5.7, +12.7]). The decline from rounds 1 to 3 was largest in those who did not report a history of COVID-19, (-64.0% [-75.6, -52.3]), compared to -22.3% ([-27.0, -17.7]) in those with SARS-CoV-2 infection confirmed on PCR. Discussion These findings provide evidence of variable waning in antibody positivity over time such that, at the start of the second wave of infection in England, only 4.4% of adults had detectable IgG antibodies using an LFIA. Antibody positivity was greater in those who reported a positive PCR and lower in older people and those with asymptomatic infection. These data suggest the possibility of decreasing population immunity and increasing risk of reinfection as detectable antibodies decline in the population.

Antibody prevalence for SARS-CoV-2 in England following first peak of the pandemic: REACT2 study in 100,000 adults (preprint)

Background England, UK has experienced a large outbreak of SARS-CoV-2 infection. As in USA and elsewhere, disadvantaged communities have been disproportionately affected. Methods National REal-time Assessment of Community Transmission-2 (REACT-2) seroprevalence study using self-administered lateral flow immunoassay (LFIA) test for IgG among a random population sample of 100,000 adults over 18 years in England, 20 June to 13 July 2020. Results Completed questionnaires were available for 109,076 participants, yielding 5,544 IgG positive results and adjusted (for test performance), re-weighted (for sampling) prevalence of 6.0% (95% CI: 5.8, 6.1). Highest prevalence was in London (13.0% [12.3, 13.6]), among people of Black or Asian (mainly South Asian) ethnicity (17.3% [15.8, 19.1] and 11.9% [11.0, 12.8] respectively) and those aged 18-24 years (7.9% [7.3, 8.5]). Care home workers with client-facing roles had adjusted odds ratio of 3.1 (2.5, 3.8) compared with non-essential workers. One third (32.2%, [31.0-33.4]) of antibody positive individuals reported no symptoms. Among symptomatic cases, the majority (78.8%) reported symptoms during the peak of the epidemic in England in March (31.3%) and April (47.5%) 2020. We estimate that 3.36 million (3.21, 3.51) people have been infected with SARS-CoV-2 in England to end June 2020, with an overall infection fatality ratio of 0.90% (0.86, 0.94). Conclusion The pandemic of SARS-CoV-2 infection in England disproportionately affected ethnic minority groups and health and care home workers. The higher risk of infection in these groups may explain, at least in part, their increased risk of hospitalisation and mortality from COVID-19.