327 results found
Ward H, Whittaker M, Flower B, et al., 2022, Population antibody responses following vaccination: an analysis of 212,102 individuals, Nature Communications, ISSN: 2041-1723
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, Wellcome Open Research, Vol: 6, Pages: 358-358
<ns4:p><ns4:bold>Background:</ns4:bold> 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.</ns4:p><ns4:p> <ns4:bold>Methods:</ns4:bold> 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</ns4:p><ns4:p> <ns4:bold>Results:</ns4:bold> 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)</ns4:p><ns4:p> <ns4:bold>Conclusions:</ns4:bold> Fortress LFIA performs well in the de
Papageorgiou V, Davies B, Cooper E, et al., 2021, Influence of material deprivation on clinical outcomes among people living with HIV in high-income countries: a systematic review and meta-analysis, AIDS and Behavior, ISSN: 1090-7165
Despite developments in HIV treatment and care, disparities persist with some not fully benefiting from improvements in the HIV care continuum. We conducted a systematic review to explore associations between social determinants and HIV treatment outcomes (viral suppression and treatment adherence) in high-income countries. A random effects meta-analysis was performed where there were consistent measurements of exposures. We identified 83 observational studies eligible for inclusion. Social determinants linked to material deprivation were identified as education, employment, food security, housing, income, poverty/deprivation, socioeconomic status/position, and social class; however, their measurement and definition varied across studies. Our review suggests a social gradient of health persists in the HIV care continuum; people living with HIV who reported material deprivation were less likely to be virologically suppressed or adherent to antiretrovirals. Future research should use an ecosocial approach to explore these interactions across the lifecourse to help propose a causal pathway.
Ward H, Flower B, Garcia PJ, et al., 2021, Global surveillance, research, and collaboration needed to improve understanding and management of long COVID, LANCET, Vol: 398, Pages: 2057-2059, ISSN: 0140-6736
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
<ns4:p><ns4:bold>Background: </ns4: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.</ns4:p><ns4:p> <ns4:bold>Methods:</ns4: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.</ns4:p><ns4:p> <ns4:bold>Results:</ns4: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.</ns4:p><ns4:p> <ns4:bold>Conclusions: </ns4: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).</ns4:p>
Chadeau M, Wang H, Eales O, et al., 2021, Randomised community surveys of SARS-CoV-2 infection and vaccine effectiveness in England: REACT-1 study., The Lancet Respiratory Medicine, ISSN: 2213-2600
Background: England experienced a third wave of the COVID-19 epidemic from end May 2021 coinciding with the rapid spread of Delta variant despite high levels of vaccination among adults. Vaccination rates (single-dose) are lower among children aged 16-17 and 12-15 years whose vaccination in England commenced in August and September respectively. Methods: The REACT-1 study involves a series of random cross-sectional surveys in the general population of England aged 5 years and over. Using RT-PCR swab-positivity data from (N=100,527) participants with valid swabs in round 14 (9 to 27 September 2021), we estimated community-based prevalence of SARS-CoV-2 and vaccine effectiveness against infection by combining data with round 13 (24 June to 12 July 2021, N=172,862).Findings: During September 2021 we estimated a mean RT-PCR positivity rate of 0.83% (0.76%, 0.89%) with a reproduction number R overall of 1.03 (0.94, 1.14). Among the 475 sequenced positive swabs, all were Delta variant; 22 (4.63%) included the Y145H mutation in the spike protein associated with the AY.4 sub-lineage, and there was one E484K mutation. Age, region, key worker status, and household size jointly contributed to the risk of swab-positivity. The highest weighted prevalence was observed among children aged 5-12 years at 2.32% (1.96%, 2.73%) and 13-17 years at 2.55% (2.11%, 3.08%). The epidemic grew in those aged 5-11 years with R of 1.42, but decreased in those aged 18-54. At ages 18-64 years, the adjusted vaccine effectiveness against infection was 62.8% (49.3%, 72.7%) after two doses compared to unvaccinated people, for all vaccines combined, and 44.8% (22.5%, 60.7%) and 71.3% (56.6%, 81.0%) for AstraZeneca and Pfizer-BioNTech, respectively. At ages >18 years, weighted prevalence of swab-positivity was 0.35% (0.31%, 0.40%) if second dose was <3 months before their swab but 0.55% (0.50%, 0.61%) for those who received their second dose 3-6 months prior, compared to 1.76% (1.60%, 1.95%) among
Routen A, O'Mahoney L, Ayoubkhani D, et al., 2021, Understanding and tracking the impact of long COVID in the United Kingdom, NATURE MEDICINE, ISSN: 1078-8956
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.
Wilson J, Wallace H, Loftus-Keeling M, et al., 2021, Swab-yourself trial with economic monitoring and testing for infections collectively (SYSTEMATIC): Part 1. A diagnostic accuracy, and cost-effectiveness, study comparing clinician-taken versus self-taken rectal and pharyngeal samples for the diagnosis of gonorrhoea and chlamydia, Clinical Infectious Diseases, Vol: 73, Pages: e3172-e3180, ISSN: 1058-4838
BackgroundUrogenital testing misses extragenital Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT). Extragenital self-sampling is frequently undertaken despite no robust RCT evidence of efficacy. We compared clinician-taken rectal and pharyngeal samples with self-taken samples for diagnostic accuracy and cost in MSM and females.MethodsProspective, convenience, sample in UK sexual health clinic. Randomised order of clinician and self-samples from pharynx and rectum, plus first catch urine (MSM) and vulvovaginal swabs (females), for NG/CT detection.ResultsOf 1793 participants (1284 females, 509 MSM), 116 had NG detected (75 urogenital site, 83 rectum, 72 pharynx); 9.4% infected females and 67.3% MSM were urogenital negative. 276 had CT detected (217 urogenital site, 249 rectum, 63 pharynx); 13.1% infected females and 71.8% MSM were urogenital negative. Sexual history did not identify those with rectal infections. Clinician-rectal and self-rectal positive percent agreements (PPA) for NG detection were 92.8% and 97.6%; clinician-rectal, and self-rectal PPA for CT detection were 95.6% and 97.2%. There was no difference in diagnostic accuracy between clinician and self-taken samples.Clinicians performed swabs quicker than participants so costs were lower. However, in asymptomatic people, non-qualified clinicians would oversee self-swabbing and these costs would be lower than clinician’s.ConclusionsThere was no difference in diagnostic accuracy of clinician compared with self-taken extragenital samples. Sexual history did not identify those with rectal infections so individuals should have extragenital clinician, or self-taken, samples. Clinician swabs cost less than self-swabs but in asymptomatic people, or doing home testing, their costs would be lower than clinician swabs.
van Bergen JEAM, Hoenderboom BM, David S, et al., 2021, Where to go to in chlamydia control? From infection control towards infectious disease control, SEXUALLY TRANSMITTED INFECTIONS, Vol: 97, Pages: 501-506, ISSN: 1368-4973
Udeh-Momoh C, Watermeyer T, Sindi S, et al., 2021, Health, lifestyle and psycho-social determinants of poor sleep quality during the Early Phase of the COVID-19 pandemic: a focus on UK older adults deemed clinically extremely vulnerable, Frontiers in Public Health, Vol: 9, Pages: 1-11, ISSN: 2296-2565
Background: Several studies have assessed the impact of COVID-19-relatedlockdownson sleep quality across global populations. However, no study to date has specifically assessed at-riskpopulations, particularly those at highest risk of complications from coronavirus infection deemed “clinically-extremely-vulnerable-(COVID-19CEV)” [as defined by Public Health England, 2020].Methods: In this cross-sectional study, we surveyed 5,558 adults aged ≥50 years (of whom 523 met criteria for COVID-19CEV) during the first pandemic wave that resulted in a nationwide-lockdown (April-June 2020) with assessments of sleep quality (an adapted sleep scale that captured multiple sleep indices before and during the lockdown), health/medical, lifestyle, psychosocial and socio demographic factors. We examined associations between these variablesand sleep quality;and explored interactions of COVID-19CEV status with significant predictors of poor sleep,to identify potential moderating factors. Results: 37% of participants reported poor sleep quality which was associated with younger age, female sex and multimorbidity. Significant associations with poor sleep included health/medical factors: COVID-19 CEV status, higher BMI, arthritis, pulmonary disease, and mental health disorders; and the following lifestyle and psychosocial factors: living alone, higher alcohol consumption, an unhealthy diet and higher depressive and anxiety symptoms. Moderators of the negative relationship between COVID-19 CEV status and good sleep quality were marital status, loneliness, anxiety and diet. Within this subgroup, less anxious and less lonely males, as well as females with healthier diets, reported better sleep. Conclusions: Sleep quality in older adults was compromised during the sudden unprecedented nation-wide lockdown due to distinct modifiable factors. An important contribution of our study is the assessment of a &ldquo
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
Georgiou Delisle T, D'Souza N, Davies B, et al., 2021, Faecal immunochemical test for suspected colorectal cancer symptoms: patient survey of usability and acceptability., BJGP Open
BACKGROUND: Recent evidence suggests that the Faecal Immunochemical Test (FIT) can rule out colorectal cancer (CRC) in symptomatic patients. To date, there is no research on usability and perception of FIT for these patients. AIM: To measure variation in attitudes and perception of FIT in patients with suspected CRC symptoms. DESIGN & SETTING: Cross sectional survey of a sub-set of participants of the NICE FIT study. METHOD: A questionnaire was co-developed with patients covering four themes: FIT feasibility, faecal aversion, patient knowledge and future intentions, on a Likert scale. Questionnaire and FIT kits were sent to patients with suspected CRC symptoms participating in the NICE FIT study. Logistic regression explored differences in patients' test perception by ethnicity, language, age, location, deprivation, FIT use and previous experience. RESULTS: 1151 questionnaires were analysed; 90.2% of patients found faecal collection straightforward, (95% CI 88.3%-91.8%), 76.3% disagreed FIT was unhygienic (95% CI 73.7%-78.6%), 78.1% preferred FIT to colonoscopy (95% CI 75.6%-80.4%). Preference for FIT over colonoscopy was weaker in patients aged 40-64 than those over 65 years (OR 0.60; 95% CI 0.43-0.84). Intention to use FIT again was stronger in patients who successfully used FIT than those unsuccessful (OR 11.08; 95% CI 2.74-44.75) and white compared to non-white patients (OR 3.20; 95% CI 1.32-7.75). CONCLUSIONS: While most patients found FIT practical and hygienic, perception differences were found. Strategies to engage patients with more negative FIT perception should underpin symptomatic FIT pathways.
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.
Elliott J, Whitaker M, Bodinier B, et al., 2021, Predictive symptoms for COVID-19 in the community: REACT-1 study of over one million people, PLoS Medicine, Vol: 18, Pages: 1-14, ISSN: 1549-1277
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 whether predictive symptoms differ between B.1.1.7 (Alpha) lineage (predominating as of April 2021in the USA, UK and elsewhere) and wild type.Methods and Findings:We obtained throat and nose swabs with valid SARS-CoV-2 polymerase chain reaction (PCR) test results from 1,147,370 volunteers aged 5 years and above (6,450 positives) in the REal-time Assessment of Community Transmission-1 (REACT-1) study. This 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 one symptom identified seven 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 seven symptoms were selected as jointly predictive of B.1.1.7 infection in round 8, although 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. Main
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
Papageorgiou V, Jones K, Halliday BP, et al., 2021, A qualitative exploration of participant and investigator perspectives from the TRED-HF trial, ESC HEART FAILURE, Vol: 8, Pages: 3760-3768, ISSN: 2055-5822
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
Papageorgiou V, Jones K, Halliday B, et al., 2021, A qualitative exploration of participant and investigator perspectives from the TRED-HF trial (therapy withdrawal in REcovered Dilated cardiomyopathy), ESC Heart Failure, ISSN: 2055-5822
Aim We explored the experiences and motivations of participants and staff who took part in the TRED-HF trial (Therapy withdrawal in REcovered Dilated cardiomyopathy). MethodsWe conducted a qualitative study, using semi-structured interviews, with participants (n=12) and the research team (n=4) from the TRED-HF trial. Interviews were carried out in 2019 and were audio-recorded and transcribed. Data were managed using NVivo and analysed using framework analysis. A patient representative provided guidance on the interpretation of findings and presentation of themes to ensure these remained meaningful, and an accurate representation, to those living with dilated cardiomyopathy.ResultsThree key themes emerged from the data: (1) perception of health; (2) experiences and relationships with healthcare services and researchers; and (3) perception of risk. Study participants held differing perceptions of their health; some did not consider themselves to have a heart condition or disagreed with the medical term ‘heart failure’. Relationships between participants, research staff and clinical management teams influenced participants’ experiences and decision-making during the trial, including following clinical advice. There were differences in participants’ perceptions of risk and their decisions to take heart failure medication after the trial was completed. Although the original TRED-HF trial did not provide the results many had hoped for, a strong motivator for taking part was the opportunity to withdraw medication in a safely monitored environment which had been previously considered by some participants before. Investigators acknowledged that the insights gained from the study can now be used to support evidence-based conversations with patients.Conclusion For people whose dilated cardiomyopathy is in remission, decisions to continue, reduce or stop their medication are influenced by perceptions of personal health, perceive risk and the important o
Udeh-Momoh CT, Watermeyer T, Price G, et al., 2021, Protocol of the cognitive health in ageing register: investigational, observational and trial studies in dementia research (CHARIOT): prospective readiness cOhort (PRO) SubStudy., BMJ Open, Vol: 11, Pages: 1-12, ISSN: 2044-6055
INTRODUCTION: The Cognitive Health in Ageing Register: Investigational, Observational and Trial Studies in Dementia Research (CHARIOT): Prospective Readiness cOhort (PRO) SubStudy (CPSS), sponsored by Janssen Pharmaceutical Research & Development LLC, is an Alzheimer's disease (AD) biomarker enriched observational study that began 3 July 2015 CPSS aims to identify and validate determinants of AD, alongside cognitive, functional and biological changes in older adults with or without detectable evidence of AD pathology at baseline. METHODS AND ANALYSIS: CPSS is a dual-site longitudinal cohort (3.5 years) assessed quarterly. Cognitively normal participants (60-85 years) were recruited across Greater London and Edinburgh. Participants are classified as high, medium (amnestic or non-amnestic) or low risk for developing mild cognitive impairment-Alzheimer's disease based on their Repeatable Battery for the Assessment of Neuropsychological Status performance at screening. Additional AD-related assessments include: a novel cognitive composite, the Global Preclinical Alzheimer's Cognitive Composite, brain MRI and positron emission tomography and cerebrospinal fluid analysis. Lifestyle, other cognitive and functional data, as well as biosamples (blood, urine, and saliva) are collected. Primarily, study analyses will evaluate longitudinal change in cognitive and functional outcomes. Annual interim analyses for descriptive data occur throughout the course of the study, although inferential statistics are conducted as required. ETHICS AND DISSEMINATION: CPSS received ethical approvals from the London-Central Research Ethics Committee (15/LO/0711) and the Administration of Radioactive Substances Advisory Committee (RPC 630/3764/33110) The study is at the forefront of global AD prevention efforts, with frequent and robust sampling of the well-characterised cohort, allowing for detection of incipient pathophysiological, cognitive and functional changes that could inform therape
Whitaker M, Elliott J, Chadeau-Hyam M, et al., 2021, Persistent symptoms following SARS-CoV-2 infection in a random community sample of 508,707 people
IntroductionLong COVID, describing the long-term sequelae after SARS-CoV-2 infection, remains a poorlydefined syndrome. There is uncertainty about its predisposing factors and the extent of theresultant public health burden, with estimates of prevalence and duration varying widely.MethodsWithin rounds 3–5 of the REACT-2 study, 508,707 people in the community in England wereasked about a prior history of COVID-19 and the presence and duration of 29 differentsymptoms. We used uni- and multivariable models to identify predictors of persistence ofsymptoms (12 weeks or more). We estimated the prevalence of symptom persistence at 12weeks, and used unsupervised learning to cluster individuals by symptoms experienced.ResultsAmong 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 leastone symptom, while 14.8% experienced three or more symptoms, lasting 12 weeks or more. Thisgives a weighted population prevalence of persistent symptoms of 5.75% (5.68, 5.81) for one and2.22% (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-19symptoms (“significant effect on my daily life”) at the time of their illness, giving a weightedprevalence overall for this group of 1.72% (1.69,1.76). The prevalence of persistent symptomswas 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 oflife. Obesity, smoking or vaping, hospitalisation , and deprivation were also associated with ahigher probability of persistent symptoms, while Asian ethnicity was associated with a lowerprobability. Two stable clusters were identified based on symptoms that persisted for 12 weeks ormore: in the largest cluster, tiredness predominated
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 (
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