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Racial/ethnic minorities have been disproportionately impacted by COVID-19. The effects of COVID-19 on the long-term mental health of minorities remains unclear. To evaluate differences in odds of screening positive for depression and anxiety among various racial and ethnic groups during the latter phase of the COVID-19 pandemic, we performed a cross-sectional analysis of 691,473 participants nested within the prospective smartphone-based COVID Symptom Study in the United States (U.S.) and United Kingdom (U.K). from February 23, 2021 to June 9, 2021. In the U.S. (n=57,187), compared to White participants, the multivariable odds ratios (ORs) for screening positive for depression were 1·16 (95% CI: 1·02 to 1·31) for Black, 1·23 (1·11 to 1·36) for Hispanic, and 1·15 (1·02 to 1·30) for Asian participants, and 1·34 (1·13 to 1·59) for participants reporting more than one race/other even after accounting for personal factors such as prior history of a mental health disorder, COVID-19 infection status, and surrounding lockdown stringency. Rates of screening positive for anxiety were comparable. In the U.K. (n=643,286), racial/ethnic minorities had similarly elevated rates of positive screening for depression and anxiety. These disparities were not fully explained by changes in leisure time activities. Racial/ethnic minorities bore a disproportionate mental health burden during the COVID-19 pandemic. These differences will need to be considered as health care systems transition from prioritizing infection control to mitigating long-term consequences. [ABSTRACT FROM AUTHOR]

The Delta (B.1.617.2) variant was the predominant UK circulating SARS-CoV-2 strain between May and December 2021. How Delta infection compares with previous variants is unknown. This prospective observational cohort study assessed symptomatic adults participating in the app-based COVID Symptom Study who tested positive for SARS-CoV-2 from May 26 to July 1, 2021 (Delta overwhelmingly the predominant circulating UK variant), compared (1:1, age- and sex-matched) with individuals presenting from December 28, 2020 to May 6, 2021 (Alpha (B.1.1.7) the predominant variant). We assessed illness (symptoms, duration, presentation to hospital) during Alpha- and Delta-predominant timeframes; and transmission, reinfection, and vaccine effectiveness during the Delta-predominant period. 3581 individuals (aged 18 to 100 years) from each timeframe were assessed. The seven most frequent symptoms were common to both variants. Within the first 28 days of illness, some symptoms were more common with Delta versus Alpha infection (including fever, sore throat, and headache) and some vice versa (dyspnoea). Symptom burden in the first week was higher with Delta versus Alpha infection; however, the odds of any given symptom lasting ≥ 7 days was either lower or unchanged. Illness duration ≥ 28 days was lower with Delta versus Alpha infection, though unchanged in unvaccinated individuals. Hospitalisation for COVID-19 was unchanged. The Delta variant appeared more (1.49) transmissible than Alpha. Re-infections were low in all UK regions. Vaccination markedly reduced the risk of Delta infection (by 69-84%). We conclude that COVID-19 from Delta or Alpha infections is similar. The Delta variant is more transmissible than Alpha; however, current vaccines showed good efficacy against disease. This research framework can be useful for future comparisons with new emerging variants. [ABSTRACT FROM AUTHOR]

Background: The Delta (B.1.617.2) SARS-CoV-2 variant was the predominant UK circulating strain between May and November 2021. We investigated whether COVID-19 from Delta infection differed from infection with previous variants in children. Methods: Through the prospective COVID Symptom Study, 109,626 UK school-aged children were proxy-reported between 28 December 2020 and 8 July 2021. We selected all symptomatic children who tested positive for SARS-CoV-2 and were proxy-reported at least weekly, within two timeframes: 28 December 2020 to 6 May 2021 (Alpha (B.1.1.7), the main UK circulating variant) and 26 May to 8 July 2021 (Delta, the main UK circulating variant), with all children unvaccinated (as per national policy at the time). We assessed illness profiles (symptom prevalence, duration, and burden), hospital presentation, and presence of long (≥28 day) illness, and calculated odds ratios for symptoms presenting within the first 28 days of illness. Results: 694 (276 younger (5–11 years), 418 older (12–17 years)) symptomatic children tested positive for SARS-CoV-2 with Alpha infection and 706 (227 younger and 479 older) children with Delta infection. Median illness duration was short with either variant (overall cohort: 5 days (IQR 2–9.75) with Alpha, 5 days (IQR 2–9) with Delta). The seven most prevalent symptoms were common to both variants. Symptom burden over the first 28 days was slightly greater with Delta compared with Alpha infection (in younger children, 3 (IQR 2–5) symptoms with Alpha, 4 (IQR 2–7) with Delta; in older children, 5 (IQR 3–8) symptoms with Alpha, 6 (IQR 3–9) with Delta infection). The odds of presenting several symptoms were higher with Delta than Alpha infection, including headache and fever. Few children presented to hospital, and long illness duration was uncommon, with either variant. Conclusions: COVID-19 in UK school-aged children due to SARS-CoV-2 Delta strain B.1.617.2 resembles illness due to the Alpha variant B.1.1.7., with short duration and similar symptom burden. [ABSTRACT FROM AUTHOR]

Worldwide, racial and ethnic minorities have been disproportionately impacted by COVID-19 with increased risk of infection, its related complications, and death. In the initial phase of population-based vaccination in the United States (U.S.) and United Kingdom (U.K.), vaccine hesitancy may result in differences in uptake. We performed a cohort study among U.S. and U.K. participants who volunteered to take part in the smartphone-based COVID Symptom Study (March 2020-February 2021) and used logistic regression to estimate odds ratios of vaccine hesitancy and uptake. In the U.S. (n = 87,388), compared to white participants, vaccine hesitancy was greater for Black and Hispanic participants and those reporting more than one or other race. In the U.K. (n = 1,254,294), racial and ethnic minority participants showed similar levels of vaccine hesitancy to the U.S. However, associations between participant race and ethnicity and levels of vaccine uptake were observed to be different in the U.S. and the U.K. studies. Among U.S. participants, vaccine uptake was significantly lower among Black participants, which persisted among participants that self-reported being vaccine-willing. In contrast, statistically significant racial and ethnic disparities in vaccine uptake were not observed in the U.K sample. In this study of self-reported vaccine hesitancy and uptake, lower levels of vaccine uptake in Black participants in the U.S. during the initial vaccine rollout may be attributable to both hesitancy and disparities in access. The authors show differences in self-reported vaccine hesitancy and uptake among participants from different racial and ethnic groups in the United States and in the United Kingdom during the initial phase of the COVID-19 vaccine rollout. [ABSTRACT FROM AUTHOR]

These authors contributed equally: Long H. Nguyen, Amit D. Joshi, David A. Drew. The original version of this Article contained an error in Table 1. [Extracted from the article]

Background: COVID-19 vaccines show excellent efficacy in clinical trials and effectiveness in real-world data, but some people still become infected with SARS-CoV-2 after vaccination. This study aimed to identify risk factors for post-vaccination SARS-CoV-2 infection and describe the characteristics of post-vaccination illness.Methods: This prospective, community-based, nested, case-control study used self-reported data (eg, on demographics, geographical location, health risk factors, and COVID-19 test results, symptoms, and vaccinations) from UK-based, adult (≥18 years) users of the COVID Symptom Study mobile phone app. For the risk factor analysis, cases had received a first or second dose of a COVID-19 vaccine between Dec 8, 2020, and July 4, 2021; had either a positive COVID-19 test at least 14 days after their first vaccination (but before their second; cases 1) or a positive test at least 7 days after their second vaccination (cases 2); and had no positive test before vaccination. Two control groups were selected (who also had not tested positive for SARS-CoV-2 before vaccination): users reporting a negative test at least 14 days after their first vaccination but before their second (controls 1) and users reporting a negative test at least 7 days after their second vaccination (controls 2). Controls 1 and controls 2 were matched (1:1) with cases 1 and cases 2, respectively, by the date of the post-vaccination test, health-care worker status, and sex. In the disease profile analysis, we sub-selected participants from cases 1 and cases 2 who had used the app for at least 14 consecutive days after testing positive for SARS-CoV-2 (cases 3 and cases 4, respectively). Controls 3 and controls 4 were unvaccinated participants reporting a positive SARS-CoV-2 test who had used the app for at least 14 consecutive days after the test, and were matched (1:1) with cases 3 and 4, respectively, by the date of the positive test, health-care worker status, sex, body-mass index (BMI), and age. We used univariate logistic regression models (adjusted for age, BMI, and sex) to analyse the associations between risk factors and post-vaccination infection, and the associations of individual symptoms, overall disease duration, and disease severity with vaccination status.Findings: Between Dec 8, 2020, and July 4, 2021, 1 240 009 COVID Symptom Study app users reported a first vaccine dose, of whom 6030 (0·5%) subsequently tested positive for SARS-CoV-2 (cases 1), and 971 504 reported a second dose, of whom 2370 (0·2%) subsequently tested positive for SARS-CoV-2 (cases 2). In the risk factor analysis, frailty was associated with post-vaccination infection in older adults (≥60 years) after their first vaccine dose (odds ratio [OR] 1·93, 95% CI 1·50-2·48; p<0·0001), and individuals living in highly deprived areas had increased odds of post-vaccination infection following their first vaccine dose (OR 1·11, 95% CI 1·01-1·23; p=0·039). Individuals without obesity (BMI <30 kg/m2) had lower odds of infection following their first vaccine dose (OR 0·84, 95% CI 0·75-0·94; p=0·0030). For the disease profile analysis, 3825 users from cases 1 were included in cases 3 and 906 users from cases 2 were included in cases 4. Vaccination (compared with no vaccination) was associated with reduced odds of hospitalisation or having more than five symptoms in the first week of illness following the first or second dose, and long-duration (≥28 days) symptoms following the second dose. Almost all symptoms were reported less frequently in infected vaccinated individuals than in infected unvaccinated individuals, and vaccinated participants were more likely to be completely asymptomatic, especially if they were 60 years or older.Interpretation: To minimise SARS-CoV-2 infection, at-risk populations must be targeted in efforts to boost vaccine effectiveness and infection control measures. Our findings might support caution around relaxing physical distancing and other personal protective measures in the post-vaccination era, particularly around frail older adults and individuals living in more deprived areas, even if these individuals are vaccinated, and might have implications for strategies such as booster vaccinations.Funding: ZOE, the UK Government Department of Health and Social Care, the Wellcome Trust, the UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging and Artificial Intelligence Centre for Value Based Healthcare, the UK National Institute for Health Research, the UK Medical Research Council, the British Heart Foundation, and the Alzheimer's Society. [ABSTRACT FROM AUTHOR]

Background: Self-reported symptoms during the COVID-19 pandemic have been used to train artificial intelligence models to identify possible infection foci. To date, these models have only considered the culmination or peak of symptoms, which is not suitable for the early detection of infection. We aimed to estimate the probability of an individual being infected with SARS-CoV-2 on the basis of early self-reported symptoms to enable timely self-isolation and urgent testing., Methods: In this large-scale, prospective, epidemiological surveillance study, we used prospective, observational, longitudinal, self-reported data from participants in the UK on 19 symptoms over 3 days after symptoms onset and COVID-19 PCR test results extracted from the COVID-19 Symptom Study mobile phone app. We divided the study population into a training set (those who reported symptoms between April 29, 2020, and Oct 15, 2020) and a test set (those who reported symptoms between Oct 16, 2020, and Nov 30, 2020), and used three models to analyse the self-reported symptoms: the UK's National Health Service (NHS) algorithm, logistic regression, and the hierarchical Gaussian process model we designed to account for several important variables (eg, specific COVID-19 symptoms, comorbidities, and clinical information). Model performance to predict COVID-19 positivity was compared in terms of sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) in the test set. For the hierarchical Gaussian process model, we also evaluated the relevance of symptoms in the early detection of COVID-19 in population subgroups stratified according to occupation, sex, age, and body-mass index., Findings: The training set comprised 182 991 participants and the test set comprised 15 049 participants. When trained on 3 days of self-reported symptoms, the hierarchical Gaussian process model had a higher prediction AUC (0·80 [95% CI 0·80-0·81]) than did the logistic regression model (0·74 [0·74-0·75]) and the NHS algorithm (0·67 [0·67-0·67]). AUCs for all models increased with the number of days of self-reported symptoms, but were still high for the hierarchical Gaussian process model at day 1 (0·73 [95% CI 0·73-0·74]) and day 2 (0·79 [0·78-0·79]). At day 3, the hierarchical Gaussian process model also had a significantly higher sensitivity, but a non-statistically lower specificity, than did the two other models. The hierarchical Gaussian process model also identified different sets of relevant features to detect COVID-19 between younger and older subgroups, and between health-care workers and non-health-care workers. When used during different pandemic periods, the model was robust to changes in populations., Interpretation: Early detection of SARS-CoV-2 infection is feasible with our model. Such early detection is crucial to contain the spread of COVID-19 and efficiently allocate medical resources., Funding: ZOE, the UK Government Department of Health and Social Care, the Wellcome Trust, the UK Engineering and Physical Sciences Research Council, the UK National Institute for Health Research, the UK Medical Research Council, the British Heart Foundation, the Alzheimer's Society, the Chronic Disease Research Foundation, and the Massachusetts Consortium on Pathogen Readiness., Competing Interests: Declaration of interests ATC reports personal fees from Pfizer, Bayer Pharma, and Boehringer Ingelheim, outside the submitted work. CJS reports grants from the Chronic Disease Research Foundation, during the conduct of the study. JCP, LP, JW, and TS report other (work) and consultancy from ZOE, during the conduct of the study. CHS reports grants from the Alzheimer's Society, during the conduct of the study. DAD reports grants from the National Institutes of Health during the conduct of the study and has previously served as a co-investigator on an unrelated trial supported by ZOE. RD reports grants from the Department of Health and Social Care, during the conduct of the study, and personal fees from ZOE, outside the submitted work. SO reports grants from the Wellcome Trust, Innovate UK Research and Innovation, and the Chronic Disease Research Foundation, during the conduct of the study. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Multiple voluntary surveillance platforms were developed across the world in response to the COVID-19 pandemic, providing a real-time understanding of population-based COVID-19 epidemiology. During this time, testing criteria broadened and health-care policies matured. We aimed to test whether there were consistent associations of symptoms with SARS-CoV-2 test status across three surveillance platforms in three countries (two platforms per country), during periods of testing and policy changes., Methods: For this observational study, we used data of observations from three volunteer COVID-19 digital surveillance platforms (Carnegie Mellon University and University of Maryland Facebook COVID-19 Symptom Survey, ZOE COVID Symptom Study app, and the Corona Israel study) targeting communities in three countries (Israel, the UK, and the USA; two platforms per country). The study population included adult respondents (age 18-100 years at baseline) who were not health-care workers. We did logistic regression of self-reported symptoms on self-reported SARS-CoV-2 test status (positive or negative), adjusted for age and sex, in each of the study cohorts. We compared odds ratios (ORs) across platforms and countries, and we did meta-analyses assuming a random effects model. We also evaluated testing policy changes, COVID-19 incidence, and time scales of duration of symptoms and symptom-to-test time., Findings: Between April 1 and July 31, 2020, 514 459 tests from over 10 million respondents were recorded in the six surveillance platform datasets. Anosmia-ageusia was the strongest, most consistent symptom associated with a positive COVID-19 test (robust aggregated rank one, meta-analysed random effects OR 16·96, 95% CI 13·13-21·92). Fever (rank two, 6·45, 4·25-9·81), shortness of breath (rank three, 4·69, 3·14-7·01), and cough (rank four, 4·29, 3·13-5·88) were also highly associated with test positivity. The association of symptoms with test status varied by duration of illness, timing of the test, and broader test criteria, as well as over time, by country, and by platform., Interpretation: The strong association of anosmia-ageusia with self-reported positive SARS-CoV-2 test was consistently observed, supporting its validity as a reliable COVID-19 signal, regardless of the participatory surveillance platform, country, phase of illness, or testing policy. These findings show that associations between COVID-19 symptoms and test positivity ranked similarly in a wide range of scenarios. Anosmia, fever, and respiratory symptoms consistently had the strongest effect estimates and were the most appropriate empirical signals for symptom-based public health surveillance in areas with insufficient testing or benchmarking capacity. Collaborative syndromic surveillance could enhance real-time epidemiological investigations and public health utility globally., Funding: National Institutes of Health, National Institute for Health Research, Alzheimer's Society, Wellcome Trust, and Massachusetts Consortium on Pathogen Readiness., Competing Interests: Declaration of interests ZOE Global codeveloped the app pro bono for non-commercial purposes. JW, JCP, and SG work for ZOE Global, and TDS is a consultant for ZOE Global. LHN, DAD, and ATC previously participated as investigators on a diet study unrelated to this work, which was supported by ZOE Global. ATC reports personal fees from Pfizer, Bayer Pharma, and Boehringer Ingelheim, outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The Pfizer-BioNTech (BNT162b2) and the Oxford-AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccines have shown excellent safety and efficacy in phase 3 trials. We aimed to investigate the safety and effectiveness of these vaccines in a UK community setting., Methods: In this prospective observational study, we examined the proportion and probability of self-reported systemic and local side-effects within 8 days of vaccination in individuals using the COVID Symptom Study app who received one or two doses of the BNT162b2 vaccine or one dose of the ChAdOx1 nCoV-19 vaccine. We also compared infection rates in a subset of vaccinated individuals subsequently tested for SARS-CoV-2 with PCR or lateral flow tests with infection rates in unvaccinated controls. All analyses were adjusted by age (≤55 years vs >55 years), sex, health-care worker status (binary variable), obesity (BMI <30 kg/m 2 vs ≥30 kg/m 2 ), and comorbidities (binary variable, with or without comorbidities)., Findings: Between Dec 8, and March 10, 2021, 627 383 individuals reported being vaccinated with 655 590 doses: 282 103 received one dose of BNT162b2, of whom 28 207 received a second dose, and 345 280 received one dose of ChAdOx1 nCoV-19. Systemic side-effects were reported by 13·5% (38 155 of 282 103) of individuals after the first dose of BNT162b2, by 22·0% (6216 of 28 207) after the second dose of BNT162b2, and by 33·7% (116 473 of 345 280) after the first dose of ChAdOx1 nCoV-19. Local side-effects were reported by 71·9% (150 023 of 208 767) of individuals after the first dose of BNT162b2, by 68·5% (9025 of 13 179) after the second dose of BNT162b2, and by 58·7% (104 282 of 177 655) after the first dose of ChAdOx1 nCoV-19. Systemic side-effects were more common (1·6 times after the first dose of ChAdOx1 nCoV-19 and 2·9 times after the first dose of BNT162b2) among individuals with previous SARS-CoV-2 infection than among those without known past infection. Local effects were similarly higher in individuals previously infected than in those without known past infection (1·4 times after the first dose of ChAdOx1 nCoV-19 and 1·2 times after the first dose of BNT162b2). 3106 of 103 622 vaccinated individuals and 50 340 of 464 356 unvaccinated controls tested positive for SARS-CoV-2 infection. Significant reductions in infection risk were seen starting at 12 days after the first dose, reaching 60% (95% CI 49-68) for ChAdOx1 nCoV-19 and 69% (66-72) for BNT162b2 at 21-44 days and 72% (63-79) for BNT162b2 after 45-59 days., Interpretation: Systemic and local side-effects after BNT162b2 and ChAdOx1 nCoV-19 vaccination occur at frequencies lower than reported in phase 3 trials. Both vaccines decrease the risk of SARS-CoV-2 infection after 12 days., Funding: ZOE Global, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, UK Medical Research Council, Wellcome Trust, UK Research and Innovation, American Gastroenterological Association., Competing Interests: Declaration of interests CM reports grants from Chronic Disease Research Foundation (CDRF) during the conduct of the study. JW, AM, LP, CH, SS, and JC report being employees of ZOE Global during the conduct of the study. ATC reports grants from Massachusetts Consortium on Pathogen Readiness during the conduct of the study, and personal fees from Bayer Pharma, Pfizer, and Boehringer Ingelheim, outside the submitted work. DAD reports grants from National Institutes of Health (NIH), Massachusetts Consortium on Pathogen Readiness, and American Gastroenterological Association, during the conduct of the study, and that he served as a co-investigator on an unrelated nutrition trial sponsored by ZOE Global. CHS reports grants from Alzheimer's Society during the conduct of the study. AMV reports grants from Medical Research Council (MRC) and personal fees from ZOE Global, during the conduct of the study. ALG reports having shares in AstraZeneca and receiving grants from Novavax, outside the submitted work. CJS reports grants from CDRF, MRC, and Wellcome Trust, during the conduct of the study. SO reports grants from Wellcome Trust, UK Research and Innovation (UKRI), and CDRF, during the conduct of the study. TDS reports being a consultant for ZOE Global, during the conduct of the study. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility., Methods: We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, R t , for the two incidence estimates., Findings: From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6-0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56-0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38-0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the R t of B.1.1.7 by a factor of 1·35 (95% CI 1·02-1·69) relative to pre-existing variants. However, R t fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant., Interpretation: The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant., Funding: Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society., Competing Interests: Declaration of interests AM, LP, SS, JC, CH, and JW are employees of Zoe Global. TDS is a consultant for Zoe Global. DAD and ATC previously served as investigators on a clinical trial of diet and lifestyle using a separate smartphone app supported by Zoe Global. ATC reports grants from the Massachusetts Consortium on Pathogen Readiness during the conduct of the study; and personal fees from Pfizer, Boehringer Ingelheim, and Bayer Pharma outside the submitted work. DAD reports grants from the US National Institutes of Health, the Massachusetts Consortium on Pathogen Readiness, and the American Gastroenterological Association during the conduct of the study. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4·0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Data for front-line health-care workers and risk of COVID-19 are limited. We sought to assess risk of COVID-19 among front-line health-care workers compared with the general community and the effect of personal protective equipment (PPE) on risk., Methods: We did a prospective, observational cohort study in the UK and the USA of the general community, including front-line health-care workers, using self-reported data from the COVID Symptom Study smartphone application (app) from March 24 (UK) and March 29 (USA) to April 23, 2020. Participants were voluntary users of the app and at first use provided information on demographic factors (including age, sex, race or ethnic background, height and weight, and occupation) and medical history, and subsequently reported any COVID-19 symptoms. We used Cox proportional hazards modelling to estimate multivariate-adjusted hazard ratios (HRs) of our primary outcome, which was a positive COVID-19 test. The COVID Symptom Study app is registered with ClinicalTrials.gov, NCT04331509., Findings: Among 2 035 395 community individuals and 99 795 front-line health-care workers, we recorded 5545 incident reports of a positive COVID-19 test over 34 435 272 person-days. Compared with the general community, front-line health-care workers were at increased risk for reporting a positive COVID-19 test (adjusted HR 11·61, 95% CI 10·93-12·33). To account for differences in testing frequency between front-line health-care workers and the general community and possible selection bias, an inverse probability-weighted model was used to adjust for the likelihood of receiving a COVID-19 test (adjusted HR 3·40, 95% CI 3·37-3·43). Secondary and post-hoc analyses suggested adequacy of PPE, clinical setting, and ethnic background were also important factors., Interpretation: In the UK and the USA, risk of reporting a positive test for COVID-19 was increased among front-line health-care workers. Health-care systems should ensure adequate availability of PPE and develop additional strategies to protect health-care workers from COVID-19, particularly those from Black, Asian, and minority ethnic backgrounds. Additional follow-up of these observational findings is needed., Funding: Zoe Global, Wellcome Trust, Engineering and Physical Sciences Research Council, National Institutes of Health Research, UK Research and Innovation, Alzheimer's Society, National Institutes of Health, National Institute for Occupational Safety and Health, and Massachusetts Consortium on Pathogen Readiness., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)