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Pregnancy is a risk factor for increased severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory infections, but the mechanisms underlying this risk are poorly understood. To gain insight into the role of pregnancy in modulating immune responses at baseline and upon SARS-CoV-2 infection, we collected peripheral blood mononuclear cells and plasma from 226 women, including 152 pregnant individuals and 74 non-pregnant women. We find that SARS-CoV-2 infection is associated with altered T cell responses in pregnant women, including a clonal expansion of CD4-expressing CD8 + T cells, diminished interferon responses, and profound suppression of monocyte function. We also identify shifts in cytokine and chemokine levels in the sera of pregnant individuals, including a robust increase of interleukin-27, known to drive T cell exhaustion. Our findings reveal nuanced pregnancy-associated immune responses, which may contribute to the increased susceptibility of pregnant individuals to viral respiratory infection., Competing Interests: Declaration of interests A.-C.V. has a financial interest in 10X Genomics. The company designs and manufactures gene-sequencing technology for use in research, and such technology is being used in this research. A.-C.V.’s interests were reviewed by The Massachusetts General Hospital and Mass General Brigham in accordance with their institutional policies. J.R.H. consults for CJ CheilJedang and Interon Laboratories. A.G.E. consults for Mirvie, Inc. outside of this work and receives research funding from Merck Pharmaceuticals outside of this work. K.J.G. has served as a consultant for BillionToOne, Aetion, Roche, and Janssen Global Services outside of this work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The gut microbiome is a critical modulator of host immunity and is linked to the immune response to respiratory viral infections. However, few studies have gone beyond describing broad compositional alterations in severe COVID-19, defined as acute respiratory or other organ failure., Methods: We profiled 127 hospitalized patients with COVID-19 (n = 79 with severe COVID-19 and 48 with moderate) who collectively provided 241 stool samples from April 2020 to May 2021 to identify links between COVID-19 severity and gut microbial taxa, their biochemical pathways, and stool metabolites., Results: Forty-eight species were associated with severe disease after accounting for antibiotic use, age, sex, and various comorbidities. These included significant in-hospital depletions of Fusicatenibacter saccharivorans and Roseburia hominis, each previously linked to post-acute COVID syndrome or "long COVID," suggesting these microbes may serve as early biomarkers for the eventual development of long COVID. A random forest classifier achieved excellent performance when tasked with classifying whether stool was obtained from patients with severe vs. moderate COVID-19, a finding that was externally validated in an independent cohort. Dedicated network analyses demonstrated fragile microbial ecology in severe disease, characterized by fracturing of clusters and reduced negative selection. We also observed shifts in predicted stool metabolite pools, implicating perturbed bile acid metabolism in severe disease., Conclusions: Here, we show that the gut microbiome differentiates individuals with a more severe disease course after infection with COVID-19 and offer several tractable and biologically plausible mechanisms through which gut microbial communities may influence COVID-19 disease course. Further studies are needed to expand upon these observations to better leverage the gut microbiome as a potential biomarker for disease severity and as a target for therapeutic intervention., (© 2023. The Author(s).)

Introduction: Data on the associations of prepandemic physical activity and sedentary behavior with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) severity, particularly milder illness, have been limited., Methods: We used data from 43,913 participants within the Nurses' Health Study II and Health Professionals Follow-Up Study who responded to periodic COVID-related surveys from May 2020 through March 2021. History of physical activity from the prepandemic period was assessed as the metabolic equivalents of task (MET)-hours per week of various activities of different intensity and sedentary behavior assessed from reports of time spent sitting from questionnaires completed 2016-2017. Multivariable logistic regression models were fitted to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for risk of SARS-CoV-2 infection and COVID-19 severity, as well as predicted COVID-19 defined using a validated symptom-based algorithm., Results: Higher levels of prepandemic physical activity were associated with a lower risk for SARS-CoV-2 infection. Compared to participants with <3 MET-hours per week, the multivariable-adjusted OR was 0.86 (95% CI: 0.74, 0.99; P trend =.07) for those with ≥27 MET-hours per week. Higher physical activity levels were also associated with lower risk of symptomatic SARS-CoV-2 infection (OR: 0.84; 95% CI: 0.72, 0.99; P trend = .05) and predicted COVID-19 (OR: 0.87; 95% CI: 0.78, 0.97; P trend = .01). Longer time sitting at home watching TV (OR: 0.85; 95% CI: 0.73, 0.97) or for other tasks (OR: 0.78; 95% CI: 0.66, 0.92) was associated with a lower risk of SARS-CoV-2 infection., Conclusions: Our findings support a protective association between prepandemic physical activity and lower risk and severity of COVID-19., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., Competing Interests: AM, CH, SJ, SS, RD, and JW are employees of Zoe Global Ltd. TDS is a consultant to Zoe Global Ltd. DAD, SEB, and ATC previously served as investigators on a clinical trial of diet and lifestyle using a separate smartphone application that was supported by Zoe Global Ltd. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Vitamin D may have a role in immune responses to viral infections. However, data on the association between vitamin D and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) severity have been limited and inconsistent., Objective: We examined the associations of predicted vitamin D status and intake with risk of SARS-CoV-2 infection and COVID-19 severity., Methods: We used data from periodic surveys (May 2020 to March 2021) within the Nurses' Health Study II. Among 39,315 participants, 1768 reported a positive test for SARS-CoV-2 infection. Usual vitamin D intake from foods and supplements were measured using a semiquantitative, pre-pandemic food-frequency questionnaire in 2015. Predicted 25-hydroxyvitamin D [25(OH)D] concentration were calculated based on a previously validated model including dietary and supplementary vitamin D intake, UV-B, and other behavioral predictors of vitamin D status., Results: Higher predicted 25(OH)D concentrations, but not vitamin D intake, were associated with a lower risk of SARS-CoV-2 infection. Comparing participants in the highest quintile of predicted 25(OH)D concentrations with the lowest, the multivariable-adjusted OR was 0.76 (95% CI: 0.58, 0.99; P-trend = 0.04). Participants in the highest quartile of UV-B (OR: 0.76; 95% CI: 0.66, 0.87; P-trend = 0.002) and UV-A (OR: 0.76; 95% CI: 0.66, 0.88; P-trend < 0.001) also had a lower risk of SARS-CoV-2 infection compared with the lowest. High intake of vitamin D from supplements (≥400 IU/d) was associated with a lower risk of hospitalization (OR: 0.51; 95% CI: 0.29, 0.91; P-trend = 0.04)., Conclusions: Our study provides suggestive evidence on the association between higher predicted circulating 25(OH)D concentrations and a lower risk of SARS-CoV-2 infection. Greater intake of vitamin D supplements was associated with a lower risk of hospitalization. Our data also support an association between exposure to UV-B or UV-A, independently of vitamin D and SARS-CoV-2 infection, so results for predicted 25(OH)D need to be interpreted cautiously., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

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., (© 2022. The Author(s).)

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/m 2 ) 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., Competing Interests: Declaration of interests JW, AM, LP, CH, SS, and JCP report being employees of ZOE during the conduct of the study. JM reports grants from the European Commission and National Institutes of Health, and has served as a co-investigator on an unrelated nutrition trial sponsored by ZOE. ATC reports grants from the 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 the National Institutes of Health, the Massachusetts Consortium on Pathogen Readiness, and the American Gastroenterological Association during the conduct of the study, and has served as a co-investigator on an unrelated nutrition trial sponsored by ZOE. LHN reports grants from the National Institutes of Health, the American Gastroenterological Association, and the Crohn's and Colitis Foundation. CHS reports grants from the Alzheimer's Society during the conduct of the study. EM reports a grant from the Medical Research Council during the conduct of the study. CJS reports grants from the Chronic Disease Research Foundation, the Medical Research Council, the Wellcome Trust, and the National Institute for Health Research (NIHR) during the conduct of the study. SO reports grants from the Wellcome Trust, UK Research and Innovation, and the Chronic Disease Research Foundation during the conduct of the study. ELD reports receiving grants from the Chronic Disease Research Foundation during the conduct of the study. TDS reports being a consultant for ZOE during the conduct of the study. All other authors declare no competing interests., (Copyright © 2022 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: Mental health issues have been reported after SARS-CoV-2 infection. However, comparison to prevalence in uninfected individuals and contribution from common risk factors (eg, obesity and comorbidities) have not been examined. We identified how COVID-19 relates to mental health in the large community-based COVID Symptom Study., Methods: We assessed anxiety and depression symptoms using two validated questionnaires in 413148 individuals between February and April 2021; 26998 had tested positive for SARS-CoV-2. We adjusted for physical and mental prepandemic comorbidities, body mass index (BMI), age and sex., Findings: Overall, 26.4% of participants met screening criteria for general anxiety and depression. Anxiety and depression were slightly more prevalent in previously SARS-CoV-2-positive (30.4%) vs SARS-CoV-2-negative (26.1%) individuals. This association was small compared with the effect of an unhealthy BMI and the presence of other comorbidities, and not evident in younger participants (≤40 years). Findings were robust to multiple sensitivity analyses. Association between SARS-CoV-2 infection and anxiety and depression was stronger in individuals with recent (<30 days) versus more distant (>120 days) infection, suggesting a short-term effect., Interpretation: A small association was identified between SARS-CoV-2 infection and anxiety and depression symptoms. The proportion meeting criteria for self-reported anxiety and depression disorders is only slightly higher than prepandemic., Competing Interests: Competing interests: AM, CH, AG, SS and JW are employees of Zoe Limited. TDS reports being a consultant for Zoe Limited during the conduct of the study. ATC previously served as an investigator on a separate study supported by Zoe Limited., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objective: Poor metabolic health and unhealthy lifestyle factors have been associated with risk and severity of COVID-19, but data for diet are lacking. We aimed to investigate the association of diet quality with risk and severity of COVID-19 and its interaction with socioeconomic deprivation., Design: We used data from 592 571 participants of the smartphone-based COVID-19 Symptom Study. Diet information was collected for the prepandemic period using a short food frequency questionnaire, and diet quality was assessed using a healthful Plant-Based Diet Score, which emphasises healthy plant foods such as fruits or vegetables. Multivariable Cox models were fitted to calculate HRs and 95% CIs for COVID-19 risk and severity defined using a validated symptom-based algorithm or hospitalisation with oxygen support, respectively., Results: Over 3 886 274 person-months of follow-up, 31 815 COVID-19 cases were documented. Compared with individuals in the lowest quartile of the diet score, high diet quality was associated with lower risk of COVID-19 (HR 0.91; 95% CI 0.88 to 0.94) and severe COVID-19 (HR 0.59; 95% CI 0.47 to 0.74). The joint association of low diet quality and increased deprivation on COVID-19 risk was higher than the sum of the risk associated with each factor alone (P interaction =0.005). The corresponding absolute excess rate per 10 000 person/months for lowest vs highest quartile of diet score was 22.5 (95% CI 18.8 to 26.3) among persons living in areas with low deprivation and 40.8 (95% CI 31.7 to 49.8) among persons living in areas with high deprivation., Conclusions: A diet characterised by healthy plant-based foods was associated with lower risk and severity of COVID-19. This association may be particularly evident among individuals living in areas with higher socioeconomic deprivation., Competing Interests: Competing interests: JW, CH, SS and JC are employees of Zoe Ltd. TDS, ERL and SB, area consultant to Zoe Ltd. DAD, JM and AC previously served as investigators on a clinical trial of diet and lifestyle using a separate mobile application that was supported by Zoe Ltd., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

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: 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: 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.)

Given the continued burden of COVID-19 worldwide, there is a high unmet need for data on the effect of social distancing and face mask use to mitigate the risk of COVID-19. We examined the association of community-level social distancing measures and individual face mask use with risk of predicted COVID-19 in a large prospective U.S. cohort study of 198,077 participants. Individuals living in communities with the greatest social distancing had a 31% lower risk of predicted COVID-19 compared with those living in communities with poor social distancing. Self-reported 'always' use of face mask was associated with a 62% reduced risk of predicted COVID-19 even among individuals living in a community with poor social distancing. These findings provide support for the efficacy of mask-wearing even in settings of poor social distancing in reducing COVID-19 transmission. Despite mass vaccination campaigns in many parts of the world, continued efforts at social distancing and face mask use remain critically important in reducing the spread of COVID-19.

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.)

Reports of long-lasting coronavirus disease 2019 (COVID-19) symptoms, the so-called 'long COVID', are rising but little is known about prevalence, risk factors or whether it is possible to predict a protracted course early in the disease. We analyzed data from 4,182 incident cases of COVID-19 in which individuals self-reported their symptoms prospectively in the COVID Symptom Study app 1 . A total of 558 (13.3%) participants reported symptoms lasting ≥28 days, 189 (4.5%) for ≥8 weeks and 95 (2.3%) for ≥12 weeks. Long COVID was characterized by symptoms of fatigue, headache, dyspnea and anosmia and was more likely with increasing age and body mass index and female sex. Experiencing more than five symptoms during the first week of illness was associated with long COVID (odds ratio = 3.53 (2.76-4.50)). A simple model to distinguish between short COVID and long COVID at 7 days (total sample size, n = 2,149) showed an area under the curve of the receiver operating characteristic curve of 76%, with replication in an independent sample of 2,472 individuals who were positive for severe acute respiratory syndrome coronavirus 2. This model could be used to identify individuals at risk of long COVID for trials of prevention or treatment and to plan education and rehabilitation services.

As no one symptom can predict disease severity or the need for dedicated medical support in coronavirus disease 2019 (COVID-19), we asked whether documenting symptom time series over the first few days informs outcome. Unsupervised time series clustering over symptom presentation was performed on data collected from a training dataset of completed cases enlisted early from the COVID Symptom Study Smartphone application, yielding six distinct symptom presentations. Clustering was validated on an independent replication dataset between 1 and 28 May 2020. Using the first 5 days of symptom logging, the ROC-AUC (receiver operating characteristic - area under the curve) of need for respiratory support was 78.8%, substantially outperforming personal characteristics alone (ROC-AUC 69.5%). Such an approach could be used to monitor at-risk patients and predict medical resource requirements days before they are required., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Individuals with cancer may be at high risk for coronavirus disease 2019 (COVID-19) and adverse outcomes. However, evidence from large population-based studies examining whether cancer and cancer-related therapy exacerbates the risk of COVID-19 infection is still limited. Data were collected from the COVID Symptom Study smartphone application since March 29 through May 8, 2020. Among 23,266 participants with cancer and 1,784,293 without cancer, we documented 10,404 reports of a positive COVID-19 test. Compared with participants without cancer, those living with cancer had a 60% increased risk of a positive COVID-19 test. Among patients with cancer, current treatment with chemotherapy or immunotherapy was associated with a 2.2-fold increased risk of a positive test. The association between cancer and COVID-19 infection was stronger among participants >65 years and males. Future studies are needed to identify subgroups by tumor types and treatment regimens who are particularly at risk for COVID-19 infection and adverse outcomes., (© 2020 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Background: As many countries seek to slow the spread of COVID-19 without reimposing national restrictions, it has become important to track the disease at a local level to identify areas in need of targeted intervention., Methods: In this prospective, observational study, we did modelling using longitudinal, self-reported data from users of the COVID Symptom Study app in England between March 24, and Sept 29, 2020. Beginning on April 28, in England, the Department of Health and Social Care allocated RT-PCR tests for COVID-19 to app users who logged themselves as healthy at least once in 9 days and then reported any symptom. We calculated incidence of COVID-19 using the invited swab (RT-PCR) tests reported in the app, and we estimated prevalence using a symptom-based method (using logistic regression) and a method based on both symptoms and swab test results. We used incidence rates to estimate the effective reproduction number, R(t), modelling the system as a Poisson process and using Markov Chain Monte-Carlo. We used three datasets to validate our models: the Office for National Statistics (ONS) Community Infection Survey, the Real-time Assessment of Community Transmission (REACT-1) study, and UK Government testing data. We used geographically granular estimates to highlight regions with rapidly increasing case numbers, or hotspots., Findings: From March 24 to Sept 29, 2020, a total of 2 873 726 users living in England signed up to use the app, of whom 2 842 732 (98·9%) provided valid age information and daily assessments. These users provided a total of 120 192 306 daily reports of their symptoms, and recorded the results of 169 682 invited swab tests. On a national level, our estimates of incidence and prevalence showed a similar sensitivity to changes to those reported in the ONS and REACT-1 studies. On Sept 28, 2020, we estimated an incidence of 15 841 (95% CI 14 023-17 885) daily cases, a prevalence of 0·53% (0·45-0·60), and R(t) of 1·17 (1·15-1·19) in England. On a geographically granular level, on Sept 28, 2020, we detected 15 (75%) of the 20 regions with highest incidence according to government test data., Interpretation: Our method could help to detect rapid case increases in regions where government testing provision is lower. Self-reported data from mobile applications can provide an agile resource to inform policy makers during a quickly moving pandemic, serving as a complementary resource to more traditional instruments for disease surveillance., Funding: Zoe Global, UK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK National Institute for Health Research, UK Medical Research Council and British Heart Foundation, Alzheimer's Society, Chronic Disease Research Foundation., (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.)

The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) pandemic presents challenges to the real-time collection of population-scale data to inform near-term public health needs as well as future investigations. We established the COronavirus Pandemic Epidemiology (COPE) consortium to address this unprecedented crisis on behalf of the epidemiology research community. As a central component of this initiative, we have developed a COVID Symptom Study (previously known as the COVID Symptom Tracker) mobile application as a common data collection tool for epidemiologic cohort studies with active study participants. This mobile application collects information on risk factors, daily symptoms, and outcomes through a user-friendly interface that minimizes participant burden. Combined with our efforts within the general population, data collected from nearly 3 million participants in the United States and United Kingdom are being used to address critical needs in the emergency response, including identifying potential hot spots of disease and clinically actionable risk factors. The linkage of symptom data collected in the app with information and biospecimens already collected in epidemiology cohorts will position us to address key questions related to diet, lifestyle, environmental, and socioeconomic factors on susceptibility to COVID-19, clinical outcomes related to infection, and long-term physical, mental health, and financial sequalae. We call upon additional epidemiology cohorts to join this collective effort to strengthen our impact on the current health crisis and generate a new model for a collaborative and nimble research infrastructure that will lead to more rapid translation of our work for the betterment of public health.

The rapid pace of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents challenges to the robust collection of population-scale data to address this global health crisis. We established the COronavirus Pandemic Epidemiology (COPE) Consortium to unite scientists with expertise in big data research and epidemiology to develop the COVID Symptom Study, previously known as the COVID Symptom Tracker, mobile application. This application—which offers data on risk factors, predictive symptoms, clinical outcomes, and geographical hotspots—was launched in the United Kingdom on 24 March 2020 and the United States on 29 March 2020 and has garnered more than 2.8 million users as of 2 May 2020. Our initiative offers a proof of concept for the repurposing of existing approaches to enable rapidly scalable epidemiologic data collection and analysis, which is critical for a data-driven response to this public health challenge. [ABSTRACT FROM AUTHOR]