ABSTRACT
Summary: Background: Studies into the bidirectional relationship between sleep and long COVID have been limited by retrospective pre-infection sleep data and infrequent post-infection follow-up. We therefore used prospectively collected monthly data to evaluate how pre-infection sleep characteristics affect risk of long COVID, and to track changes in sleep duration during the year after SARS-CoV-2 infection. Methods: COVIDENCE UK is a prospective, population-based UK study of COVID-19 in adults. We included non-hospitalised participants with evidence of SARS-CoV-2 infection, and estimated odds ratios (ORs) for the association between pre-infection sleep characteristics and long COVID using logistic regression, adjusting for potential confounders. We assessed changes in sleep duration after infection using multilevel mixed models. We defined long COVID as unresolved symptoms at least 12 weeks after infection. We defined sleep quality according to age-dependent combinations of sleep duration and efficiency. COVIDENCE UK is registered with ClinicalTrials.gov, NCT04330599 . Findings: We included 3994 participants in our long COVID risk analysis, of whom 327 (8.2%) reported long COVID. We found an inverse relationship between pre-infection sleep quality and risk of long COVID (medium vs good quality: OR 1.37[95% CI 1.04-1.81]; medium–low vs good: 1.55 [1.12-2.16]; low vs good: 1.94 [1.11–3.38]). Greater variability in pre-infection sleep efficiency was also associated with long COVID (OR per percentage-point increase 1.06 [1.01–1.11]). We assessed post-infection sleep duration in 6860 participants, observing a 0.11 h (95% CI 0.08–0.13) increase in the first month after infection compared with pre-infection, with larger increases for more severe infections. After 1 month, sleep duration largely returned to pre-infection levels, although fluctuations in duration lasted up to 6 months after infection among people reporting long COVID. Interpretation: Our findings highlight the bidirectional relationship between sleep and long COVID. While poor-quality sleep before SARS-CoV-2 infection associates with increased risk of long COVID thereafter, changes in sleep duration after infection in these non-hospitalised cases were modest and generally quick to resolve.
Subject(s)
COVID-19 , Sleep Wake DisordersABSTRACT
Background: Randomised controlled trials (RCT) to determine the influence of vitamin D on bone mineral content (BMC) and fracture risk in children of Black African ancestry are lacking.Methods: We conducted a sub-study nested within a Phase 3 RCT of weekly oral supplementation with 10,000 IU vitamin D3 in HIV-uninfected Cape Town schoolchildren of Black African ancestry aged 6-11 years. Outcomes were BMC at the whole body less head (WBLH) and lumbar spine (LS) and serum concentrations of 25-hydroxyvitamin D3 (25[OH]D3), parathyroid hormone (PTH) and bone turnover markers. Incidence of fractures was an outcome of the main trial.Findings: 1682 children were enrolled in the main trial, of whom 450 also participated in the sub-study. Among sub-study participants, end-trial serum 25(OH)D3 concentrations were higher for participants allocated to vitamin D vs. placebo (adjusted mean difference [aMD] 39.9 nmol/L, 95% CI 36.1 to 43.6, P<0.001) and serum PTH concentrations were lower (aMD -0.55 pmol/L, 95% CI -0.94 to -0.17, P=0.005). However, no interarm differences were seen for WBLH BMC (aMD -8.0 g, 95% CI -30.7 to 14.7) or LS BMC (aMD -0.3 g, 95% CI -1.3 to 0.8), or for serum concentrations of bone turnover markers (P≥0.28). In the main trial, allocation did not influence fracture risk (adjusted odds ratio 0.70, 95% CI 0.27 to 1.85, P=0.48).Interpretation: Weekly vitamin D supplementation elevated serum 25(OH)D3 concentrations and suppressed serum PTH concentrations in HIV-uninfected South African schoolchildren of Black African ancestry but did not influence BMC, bone turnover markers or fracture risk.FUNDING: Medical Research CouncilTrial Registration: Registered on the South African National Clinical Trials Register (DOH-27-0916-5527) and ClinicalTrials.gov (ref NCT02880982).Funding: This research was funded by the UK Medical Research Council (refs MR/R023050/1 and MR/M026639/1, both awarded to ARM). RJW was supported by Wellcome (104803, 203135). He also received support from the Francis Crick Institute which is funded by Cancer Research UK (FC2112), the UK Medical Research Council (FC2112) and Wellcome (FC2112). Declaration of Interest: ARM declares receipt of funding in the last 36 months to support vitamin D research from the following companies who manufacture or sell vitamin D supplements: Pharma Nord Ltd, DSM Nutritional Products Ltd, Thornton & Ross Ltd and Hyphens Pharma Ltd. ARM also declares receipt of vitamin D capsules for clinical trial use from Pharma Nord Ltd, Synergy Biologics Ltd and Cytoplan Ltd; support for attending meetings from Pharma Nord Ltd and Abiogen Pharma Ltd; receipt of consultancy fees from DSM Nutritional Products Ltd and Qiagen Ltd; receipt of a speaker fee from the Linus Pauling Institute; participation on Data and Safety Monitoring Boards for the VITALITY trial (Vitamin D for Adolescents with HIV to reduce musculoskeletal morbidity and immunopathology, Pan African Clinical Trials Registry ref PACTR20200989766029) and the Trial of Vitamin D and Zinc Supplementation for Improving Treatment Outcomes Among COVID-19 Patients in India (ClinicalTrials.gov ref NCT04641195); and unpaid work as a Programme Committee member for the Vitamin D Workshop. All other authors declare that they have no competing interests.Ethical Approval: The trial was sponsored by Queen Mary University of London, approved by the University of Cape Town Faculty of Health Sciences Human Research Ethics Committee (Ref: 796/2015) and the London School of Hygiene and Tropical Medicine Observational/Interventions Research Ethics Committee (Ref: 7450-2).
Subject(s)
HIV Infections , Bone Diseases, Metabolic , Musculoskeletal Diseases , Parathyroid Diseases , COVID-19 , Fractures, BoneABSTRACT
Prospective population-based studies investigating associations between reactive symptoms following SARS-CoV-2 vaccination and serologic responses to vaccination are lacking. We therefore conducted such a study in 9003 adults from the United Kingdom (UK) general population receiving SARS-COV-2 vaccines as part of the national vaccination programme. Data relating to incidence and type of reactive symptoms after vaccination were captured using online questionnaires, along with information on 56 potential determinants of symptom risk. Titres of combined IgG/IgA/IgM responses to SARS-CoV-2 spike (S) glycoprotein were determined in eluates of dried blood spots collected from all participants before and after vaccination. 4262 (47.3%) participants experienced systemic reactive symptoms after a first vaccine dose. Factors associating with lower risk of such symptoms included older age (aOR per additional 10 years of age 0.85, 95% CI 0.81–0.90), male vs. female sex (aOR 0.59, 95% CI 0.53–0.65) and receipt of an mRNA vaccine vs. ChAdOx1 nCoV-19 (0.29, 0.26–0.32 for BNT162b2; 0.06, 0.01–0.26 for mRNA-1273). Higher risk of such symptoms was associated with a history of symptomatic SARS-CoV-2 infection prior to vaccination (2.23, 1.78–2.81) and presence vs. absence of self-rated anxiety or depression at cohort enrolment (1.24, 1.12–1.39). Post-vaccination anti-S titres were higher among participants who experienced reactive symptoms after vaccination vs. those who did not (P < 0.001). We conclude that factors influencing risk of systemic symptoms after SARS-CoV-2 vaccination include demographic characteristics, pre-vaccination SARS-CoV-2 serostatus and vaccine type. Participants experiencing reactive symptoms following SARS-CoV-2 vaccination had higher post-vaccination titres of IgG/A/M anti-S antibodies. Improved public understanding of the frequency of reactogenic symptoms and their positive association with vaccine immunogenicity could potentially increase vaccine uptake.
Subject(s)
COVID-19ABSTRACT
BACKGROUND: Vitamin D metabolites support innate immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory pathogens. Randomized controlled trials of vitamin D to prevent coronavirus disease 2019 (Covid-19) have not yet reported. METHODS: We randomly assigned 6200 U.K. adults to receive an offer of a postal finger-prick 25-hydroxyvitamin D (25[OH]D) test with provision of a 6-month supply of higher-dose vitamin D (3200 IU/d, n=1550) or lower-dose vitamin D (800 IU/d, n=1550) to those with blood 25(OH)D concentration <75 nmol/L, vs. no offer of testing or supplementation (n=3100). The primary outcome was the proportion of participants experiencing at least one swab test- or doctor-confirmed acute respiratory infection (ARI) of any cause at six months. Secondary outcomes included incidence of swab test-confirmed Covid-19. RESULTS: Of 3100 participants offered testing, 2958 (95.4%) accepted, and 2690 (86.8%) had 25(OH)D <75 nmol/L and were sent vitamin D supplements (1356 higher-dose, 1334 lower-dose). 76 (5.0%) vs. 87 (5.7%) vs. 136 (4.6%) participants in higher-dose vs. lower-dose vs. no-offer groups experienced at least one ARI of any cause (odds ratio [OR] for higher-dose vs. no-offer 1.09, 95% CI 0.82-1.46; lower-dose vs. no-offer 1.26, 0.96-1.66). 45 (3.0%) vs. 55 (3.6%) vs. 78 (2.6%) participants in higher-dose vs. lower-dose vs. no-offer groups developed Covid-19 (OR for higher-dose vs. no-offer 1.13, 0.78-1.63; lower-dose vs. no-offer 1.39, 0.98-1.97). CONCLUSIONS: Among adults with a high baseline prevalence of vitamin D insufficiency, implementation of a test-and-treat approach to vitamin D replacement did not reduce risk of all-cause ARI or Covid-19.
Subject(s)
Coronavirus Infections , Severe Acute Respiratory Syndrome , Addison Disease , Respiratory Tract Infections , COVID-19ABSTRACT
Background Socio-economic deprivation is well recognised as a risk factor for developing COVID-19. However, the impact of COVID-19 on economic vulnerability has not previously been characterised. Objective To determine whether COVID-19 has a significant impact on adequacy of household income to meet basic needs (primary outcome) and work absence due to sickness (secondary outcome), both at the onset of illness (acutely) and subsequently (long-term). Design Multivariate mixed regression analysis of self-reported data from monthly on-line questionnaires, completed 1 st May 2020 to 28 th October 2021, adjusting for baseline characteristics including age, sex, socioeconomic status and self-rated health. Setting and Participants Participants (n=16,910) were UK residents aged 16 years or over participating in a national longitudinal study of COVID-19 (COVIDENCE UK). Results Incident COVID-19 was independently associated with increased odds of participants reporting household income as being inadequate to meet their basic needs, both acutely (adjusted odds ratio [aOR) 1.39, 95% confidence interval [CI] 1.12 to 1.73) and in the long-term (aOR 1.15, 95% CI 1.00 to 1.33). Exploratory analysis revealed the long-term association to be restricted to those who reported ‘long COVID’, defined as the presence of symptoms lasting more than 4 weeks after the acute episode (aOR 1.39, 95% CI 1.10 to 1.77). Incident COVID-19 associated with increased odds of reporting sickness absence from work in the long-term (aOR 5.29, 95% CI 2.76 to 10.10) but not acutely (aOR 1.34, 95% CI 0.52 to 3.49). Conclusions We demonstrate an independent association between COVID-19 and increased risk of economic vulnerability, both acutely and in the long-term. Taking these findings together with pre-existing research showing that socio-economic disadvantage increases the risk of developing COVID-19, this may generate a ‘vicious cycle’ of impaired health and poor economic outcomes. Trial registration NCT04330599 Summary Box What is already known on this topic Socioeconomic deprivation is recognised as a major risk factor for incidence and severity of COVID-19 disease, mediated via factors including increased occupational and household exposure to SARS-CoV-2 and greater physical vulnerability due to comorbidities The potential for COVID-19 to act as a cause, rather than a consequence, of economic vulnerability has not previously been characterised. What this study adds We demonstrate an independent association between incident COVID-19 and subsequent self-report of household income being inadequate to meet basic needs, both acutely and in the long term Incident COVID-19 was also associated with increased odds of subsequent self-report of sickness absence from work in the long-term.
Subject(s)
COVID-19ABSTRACT
Summary Background Antibody responses to SARS-CoV-2 vaccination vary for reasons that remain poorly understood. Methods We tested for presence of combined IgG, IgA and IgM (IgGAM) anti-spike antibodies before and after administration of two doses of ChAdOx1 nCoV-19 (ChAdOx1, Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech) in UK adults participating in a population-based longitudinal study who received their first dose of vaccine from December 15, 2020 to July 10, 2021. Information on sixty-six potential sociodemographic, behavioural, clinical, pharmacological and nutritional determinants of serological response to vaccination was captured using serial online questionnaires. We used logistic regression to estimate multivariable-adjusted odds ratios (aORs) for associations between independent variables and risk of seronegativity following two vaccine doses. Participants who were seronegative after receiving two vaccine doses were offered an additional antibody test following subsequent administration of a ‘booster’ dose of BNT162b2 or mRNA-1273 (Moderna) from September 23 to December 12, 2021. Findings Serology results following two vaccine doses were available for 9,101 participants, of whom 5,770 (63.4%) received ChAdOx1 and 3,331 (36.6%) received BNT162b2. Anti-spike IgGAM was undetectable in 378 (4.2%) participants at a median of 8.6 weeks (IQR 6.4-10.7 weeks) after their second dose of vaccine. Seronegativity following two doses of SARS-CoV-2 vaccination was associated with administration of ChAdOx1 vs BNT162b2 (aOR 7.03, 95% CI 4.39-11.24), shorter interval between first and second vaccine doses (aOR 2.37, 1.06-5.26, for <6 weeks vs >10 weeks; aOR 1.59, 1.18-2.13, for 6-10 weeks vs >10 weeks), poorer self-assessed general health (aOR 3.33, 1.49-7.46, for poor vs excellent), immunodeficiencies (aOR 6.75, 2.63-17.35) and prescription of systemic immunosuppressants (aOR 3.76, 2.44-5.78). By contrast, pre-vaccination SARS-CoV-2 seropositivity (aOR 0.16, 0.04-0.70, for symptomatic seropositives vs seronegatives) and supplemental vitamin D intake (aOR 0.73, 0.53-0.99) were associated with reduced risk of post-vaccination seronegativity. 247/378 (65.3%) of participants who were seronegative after two doses of ChAdOx1 vs BNT162b2 provided a third sample at a median of 7.8 weeks (IQR 5.8-10.4) after receiving a booster dose of BNT162b2 or mRNA-1273: eight (3.2%) of them remained seronegative after three vaccine doses, all of whom either had a primary immunodeficiency or were taking systemic immunosuppressant drugs. Interpretation We identify multiple determinants of antibody responses to two doses of ChAdOx1 or BNT162b2, many of which are potentially modifiable. Booster doses of BNT162b2 or mRNA-1273 were highly effective in achieving seroconversion in those who failed to mount antibody responses following two doses of ChAdOx1 or BNT162b2. Study registration https://clinicaltrials.gov/ct2/show/NCT04330599 Funding Barts Charity, Fischer Family Trust, The Exilarch’s Foundation, DSM Nutritional Products, Health Data Research UK Research in context Evidence before this study We searched PubMed, medRxiv, and Google Scholar for papers published from January 1, 2020, to February 1, 2022, using the search terms (antibody OR humoral OR serologic* OR immunogenic*) AND (SARS-CoV-2 vaccine OR ChAdOx1 or BNT162b2 coronavirus), with no language restrictions. Population-based studies investigating multiple potential determinants of vaccine immunogenicity in people with known pre-vaccination SARS-CoV-2 serostatus are lacking. Added value of this study This large population-based study, conducted in a population with known pre-vaccination SARS-CoV-2 serostatus, examines a comprehensive range of potential sociodemographic, behavioural, clinical, pharmacological and nutritional determinants of antibody responses to administration of two major SARS-CoV-2 vaccines (i.e., ChAdOx1 or BNT162b2), many of which have not previously been investigated. It is also the first population-based study to characterise antibody responses to booster doses of SARS-CoV-2 vaccines in adults who were seronegative after their primary course of vaccination. Implications of all the available evidence Increased risk of seronegativity following two doses of SARS-CoV-2 vaccines was associated with administration of ChAdOx1 vs BNT162b2, shorter interval between first and second vaccine doses, poorer self-assessed general health, immunocompromise and SARS-CoV-2 seronegativity pre-vaccination. Regular intake of vitamin D supplements was associated with reduced risk of post-vaccination seronegativity. Randomised controlled trials are now needed to test for causality. Booster doses of BNT162b2 or mRNA-1273 were highly effective in achieving seroconversion in the majority of people who failed to mount antibody responses following a primary course of vaccination, the few exceptions being a subset of those with primary immunodeficiency or systemic immunosuppressant drugs.
Subject(s)
Immunologic Deficiency SyndromesABSTRACT
Background: Prospective population-based studies investigating multiple determinants of pre-vaccination antibody responses to SARS-CoV-2 are lacking.Methods: We did a prospective population-based study in SARS-CoV-2 vaccine-naive UK adults between May 1 and Nov 2, 2020. Information on 88 potential risk factors was obtained through online questionnaires, and combined IgG/IgA/IgM responses to SARS-CoV-2 spike glycoprotein were determined in dried blood spots. We used logistic and linear regression to estimate adjusted odds ratios (aORs) and adjusted geometric mean ratios (aGMRs) for potential determinants of SARS-CoV-2 seropositivity (all participants) and antibody titres (seropositive participants only), respectively.Findings: 1696 (15.2%) of 11,130 participants were seropositive. Factors independently associated with increased risk included frontline health/care occupation (aOR 1.86, 95% CI 1.49–2.33), international travel (1.22, 1.08–1.37), BMI >30 vs <25 kg/m² (1.22, 1.05–1.42), Asian/Asian British vs White ethnicity (1.65, 1.10–2.47), and alcohol consumption ≥15 vs 0 units/week (1.26, 1.06–1.49). Light physical exercise associated with decreased risk (0.80, 0.69–0.93, for ≥10 vs 0–4 h/week). Higher titres associated with frontline health/care occupation (aGMR 1.26, 95% CI 1.13–1.41), international travel (1.10, 1.04–1.16), BMI >30 vs <25 kg/m² (1.09, 1.01–1.17), and Asian/Asian British vs White ethnicity (1.23, 1.03–1.46); these associations were not substantially attenuated by adjustment for disease severity.Interpretation: Higher alcohol consumption and reduced physical exercise represent new modifiable risk factors for SARS-CoV-2 infection. Recognised associations between Asian/Asian British ethnic origin and obesity and increased risk of SARS-CoV-2 seropositivity were independent of other sociodemographic, clinical, or behavioural factors investigated.Funding: Barts Charity, Health Data Research UK.Declaration of Interest: JS declares receipt of payments from Reach plc for news stories written about recruitment to, and findings of, the COVIDENCE UK study. AS is a member of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group and its Standing Committee on Pandemics. He is also a member of the UK Government’s NERVTAG’s Risk Stratification Subgroup. ARM declares receipt of funding in the last 36 months to support vitamin D research from the following companies who manufacture or sell vitamin D supplements: Pharma Nord Ltd, DSM Nutritional Products Ltd, Thornton & Ross Ltd, Cytoplan Ltd and Hyphens Pharma Ltd. ARM also declares support for attending meetings from the following companies who manufacture or sell vitamin D supplements: Pharma Nord Ltd and Abiogen Pharma Ltd. ARM also declares participation on the Data and Safety Monitoring Board for the Chair, DSMB, VITALITY trial (Vitamin D for Adolescents with HIV to reduce musculoskeletal morbidity and immunopathology). ARM also declares unpaid work as a Programme Committee member for the Vitamin D Workshop. ARM also declares receipt of vitamin D capsules for clinical trial use from Pharma Nord Ltd, Synergy Biologics Ltd and Cytoplan Ltd.Ethical Approval: COVIDENCE UK was sponsored by Queen Mary University of London and approved by Leicester South Research Ethics Committee (ref 20/EM/0117). It is registered withClinicalTrials.gov (NCT04330599).
Subject(s)
HIV Infections , Alcoholism , COVID-19 , HIV Seropositivity , ObesityABSTRACT
Background: The COVID-19 pandemic is a novel population-level stressor. As such, it is important to examine pandemic-related changes in mental health and to identify which individuals are at greatest risk of worsening symptoms. Methods: Online questionnaires were administered to 34,465 individuals in the UK, recruited from existing cohorts or via social media. Around one third (n = 12,718) with prior diagnoses of depression or anxiety completed pre-pandemic mental health assessments, allowing prospective investigation of symptom change. We examined changes in depression, anxiety and PTSD symptoms using prospective, retrospective and global ratings of change assessments. We also examined the effect of key risk factors on changes in symptoms.Outcomes: Prospective analyses showed small decreases in depression (PHQ-9: - .43 points) and anxiety symptoms (GAD-7: -.33 points), and increases in PTSD symptoms (PCL-6: .22 points). Conversely, retrospective analyses demonstrated large significant increases in depression (2.40 points) and anxiety symptoms (1.97 points) and 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Using both prospective and retrospective symptom measures, regression analyses demonstrated that worsening depression, anxiety and PTSD symptoms were associated with i) prior mental health diagnoses, ii) female gender; iii) young age, and iv) unemployed or student status.Interpretation: We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously-reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias underestimating prior symptom severity.
Subject(s)
Anxiety Disorders , Intellectual Disability , COVID-19 , Stress Disorders, Post-TraumaticABSTRACT
Background: Risk factors for severe COVID-19 include older age, male sex, obesity, Black or Asian ethnicity and underlying medical conditions. Whether these factors also influence susceptibility to developing COVID-19 is uncertain. Methods: We undertook a prospective, population-based cohort study (COVIDENCE UK) from 1 st May 2020 to 5 th February 2021 . Baseline information on potential risk factors was captured by an online questionnaire. Monthly follow-up questionnaires captured incident COVID-19. We used logistic regression models to estimate multivariable-adjusted odds ratios (aORs) for associations between potential risk factors and risk of COVID-19. Findings: We recorded 446 incident cases of COVID-19 in 15,227 participants (2.9%). Increased risk of developing COVID-19 was independently associated with Asian/Asian British vs . White ethnicity (aOR 2.31, 95% CI 1.35-3.95), household overcrowding (aOR per additional 0.5 people/bedroom 1.26, 1.11-1.43) , any vs . no visits to/from other households in previous week (aOR 1.33, 1.07-1.64), number of visits to indoor public places (aOR per extra visit per week 1.05, 1.01-1.09), frontline occupation excluding health/social care vs. no frontline occupation (aOR 1.49, 1.12-1.98), and raised body mass index (BMI) (aOR 1.51 [1.20-1.90] for BMI 25.0-30.0 kg/m 2 and 1.38 [1.05-1.82] for BMI >30.0 kg/m 2 vs. BMI <25.0 kg/m 2 ). Atopic disease was independently associated with decreased risk (aOR 0.76, 0.59-0.98). No independent associations were seen for age, sex, other medical conditions, diet, or micronutrient supplement use. Interpretation: After rigorous adjustment for factors influencing exposure to SARS-CoV-2, Asian/Asian British ethnicity and raised BMI were associated with increased risk of developing COVID-19, while atopic disease was associated with decreased risk. Trial Registration: It is registered with ClinicalTrials.gov (NCT04330599). Funding: Barts Charity, Health Data Research UK Declaration of Interest: None to declare. Ethical Approval: The study was sponsored by Queen Mary University of London and approved by<br>Leicester South Research Ethics Committee (ref 20/EM/0117).
Subject(s)
COVID-19 , Obesity , Dermatitis, AtopicABSTRACT
Summary Background Risk factors for severe COVID-19 include older age, male sex, obesity, Black or Asian ethnicity and underlying medical conditions. Whether these factors also influence susceptibility to developing COVID-19 is uncertain. Methods We undertook a prospective, population-based cohort study (COVIDENCE UK) from 1 st May 2020 to 5 th February 2021. Baseline information on potential risk factors was captured by an online questionnaire. Monthly follow-up questionnaires captured incident COVID-19. We used logistic regression models to estimate multivariable-adjusted odds ratios (aORs) for associations between potential risk factors and risk of COVID-19. Findings We recorded 446 incident cases of COVID-19 in 15,227 participants (2.9%). Increased risk of developing COVID-19 was independently associated with Asian/Asian British vs . White ethnicity (aOR 2.31, 95% CI 1.35-3.95), household overcrowding (aOR per additional 0.5 people/bedroom 1.26, 1.11-1.43), any vs . no visits to/from other households in previous week (aOR 1.33, 1.07-1.64), number of visits to indoor public places (aOR per extra visit per week 1.05, 1.01-1.09), frontline occupation excluding health/social care vs . no frontline occupation (aOR 1.49, 1.12-1.98), and raised body mass index (BMI) (aOR 1.51 [1.20-1.90] for BMI 25.0-30.0 kg/m 2 and 1.38 [1.05-1.82] for BMI >30.0 kg/m 2 vs . BMI <25.0 kg/m 2 ). Atopic disease was independently associated with decreased risk (aOR 0.76, 0.59-0.98). No independent associations were seen for age, sex, other medical conditions, diet, or micronutrient supplement use. Interpretation After rigorous adjustment for factors influencing exposure to SARS-CoV-2, Asian/Asian British ethnicity and raised BMI were associated with increased risk of developing COVID-19, while atopic disease was associated with decreased risk. Funding Barts Charity, Health Data Research UK