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Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK)

Holt et al., Thorax, doi:10.1136/thoraxjnl-2021-217487, COVIDENCE UK, NCT04330599
Mar 2021  
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Case -3% Improvement Relative Risk Vitamin C for COVID-19  COVIDENCE UK  Prophylaxis Does vitamin C reduce COVID-19 infections? Prospective study of 15,227 patients in the United Kingdom (May 2020 - Feb 2021) No significant difference in cases c19early.org Holt et al., Thorax, March 2021 Favorsvitamin C Favorscontrol 0 0.5 1 1.5 2+
Vitamin C for COVID-19
6th treatment shown to reduce risk in September 2020, now with p = 0.00000002 from 73 studies, recognized in 12 countries.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 109 treatments. c19early.org
Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency. NCT04330599 (history). COVIDENCE UK.
Meta analysis of all vitamin C studies shows benefit for clinical outcomes but not for viral or case outcomes, consistent with an intervention that may have limited or no direct antiviral effect, but minimizes progression via other mechanisms (for example by aiding the immune system, minimizing immune over-activation, minizing secondary complications, or aiding recovery).
This is the 17th of 73 COVID-19 controlled studies for vitamin C, which collectively show efficacy with p=0.00000002 (1 in 50 million).
21 studies are RCTs, which show efficacy with p=0.0012.
This study is excluded in the after exclusion results of meta analysis: significant unadjusted confounding possible.
risk of case, 2.9% higher, RR 1.03, p = 0.86, treatment 49 of 1,580 (3.1%), control 397 of 13,647 (2.9%), adjusted per study, odds ratio converted to relative risk, minimally adjusted, group sizes approximated.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Holt et al., 30 Mar 2021, prospective, United Kingdom, peer-reviewed, 34 authors, study period 1 May, 2020 - 5 February, 2021, trial NCT04330599 (history) (COVIDENCE UK). Contact: a.martineau@qmul.ac.uk.
This PaperVitamin CAll
Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK)
Hayley Holt, Mohammad Talaei, Matthew Greenig, Dominik Zenner, Jane Symons, Clare Relton, Katherine S Young, Molly R Davies, Katherine N Thompson, Jed Ashman, Sultan Saeed Rajpoot, Ahmed Ali Kayyale, Sarah El Rifai, Philippa J Lloyd, David Jolliffe, Olivia Timmis, Sarah Finer, Stamatina Iliodromiti, Alec Miners, Nicholas S Hopkinson, Bodrul Alam, Graham Lloyd-Jones, Thomas Dietrich, Iain Chapple, Paul E Pfeffer, David Mccoy, Gwyneth Davies, Ronan A Lyons, Christopher Griffiths, Frank Kee, Aziz Sheikh, Gerome Breen, Seif O Shaheen, Professor Adrian R Martineau
Thorax, doi:10.1136/thoraxjnl-2021-217487
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, populationbased cohort study (COVIDENCE UK) from 1 May 2020 to 5 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 ORs (aORs) for associations between potential risk factors and odds of COVID-19. Results We recorded 446 incident cases of COVID-19 in 15 227 participants (2.9%). Increased odds of developing COVID-19 were independently associated with Asian/Asian British versus white ethnicity (aOR 2.28, 95% CI 1.33 to 3.91), household overcrowding (aOR per additional 0.5 people/bedroom 1.26, 1.11 to 1.43), any versus no visits to/from other households in previous week (aOR 1.31, 1.06 to 1.62), number of visits to indoor public places (aOR per extra visit per week 1.05, 1.02 to 1.09), frontline occupation excluding health/social care versus no frontline occupation (aOR 1.49, 1.12 to 1.98) and raised body mass index (BMI) (aOR 1.50 (1.19 to 1.89) for BMI 25.0-30.0 kg/m 2 and 1.39 (1.06 to 1.84) for BMI >30.0 kg/m 2 versus BMI <25.0 kg/m 2 ). Atopic disease was independently associated with decreased odds (aOR 0.75, 0.59 to 0.97). No independent associations were seen for age, sex, other medical conditions, diet or micronutrient supplement use. Conclusions After rigorous adjustment for factors influencing exposure to SARS-CoV-2, Asian/Asian British ethnicity and raised BMI were associated with increased odds of developing COVID-19, while atopic disease was associated with decreased odds. Trial registration number ClinicalTrials. gov Registry (NCT04330599). INTRODUCTION COVID-19 has taken a heavy toll on the health of populations globally. [1][2][3] Risk factors for severe and fatal disease are well recognised, and include male sex, black or Asian ethnic origin, obesity, deprivation and a range of comorbidities including diabetes mellitus, cardiovascular disease, COPD and hypertension. 4 5 Characterisation of risks for milder disease has been relatively neglected, but is important, both from a public health perspective (since it drives transmission to individuals at risk of severe disease), and from a biological perspective (since understanding susceptibility factors can provide insights into pathogenesis). There is growing evidence from population-based studies to suggest that at least some risk factors for Key messages What is the key question? ► How do demographic, socioeconomic, lifestyle, dietary, pharmacological and comorbidity factors relate to the risk of developing COVID-19 in the general adult population of the UK? What is the bottom line? ► After rigorous adjustment for factors..
Supplementary Appendix: Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK) Table of Contents Supplementary Supplementary Methods Sample size The sample size required to detect an odds ratio of at least 1.08 (effect size) for a binary exposure variable with maximum variability (probability = 0.50 changing to 0.52) and correlated with other variables in the model (R 2 = 0.4), with a power of 90% using a two-sided test with 5% significance level was estimated as 10,964, using the 'powerlog' program in Stata 14.2 (College Station, TX). Assuming 10% censoring at baseline (prevalent COVID-19 and missing) and 20% loss to follow-up, we aimed to recruit a minimum of 15,228 participants. No upper limit for sample size was specified. Statistical methods Statistical analyses were performed using Stata 14.2. Putative risk factors for COVID-19 were selected a priori and classified into the following groups: socio-demographic, occupational and lifestyle factors; longstanding medical conditions, medication use and vaccination status; and diet and supplemental micronutrient intake. To produce patient-level covariates for each class of medications investigated, participant answers were mapped to drug classes listed on the British National Formulary (BNF) or the DrugBank and Electronic Medicines Compendium databases if not explicitly listed on the BNF; further details of the computational methods used to achieve this are presented in supplementary..
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