Abstract: Brain, Behavior, and Immunity 87 (2020) 184–187 Contents lists available at ScienceDirect Brain, Behavior, and Immunity journal homepage: www.elsevier.com/locate/ybrbi Lifestyle risk factors, inflammatory mechanisms, and COVID-19 hospitalization: A community-based cohort study of 387,109 adults in UK T Mark Hamera,⁎, Mika Kivimäkib, Catharine R. Galec,d, G. David Battyb a Division of Surgery and Interventional Sciences, Faculty Medical Sciences, University College London, London, UK Department of Epidemiology and Public Health, University College London, UK c MRC Lifecourse Epidemiology Unit, University of Southampton, UK d Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, UK b ARTICLE INFO ABSTRACT Keywords: Physical activity Smoking Obesity Infection Coronavirus C-reactive protein Population cohort We conducted the first large-scale general population study on lifestyle risk factors (smoking, physical inactivity, obesity, and excessive alcohol intake) for COVID-19 using prospective cohort data with national registry linkage to hospitalisation. Participants were 387,109 men and women (56.4 ± 8.8 yr; 55.1% women) residing in England from UK Biobank study. Physical activity, smoking, and alcohol intake, were assessed by questionnaire at baseline (2006–2010). Body mass index, from measured height and weight, was used as an indicator of overall obesity. Outcome was cases of COVID-19 serious enough to warrant a hospital admission from 16-March-2020 to 26-April-2020. There were 760 COVID-19 cases. After adjustment for age, sex and mutually for each lifestyle factor, physical inactivity (Relative risk, 1.32, 95% confidence interval, 1.10, 1.58), smoking (1.42;1.12, 1.79) and obesity (2.05 ;1.68, 2.49) but not heavy alcohol consumption (1.12; 0.93, 1.35) were all related to COVID19. We also found a dose-dependent increase in risk of COVID-19 with less favourable lifestyle scores, such that participants in the most adverse category had 4-fold higher risk (4.41; 2.52–7.71) compared to people with the most optimal lifestyle. C-reactive protein levels were associated with elevated risk of COVID-19 in a dose-dependent manner, and partly (10–16%) explained associations between adverse lifestyle and COVID-19. Based on UK risk factor prevalence estimates, unhealthy behaviours in combination accounted for up to 51% of the population attributable fraction of severe COVID-19. Our findings suggest that an unhealthy lifestyle synonymous with an elevated risk of non-communicable disease is also a risk factor for COVID-19 hospital admission, which might be partly explained by low grade inflammation. Adopting simple lifestyle changes could lower the risk of severe infection.