Objectives To investigate the associations of physical activity level with COVID-19 mortality risk across body mass index (BMI) categories, and to determine whether any protective association of a higher physical activity level in individuals with obesity may be explained by favourable levels of cardiometabolic and inflammatory biomarkers. Design Prospective cohort study (baseline data collected between 2006 and 2010). Physical activity level was assessed using the International Physical Activity Questionnaire (high: ≥3000 Metabolic Equivalent of Task (MET)-min/week, moderate: ≥600 MET-min/week, low: Not meeting either criteria), and biochemical assays were conducted on blood samples to provide biomarker data. Setting UK Biobank. Main outcome measures Logistic regressions adjusted for potential confounders were performed to determine the associations of exposure variables with COVID-19 mortality risk. Mortality from COVID-19 was ascertained by death certificates through linkage with National Health Service (NHS) Digital. Results Within the 259 397 included participants, 397 COVID-19 deaths occurred between 16 March 2020 and 27 February 2021. Compared with highly active individuals with a normal BMI (reference group), the ORs (95% CIs) for COVID-19 mortality were 1.61 (0.98 to 2.64) for highly active individuals with obesity, 2.85 (1.78 to 4.57) for lowly active individuals with obesity and 1.94 (1.04 to 3.61) for lowly active individuals with a normal BMI. Of the included biomarkers, neutrophil count and monocyte count were significantly positively associated with COVID-19 mortality risk. In a subanalysis restricted to individuals with obesity, adjusting for these biomarkers attenuated the higher COVID-19 mortality risk in lowly versus highly active individuals with obesity by 10%. Conclusions This study provides novel evidence suggesting that a high physical activity level may attenuate the COVID-19 mortality risk associated with obesity. Although the protective association may be partly explained by lower neutrophil and monocyte counts, it still remains largely unexplained by the biomarkers included in this analysis.
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