Associations of sleep and circadian phenotypes with COVID-19 susceptibility and hospitalization: an observational cohort study based on the UK Biobank and a two-sample Mendelian randomization study

Study Objectives Sleep and circadian phenotypes are associated with several diseases. The present study aimed to investigate whether sleep and circadian phenotypes were causally linked with coronavirus disease 2019 (COVID-19)-related outcomes. Methods Habitual sleep duration, insomnia, excessive daytime sleepiness, daytime napping, and chronotype were selected as exposures. Key outcomes included positivity and hospitalization for COVID-19. In the observation cohort study, multivariable risk ratios (RRs) and their 95% confidence intervals (CIs) were calculated. Two-sample Mendelian randomization (MR) analyses were conducted to estimate the causal effects of the significant findings in the observation analyses. Odds ratios (ORs) and the corresponding 95% CIs were calculated and compared using the inverse variance weighting, weighted median, and MR-Egger methods. Results In the UK Biobank cohort study, both often excessive daytime sleepiness and sometimes daytime napping were associated with hospitalized COVID-19 (excessive daytime sleepiness [often vs. never]: RR = 1.24, 95% CI = 1.02-1.5; daytime napping [sometimes vs. never]: RR = 1.12, 95% CI = 1.02-1.22). In addition, sometimes daytime napping was also associated with an increased risk of COVID-19 susceptibility (sometimes vs. never: RR = 1.04, 95% CI = 1.01-1.28). In the MR analyses, excessive daytime sleepiness was found to increase the risk of hospitalized COVID-19 (MR IVW method: OR = 4.53, 95% CI = 1.04-19.82), whereas little evidence supported a causal link between daytime napping and COVID-19 outcomes. Conclusions Observational and genetic evidence supports a potential causal link between excessive daytime sleepiness and an increased risk of COVID-19 hospitalization, suggesting that interventions targeting excessive daytime sleepiness symptoms might decrease severe COVID-19 rate.