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

Abstract

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. Beta values 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.

Multidimensional Sleep Health Prior to SARS-CoV-2 Infection and Risk of Post–COVID-19 Condition

“…13,14 Unhealthy sleep dimensions individually and in combination (eg, late chronotype, short or long duration of sleep, snoring and sleep apnea, and daytime sleepiness) are prospectively associated with COVID-19 susceptibility, severity, and mortality. [15][16][17][18] Mendelian randomization analyses have further identified insomnia, extreme sleep duration, and excessive daytime sleepiness as causal risk factors for the severity of COVID-19 and other respiratory infections. 16,17,19 These unhealthy sleep dimensions have been linked to chronic low-grade inflammation and immune abberations, 12,20,21 which have been implicated in the pathogenesis of PCC and other postinfection syndromes, such as postviral fatigue syndrome.…”

“…[15][16][17][18] Mendelian randomization analyses have further identified insomnia, extreme sleep duration, and excessive daytime sleepiness as causal risk factors for the severity of COVID-19 and other respiratory infections. 16,17,19 These unhealthy sleep dimensions have been linked to chronic low-grade inflammation and immune abberations, 12,20,21 which have been implicated in the pathogenesis of PCC and other postinfection syndromes, such as postviral fatigue syndrome. [22][23][24] Despite experimental evidence supporting the role of sleep deprivation and disturbances in infectious disease prognosis via immune dysfunction, 20,25 the association between sleep health prior to SARS-CoV-2 infection and risk of PCC has not been investigated.…”

“…The COVID-19 pandemic compounded both the severity of preexisting sleep disorders and the high prevalence of sleep disturbances . Unhealthy sleep dimensions individually and in combination (eg, late chronotype, short or long duration of sleep, snoring and sleep apnea, and daytime sleepiness) are prospectively associated with COVID-19 susceptibility, severity, and mortality . Mendelian randomization analyses have further identified insomnia, extreme sleep duration, and excessive daytime sleepiness as causal risk factors for the severity of COVID-19 and other respiratory infections .…”

Short Sleep Duration is Associated with Prolonged Virus Shedding in SARS-CoV-2 Omicron-Infected Patients

“…Daytime sleepiness is also found to be a risk for COVID-19 hospitalization. 29 The mechanism underlying the link between short sleep and prolonged virus shedding in SARS-CoV-2 Omicroninfected patients is still unknown. One plausible mechanism could be the adverse effect of insufficient sleep on immune system.…”

Sleep and circadian phenotypes: risk factors for COVID-19 severity?

“…In SLEEP , Zheran Liu et al [ 5 ] address this issue by analyzing epidemiological and genetic data from the community-based UK Biobank and the COVID-19 Host Genetic Initiative using Mendelian randomization (MR) analyses. This study is notable given the large number of participants enrolled (>500 000) with both phenotypic and genotypic data acquired at baseline between 2006 and 2010.…”