Pre-pandemic Sleep Disorders Associated With Risk of Long COVID, Study Finds

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Long COVID is the latest entry on the growing list of medical and mental health conditions that healthy sleep appears to protect against, researchers report.

Their hypothesis made sense: A previous study had linked poorer sleep patterns with worse COVID-19 outcomes, including hospitalization and mortality. And while the cause of long COVID (technically called post-COVID-19 condition or PCC) is still unknown, some of its wide range of symptoms — depression, fatigue, brain fog, difficulties performing routine daily functions — overlap with those caused by various patterns of unhealthy sleep.

Siwen Wang, M.D., and her Harvard colleagues used data from the Nurses' Health Study II to study the association between sleep problems and long COVID.

The prospective cohort study relied on the voluminous amount of information available from a cohort of participants in the long-running Nurses’ Health Study II who had tested positive for COVID-19. The findings were published in JAMA Network Open on May 30. First author Siwen Wang, M.D.,and the other authors are affiliated with Harvard’s public health school or its medical school.

Sleep health was measured before (June 2015 through May 2017) and early in (April through August 2020) the pandemic. A pre-pandemic healthy sleep score (0 to 5, with 5 being the healthiest) was determined from a combination of measures for each of five sleep dimensions, with healthy being seven to eight hours of sleep daily, low insomnia symptoms, no snoring, no frequent daytime dysfunction and chronotype (“morning person”). A simpler score was developed for sleep quality early in pandemic.

Symptoms of long COVID (defined as lasting four or more weeks) were self-reported during one year of follow-up. The analysis included 1,979 women, 44% of whom reported long COVID symptoms.

The researchers found a dose-response relationship between healthier sleep score and lower risk of developing long COVID: Participants with the healthiest sleep score (5) had a 30% lower risk of developing long COVID than those with the unhealthiest scores (0 or 1, which were combined for the analysis because very few had scores of 0).

The strongest associations with long COVID were found for the specific sleep-related measures of daytime dysfunction before the pandemic and sleep quality during the pandemic.

Multiple alternative analyses and exclusions of numerous covariates did not change the same findings. Redefining long COVID as lasting eight or more weeks (instead of four) made no difference; nor did depression or anxiety, or the severity of the acute phase of COVID-19 infection.

Although the findings were clear, there are questions about how much they can be generalized to the broader population. The participants were all female healthcare workers (43% on the front line) during a hugely disruptive pandemic and middle age or older (55 to 75, with a median age of 64.7). Additionally, almost all (97%) of participants were White women.

Wang, a research fellow in the Department of Nutrition at the Harvard T.H. Chan School of Public Health, and colleagues pointed to several pathophysiologic pathways as possibly explaining their findings.

All the measures of sleep quality that were included in their analysis “have been linked to systemic inflammation and immune aberrations,” they wrote, and “the proinflammatory state may predispose those with poor sleep health to the occurrence of cytokine storms,” which some have proposed to be involved with long COVID. “Furthermore," they wrote, "short sleep duration and insomnia have been implicated in the development of autoimmune antibodies, which have also been found in higher concentrations among patients with persistent COVID-19–related symptoms.” They also mentioned tht Impaired regulation of the gut microbiome, perhaps due to immune function, might be a “shared pathologic process” between sleep disorders and long COVID.