Individuals with preexisting sleep disturbances including obstructive sleep apnea (OSA), insomnia, and abnormal sleep duration showed significantly increased vulnerability to COVID-19, as well as an increased risk for hospitalization, mortality, and long COVID, according to new data from more than 8 million individuals.
Sleep disturbances, though common in the general population, are generally overlooked as a risk factor for COVID-19, wrote Jiawei Zhou, MD, of The First Hospital of China Medical University, Shenyang, China, and colleagues. Most previous research has focused on the impact of COVID-19 on sleep disturbances, not the impact of sleep disturbances on COVID-19, and most studies on the latter topic have focused only on OSA, the researchers wrote.
In a meta-analysis published in eClinicalMedicine, part of The Lancet Discovery Science, the researchers identified 48 observational studies published between October 27, 2023, and May 8, 2024, that involved COVID-19 and sleep disturbances including OSA, insomnia, abnormal sleep duration, and night shift work, among others. The study population included 8,664,026 adults.
The primary outcomes were COVID-19 susceptibility, hospitalization, mortality, and long COVID. Overall, the presence of preexisting sleep disturbances was associated with a significantly increased risk for each of these outcomes, with odds ratios (ORs) of 1.12, 1.25, 1.45, and 1.36, respectively.
In subgroup analyses, the association between preexisting sleep disturbances and greater susceptibility and hospitalization was higher in younger adults (younger than 60 years) than in older adults (aged 60 years and older), but the risk for death was lower in younger adults with sleep disturbances than in older adults with sleep disturbances (OR, 1.22 vs OR, 2.07, respectively). Men with sleep disturbances had a higher risk for COVID-19 mortality than women with sleep disturbances.
Preexisting sleep disturbances overall were significantly associated with long COVID and more so in a subgroup analysis of patients whose definition of long COVID was symptoms lasting 3 or more months vs those lasting 1 month (P = .029).
When the researchers broke down associations with COVID-19 outcomes and specific sleep disturbances, they found significant associations between OSA and all four primary outcomes. Abnormal sleep duration was associated with an increased risk for COVID-19 susceptibility, hospitalization, and long COVID. Night shift work was associated with an increased risk for COVID-19 susceptibility and hospitalization, and insomnia was associated with an increased risk for long COVID.
Although the exact mechanism behind the associations between preexisting sleep disturbances and COVID-19 outcomes is uncertain, persistent sleep deprivation could set the stage in various ways, including the promotion of elevated C-reactive protein and interleukin-6 levels, the researchers wrote.
"Overall, the compromised innate and adaptive immune functions combined with a persistent inflammatory state may explain the higher risk of susceptibility, severity, and longer recovery time observed in patients with sleep disturbances. Fortunately, early intervention for sleep disturbances could attenuate the adverse effects of COVID-19," they noted in their discussion.
The findings were limited by several factors including the observational nature of the studies and the heterogeneity of outcomes, the researchers wrote. Looking ahead, randomized, controlled trials are needed to examine the effect of interventions for sleep disturbances in the prevention and course of COVID-19, they said.
However, the study is the first known to examine multiple types of sleep disturbances and their possible influences on the full clinical course of COVID-19 and support the need for early evaluation and intervention for individuals with sleep disturbances to reduce short-term and long-term effects of the disease, the researchers concluded.
Findings Reflect the Need to Address Sleep Issues Early
Although the results of the current study were not surprising, "it is always worth doing meta-analyses to see if there is a potential signal in the published data to suggest a need for a new study," said Arjun Chatterjee, MD, professor of pulmonary, critical care, allergy, and immunologic diseases at Wake Forest University, Winston-Salem, North Carolina, in an interview.
"Lack of sleep, whether acute active deprivation (zero sleep for one night) or subacute/chronic sleep debt, such as only 5 hours per night, has been demonstrated to affect lymphocyte proliferation, reduce immune globulin levels, increase inflammatory markers, shorten telomeres, and affect the immune system in various ways," said Chatterjee, who was not involved in the meta-analysis.
The clinical takeaway from the current meta-analysis is that adequate sleep is important for various reasons, Chatterjee said. "Sleep disruption affects health across a spectrum of systems; adding an annual sleep wellness and screening event to healthcare visits is probably worth the investment," he noted.
Much more is needed in the way of additional research, Chatterjee told Medscape Medical News. Notably, studies are needed to examine what sleep disruption does to immune status, as well as all other physiologic and mental health systems, he said.
The study was supported by the National Natural Science Foundation of China and the Key Laboratory of Respiratory Diseases of Liaoning Province. The researchers had no financial conflicts to disclose. Chatterjee had no financial conflicts to disclose.