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.
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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 Arun 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.
Background
The COVID-19 pandemic has caused significant global morbidity and mortality, with long COVID emerging as a major concern, affecting at least 65 million people worldwide.
Long COVID encompasses a range of symptoms and new-onset diseases, posing ongoing health and economic burdens. Sleep disturbances, such as insomnia and obstructive sleep apnea (OSA), were prevalent during the pandemic, affecting 40.49% of the global population. These disturbances are known to be linked to immune deficiency and inflammation, exacerbating the impact of COVID-19.
While previous studies have shown that OSA increases the severity and mortality of COVID-19, other sleep disturbances and their role in long COVID remain less explored.
Conflicting evidence exists regarding the relationship between sleep disturbances and long COVID, with some studies indicating a positive association between conditions like OSA and insomnia, while others find no significant link.
Comprehensive research is needed to understand these connections and effectively address long COVID. Therefore, researchers in the present meta-analysis aimed to examine the effect of pre-existing sleep disturbances on COVID-19 outcomes.
About the study
A total of 48 relevant observational studies with 8,664,026 participants were included from databases including Web of Science, PubMed, and Embase. The studies investigated COVID-19 susceptibility (22), hospitalization (12), mortality (16), and long COVID (11).
Case reports, brief communications, letters, reviews, and preprints were excluded. Most studies were conducted in the United States of America, and up to 72% of the participants were male. The studies focused on four sleep disturbances: OSA, insomnia, abnormal sleep duration, and night-shift work.
Two researchers extracted and assessed data. They collected basic information (author, year, study design, region, sample size, age, gender), types of sleep disturbances, and COVID-19 outcomes.
Odds ratios (ORs) were calculated from available data or other ratios if necessary. Quality was evaluated using the Agency for Healthcare Research and Quality for cross-sectional studies and the Newcastle–Ottawa Scale for cohort/case-control studies.
Statistical methods included pooled ORs, heterogeneity assessment, subgroup analysis, sensitivity analyses, Egger’s test, and the trim-and-fill method for publication bias evaluation.
Results and discussion
Participants with pre-existing sleep disturbances were more susceptible to COVID-19 (OR = 1.12). Specific disturbances like OSA, abnormal sleep duration, and night shift work also increased COVID-19 occurrence.
Higher susceptibility was found in low- and middle-income countries compared to high-income countries and in studies with unadjusted ORs. Younger individuals with sleep disturbances showed increased susceptibility (OR = 1.20), while older individuals did not.
Further, patients with pre-existing sleep disturbances had a higher risk of COVID-19 hospitalization (OR = 1.25), with all sleep disturbances except insomnia contributing to this increased risk. The association was stronger in patients younger than 60 years.
Pre-existing sleep disturbances were also found to increase COVID-19 mortality (OR = 1.45), mainly due to OSA. This risk was higher in older patients and males. Diabetes was found to be a significant source of heterogeneity, with a stronger association between sleep disturbances and COVID-19 mortality in diabetic patients as compared to the general population.
Moreover, pre-existing sleep disturbances significantly increased the risk of developing long COVID (OR = 1.36). The association was stronger for long COVID defined as symptoms lasting ≥3 months compared to ≥1 month.
Subgroup analysis confirmed that OSA increased long COVID risk in both definitions (3-month: OR = 1.75, 1-month: OR = 1.12). Therefore, OSA may be a potential risk factor for long COVID, but further research is warranted to confirm these findings.
Asymmetric funnel plots indicated potential publication bias for COVID-19 susceptibility, hospitalization, and mortality studies. Subgroup and sensitivity analyses aligned with the main findings, confirming the robustness of the study.
The study highlights the importance of addressing sleep disturbances in COVID-19 management and prevention strategies. It is the first meta-analysis to investigate the impact of all sleep disturbances (not only OSA) on the total clinical course of COVID-19. However, the study is limited by high heterogeneity among outcomes, the observational nature of all included studies, and the inability to confirm causal relationships.
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