Pre-existing sleep disturbances and risk of COVID-19: a meta-analysis
Jiawei Zhou, Xia Li, Ting Zhang, Ziyan Liu, Peng Li, Na Yu, Wei Wang
eClinicalMedicine, doi:10.1016/j.eclinm.2024.102719
Background Sleep disturbances are widespread but usually overlooked health risk factors for coronavirus disease 2019 (COVID-19). We aimed to investigate the influence of pre-existing sleep disturbances on the susceptibility, severity, and long-term effects of COVID-19. Methods We searched PubMed, Web of Science, and Embase for relevant articles from inception to October 27, 2023 and updated at May 8, 2024. Sleep disturbances included obstructive sleep apnea (OSA), insomnia, abnormal sleep duration, night-shift work, and any other sleep disturbances. Outcomes were COVID-19 susceptibility, hospitalization, mortality, and long COVID. The effect sizes were pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). This study is registered with PROSPERO (CRD42024503518). Findings A total of 48 observational studies (n = 8,664,026) were included. Pre-existing sleep disturbances increased the risk of COVID-19 susceptibility (OR = 1.12, 95% CI 1.07-1.18), hospitalization (OR = 1.25, 95% CI 1.15-1.36), mortality (OR = 1.45, 95% CI 1.19-1.78), and long COVID (OR = 1.36 95% CI 1.17-1.57). Subgroup analysis showed that younger individuals with sleep disturbances were associated with higher susceptibility and hospitalization and a lower risk of mortality than older individuals. Males with sleep disturbances were associated with higher mortality. For specific sleep disturbances, the susceptibility and hospitalization of COVID-19 were associated with OSA, abnormal sleep duration, and night-shift work; mortality of COVID-19 was linked to OSA; risk of long COVID was related to OSA, abnormal sleep duration and insomnia. Interpretation Pre-existing sleep disturbances, especially OSA, increased the risk of COVID-19 susceptibility, hospitalization, mortality, and long COVID. Age and sex played important roles in the effect of sleep disturbances on COVID-19.
Declaration of interests None. Appendix A. Supplementary data Supplementary data related to this article can be found at https://doi. org/10.1016/j.eclinm.2024.102719.
References
Akbarpour, Khalyfa, Qiao, Altered CD8+ T-cell lymphocyte function and TC1 cell stemness contribute to enhanced malignant tumor properties in murine models of sleep apnea, Sleep
Besedovsky, Lange, Haack, The sleep-immune crosstalk in health and disease, Physiol Rev
Bollinger, Bollinger, Skrum, Dimitrov, Lange et al., Sleep-dependent activity of T cells and regulatory T cells, Clin Exp Immunol
Chen, Morin, Ivers, The association of insomnia with long COVID: an international collaborative study (ICOSS-II), Sleep Med
Cortellini, Gennari, Pommeret, COVID-19 sequelae and the host proinflammatory response: an analysis from the OnCovid registry, J Natl Cancer Inst
Cubillos-Zapata, Balbás-García, Ortiz, Agedependent hypoxia-induced PD-L1 upregulation in patients with obstructive sleep apnoea, Respirology
Davis, Mccorkell, Vogel, Topol, Long COVID: major findings, mechanisms and recommendations, Nat Rev Microbiol
Duval, Tweedie, Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis, Biometrics
Fink, Engle, Ursin, Tang, Klein, Biological sex affects vaccine efficacy and protection against influenza in mice, Proc Natl Acad Sci U S A
Gao, Wei, Wang, Causal associations between obstructive sleep apnea and COVID-19: a bidirectional Mendelian randomization study, Sleep Med
Genzor, Prasko, Mizera, Risk of severe COVID-19 in non-adherent OSA patients, Patient Prefer Adherence
Ghosh, Klein, Sex drives dimorphic immune responses to viral infections, J Immunol
Hariyanto, Kurniawan, Obstructive sleep apnea (OSA) and outcomes from coronavirus disease 2019 (COVID-19) pneumonia: a systematic review and meta-analysis, Sleep Med
Hu, Han, Ren, Wang, Yang, Significant association of obstructive sleep apnoea with increased risk for fatal COVID-19: a quantitative meta-analysis based on adjusted effect estimates, Sleep Med Rev
Irwin, Olmstead, Carroll, Sleep disturbance, sleep duration, and inflammation: a systematic review and meta-analysis of cohort studies and experimental sleep deprivation, Biol Psychiatry
Jahrami, Alhaj, Humood, Sleep disturbances during the COVID-19 pandemic: a systematic review, metaanalysis, and meta-regression, Sleep Med Rev
Kheirandish-Gozal, Gozal, Obstructive sleep apnea and inflammation: proof of concept based on two illustrative cytokines, Int J Mol Sci
Lin, Zhou, Liu, Short sleep duration is associated with prolonged virus shedding in SARS-CoV-2 omicron-infected patients, Nat Sci Sleep
Lorenzo, De Oliveira Marchioro, Greco, Suchecki, Sleep-deprivation reduces NK cell number and function mediated by β-adrenergic signalling, Psychoneuroendocrinology
Mandel, Abedian, Risk of post-acute sequelae of SARS-CoV-2 infection associated with pre-coronavirus disease obstructive sleep apnea diagnoses: an electronic health record-based analysis from the RECOVER initiative, Sleep
Nadeem, Molnar, Madbouly, Serum inflammatory markers in obstructive sleep apnea: a meta-analysis, J Clin Sleep Med
Papadopoulos, Li, Samplaski, Why does COVID-19 kill more elderly men than women? Is there a role for testosterone?, Andrology
Prather, Janicki-Deverts, Hall, Cohen, Behaviorally assessed sleep and susceptibility to the common cold, Sleep
Pływaczewska-Jakubowska, Chudzik, Babicki, Kapusta, Jankowski, Lifestyle, course of COVID-19, and risk of Long-COVID in non-hospitalized patients, Front Med
Sang, Lin, Yang, Prolonged sleep deprivation induces a cytokine-storm-like syndrome in mammals, Cell
Schultheiß, Willscher, Paschold, The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19, Cell Rep Med
Taha, Saed, Moawad, Safety and efficacy of melatonin as an adjuvant therapy in COVID-19 patients: systematic review and meta-analysis, Adv Med Sci
Viveiros, Gheblawi, Aujla, Sex-and age-specific regulation of ACE2: insights into severe COVID-19 susceptibility, J Mol Cell Cardiol
Zheng, Liu, Le, A human circulating immune cell landscape in aging and COVID-19, Protein Cell
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'2019 (COVID-19) pneumonia: a systematic review and meta-analysis',
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'electronic health record-based analysis from the RECOVER initiative',
'volume': '46',
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'article-title': 'The association of insomnia with long COVID: an international '
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'doi-asserted-by': 'crossref',
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'year': '2023',
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'doi-asserted-by': 'crossref',
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'β-adrenergic signalling',
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'year': '2009',
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'mammals',
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'year': '2023',
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'article-title': 'Sleep disturbance, sleep duration, and inflammation: a systematic '
'review and meta-analysis of cohort studies and experimental sleep '
'deprivation',
'volume': '80',
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'article-title': 'Safety and efficacy of melatonin as an adjuvant therapy in COVID-19 '
'patients: systematic review and meta-analysis',
'volume': '68',
'author': 'Mohamed Taha',
'year': '2023',
'journal-title': 'Adv Med Sci'},
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'doi-asserted-by': 'crossref',
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'year': '2022',
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'year': '2018',
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'susceptibility',
'volume': '164',
'author': 'Viveiros',
'year': '2022',
'journal-title': 'J\xa0Mol Cell Cardiol'},
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'DOI': '10.1111/andr.12868',
'article-title': 'Why does COVID-19 kill more elderly men than women? Is there a role for '
'testosterone?',
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'author': 'Papadopoulos',
'year': '2021',
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'bidirectional Mendelian randomization study',
'volume': '101',
'author': 'Gao',
'year': '2023',
'journal-title': 'Sleep Med'},
{ 'issue': '7',
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'doi-asserted-by': 'crossref',
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'DOI': '10.1111/resp.13470',
'article-title': 'Age-dependent hypoxia-induced PD-L1 upregulation in patients with '
'obstructive sleep apnoea',
'volume': '24',
'author': 'Cubillos-Zapata',
'year': '2019',
'journal-title': 'Respirology'},
{ 'issue': '2',
'key': '10.1016/j.eclinm.2024.102719_bib26',
'doi-asserted-by': 'crossref',
'DOI': '10.1093/sleep/zsw040',
'article-title': 'Altered CD8+ T-cell lymphocyte function and TC1 cell stemness '
'contribute to enhanced malignant tumor properties in murine models of '
'sleep apnea',
'volume': '40',
'author': 'Akbarpour',
'year': '2017',
'journal-title': 'Sleep'},
{ 'issue': '7',
'key': '10.1016/j.eclinm.2024.102719_bib27',
'doi-asserted-by': 'crossref',
'first-page': '979',
'DOI': '10.1093/jnci/djac057',
'article-title': 'COVID-19 sequelae and the host proinflammatory response: an analysis '
'from the OnCovid registry',
'volume': '114',
'author': 'Cortellini',
'year': '2022',
'journal-title': 'J\xa0Natl Cancer Inst'},
{ 'issue': '6',
'key': '10.1016/j.eclinm.2024.102719_bib28',
'article-title': 'The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute '
'sequelae of COVID-19',
'volume': '3',
'author': 'Schultheiß',
'year': '2022',
'journal-title': 'Cell Rep Med'},
{ 'issue': '10',
'key': '10.1016/j.eclinm.2024.102719_bib29',
'doi-asserted-by': 'crossref',
'first-page': '1003',
'DOI': '10.5664/jcsm.3070',
'article-title': 'Serum inflammatory markers in obstructive sleep apnea: a meta-analysis',
'volume': '9',
'author': 'Nadeem',
'year': '2013',
'journal-title': 'J\xa0Clin Sleep Med'},
{ 'issue': '3',
'key': '10.1016/j.eclinm.2024.102719_bib30',
'doi-asserted-by': 'crossref',
'first-page': '459',
'DOI': '10.3390/ijms20030459',
'article-title': 'Obstructive sleep apnea and inflammation: proof of concept based on two '
'illustrative cytokines',
'volume': '20',
'author': 'Kheirandish-Gozal',
'year': '2019',
'journal-title': 'Int J Mol Sci'}],
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