Does obstructive sleep apnea lead to increased risk of COVID-19 infection and severity?
Tufik S, Gozal D, Ishikura IA, Pires GN, Andersen ML. Does obstructive sleep apnea lead to increased risk of COVID-19 infection and severity? J Clin Sleep Med. 2020;16(8):1425–1426.
COVID-19 usually manifests as respiratory compromise, particularly in the severe presentations of the disease, being particularly likely among people aged >60 years, men, and those with obesity and cardiometabolic dysfunction. 1,2Severe COVID-19 is associated with a variety of proinflammatory mediators playing a role in the pathophysiology of the disease and with recruitment of the coagulation cascade with its attendant consequences.3,4
Although most confirmed COVID-19 cases are associated with a common clinical presentation of respiratory failure, considerable concern has emerged in light of the serious cardiovascular manifestations observed in patients with COVID-19.5 The putative mechanisms involved in cardiovascular outcomes in COVID-19 may include6 direct myocardial injury (involving the angiotensin-converting enzyme 2 signaling pathway), systemic inflammation, altered myocardial demand-supply balance (leading to acute myocardial ischemia), and electrolyte imbalance (increasing the vulnerability to various tachyarrhythmias). Indeed, evidence of cardiac injury, shock, and arrhythmias is present in 7.2%, 8.7%, and 16.7% of patients, respectively—that is, higher than the prevalence among patients in intensive care units who are not infected with SARS-CoV-2.7 Therefore, it is possible that an arrhythmogenic effect of COVID-19 potentially contributes to adverse disease outcomes. The cardiac outcomes of COVID-19 seem to be multifactorial, in light of other concurrent symptoms, all of which may exert proarrhythmic potential such as fever and tachycardia, high inflammatory status, catecholamine adrenergic response, and possible myocardial damage directly influenced by the virus.3,8
Individuals with pre-existing cardiovascular disease may be predisposed to COVID-19 infection and be at elevated risk of adverse outcomes.2,9 This association is remarkably similar to the many observational studies showing an association between sleep apnea and heart rhythm disorders.10 Accordingly, we believe that the underlying presence of OSA may not only facilitate susceptibility to SARS-CoV-2 infection but also be an inherent risk factor for severe COVID-19 and increase the overall mortality of the disease.
OSA is the most common sleep-related breathing disorder and is highly prevalent, possibly affecting up to 1 billion people around the world.11,12 It is characterized by transient increases in upper airway resistance, causing reductions or interruption of the airflow accompanied by increased respiratory effort.10 During OSA episodes, higher sympathetic outflow promotes the release of catecholamines and their effect on myocardial tissue in addition to elevated systemic blood pressure and tachycardia.10 These responses to both hypoxemia and arousal lead to increased oxygen demand and tissue hypoxia, resulting in myocardial ischemia and thereby facilitating the triggering of both atrial and ventricular arrhythmias.10 Thus, we call attention to the potential contribution of the intermittent hypoxia that characterizes patients with OSA, which can further interfere with lung ventilation. This severity of hypoxia may further interact with pulmonary parenchymal involvement along with pulmonary vascular endothelial dysfunction resulting from the infectious response to SARS-CoV-213 and could be a potential reason for the enhanced severity and adverse outcomes of OSA, as exemplified by a functional cardiac overload in this context. In addition, older age facilitates the occurrence of OSA, obesity is a major risk factor for OSA, and male sex is clearly overrepresented in patients with OSA when compared to premenopausal women. These factors are essentially identical to the risk factors associated with increased severity and mortality of COVID-19.
Another factor that merits attention is the relationship between OSA and arrhythmias. Nocturnal cardiac arrhythmias are present in 40% of all patients with OSA and in 92.3% of patients with severe OSA.14,15 Although OSA has been shown to promote the onset of atrial fibrillation, it has also been associated with atrial fibrillation recurrence after antiarrhythmic drug treatment, electrical cardioversion, and ablation therapy,16–18 thereby posing an obstacle to the successful treatment of arrhythmic episodes.
Thus, as COVID-19 impacts the cardiovascular system, pre-existing cardiovascular disease associated with coexisting morbidities, such as OSA, may exacerbate the clinical course evolution of COVID-19, leading to increased probability of intensive care unit requirements. However, although there is not an established therapeutic regimen for COVID-19 to date, several drugs are being tentatively used based on their anti-SARS-CoV-2 in vitro properties, such as chloroquine, hydroxychloroquine, and some antiretrovirals. Note that these drugs could also contribute to adverse outcomes, particularly arrhythmias, especially in the presence of long QT syndrome or other conduction defects.19
As researchers have observed, among the prominent risk factors for COVID-19 are cardiovascular and respiratory diseases, age >60 years, obesity, and male sex, yet little attention has been given to OSA, a condition whose prevalence and severity are remarkably affected by similar risk factors. Aggravating this scenario, many patients with OSA are currently undiagnosed and/or untreated because of the high costs of polysomnography and limited access to specialized sleep clinics.
Given these considerations, we highlight the presence of OSA as a potential comorbidity that merits inclusion as a risk for negative outcomes (such as intensive care unit admission, assisted ventilation, or death) in patients with COVID-19. OSA could act as a facilitator of SARS-CoV-2 infection, and once infection has occurred it could trigger a higher incidence of cardiovascular outcomes, such as arrhythmias, cardiac ischemia, and hypercoagulability states, leading to an unfavorable clinical progression.
COVID-19 remains a serious public health concern worldwide even after 5 months since the first case of the disease and has already affected millions of people. The current uncertainties regarding COVID-19 prevention, diagnosis, prognosis, and treatment should encourage researchers to intensify clinical and epidemiological studies. As such, we strongly recommend screening for OSA using currently available simple tools20 to enable the better delineation of risk factors and thereby formulate more accurate prevention strategies and therapeutic approaches.
S.T., I.A.I., G.N.P. and M.L.A. works are supported by grants from Associação Fundo de Incentivo à Pesquisa (AFIP) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). S.T. and M.L.A. received fellowships from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). D.G. is supported by National Institutes of Health grants HL130984 and HL140548. The authors have no further conflicts of interest to declare.
1. . Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395(10224):565–574. https://doi.org/10.1016/S0140-6736(20)30251-8
4. Kollias A, Kyriakoulis KG, Dimakakos E, Poulakou G, Stergiou GS, Syrigos K. Thromboembolic risk and anticoagulant therapy in COVID-19 patients: emerging evidence and call for action. Br J Haematol. Published online April 18, 2020. https://doi.org/10.1111/bjh.16727
5. Guo T, Fan Y, Chen M, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol. Published online March 27, 2020. https://doi.org/10.1001/jamacardio.2020.1017
8. . Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic. J Am Coll Cardiol. 2020;75(18):2352–2371. https://doi.org/10.1016/j.jacc.2020.03.031
13. Liu PP, Blet A, Smyth D, Li H. The science underlying COVID-19: implications for the cardiovascular system. Circulation. Published online April 15, 2020. https://doi.org/10.1161/CIRCULATIONAHA.120.047549
14. . Sleep apnea and nocturnal cardiac arrhythmia: a populational study. Arq Bras Cardiol. 2014;103(5):368–374.
16. . Obstructive sleep apnea and the recurrence of atrial fibrillation. Circulation. 2003;107(20):2589–2594. https://doi.org/10.1161/01.CIR.0000068337.25994.21
18. . Concomitant obstructive sleep apnea increases the recurrence of atrial fibrillation following radiofrequency catheter ablation of atrial fibrillation: clinical impact of continuous positive airway pressure therapy. Heart Rhythm. 2013;10(3):331–337. https://doi.org/10.1016/j.hrthm.2012.11.015
19. Wu CI, Postema PG, Arbelo E, et al. SARS-CoV-2, COVID-19, and inherited arrhythmia syndromes. Heart Rhythm. Accepted manuscript. Published online April 28, 2020. https://doi.org/10.1016/j.hrthm.2020.03.024. https://doi.org/10.1016/j.hrthm.2020.03.024
20. Duarte RL, Magalhães-da-Silveira FJ, Oliveira-e-Sá TS, et al. Obstructive sleep apnea screening with a 4-item instrument, named GOAL questionnaire: development, validation and comparative study with No-Apnea, STOP-Bang, and NoSAS. Nat Sci Sleep. January 23, 2020;12:57–67. https://doi.org/10.2147/NSS.S238255