OSA as a probable risk factor for severe COVID-19

Citation:

McSharry D, Lam MT, Malhotra AT. OSA as a probable risk factor for severe COVID-19. J Clin Sleep Med. 2020;16(9):1649.

It is prudent to examine whether patients with obstructive sleep apnea (OSA) are at risk for severe COVID-19. Salles et al,¹ we, and others believe there are mechanistic links between OSA and COVID-19 severity. First, severe COVID-19 and OSA share common risk factors: obesity, cardiovascular disease, hypertension, diabetes, age, and male sex. In severe COVID-19 cases, pulmonary infection by the SARS-CoV-2 virus results in massive infiltration of proinflammatory monocytes and neutrophils, leading to acute respiratory distress syndrome, sepsis, and death. As Salles et al¹ pointed out, sleep deprivation increases interleukin-6, interleukin-17, and tumor necrosis factor-α that promote inflammatory activity in neutrophils. Elevated interleukin-6 and tumor necrosis factor-α are implicated in severe COVID-19. Mechanistically, sleep disruption promotes the infiltration of neutrophils and monocytes to the sites of inflammation.² In various animal models of sepsis, sleep disruption by sleep fragmentation, intermittent hypoxia, or rapid eye movement sleep deprivation led to high mortality after septic challenge. Furthermore, mice deficient in a neuron-specific receptor responsible for homeostatic sleep were more susceptible to influenza viral challenge.³ Adequate sleep is protective during sepsis and pulmonary infection, which is a notion supported by epidemiologic studies. Last, OSA leads to dysregulation of the renin-angiotensin-aldosterone axis, further providing a potential link in viral entry through angiotensin-converting enzyme (ACE)-2 receptors. Taken together, there is a strong biological plausibility linking OSA with an increased risk of severe COVID-19.

The Coronavirus Sars-Cov2 & Diabetes Outcomes study (CORONADO) is one of the first studies that provides evidence associating OSA to the severity of COVID-19.⁴ CORONADO is a multicenter observational study in France that analyzed data from 1317 patients with diabetes hospitalized for COVID-19. Patients classified as treated OSA before admission had a higher odds ratio of death by day 7 (adjusted odds ratio, 2.65), suggesting that a diagnosis of OSA is an independent risk factor for poor COVID-19 outcome. It is important to note that the patients in this study were not evaluated for undiagnosed or untreated OSA. One would hypothesize a worse outcome if patients with COVID-19 have underlying untreated OSA. If the evidence supports the hypothesis that OSA worsens COVID-19 outcomes, then we have tools to intervene. Newly diagnosed patients with somnolent OSA should be treated. Screening patients who have been hospitalized with COVID-19 with tools such as the STOP-BANG questionnaire could identify patients at risk for adverse outcomes. Finally, adequate sleep is essential for developing a robust and long-lasting adaptive immunity.⁵ Optimal sleep is crucial for survivors of COVID-19 and for our society in building herd immunity with vaccination against the SARS-CoV-2 virus. Research into links between OSA and COVID-19 is thus urgently needed.

DISCLOSURE STATEMENT

All authors have seen and approved the manuscript. Research, literature review, and manuscript preparation done by all authors in Ireland and the United States. ResMed provided a philanthropic donation to University of California, San Diego, in support of a sleep center. The authors report no conflicts of interest.