Obstructive Sleep Apnea as a Risk Factor for Adverse Outcomes in COVID-19

Obstructive Sleep Apnea as a Risk Factor for Adverse Outcomes in COVID-19

By: Kara Dupuy-McCauley, MD, and Lauren Tobias, MD
Sleep Medicine Network
Published: March 3, 2021

Obstructive sleep apnea (OSA) shares several risk factors with COVID-19, including an increased incidence and severity in patients with male sex, obesity, hypertension, diabetes mellitus, and cardiovascular disease. Both diseases are highly prevalent, so understanding their relationship may elucidate opportunities to improve care for patients with COVID-19. Here, we briefly review emerging literature that suggests OSA may be an independent risk factor for poor outcomes from COVID-19.

What the Literature Says

A large, retrospective study of 4,668 patients with positive COVID-19 RNA PCR results found that those with a previous diagnosis of OSA had an increased all-cause mortality rate compared with their non-OSA counterparts (11.7% vs 6.9%; P < .001; odds ratio [OR], 1.79; 95% confidence interval [CI], 1.31-2.45).¹ However, the relationship between OSA and higher mortality was attenuated after adjustment for body mass index (BMI) and other comorbidities typically associated with sleep apnea, including asthma, emphysema, hypertension, chronic bronchitis, and type 2 diabetes (OR, 1.16; 95% CI, 0.8-1.68). An exploratory analysis showed that documentation of continuous positive airway pressure use in the prior year was associated with a nonsignificant trend toward decreasing the risk of death from COVID-19.

Another retrospective study examined more than 5 million patients in the Chicago metropolitan area, including 9,405 who had previously tested positive for COVID-19.² OSA was more prevalent among those who had required hospitalization compared with those who did not (15.3% vs 3.4%; P < .0001; OR, 5.20; 95% CI, 4.43-6.12). OSA was also more common in patients who had suffered from respiratory failure (19.4% vs 4.5%; P < .0001; OR, 5.16; 95% CI, 4.41-6.03). OSA remained associated with both an increased risk of hospitalization (OR, 1.65; 95% CI, 1.36-2.02) and of respiratory failure (OR, 1.98; 95% CI, 1.65-2.37) due to COVID-19 after adjusting for diabetes, hypertension, and BMI.

Finally, a Finnish study of 445 patients found that while patients with OSA had the same risk of contracting COVID-19 as those without OSA, their risk of hospitalization was higher (P = .045; OR, 2.93; 95% CI, 1.02-8.39), even after adjustment for age, sex, BMI, hypertension, diabetes, coronary heart disease, asthma, and COPD.³

Potential Mechanisms

Why might OSA portend worse outcomes from COVID-19? Several mechanisms have been postulated. OSA is associated with a proinflammatory state that may worsen the inflammatory response to COVID-19 and with cyclic hypoxemia may further compound the hypoxemia present in COVID-19 pneumonia, thus conferring an elevated risk of requiring invasive mechanical ventilation.⁴ OSA is also associated with sympathetic activation, which may further exaggerate this inflammatory response to COVID-19.⁵

These findings suggest that OSA may increase adverse outcomes in COVID-19, prompting several questions regarding the management of patients with OSA in both inpatient and outpatient settings. Is there a role for more liberal use of PAP in hospitalized patients with OSA? Might PAP adherence at home prevent progression to severe disease in those infected with SARS-CoV-2? At a minimum, these data should compel us to educate patients with OSA that they are at a higher risk for complications from COVID-19, inviting dialogue about the importance of vaccination. Further research will be important in delineating the mechanisms by which OSA appears to increase susceptibility to adverse outcomes in COVID-19.

References

1. Cade BE, Dashti HS, Hassan SM, Redline S, Karlson EW. Sleep apnea and COVID-19 mortality and hospitalization. Am J Respir Crit Care Med. 2020;202(10):1462-1464.
2. Maas MB, Kim M, Malkani RG, Abbott SM, Zee PC. Obstructive sleep apnea and risk of COVID-19 infection, hospitalization and respiratory failure. Sleep Breath. 2020.
3. Strausz S, Kiiskinen T, Broberg M, et al. Sleep apnoea is a risk factor for severe COVID-19 . BMJ Open Respiratory Research. 2021;8(1):e000845.
4. Memtsoudis SG, Ivascu NS, Pryor KO, Goldstein PA. Obesity as a risk factor for poor outcome in COVID-19-induced lung injury: the potential role of undiagnosed obstructive sleep apnoea. Br J Anaesth. 2020;125(2):e262-e263.
5. Mello MT, Silva A, Guerreiro RC, et al. Sleep and COVID-19: considerations about immunity, pathophysiology, and treatment. Sleep Sci. 2020;13(3):199-209.

Kara Dupuy-McCauley, MD

Dr. Dupuy-McCauley is a Senior Associate Consultant in Pulmonary and Sleep Medicine and Instructor of Medicine at Mayo Clinic in Rochester, MN

Lauren Tobias, MD

Dr. Tobias is the Medical Director of the Sleep Medicine Program at the Veterans Affairs Connecticut Healthcare System in West Haven, as well as an Assistant Professor of Medicine at Yale University School of Medicine in New Haven, CT