COVID-19: Could Obstructive Sleep Apnea Independently Raise Morbidity, Mortality Risk?

Data point to several potential mechanisms through which obstructive sleep apnea (OSA) could independently raise the risk of COVID-19-related morbidity and mortality, especially among those with common risk factors and comorbidities associated with OSA, according to a new systematic review published in Sleep Medicine Reviews.

“It is clear that the pandemic has had a major effect on the treatment, management, and diagnosis of OSA and moving forward it may be necessary to explore new diagnosis and treatment pathways for these individuals,” the authors of the study wrote.

Lead study author Michelle Miller, BSc, PhD, with the Warwick Medical School at the University of Warwick in Coventry, United Kingdom, answered our questions about these findings and what they could mean for clinical practice.

Neurology Learning Network: Could you discuss some of the potential mechanisms by which OSA may independently increase risk of morbidity and mortality associated with COVID-19?

Dr Miller: The findings from our study suggest that many of the risk factors and comorbidities associated with OSA—which include obesity, hypertension, and diabetes mellitus—are associated with poor COVID-19 outcomes. The Data from the Coronavirus SARS-CoV-2 and Diabetes Outcomes (CORONADO) study, which was conducted among individuals with diabetes who were admitted to intensive care, suggested that that those individuals who were also previously receiving treatment for OSA were at increased risk of death from COVID-19 compared with those who were not being treated for known OSA. It remains to be determined if this increased risk would be seen among individuals with OSA but without diabetes.

There are plausible mechanisms by which OSA may independently increase one's risk of morbidity and mortality associated with COVID-19:

  1. OSA causes interruptions in breathing which may lead to an increase in oxidative stress and inflammation. Increased levels of inflammatory markers and a ‘cytokine storm’ have been reported among patients with COVID-19 and pneumonia and among those with subsequent multi-organ failure. It has been suggested that the sleep hormone melatonin may be beneficial for the treatment of COVID-19. This may decrease oxidative stress and inflammatory response. It might also improve sleep quality, which might also be beneficial for better clinical outcomes for COVID-19 patients.
  2. Vitamin D enhances cellular immunity, in part by reducing the cytokine storm induced by the innate immune system. Low levels of vitamin D have been shown to be associated with OSA severity and it has been suggested that low levels of vitamin D may in part be associated with poor COVID-19 outcomes. However, this suggestion was not supported by data from the UK Biobank study following adjustment for potential confounding factors.
  3. The renin-angiotensin-aldosterone system (RAAS) is important for blood pressure regulation. Angiotensin-converting enzyme 2 has been identified as the entry receptor of SARS-CoV-2. Many individuals with OSA have resistant hypertension, and it remains to be determined whether individuals, in whom there is an increased stimulation of the RAAS from OSA, are at increased risk of the cardiovascular complications and comorbidities seen among patients with COVID-19.

NLN: You and your colleagues concluded that, due to the ongoing pandemic, it may be necessary to explore new treatment pathways for OSA. Could you elaborate on this?

Dr Miller: Many sleep clinics are managed by respiratory consultants who have been seconded to COVID-19-related duties, resulting in major effects on the diagnosis, treatment, and management of sleep disorders. It may be necessary to explore new diagnosis and treatment pathways for these individuals. This may include the increased use of telemedicine, drive-through pick up of home testing kits, and the use of disposable diagnostic tools and noncontact sleep surveillance for OSA diagnosis.

NLN: What areas of future research are still needed in this area?

Dr Miller: First, we need to corroborate the data that individuals with diabetes who are also being treated for OSA have an increased risk of poor COVID-19 outcomes. Second, it will be necessary to determine whether individuals with OSA, but without diabetes, are at increased risk of poor COVID-19 outcomes.

Third, it will be key to understand what effect treatment compliance for OSA has on COVID-19 outcomes. And finally, because OSA remains a very underdiagnosed condition, it is not known whether the presence of undiagnosed OSA confers increased risk of poor COVID-19 outcomes.

NLN: What key takeaways about this topic do you hope to leave with neurologists and neurology providers?

Dr Miller: Untreated OSA is associated with many poor health outcomes and risk of harm to the individual and others if accompanied with daytime sleepiness, leading to poor performance, drowsy driving, and increased risk of accidents. Its diagnosis, treatment, and effective management needs to be maintained during the pandemic even if face-to face appointments are not possible. It is not known if the presence of undiagnosed OSA confers increased risk of poor COVID-19 outcomes.

Many COVID-19 patients have pulmonary fibrosis, which itself is a risk factor for future development of OSA. Discharged patients who had COVID-19 need to be monitored for thrombotic and fibrotic effects and subsequent potential development of OSA.

—Christina Vogt

Miller MA, Cappuccio FP. A systematic review of COVID-19 and obstructive sleep apnoea. Sleep Med Rev. 2021;55:101382. doi:10.1016/j.smrv.2020.101382