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Are People With Sleep-Disordered Breathing at Increased Risk for COVID-19?

  • Authors: News Author: Damian McNamara; CME Author: Charles P. Vega, MD
  • CME / ABIM MOC / CE Released: 12/30/2021
  • Valid for credit through: 12/30/2022
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  • Credits Available

    Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 0.25 ABIM MOC points

    Nurses - 0.25 ANCC Contact Hour(s) (0 contact hours are in the area of pharmacology)

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Target Audience and Goal Statement

This activity is intended for all primary care physicians, sleep medicine specialists, infectious disease specialists, nurses, pharmacists, and other members of the healthcare team who care for patients with sleep-disordered breathing (SDB).

The goal of this activity is to assess the effects of SDB on the incidence and severity of COVID-19.

Upon completion of this activity, participants will:

  • Distinguish chronic disease risk factors for severe COVID-19
  • Evaluate the effects of SDB on the incidence and severity of COVID-19
  • Outline implications for the healthcare team


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News Author

  • Damian McNamara

    Journalist, Medscape Medical News


    Disclosure: Damian McNamara has disclosed no relevant financial relationships.

CME Author

  • Charles P. Vega, MD

    Health Sciences Clinical Professor of Family Medicine
    University of California, Irvine School of Medicine


    Disclosure: Charles P. Vega, MD, has disclosed the following relevant financial relationships:
    Served as an advisor or consultant for: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Editor/CME Reviewer/Nurse Planner

  • Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP

    Associate Director, Accreditation and Compliance
    Medscape, LLC


    Disclosure: Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP, has disclosed no relevant financial relationships.

CE Reviewer

  • Esther Nyarko, PharmD

    Director, Accreditation and Compliance
    Medscape, LLC


    Disclosure: Esther Nyarko, PharmD, has disclosed no relevant financial relationships.

None of the nonfaculty planners for this educational activity have relevant financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

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Are People With Sleep-Disordered Breathing at Increased Risk for COVID-19?

Authors: News Author: Damian McNamara; CME Author: Charles P. Vega, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 12/30/2021

Valid for credit through: 12/30/2022


Note: The information on the coronavirus outbreak is continually evolving. The content within this activity serves as a historical reference to the information that was available at the time of this publication. We continue to add to the collection of activities on this subject as new information becomes available. It is the policy of Medscape Education to avoid the mention of brand names or specific manufacturers in accredited educational activities. However, manufacturer names related to COVID-19 vaccines may be provided in this activity to promote clarity. The use of manufacturer names should not be viewed as an endorsement by Medscape of any specific product or manufacturer.

Clinical Context

Multiple chronic health conditions have been found to increase the risk for severe COVID-19, and the list of these conditions has grown over time. The US Centers for Disease Control and Prevention lists cancer and chronic kidney disease, regardless of stage, as factors associated with a higher risk for severe COVID-19. Chronic liver disease, including nonalcoholic fatty liver disease, made the list as well. Multiple pulmonary conditions may raise the risk for severe COVID-19, including pulmonary hypertension and a history of pulmonary embolism.

Dementia is a risk factor for severe COVID-19, as are psychiatric disorders, such as depression and schizophrenia are as well. Finally, adults with a body mass index ≥ 25 kg/m2 are at higher risk for severe COVID-19.

Sleep apnea has not been thoroughly evaluated as a risk factor for incident COVID-19 or severe infection. The current study by Pena Orbea addresses those issues.

Study Synopsis and Perspective

People with sleep-disordered breathing (SDB) or sleep-related hypoxia -- low oxygen levels during sleeping -- are no more likely than other adults to get infected with SARS-CoV-2 and develop COVID-19; however, if infected, they are at a 31% higher risk of getting hospitalized or dying from the illness, new research reveals.

Investigators looked at more than 360,000 patients tested for COVID-19 at the Cleveland Clinic system. This group included about 5400 people who also completed a sleep study.

They also accounted for other factors that could alter COVID-19 risk, including obesity, heart and lung disease, cancer, and smoking.

"In those with COVID-19, baseline oxygen lowering during sleep was associated with increased association with hospitalization and mortality, even after consideration of factors which could confound this relationship," Cinthya Pena Orbea, MD, told Medscape Medical News.

The study was published November 1 in JAMA Network Open.[2]

When asked if she was surprised by the 31% increased risk, Pena Orbea said, "While this was consistent with our a priori hypotheses and we were careful to take in to account pulmonary disease and smoking history, we still identified a statistically significant association."

Pena Orbea is on staff at the Sleep Disorder Center and is assistant professor of medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in Cleveland, Ohio.

Identifying another group at potentially higher risk for adverse outcomes could help allocate COVID-19 resources earlier or more appropriately, senior study author Reena Mehra, MD, director of sleep disorder research at Cleveland Clinic, said in a news release.[3]

"As the COVID-19 pandemic continues and the disease remains highly variable from patient to patient, it is critical to improve our ability to predict who will have more severe illness," she said.

A clinical implication of the study "is that should a patient with sleep apnea develop COVID-19 infection, then perhaps they should be prioritized or triaged to receive anti-COVID therapies that have been in short supply at times," Indira Gurubhagavatula, MD, MPH, chair of the American Academy of Sleep Medicine's COVID-19 Task Force, told Medscape Medical News when asked to comment.

Exact Mechanism a Mystery

The reason SDB could 'prime' people for more severe COVID-19 outcomes remains unknown, but inflammation may play a role, Mehra noted.

Gurubhagavatula said that makes sense: "We know that people who develop severe COVID-19 infection seem to do so because of a 'cytokine storm,' which is an overwhelming inflammatory load that leads to injury to organs, including lung tissue.

"We also know that sleep apnea itself causes increased inflammation," added Gurubhagavatula, who is also associate professor of medicine at the Perelman School of Medicine in the division of sleep medicine at the University of Pennsylvania and on staff at the Crescenz VA Medical Center in Philadelphia, Pennsylvania.

Previous studies do, however, seem to agree that inflammation could be key. Other researchers, for example, have linked hypoxemia to signs of inflammation, including higher white blood cell counts, neutrophil counts, D-dimer levels, and C-reactive protein levels in people with COVID-19.

Hypoxia could also have direct effects on the lungs, including microinfarcts, pulmonary parenchymal inflammation, hypoxic pulmonary vasoconstriction, and lung injury.

"Therefore, it has been postulated that progressive hypoxia may act as an amplifier of COVID-19 disease," Pena Orbea and co-authors noted. 

Large, Retrospective Analysis

The investigators studied the records of 350,710 individuals tested for SARS-CoV-2 between March 8 and November 30, 2020. They focused on the 5402 who also had a sleep study result in the Cleveland Clinic Sleep Study Registry.

Within this group, about 36% tested positive, and among those persons who tested positive, approximately 53% also had SDB at baseline.

Specifically, they looked at the frequency of sleep apnea and hypopnea and occurrence of sleep-related hypoxemia, defined as total sleep time (TST) where oxygen saturation was < 90%.

Researchers compared each person who tested positive for SARS-CoV-2 with 3 other individuals with a negative result, matched for race, sex, ethnicity, testing interval, and age within 8 years.

Stratifying Risk

The 31% increased risk for hospitalization and death comes from people who spent more than 1.8% of their TST with oxygen saturation < 90% compared with others with ≤ 1.8% of their TST below this level (HR = 1.31 [95% CI: 1.08, 1.57]; P = .005).

Furthermore, compared with individuals who spent ≤ 0.1% of their TST with an oxygen saturation < 90%, persons who spent between 1.8% and 12.8% of their TST below this level had a 42% greater likelihood of hospitalization and death (HR = 1.42 [95% CI: 1.08, 1.87]; P  =  .013).

After excluding individuals receiving positive airway pressure (PAP) therapy, associations among sleep apnea measures, COVID-19 clinical outcomes, hospitalizations, and mortality remained consistent with the primary results.

The mean age among the 5402 participants was 57 ± 15 years, and 55% were women. A total of 31% of the study cohort were Black, 60% were White, and 8% identified as other race or ethnicity, with some overlap.

A "Highly Relevant" Study

"This is a well-done, comprehensive, and highly relevant study that contained many strengths, including its large size and scope," Gurubhagavatula said.

She applauded the authors for using a relevant, validated metric to measure the degree of hypoxia and for including a diverse patient population.

The retrospective, case-control study design could leave open the possibility of unmeasured factors explaining the outcome, Gurubhagavatula said; "however, the authors did attempt to control for many of those potential factors and found that the association between severe outcomes related to COVID-19 and low oxygen levels during the sleep study still persisted."

In fact, she said, the associations in the study might be more robust in reality because "some sleep labs were closed early on in the pandemic, and some patients were not able to get tested for COVID-19 due to lack of availability of testing."

Next Steps

The research also offers important clues as to how to move forward in managing the large population of patients who have sleep apnea and develop COVID-19, Gurubhagavatula said.

Unanswered questions, for example, include: Should we encourage patients who are on continuous positive airway pressure (CPAP) to use their machines fully to limit their risk of developing worse outcomes from COVID-19? Should we prioritize patients with obstructive sleep apnea who develop COVID-19 in receiving therapies against the infection? 

Pena Orbea and colleagues plan to continue this research. One question, for example, is whether treating hypoxia with supplemental oxygen or PAP could reduce the risk for COVID-19 severe outcomes. Another avenue of future work is to evaluate the potential role of hypoxia in sleep difficulties associated with long COVID.

Study Highlights

  • The study retrospectively assessed adults aged ≥ 18 years who were tested for SARS-CoV-2 infection in a large US health system between March and November 2020. All study participants had previously undergone a sleep study for SDB.
  • The main study variables were the presence of SDB, as determined by the Apnea-Hypopnea Index, and sleep-related hypoxemia, which was defined by the percentage of TST at an oxygen saturation < 90%.
  • The study outcomes included COVID-19 and severe COVID-19, which was defined by hospitalization, use of supplemental oxygen, ventilation support, or mortality.
  • Investigators adjusted the study analysis to account for demographic, disease, and health habit variables.
  • 350,710 adults were tested for SARS-CoV-2 during the study period: 5402 of these patients had a previous sleep study and were included in the study sample. The mean age of patients was 56.5 ± 14.9 years, and 55.6% were women. The study cohort was diverse in terms of race and ethnicity.
  • 35.8% of patients had a positive test for SARS-CoV-2. Men and White patients had higher rates of positive tests, as did persons with an elevated BMI.
  • There was no association between sleep apnea measures and the incidence of a positive SARS-CoV-2 test on fully adjusted analysis.
  • SDB alone was not associated with a higher risk for severe COVID-19.
  • Still, a median TST < 90% was associated with a nearly 40% increase in the risk for severe COVID-19. When the mean arterial oxygen saturation (SaO2) increased by 5%, the odds ratio for severe COVID-19 fell by 27%. The respective decreases in the rates of hospitalization and mortality, specifically, with each 5% increase in mean and nadir SaO2 were 19% and 6%.
  • The overall association between sleep-related hypoxemia and risk for COVID-19 was only significant for women, but analyses based on age and race failed to alter the significant result.
  • The study results were unchanged after exclusion of patients receiving PAP treatment.

Clinical Implications

  • Chronic illnesses associated with a higher risk for severe COVID-19 include chronic kidney disease, regardless of stage, and chronic liver disease, including nonalcoholic fatty liver disease. Multiple pulmonary conditions may raise the risk for severe COVID-19, including pulmonary hypertension and a history of pulmonary embolism. Dementia is a risk factor for severe COVID-19, as are psychiatric disorders, such as depression and schizophrenia. Finally, adults with a BMI ≥ 25 kg/m2 are at higher risk for severe COVID-19.
  • The current study by Pena Orbea finds that positive sleep apnea tests are not risk factors for COVID-19. Sleep-related hypoxemia, but not SDB, was associated with a higher risk for severe COVID-19.
  • Implications for the healthcare team: The healthcare team should promote the prevention of COVID-19 among adults with sleep-related hypoxemia.


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