Article coming soon
Sleep-related hypoxia did not affect the risk of contracting COVID-19, but those with sleep-disordered breathing who contracted the virus had a higher risk of being hospitalized or dying.
Sleep apnea and sleep-related hypoxia — treated or untreated — did not affect the likelihood of contracting COVID-19, according to a study published Nov. 10 in JAMA Network Open. But when the results of those who had COVID-19 were adjusted for body mass index (BMI) and other comorbidities, those with sleep hypoxia were more likely to be hospitalized and die.
Cinthya Pena Orbea, MD, the study’s first author and a sleep specialist at the Cleveland Clinic in Ohio, pointed out that previous studies had shown that patients with untreated sleep disorders were generally more likely to suffer from cardiovascular disease and higher mortality rates. She said his study highlighted the need to better understand how the biological pathways of sleep-disordered breathing can affect outcomes after contracting the virus.
“We know that sleep disorders are associated with susceptibility to COVID infection, but we have not found that sleep apnea, as defined by the Apnea Hypoxemia Index and sleep-related hypoxia, increases the risk of COVID-19 infection, and we were surprised when we saw these results,” said Dr. Pena Orbea, who is also an assistant professor of medicine. “However, our study suggests that in patients with COVID-19, those in whom oxygen levels initially fall during sleep (sleep-related hypoxemia) are at increased risk of worsening health-related outcomes from COVID-19.”
“The one factor that remained worrisome and consistent no matter what analysis they threw at it was hypoxia — which they defined as the total time during sleep that oxygen saturation was less than 90 percent. They found that even if only 1.8 percent of your sleep was less than 90 percent, there was an increased risk.” – DR. MICHAEL S. JAFFE
The study included 350,710 people who were tested for SARS-CoV-2 between March 8, 2020 and November 30, 2020 at the Cleveland Clinic Health System in Ohio and Florida. Researchers focused on 5,402 people who took part in a previous sleep study — 35.8 percent of whom subsequently tested positive for COVID-19. The median age was 56.4 years, 60.3 percent were white, 31.4 percent were black, and 55.6 percent were women.
Patients who were positive for SARS-CoV-2 had a higher apnea-hypopnea index [AHI]) score (p<0.001) and prolonged time with oxygen saturation <90 (p=0.02). The researchers defined sleep-related hypoxemia as the percentage of total sleep time with less than 90 percent oxygen saturation.
Investigators developed a propensity score for SARS-CoV-2 positivity derived from a regression model that included age, gender, race, BMI, diabetes, heart failure and other comorbidities. They developed a time-to-event analysis using symptom onset date as the start date to investigate the association between SDB and sleep-related hypoxic chronic exposures and worsening clinical outcomes, including hospitalization and death.
No sleep-related breathing disorders were associated with SARS-CoV-2 positivity, but sleep-related hypoxia was associated with a 31 percent higher hospital admission and mortality rate (p=0.005).
dr Pena Orbea said further research could include examining whether a treatment like CPAP changes COVID outcomes. The publication also questioned whether hypoxia might play a role in the vaccine’s effectiveness.
“The next step of this study would be to try to understand the mechanistic pathways in which hypoxemia produces this deterioration in outcomes,” said Dr. Pena Orbea. “That would be a starting point for developing risk stratification strategies in patients with sleep-disordered breathing.”
Neurologists who spoke to Neurology Today said the study was particularly powerful because the authors excluded comorbidities, but they weren’t surprised by the results and would like to see more studies, particularly regarding the use of CPAP treatment for prevention or combating SARS-CoV -2 infections and outcomes.
Liza Ashbrook, MD, an assistant professor of neurology at the University of California, San Francisco, said it makes sense to think of hypoxemia as a “booster.”
“I have a very strong belief that if someone sits in oxygen saturations overnight in their 80s, it will exacerbate the damage caused by COVID,” said Dr. Ashbrook. “If you have two situations (hypoxemia and COVID-19) with similar outcomes, it will only increase the risk of adverse events.”
Michael S. Jaffee, MD, FAAN, FANA, the vice chair and associate professor of neurology at the University of Florida, said it makes sense to look at sleep breathing disorders and COVID-19 infections because obstructive sleep apnea is often associated with it Linked to this are other chronic diseases that affect the immune system, such as high blood pressure, diabetes and obesity, which could put patients at increased risk for developing COVID-19.
“The only factor that remained worrisome and consistent no matter what analysis they threw at it was hypoxia — what they defined as the total time during sleep that oxygen saturation was less than 90 percent,” said Dr. jaffee “They found that there was an increased risk even if just 1.8 percent of your sleep accounted for less than 90 percent.”
“And you can imagine that if you have an infection that affects your lungs, it’s going to affect your oxygen saturation, just by the infection itself,” he continued. “So if you’re already starting past eight, with an underlying condition like obstructive sleep apnea that might already be causing low oxygen saturation, that’s really going to exacerbate or amplify the side effects that you might be experiencing with that infection.”
In the study, 16.8 percent of those who were treated with a CPAP machine and had participated in a previous sleep study tested positive for COVID. However, the study did not determine whether treatment, either CPAP or supplemental oxygen, affected outcome.
Respondents said it was not immediately clear how or if the study would impact the treatment of patients with sleep-disordered hypoxemia, but emphasized the need to both identify and treat patients with the condition.
Sigrid C. Veasey, MD, DABSM, pulmonologist and sleep specialist, professor of medicine at the University of Pennsylvania Medical School, said about 40 percent of patients in hospitals have obstructive sleep apnea “on any given day.”
She said one of the next steps would be to figure out the mechanisms how sleep-related hypoxemia might contribute to a poor response to COVID, to better target patients who may be more at risk.
“It may not be every single patient with obstructive sleep apnea who is at risk, but it may be a particular factor that oxygen levels often drop below 60. For example, patients with an underlying lung disease, smokers and others with low oxygen levels,” said Dr. Veasey.
“…our study suggests that in patients with COVID-19, those who initially have decreased oxygen levels during sleep (sleep-related hypoxemia) are at increased risk for worsening health-related outcomes from COVID-19.” DR. CINTHYA PENA ORBEA
“So how do we really find the patients with the greatest risk from the group of sleep-related hypoxia patients? And how do we find the mechanisms for this? Veasey. Since all of these patients were in hospitals, she said, and they were drawing blood from the patients, it would be nice to follow up to see if biomarkers exist for these patients.
dr Veasey said it would also be important to see if there are some synergies between the disorders. For example, to see if there was an increased risk for smokers who also had low oxygen levels, or for those with poorly managed type 2 diabetes. This would be another way to target patients who may be at greater risk of higher mortality from COVID-19.
It’s unclear whether new patients with sleep disorders would have these problems triggered by a COVID diagnosis, several neurologists told Neurology Today.
But dr Jaffee said the study could be a red flag for sleep specialists when it comes to treating patients they know with sleep-related hypoxia and making sure they are following their treatment plans, knowing they are at increased risk of worsening COVID outcomes are.
“Particularly if patients have severe obstructive sleep apnea and we know they have hypoxemia or low hypoxia, I would advise that if they develop symptomatic COVID, they are at risk of worse outcomes,” said Dr. Jaffe, adding that if this were the case there would be a greater argument in favor of vaccination to minimize the severity of symptoms in the event of infection.
“This article has shown us that the most important aspect for these patients when thinking about COVID risk is hypoxia,” continued Dr. Jaffee gone. “So, as part of the follow-up, we want to get some form of oximetry overnight to make sure that even after a while on the CPAP, the oxygen stays in the normal range and that mild hypoxemia isn’t occurring because of the amount of hypoxia that’s considered compromised in this article.” was actually less than 90 percent.”
dr Pena Orbea reported receiving grants from the American Academy of Sleep Medicine outside of the submitted work.