Adults who have obstructive sleep apnea have up to an 75% increased risk, on average, of developing long Covid after a SARS-CoV-2 infection compared with people without sleep apnea, a new study found.

Women with obstructive sleep apnea had up to an 89% increased risk, while men had a 59% higher risk, according to the analysis of electronic health data on nearly 1.8 million people.

Obstructive sleep apnea is a potentially dangerous disorder in which breathing stops for about 10 seconds multiple times during the night due to a blockage of the airways by heavy or relaxed soft tissues in the mouth and throat.

A second analysis of medical records of a smaller group of 330,000 adults found the risk to be only 12%, according to the study, which is part of RECOVER, or Researching Covid to Enhance Recovery. RECOVER is a National Institutes of Health initiative dedicated to understanding why some people develop long Covid and how best to detect, treat, and prevent the condition.

Why the huge difference in numbers? People in the larger study had additional health concerns, or comorbidities, such as obesity, diabetes, high blood pressure and heart disease, said senior study author Lorna Thorpe, co-lead of the RECOVER Clinical Science Core at NYU Langone Health.

"The range of 12% to 75% is likely due to a combination of different study populations and different levels of comorbidities, but also different definitions of long Covid," she said. "We didn't even have a working definition for long Covid until October 2021.

"I believe the risk is likely to be in the middle, but we will need additional studies to tease that out," added Thorpe, a professor and director of the division of epidemiology at NYU Grossman School of Medicine.

A third analysis of medical records of 102,000 children with sleep apnea found no correlation between sleep apnea and long Covid after the various confounding health conditions were factored out, "which, of course, is great news," Thorpe said.

"By using three very large networks of electronic health records, we were able to do this study three times, which is one of the strengths of the research," she added. "This study is the first collaboration of this focus and scale to find that adults with sleep apnea are at greater risk for long Covid."

This is an "important study" on long Covid, said Dr. Sairam Parthasarathy, a principal investigator of the University of Arizona Health Sciences RECOVER Adult Study and professor of medicine.

"Research needs to be done in a prospective study to verify this association, and if found to be true these findings have implications for treatment of long Covid," said Parthasarathy, who was not involved in the study.

"It is important to note that some of the symptoms of long Covid such as fatigue may be related to obstructive sleep apnea, and that the treatment of obstructive sleep apnea may improve such long Covid-related symptoms," he added.

Government-backed initiative

The study, published Thursday in the journal Sleep, is one of a several studies released since Congress allocated $1.15 billion to NIH in January 2021, to study the long-term effects of Covid over a four-year period. To date, the agency says it has used about $811 million to fund research.

Researchers wanted to investigate the role of sleep apnea in long Covid due to the well-known association between the condition and poorer outcomes after a Covid infection.

"People with sleep apnea are at higher risk for a more severe case of Covid-19, admission to intensive care at the hospital and for mortality," Thorpe said.

"Obstructive sleep apnea can result in increased inflammation, potentially disrupted sleep leading to an increased propensity to develop infections and reduced immunity," said Dr. Bhanu Prakash Kolla, a sleep medicine specialist in the Center for Sleep Medicine at the Mayo Clinic in Rochester, Minnesota.

"This could potentially explain the pathway by which obstructive sleep apnea leads to an increased risk of having Covid and also ... (long Covid)," said Kolla, who was not involved in the study.

Risk in women vs. men

Sleep apnea is an underdiagnosed condition regardless of gender, said the University of Arizona's Parthasarathy.

"It is conservatively estimated that 80% of patients with obstructive sleep apnea (OSA) are not diagnosed," he said. In addition, "an assumption with these analyses is that patients with OSA are likely to be treated. However, nearly half of them are not using the treatment."

Why would women have up to an 89% higher risk compared with 59% in men? The study did not address that issue.

However, "one can postulate this difference may be based on what we know about sex differences in sleep and immune responses," said Dr. Phyllis Zee, director of the Center for Circadian and Sleep Medicine at Northwestern University Feinberg School of Medicine in Chicago.

Zee, who was not involved with the new research, coauthored one of the first published studies on the link between sleep apnea and serious Covid infection.

"Women typically have stronger immune responses to viral infections, and thus also vulnerability for post-infection inflammation," Zee said. "Women in general have more insomnia and with long Covid tend to present with fatigue and insomnia symptoms, which are also common symptoms of long Covid."

Another reason could be that sleep apnea has historically been considered a male disease, Thorpe said, which could mean that by the time a woman is diagnosed her apnea is more advanced.

"It could be that the women who are documented in electronic health records have more severe sleep apnea because physicians more often look for sleep apnea among men," she said.

As scientists continue to learn more about long Covid, further information will become available, Thorpe said. In the meantime, people who have sleep apnea — or who snore, snort and stop breathing at night, which are all signs of the condition — should be exceedingly careful when they contact Covid.

"People with sleep apnea who get infected with Covid should seek early treatment and consider getting Paxlovid, the oral medication prescribed to reduce risk of severe outcomes," Thorpe said. "They should also keep up with their vaccinations to lower the risk of infection in the first place."