Association of Obstructive Sleep Apnea with Post-Acute Sequelae of SARS-CoV-2 infection, 2024, Quan et al.

[nataliezzz]

Association of Obstructive Sleep Apnea with Post-Acute Sequelae of SARS-CoV-2 infection

Spoiler: Authors

Stuart F Quan, Matthew D Weaver, Mark É Czeisler, Laura K Barger, Lauren A Booker, Mark E Howard, Melinda L Jackson, Rashon I Lane, Christine F McDonald, Anna Ridger, Rebecca Robbins, Prerna Varma, Joshua F Wiley, Shantha MW Rajaratnam, Charles A Czeisler

https://pmc.ncbi.nlm.nih.gov/articles/PMC11144080/ (PDF available)

Background: Obstructive sleep apnea is associated with COVID-19 infection. Less clear is whether obstructive sleep apnea is a risk factor for the development of post-acute sequelae of SARS-CoV-2 infection (PASC).

Study design: Cross-sectional survey of a general population of 24,803 US adults to determine the association of obstructive sleep apnea with PASC.

Results: COVID-19 infection occurred in 10,324 (41.6%) participants. Prevalence of persistent (>3 months post infection) putative PASC-related physical and mental health symptoms ranged from 6.5% (peripheral edema) to 19.6% (nervous/anxious). In logistic regression models, obstructive sleep apnea was associated with all putative PASC-related symptoms with the highest adjusted odds ratios being fever (2.053) and nervous/anxious (1.939). In 4 logistic regression models of overall PASC derived from elastic net regression, obstructive sleep apnea was associated with PASC (range of adjusted odds ratios: 1.934-2.071); this association was mitigated in those with treated obstructive sleep apnea. In the best fitting overall model requiring ≥3 symptoms, PASC prevalence was 21.9%.

Conclusion: In a general population sample, obstructive sleep apnea is associated with the development of PASC-related symptoms and a global definition of PASC. Treated obstructive sleep apnea mitigates the latter risk. The presence of 3 or more PASC symptoms may be useful in identifying cases and for future research.

 

[Snow Leopard]

This just reflects a lack of specificity of symptom reporting as a binary (does symptom exist or not). Symptoms can have numerous causes. COVID may also exacerbate obstructive sleep apnea. I wonder if the results would be different for severe symptoms vs moderate or mild symptoms.

 

[nataliezzz]

This just reflects a lack of specificity of symptom reporting as a binary (does symptom exist or not). Symptoms can have numerous causes. COVID may also exacerbate obstructive sleep apnea. I wonder if the results would be different for severe symptoms vs moderate or mild symptoms.

Yeah, reading this paper...lots of weaknesses. This is how diagnosis of OSA was established:

Participants were considered to have obstructive sleep apnea if they endorsed currently having the condition, whether treated or not, or if they had 2 or more symptoms of obstructive sleep apnea.
1) snoring “Three or more times a week” and witnessed apnea or sleepiness “Once or twice a week”
2) witnessed apnea and sleepiness “Once or twice a week.

This is how PASC was determined (so it doesn't seem like there actually needed to be a temporal relationship with infection and onset of symptoms? But I'm not sure how to interpret "experienced the symptom more than 2 weeks after their COVID-19 infection..."):

Ascertainment of past COVID-19 infection was obtained using responses from the following questions related to COVID-19 testing or the presence of loss of taste or smell:
1. “Have you ever tested positive?”
2. “Despite never testing positive, are you confident that you have had COVID-19?”
3. “Despite never testing positive, have you received a clinical diagnosis of COVID-19?”
4. “Have you experienced a problem with decreased sense of smell or taste at any point since January 2020?”

Participants who endorsed any of items #1-4 were asked to provide the date of their positive test or onset of infection. Additionally, they were asked if they experienced any of the general health symptoms listed in Table 1 more than 2 weeks after their infection. For each symptom, participants who endorsed having experienced the symptom more than 2 weeks after their COVID-19 infection, or indicated that they were currently having the symptom, were asked how long their symptoms persisted after their infection.

Initially, using positive COVID-19 status as a binary outcome, we performed an elastic net regression using 10-fold cross-validation to select the most relevant symptoms that would contribute to an overall model of PASC. Next, a PASC score was calculated using a multiple linear regression using the symptom variables selected (n = 13) weighted by the elastic net coefficients. For 2 models, overall PASC (symptoms present >3 months) was defined as a score exceeding the 95th and 99th percentiles, respectively, of the calculated scores of participants who had no evidence for COVID-19 infection. For 2 additional models, the symptom variables were summed; overall PASC was defined as a score of ≥2 and ≥3, which represent the 97.5th and 99th percentiles, respectively, of scores of participants who had no evidence of COVID-19 infection.

The most notable finding is probably: "Current or past treatment of obstructive sleep apnea also showed a strong relationship with PASC. However, current treatment of obstructive sleep apnea alone was not associated with PASC in all 4 models." Multiple things could be contributing there, including, as they noted: "our previous observation that risk of COVID-19 infection was reduced in those with treated obstructive sleep apnea."

Re: whether COVID can exacerbate OSA (as in the obstructive sleep-disordered breathing itself, not symptoms), this is what I found:

Sleep Apnea Pathophysiology in Patients with a History of COVID-19 - PMC

Background: Emerging evidence suggests that COVID-19 may influence obstructive sleep apnea (OSA) pathophysiology by affecting upper airway collapsibility, ventilatory control, and arousal responses, raising the possibility of a bidirectional ...

pmc.ncbi.nlm.nih.gov

A case–control study: 60 participants with a history of COVID-19 and 60 controls matched for age/gender/BMI/OSA presence underwent overnight in-hospital polysomnography before the pandemic. Key pathophysiological traits (collapsibility, loop gain, arousal threshold, muscle compensation) estimated from polysomnographic signals were compared, with adjustment for age, sex, BMI, and apnea–hypopnea index. The participants exhibited no meaningful differences in their average levels of collapsibility, loop gain, or arousal threshold levels and showed similar levels of muscle compensation. However, a greater ventilatory response to arousal was associated with COVID-19 history.

There's also this preprint that I haven't really looked at, but they used a retrospective study design, so you can't know how many people without a pre-COVID OSA diagnosis actually had OSA given that many people with OSA are asymptomatic.

Risk of new-onset obstructive sleep apnea up to 4.5 years after COVID-19 in the urban population

Rationale Obstructive sleep apnea (OSA) is linked to cardiovascular, metabolic, and cognitive morbidity. Although COVID-19 has been associated with long-term respiratory and neurological sequelae, its role in precipitating new-onset OSA remains unclear. Objectives To evaluate whether SARS-CoV-2...

www.medrxiv.org