Effect of High-Risk Obstructive Sleep Apnea on Clinical Outcomes in Adults with Coronavirus Disease 2019: A Multicenter, Prospective, Observational Clinical Trial

Yüksel Peker, Yeliz Celik, Semih Arbatli, Sacide Rana Isik, Baran Balcan, Ferhan Karataş, Fatma Işıl Uzel, Levent Tabak, Betül Çetin, Arzu Baygül, Ayşe Bilge Öztürk, Elif Altuğ, Sinem İliaz, Cetin Atasoy, Mahir Kapmaz, Duygu Yazici, Hasan Bayram, Birsen Durmaz Çetin, Benan Çağlayan, OSACOVID-19 Study Collaborators, Önder Ergönül, Şiran Keske, Suda Tekin, Pelin İrkören, Mehmet Karaca, Bilgin Sait, Nahit Çakar, Evren Şentürk, Gülay Kır, Semra Ugur, Ayla Esin, Fatma Yurdakul, Boğaç Özserezli, İpek Erus, Zeynep Atçeken, Saide Aytekin, Gökhan Erdoğan, Nur Konyalilar, Özgecan Kayalar, Yüksel Peker, Yeliz Celik, Semih Arbatli, Sacide Rana Isik, Baran Balcan, Ferhan Karataş, Fatma Işıl Uzel, Levent Tabak, Betül Çetin, Arzu Baygül, Ayşe Bilge Öztürk, Elif Altuğ, Sinem İliaz, Cetin Atasoy, Mahir Kapmaz, Duygu Yazici, Hasan Bayram, Birsen Durmaz Çetin, Benan Çağlayan, OSACOVID-19 Study Collaborators, Önder Ergönül, Şiran Keske, Suda Tekin, Pelin İrkören, Mehmet Karaca, Bilgin Sait, Nahit Çakar, Evren Şentürk, Gülay Kır, Semra Ugur, Ayla Esin, Fatma Yurdakul, Boğaç Özserezli, İpek Erus, Zeynep Atçeken, Saide Aytekin, Gökhan Erdoğan, Nur Konyalilar, Özgecan Kayalar

Abstract

Rationale: Coronavirus disease (COVID-19) is an ongoing pandemic, in which obesity, hypertension, and diabetes have been linked to poor outcomes. Obstructive sleep apnea (OSA) is associated with these conditions and may influence the prognosis of adults with COVID-19. Objectives: To determine the effect of OSA on clinical outcomes in patients with COVID-19. Methods: The current prospective observational study was conducted in three hospitals in Istanbul, Turkey from March 10 to June 22, 2020. The participants were categorized as high-risk or low-risk OSA according to the Berlin questionnaire that was administered in the out-patient clinic, in hospital, or shortly after discharge from hospital blinded to the clinical outcomes. A modified high-risk (mHR)-OSA score based on the snoring patterns (intensity and/or frequency), breathing pauses, and morning/daytime sleepiness, without taking obesity and hypertension into account, were used in the regression models. Results: The primary outcome was the clinical improvement defined as a decline of two categories from admission on a 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death) on Days 7, 14, 21, and 28, respectively. Secondary outcomes included clinical worsening (an increase of 1 category), need for hospitalization, supplemental oxygen, and intensive care. In total, 320 eligible patients (median [interquartile range] age, 53.2 [41.3-63.0] yr; 45.9% female) were enrolled. In all, 121 (37.8%) were categorized as known (n = 3) or high-risk OSA (n = 118). According to the modified scoring, 70 (21.9%) had mHR-OSA. Among 242 patients requiring hospitalization, clinical improvement within 2 weeks occurred in 75.4% of the mHR-OSA group compared with 88.4% of the modified low-risk-OSA group (P = 0.014). In multivariate regression analyses, mHR-OSA (adjusted odds ratio [OR], 0.42; 95% confidence interval [CI], 0.19-0.92) and male sex (OR, 0.39; 95% CI, 0.17-0.86) predicted the delayed clinical improvement. In the entire study population (n = 320), including the nonhospitalized patients, mHR-OSA was associated with clinical worsening (adjusted hazard ratio, 1.55; 95% CI, 1.00-2.39) and with the need for supplemental oxygen (OR, 1.95; 95% CI, 1.06-3.59). Snoring patterns, especially louder snoring, significantly predicted delayed clinical improvement, worsening, need for hospitalization, supplemental oxygen, and intensive care. Conclusions: Adults with mHR-OSA in our COVID-19 cohort had poorer clinical outcomes than those with modified low-risk OSA independent of age, sex, and comorbidities. Clinical trial registered with www.clinicaltrials.gov (NCT04363333).

Keywords: COVID-19; clinical outcomes; hospitalization; intensive care; obstructive sleep apnea.

Figures

Figure 1.
Figure 1.
Flow of patients through the study. COVID-19 = coronavirus disease; ICU = intensive care unit.
Figure 2.
Figure 2.
Distribution of proportion falling into each category of the 7-category scale from admission to Day 28 among 242 hospitalized patients with modified high-risk OSA and modified low-risk OSA. hosp. = hospitalization; ICU = intensive care unit; OSA = obstructive sleep apnea.
Figure 3.
Figure 3.
(A) Odds ratios with 95% CIs for the clinical improvement within 2 weeks for 242 hospitalized patients with coronavirus disease (COVID-19) in a multivariate logistic regression analysis (modified high-risk OSA adjusted for age, sex, BMI, and hypertension). (B) Odds ratios with 95% CIs for the clinical improvement within 2 weeks for 242 hospitalized patients with COVID-19 in a multivariate logistic regression analysis (louder snoring adjusted for age, sex, BMI, and hypertension). *Louder than talking/very loud (can be heard in adjacent rooms). BMI = body mass index; CI = confidence interval; OSA = obstructive sleep apnea.
Figure 4.
Figure 4.
Cumulative incidence of clinical worsening in the entire study population of 320 cases with coronavirus disease (COVID-19) in a Cox proportional hazard model, adjusted for covariates. CI = confidence interval; HR = hazard ratio; mHR = modified high-risk; mLR = modified low-risk; OSA = obstructive sleep apnea.

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