Coronavirus disease 2019 (COVID-19) has severely affected healthcare systems worldwide. Although age, hypertension, cardiovascular disease, lung disease, and diabetes mellitus are apparently the main risk factors for poorer outcomes in COVID-19 [1], a possible role has also been ascribed to sleep-disordered breathing (SDB) [2-4]. A recent preliminary study that collected questionnaire data in a case series of COVID-19 pneumonia showed that 25% of patients presented a history of SDB [5]. In recent months, a number of studies have suggested that the presence of obstructive sleep apnea (OSA) as a comorbidity in patients with COVID-19 increases the risk of hospitalization and mortality [6,7].

A study reported that OSA is a risk factor of COVID-19 in South Korea [8]. In an analysis of the National Health Insurance Service (NHIS)-COVID-19 cohort, OSA was associated with a 1.65-fold higher incidence of COVID-19 than in the control group. However, this was the only study in South Korea to mention the association between COVID-19 and SDB, and there have been no studies on the clinical characteristics and prognosis of patients with sleep apnea and COVID-19 in South Korea. Due to the limitations of the NHIS data, there have been few reports describing patients admitted to the hospital with COVID-19 in South Korea. A better characterization of COVID-19 infection in patients with SDB is important for understanding the clinical course and outcomes of COVID-19 and determining the critical care capacity and decision-making process for therapeutic interventions. The aim of our report is to describe the demographic characteristics, coexisting conditions, imaging findings, and outcomes of patients with SDB and COVID-19 in South Korea.

We identified 7 patients (4 men, 3 women) with nighttime hypoxemia during hospitalization, and all patients had confirmed OSA after COVID-19 treatment. The baseline characteristics of all participants are shown in Table 1. The participants’ mean age was 45.4±16.3 years, their mean body mass index was 33.4±6.0 kg/m², and the prevalence of smoking was 28.6%. The common comorbidities were hypertension and hyperlipidemia. None of the patients had diagnosed coronary heart disease or stroke. Six patients presented COVID-19-related pneumonia in the chest X-rays and underwent oxygen therapy in the medical ward or intensive care unit (ICU). Three patients were hospitalized in the ICU during the acute phase, with a mean ICU stay of 11 days. In the ICU, all patients received oxygen by high-flow nasal cannula; however, we did not administer continuous positive airway pressure (CPAP) or bilevel positive airway pressure therapy. All patients were discharged without supplementary oxygen.

We documented a mean follow-up time of 7.7 weeks (range 5–9 weeks) after COVID-19 infection. The laboratory polysomnography showed a mean AHI of 59.0±38.5/h and an oxygen desaturation index of 57.6±39.7/h. The mean lowest oxygen saturation was 77.9%±9.8%. Regarding the sleep questionnaires, we found no significant subjective sleepiness according to the Epworth sleepiness scale questionnaire. Four of the patients (57.1%) showed a high-risk of OSA according to the Berlin questionnaire. Of the 7 patients, 6 underwent CPAP titration. The mean positive airway pressure was 9.3 cm H₂O.

This case series describes 7 patients diagnosed with SDB with nocturnal hypoxemia and laboratory-confirmed COVID-19 infection. According to the current literature, this is the first description aimed at evaluating the association between undiagnosed SDB and COVID-19 outcomes in South Korea. Our findings support the association between SDB and poorer COVID-19 outcomes.

The patients in our series presented with moderate to severe COVID-19 infection. COVID-19 severity was defined based on the World Health Organization’s Clinical Progression Scale: 1) mild disease—outpatient care; 2) moderate disease—hospitalization; and 3) severe disease—intensive care or death [11]. All patients were admitted to our hospital, and 6 patients presented with COVID-19-related hypoxemia and pneumonia. Among those who required oxygen therapy, 3 underwent high-flow oxygen therapy up to a fraction of inspired oxygen of 70%.

Although our study is a retrospective analysis, it can be of clinical significance in suggesting that patients with severe COVID-19 who do not have significant subjective sleepiness or those who have not been assigned to a high-risk group in the Berlin questionnaire are likely to have undiagnosed sleep apnea. Previous studies evaluating the association between SDB and COVID-19 have suggested this association. In the CORONADO observational study, treated SDB was reported to be an independent risk of mortality after 7 days, with an odds ratio (OR) of 2.8 (confidence interval [CI], 1.46–5.38) [12]. In another study that included 46 patients hospitalized due to COVID-19, sleep apnea was diagnosed in 75% of the sample [13]. In an observational study in the United States, patients with SDB had an OR of 1.53 (CI, 1.09–2.15) for mortality and an OR of 1.29 (CI, 1.03–1.62) for ICU admission [6]. The plausible mechanisms for these associations include systemic and chronic inflammation, which are commonly observed in patients with untreated SDB. Published studies have suggested that when controlling for obesity, the presence of OSA is associated with decreased pulmonary function, decreased lungtransfer factor for carbon monoxide, and increased lung inflammation [14]. These conditions might therefore explain, at least in part, why patients with OSA are generally at increased risk for pneumonia [15]. These observations might therefore provide for the possibility of increased disease severity in the COVID-19 setting. In this context, the pathophysiology associated with untreated OSA might not only present a predisposing factor for developing severe or critical illness in COVID-19 but also, once infection has occurred, repeated airway obstruction with the generation of negative intrathoracic pressure and associated shear forces that can lead to worsening lung injury [16].

In this study, we found that 7 patients with undiagnosed sleep apnea presented with very high body mass and oxygen desaturation indices compared with the patients with sleep apnea generally treated at sleep clinics in South Korea. Although it is difficult to generalize due to the small number of samples, this finding suggests that patients with obesity and hypoxemia during sleep, even after recovery from moderate to severe COVID-19, are more likely to have undiagnosed sleep apnea.

The management of patients with OSA in sleep centers includes diagnostic procedures such as polysomnography and treatment with positive air pressure. Given the risk of spreading the virus in both of these procedures, many sleep centers in Western countries have suspended routine procedures, limiting activity to urgent cases. In the early days of the pandemic, numerous national sleep medicine societies provided guidelines for implementing these infection control strategies in sleep centers. An early mitigation strategy document from the authoritative American Academy of Sleep Medicine strongly recommended postponing non-urgent procedures [17], recommendations that were confirmed worldwide [18-21]. For many months, patients with suspected OSA, who usually have waited a varying amount of time from the first triage visit to treatment, therefore had to endure a further delay in getting treated.

The situation for sleep medicine in South Korea is not much different, with delays in the diagnosis and treatment of patients with sleep apnea given the rise in the number of centers postponing polysomnography in the early stages of the pandemic or conducting polysomnography only if the COVID-19 test were negative. Given that the first recommendations from the sleep societies were from last year, updated protocols are needed. In this context, we provide an example for the clinical suspicion and diagnosis of sleep apnea.

A potential contributor to the high morbidity among COVID-19 patients with obesity might be the high prevalence of undiagnosed OSA. Although it is difficult to actively diagnose sleep apnea in the current pandemic situation, attention needs to be paid as to whether a COVID-19 patient with moderate or higher severity has been underdiagnosed for this disease.

The study’s main limitations are related to the small sample size; however, this study provides evidence regarding the association between undiagnosed OSA and acute COVID-19 in a South Korean population. This study also has an inclusion bias as a methodological limitation, and the conclusions are restricted to the data obtained from the included patients. While taking all these issues into account, we believe that the results of this study can provide an insight into the association between OSA and COVID-19 in South Korea. Although COVID-19 severity can vary among individuals, the disease can have poor outcomes, and as the pandemic progresses, medical resources are being depleted. It is therefore important to identify the risk factors, as this can be beneficial for high-risk patients. Further studies are needed with larger study populations pertaining specifically to OSA and COVID-19 patients.