以TriNetX大數據臨床病歷資料庫探討感染新冠肺炎後與阻塞性睡眠呼吸中止症之關聯性研究

研究目的在之前的文獻已指出，阻塞性睡眠呼吸中止症是導致嚴重性COVID-19感染的危險因子之一。然而，對COVID-19感染者，之後罹患阻塞性睡眠呼吸中止症的發生率的研究相對較少。本研究的目的是探討COVID-19感染後發生阻塞性睡眠呼吸中止症的風險是否會較高。研究方法及資料本研究為使用TriNetX U.S. collaborative network大數據資料庫的回顧性研究，納入2020年1月1日至2022年6月30日，所有接受SARS-CoV-2核酸檢測的參與者。根據核酸檢測（PCR）陽性與否，將研究族群分為兩?。追蹤時間從PCR檢測日開始，持續至12個月。使用Cox proportional hazards model計算感染COVID-19後的病人與完全沒有感染過COVID-19的人相比，新診斷阻塞性睡眠呼吸中止症的風險比（HRs）和95%的信賴區間（CIs）。再對性?、年齡、種族和BMI進行分層分析及敏感性測試。研究結果COVID-19?與阻塞性睡眠呼吸中止症的風險增加有關，追蹤3個月（HR: 1.51, 95% CI: 1.48-1.54），追蹤1年（HR: 1.57, 95% CI: 1.55-1.60）。阻塞性睡眠呼吸中止症風險的Kaplan-Meier曲線顯示，在感染COVID-19後的3個月和1年之後，兩組之間有顯著差異（Log-Rank test，P < 0.001）。在COVID-19患者中，年齡小於65歲?（HR: 1.50, 95％CI: 1.47-1.52）和年齡大於或等於65歲?（HR: 1.69, 95％CI: 1.64-1.73）的阻塞性睡眠呼吸中止症風險都顯著，以年齡大於65歲者略高。此外，阻塞性睡眠呼吸中止症的風險在男性和女性COVID-19?都顯著。與對照組相比，COVID-19感染者的阻塞性睡眠呼吸中止症的風險不論在白人（HR:1.62, 95% CI: 1.59-1.64）、黑人/非裔美國人（HR:1.50, 95% CI: 1.45-1.55）、亞裔（HR: 1.46, 95% CI: 1.32-1.62）和美洲印第安人/阿拉斯加原住民（HR: 1.36, 95% CI: 1.07-1.74）各組中都增加。再以EMEA（Europe, Middle East, and Africa）collaborative network分析及罹患COVID-19合併服用抗病毒藥物及住院的病患和未得過COVID-19的病患比較，作敏感性分析也獲得類似的結果。結論與建議COVID-19 感染後的病患罹患睡眠呼吸中止症的機率相對高於未感染過COVID-19的病患。醫生應評估 COVID-19 感染後的患者是否有罹患阻塞性睡眠呼吸中止症，以幫助預防未來長期不良影響，包括心血管和神經血管疾病。

Objective：Obstructive sleep apnea is a well?known risk factor regarding the severity of COVID?19 infection. However, to date, relatively little research performed on the incidence of obstructive sleep apnea in COVID?19 survivors. The purpose of this study was to investigate the risk of obstructive sleep apnea after COVID?19 infection. Methods and Materials：This study was based on data collected from the US Collaborative Network in TriNetX. From January 1, 2020 to June 30, 2022, participants who underwent the SARS?CoV?2 test were included in the study. Based on their positive or negative results of the COVID?19 test results (the polymerase chain reaction [PCR] test), we divided the study population into two groups. The duration of follow-up began when the PCR test was administered and continued for 12 months. Hazard ratios (HRs) and 95% confidence intervals (CIs) for newly diagnosed COVID?19positive subjects for obstructive sleep apnea were calculated using the Cox proportional hazards model and compared to those without COVID?19 infection. Subgroup analyses were performed for the age, sex, and race, groups.Results：The COVID?19 group was associated with an increased risk of obstructive sleep apnea, at both 3 months of follow?up (HR: 1.51, 95% CI: 1.48-1.54), and 1 year of follow-up (HR: 1.57, 95% CI: 1.55-1.60). Kaplan-Meier curves regarding the risk of obstructive sleep apnea revealed a significant difference of probability between the two cohorts in the follow?up periods of 3 months and 1 year (Log?Rank test, p < 0.001). The risks of obstructive sleep apnea among COVID?19 patients were significant in the less than 65 year of age group (HR: 1.50, 95% CI: 1.47-1.52), as well as in the group older than or equal to 65 years (HR:1.69, 95% CI: 1.64-1.73). Furthermore, the risks of obstructive sleep apnea were evident in both the male and female COVID?19 groups. Compared to the control group, the risks of obstructive sleep apnea in the COVID?19 participants increased in the subgroups of White (HR: 1.62, 95% CI: 1.59-1.64), Blacks/African Americans (HR: 1.50, 95% CI: 1.45-1.55), Asian (HR: 1.46, 95% CI: 1.32-1.62) and American Indian/Alaska Native (HR: 1.36, 95% CI: 1.07-1.74).Conclusion and Suggestion：In conclusion, the incidence of newly diagnosis obstructive sleep apnea could be substantially higher after COVID?19 infection than non?COVID?19 comparison group. Physicians should evaluate obstructive sleep apnea in patients after COVID?19 infection to help prevent future long?term adverse effects from occurring in the future, including cardiovascular and neurovascular disease.