探討HIV病人合併感染新冠肺炎後之長期症狀:盛行率、嚴重度及相關因素

研究背景 2023年9月，台灣新冠肺炎染疫數累計超過一千萬人次，許多人進入復原期。然而，確診者的身心復原程度及速度難以預測，症狀可能持續超過數月且遍及全身，包含神經系統、心血管系統、呼吸道及腸胃道；根據國外研究顯示高達70%以上的生存者可能經歷至少大於一種的長期症狀。然而針對特殊疾病族群的長期症狀研究不論本土或國際均屬少見。舉例而言，感染人類免疫缺乏病毒(HIV)者，因生理上的免疫功能異常、多重慢病史、多重用藥史，加上長期以來社會的標籤化，使得HIV合併感染COVID-19者更顯脆弱與敏感；但對此族群之實證資料仍非常匱乏，其長期症狀嚴重度及相關風險因子有待釐清。研究目標本研究旨在調查HIV患者感染新冠肺炎6-8個月後，其長期新冠肺炎症狀(Post COVID-19 Syndrome, PCS)之盛行率、嚴重度及預測因子，並比較其與非HIV之新冠肺炎患者間的PCS差異。研究設計及方法本研究為回溯性世代研究(Retrospective cohort study)、為一大型調查研究之子計畫。母計畫(2021年11月至2022年8月)主要目的為追蹤確診後不同時間點之新冠肺炎長期症狀變化(臺大醫院倫委會編號:202106071RINB)。本研究於於2023年2月至5月間，首先招募HIV感染者且確診新冠肺炎已達6-8個月的20歲以上成年人。以問卷調查其感染新冠肺炎前後之整體症狀、功能及生活品質。接著再從母研究之群體中，按照本案研究參與條件，篩選出非HIV感染者且確診新冠肺炎已達6-8個月的對照組。統計方法使用成對樣本t檢定分析HIV組確診前後症狀嚴重度之變化；獨立樣本t檢定分析HIV組及對照組間症狀嚴重度差異；多元線性迴歸檢測PCS嚴重度之風險因子。研究結果本研究共分析130位個案，包含66位HIV組，及自母研究篩選出的64位對照組。篩選條件依據HIV人口學特性，設定為男性及20歲以上。HIV組平均年齡為38歲(SD=6.4)，對照組平均年齡則為51.1歲(SD=17.2)，兩組皆以有慢性病史者及無抽菸者占多數；確診新冠肺炎當時自覺症狀嚴重度部分，兩組皆為無症狀或輕症者為主。依據HIV族群PCS的盛行率，前五大依序為生活品質下降(54.5%)、睡眠障礙(47%)、情緒功能下降(40.9%)、腹瀉(39.4%)及疲憊(36.4%)。PCS嚴重度變化部分，比較HIV患者感染新冠肺炎前及6-8個月後，情緒功能(p=0.047)與生活品質(p=0.012)皆有顯著下降、CAT量表所涵蓋的呼吸道阻塞症狀則呈現顯著上升(p=0.008)，表示確診半年以上，部分症狀仍顯著較嚴重。比較HIV與對照組感染新冠肺炎6-8個月後，HIV組之情緒功能(p=0.02)與生活品質(p=0.014)顯著較對照組差。預測HIV患者PCS嚴重度之相關風險因子，四個模型均達統計顯著意義，其中有三個的總解釋變異量達中等效力，包括多重共病者(含梅毒、C型肝炎或癌症病史)，其睡眠品質與生活品質較差；BMI數值愈高且有多重共病者，其疲憊症狀愈嚴重；無抽菸習慣者，其情緒功能愈差。討論本研究為國內第一個調查HIV患者感染新冠肺炎前及6-8個月後，其長期症狀表現之盛行率、嚴重度變化與相關因子之研究；亦是國際間少見之比較HIV與非HIV感染者間PCS差異之研究。研究結果顯示，HIV族群在新冠肺炎後6-8個月仍存在多種、顯著且日漸嚴重之PCS，且其PCS側寫與非HIV族群不同，有些PCS相較非HIV之感染者更為嚴重。部分人口學資料及HIV疾病相關資料可預測特定PCS，但未發現HIV疾病抽血數據與PCS間的關係。結論與建議不論與確診新冠肺炎前，或是與非HIV感染新冠肺炎者相比，HIV族群在確診新冠肺炎後6-8個月，其情緒功能和生活品質均顯著下降，這兩個困擾亦是盛行率較高的PCS。身體質量指數(BMI)愈高、多重共病者以及無抽菸習慣者，可預測嚴重PCS之產生。建議未來建構更多大型研究，確認HIV族群PCS變化、探討嚴重PCS之預防、識別或管理。

關鍵字

COVID-19急性感染後徵候群；人類免疫缺陷病毒；回溯性世代研究；盛行率；預測因子

並列摘要

Background: In September 2023, the cumulative number of COVID-19 infections in Taiwan exceeded 10 million, with many individuals entering the recovery phase. However, physical and mental recovery among those infected are difficult to predict, as symptoms can persist for several months and affect multiple systems. According to studies, over 70% of survivors may experience at least one long-term symptom. Research on long-term symptoms in specific populations is rare. For instance, individuals infected with human immunodeficiency virus (HIV) are particularly vulnerable and sensitive due to physiological immune dysfunction, multiple chronic conditions, polypharmacy, and social stigmatization. Nevertheless, evidence-based data on this population is extremely scarce, and the severity and risk factors of long-term symptoms remain unclear. This study aims to investigate the prevalence, severity, and predictors of long-term COVID-19 symptoms (Post COVID-19 Syndrome, PCS) 6-8 months after infection among HIV patients, and to compare PCS differences between HIV and non-HIV COVID-19 patients. Methods: This study is a retrospective cohort study and a subproject of a larger study. The main project (November 2021 to August 2022) aimed to track changes in long-term COVID-19 symptoms at different time points post-diagnosis. From February to May 2023, we recruited HIV-infected individuals over 20 years old who had been diagnosed with COVID-19 for 6-8 months. A questionnaire was used to survey overall symptoms, function, and quality of life before and after COVID-19 infection. A comparison group of non-HIV-infected individuals was then selected from the main study cohort according to the inclusion criteria. Statistical methods included paired t-tests, independent t-tests, and multiple linear regression. Results: A total of 130 cases were analyzed, including 66 in the HIV group and 64 in the comparison group selected from the main study. Based on the demographic characteristics of the HIV population, inclusion criteria were set as males over 20 years old. The average age in the HIV group was 38 years old (SD=6.4), while the comparison group was 51.1 years old (SD=17.2). The five most prevalent PCS in the HIV group were decreased quality of life (54.5%), sleep disturbances (47%), reduced emotional function (40.9%), diarrhea (39.4%), and fatigue (36.4%). Changes in PCS severity showed significant declines in emotional function (p=0.047) and quality of life (p=0.012) in the HIV group compared to pre-COVID-19 infection, while the CAT scale significantly increased (p=0.008), indicating some symptoms remained significantly severe more than six months post-diagnosis. Comparisons between the HIV and non-HIV groups 6-8 months post-COVID-19 infection showed significantly worse emotional function (p=0.02) and quality of life (p=0.014) in the HIV group. Predictors of PCS severity in HIV patients revealed statistically significant models, with three showing moderate power of explained variation. Predictors included multiple comorbidities, higher BMI and non-smokers. Discussion: This study is the first in Taiwan to investigate the prevalence, severity changes, and related factors of long-term symptoms before and 6-8 months after COVID-19 infection among HIV patients. It is also among the few internationally to compare PCS differences between HIV and non-HIV infected individuals. The results indicate that the HIV population still experiences multiple, significant, and progressively severe PCS 6-8 months after COVID-19 infection, with different PCS profiles compared to non-HIV individuals, with some PCS being more severe. Certain demographic and HIV-related data can predict specific PCS, but no relationship between HIV-related blood test and PCS was found. Conclusion: Compared to both pre-COVID-19 infection and non-HIV COVID-19 patients, the HIV population shows significantly decreased emotional function and quality of life 6-8 months post-COVID-19 infection. Higher BMI, multiple comorbidities, and non-smoker are predictors of severe PCS. Future large-scale studies are recommended to confirm PCS changes in the HIV population, and to explore the prevention, identification, and management of severe PCS.