COVID-19 對黴漿菌肺炎疫情影響之評估：使用 TriNetX 資料庫的多中心回溯性世代研究

背景COVID-19 大流行已顯著重塑呼吸道傳染病的流行病學。儘管病毒併發症已被廣泛研究，SARS-CoV-2 與次發性細菌感染，如肺炎黴漿菌（Mycoplasma pneumoniae）之間的關聯仍缺乏深入探討。鑑於該病毒具有免疫調節效應，例如淋巴球減少、細胞激素失衡及微生物群落失調，越來越多人擔憂，先前感染 SARS-CoV-2 可能會提高對細菌共同感染的易感性。目的本研究利用 TriNetX 研究網絡——一個全球聯合健康數據庫，探討先前 COVID-19 感染與後續肺炎黴漿菌感染之間的關聯性。方法本研究採用多中心回溯性世代研究設計，分析 2020 至 2024 年的電子健康紀錄。COVID-19 陽性與陰性族群進行 1:1 傾向分數配對（每組 n = 12,817）。肺炎黴漿菌感染的發生率透過風險比（HR）、Kaplan-Meier 存活曲線，以及在不同人口與臨床變項中的子群分析進行評估。結果曾感染 COVID-19 的患者罹患肺炎黴漿菌的風險顯著上升（風險比 HR = 1.226；95% 信賴區間：1.157–1.300；p < 0.001），此風險在不同性別（男性：1.273；女性：1.212）、年齡 ≥60 歲（1.208）以及疫苗接種狀態（未接種：1.227；已接種：1.179）間皆一致。Kaplan-Meier 曲線顯示在 12 個月內感染率持續分歧，顯示長期易感性。此關聯在不同 COVID-19 病程嚴重度及診斷年份中均維持穩定。結論先前感染 COVID-19 與較高的肺炎黴漿菌感染風險相關，且其影響在各亞族群中持續存在。研究結果支持加強 COVID-19 康復後的監測，尤其針對年長者及未接種疫苗者。未來仍需進一步研究以釐清免疫機制並制定預防策略。

BackgroundThe COVID-19 pandemic has significantly reshaped the epidemiology of respiratory infectious diseases. Although viral complications have been extensively studied, the link between SARS-CoV-2 and secondary bacterial infections, such as Mycoplasma pneumoniae, remains underexplored. Given the virus’s immunomodulatory effects, such as lymphopenia, cytokine imbalance, and microbiota disruption, there is growing concern that prior SARS-CoV-2 infection may increase vulnerability to bacterial co-infections.Objectives:This study investigates the association between prior COVID-19 infection and subsequent Mycoplasma pneumoniae infection using real-world data from the TriNetX Research Network, a global federated health database.Methods:A multicenter, retrospective cohort design was employed, analyzing electronic health records from 2020 to 2024. COVID-19-positive and -negative cohorts were propensity score matched 1:1 (n = 12,817 per group). Incidence of Mycoplasma pneumoniae was assessed using hazard ratios (HRs), Kaplan-Meier survival curves, and subgroup analysis across demographic and clinical variables.Results:Post-COVID-19 patients had a higher risk of Mycoplasma pneumoniae infection (HR = 1.226; 95% CI: 1.157–1.300; p < 0.001), consistent across sex (male: 1.273; female: 1.212), age ≥60 (1.208), and vaccination status (unvaccinated: 1.227; vaccinated: 1.179). Kaplan-Meier curves showed sustained divergence over 12 months, indicating prolonged susceptibility. The association held regardless of COVID-19 severity or diagnosis year.Conclusion:Prior COVID-19 infection is linked to a higher risk of Mycoplasma pneumoniae, with lasting effects across subgroups. Findings support stronger post-COVID monitoring, particularly for older and unvaccinated individuals. Further studies are needed to clarify immune mechanisms and guide prevention.