Xie Qianhan, Ni Jiali, Yu Ling, Guo Wanru, Ding Cheng, Wang Fengjiao, Wu Yechen, Xu Kaijin, Chen Yanfei
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Jinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong, China.
Microbiol Spectr. 2025 Jul;13(7):e0300724. doi: 10.1128/spectrum.03007-24. Epub 2025 May 23.
Pulmonary sequelae associated with COVID-19 are an increasing concern. Emerging evidence suggests that gut dysbiosis may contribute to post-acute COVID-19 syndromes; yet, the specific link between gut mycobiota and pulmonary sequelae remains unclear. We conducted a prospective study with 46 COVID-19 patients and 37 healthy controls. Longitudinal assessments of gut mycobiota were performed at admission, 6 months, 1 year, and 2 years post-discharge using internal transcribed spacer (ITS) 3-4 sequencing. At the 2-year follow-up, pulmonary function tests and chest computed tomography (CT) scans were also performed and correlated with gut mycobiota. While pulmonary function remained well-preserved, radiographic abnormalities persisted in a small subset of patients at 2 years. During the acute phase, fungal richness, as indicated by Chao1 and Shannon indices, was significantly lower than in controls, but gradually returned to normal levels after 6 months of recovery. Genus , elevated during the acute phase, reverted to control levels after 6 months. At the 2-year follow-up, there was an increased presence of , , and and a decreased presence of , , and . In addition, , , and were especially enriched in patients without residual CT abnormalities at 2 years. At 2 years post-discharge, significant correlations were observed between pulmonary function and gut mycobiota, including negative correlations between and PEF, as well as negative correlations between and DLCO. This study reveals the longitudinal shifts in gut mycobiota over 2 years post-discharge in COVID-19 patients. Significant correlations were observed between pulmonary function and the gut mycobiota, suggesting a potential detrimental effect on lung function, offering potential insights into the pathogenesis of post-acute COVID-19 syndromes.
This article elucidates the intricate process of gut mycobiota reconstitution within a 2-year timeframe following COVID-19 infection and establishes a significant link between the gut mycobiota and the recuperation of pulmonary function. Our research suggests that the gut mycobiota could be utilized as diagnostic indicators for post-acute COVID-19 syndromes and may offer avenues for developing therapeutic interventions.
与新型冠状病毒肺炎(COVID-19)相关的肺部后遗症日益受到关注。新出现的证据表明,肠道菌群失调可能导致COVID-19急性后综合征;然而,肠道真菌群与肺部后遗症之间的具体联系仍不清楚。我们对46例COVID-19患者和37名健康对照者进行了一项前瞻性研究。使用内转录间隔区(ITS)3-4测序在入院时、出院后6个月、1年和2年对肠道真菌群进行纵向评估。在2年随访时,还进行了肺功能测试和胸部计算机断层扫描(CT)扫描,并将其与肠道真菌群进行关联分析。虽然肺功能保持良好,但仍有一小部分患者在2年时存在影像学异常。在急性期,Chao1和香农指数所示的真菌丰富度显著低于对照组,但在恢复6个月后逐渐恢复到正常水平。属在急性期升高,6个月后恢复到对照水平。在2年随访时,、和的存在增加,而、和的存在减少。此外,、和在2年时无残留CT异常的患者中尤其富集。出院后2年,观察到肺功能与肠道真菌群之间存在显著相关性,包括与呼气峰值流速(PEF)之间的负相关性,以及与一氧化碳弥散量(DLCO)之间的负相关性。本研究揭示了COVID-19患者出院后2年内肠道真菌群的纵向变化。观察到肺功能与肠道真菌群之间存在显著相关性,提示其对肺功能可能有潜在有害影响,为COVID-19急性后综合征的发病机制提供了潜在见解。
本文阐明了COVID-19感染后2年内肠道真菌群重建的复杂过程,并建立了肠道真菌群与肺功能恢复之间的重要联系。我们的研究表明,肠道真菌群可作为COVID-19急性后综合征的诊断指标,并可能为开发治疗干预措施提供途径。