Longitudinal alterations of gut mycobiota during 2 years after COVID-19 and its correlation with pulmonary sequela

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 Candida, elevated during the acute phase, reverted to control levels after 6 months. At the 2-year follow-up, there was an increased presence of Hanseniaspora, Issatchenkia, and Saturnispora and a decreased presence of Aspergillus, Penicillium, and Rhodotorula. In addition, Pichia, Saccharomycopsis, and Cladosporium 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 Hanseniaspora and PEF, as well as negative correlations between Saturnispora 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.