Gut microbiome associates with phenotypic manifestations of post-acute COVID-19 syndrome

Our current understanding of post-acute COVID-19 syndrome (PACS) is limited. In this study, we delineate the role of the gut microbiome in the heterogeneity of PACS and develop a multi-label model for predicting PACS symptoms using both clinical and metagenomic data from 1207 post-COVID-19 subjects. Our processed data covered 585 bacterial species and 500 microbial pathways, altogether explaining 12.7% of the inter-individual variation of PACS. Analysis showed that gut microbiome mediates the associations between host risk factors and PACS. Three gut microbiome-based enterotypes were identified in subjects with PACS and exhibited correlations with different phenotypic manifestations. Symptom-specific gut microbiome signatures were identified for individual symptoms of PACS at both composition and function levels. The trained model showed an accuracy of 0.89 in labelling individual symptoms of PACS in the test set and maintained a sensitivity of 86% and a specificity of 82% in predicting possible symptoms in an independent longitudinal cohort of subjects before they developed PACS. This study demonstrated that gut microbiome is associated with phenotypic manifestations of PACS, which has potential clinical utility for the prediction and diagnosis of PACS and warrants further exploration.