Lung and gut microbiota are associated with long-term pulmonary function recovery after severe COVID-19: a 1-year follow-up study

<bold>Introduction:</bold> Severe SARS-CoV-2 infection induces disrupted airway and gut microbiota during acute disease which may persist and contribute to the development of post-acute pulmonary sequelae. This follow-up study investigated the oropharyngeal (OP) and gut microbiota and the association with lung function after severe COVID-19. <bold>Methods:</bold> We performed 16S rRNA-amplicon sequencing on OP and rectal swabs at 3-, 6- and 12-months post-hospitalisation from 83 subjects previously admitted to the ICU with severe COVID-19 (Swiss COVIDlung study, <ext-link>NCT04581135</ext-link>). Subjects underwent 1-3 follow-up visits during which lung function testing was performed to investigate correlations with the microbiota. <bold>Results:</bold> Up to 12 months after hospitalisation, patients who suffered from COVID-19-related ARDS had a distinct OP microbiota from those who did not develop ARDS, with a decreased alpha diversity (p<0.004). Relative to COVID-19 ARDS status, bacterial diversity in both the gut and the respiratory tract was significantly correlated with lung function improvement. Trajectory analysis revealed that patients with TLC, FVC or DLCO > LLN at all 3 visits had a distinct OP and gut microbiota composition compared to patients whose lung function never recovered, characterized by the presence of differentially abundant taxa. Also, the gut microbiota of patients recovering in TLC harboured an increased relative abundance of short-chain fatty acid-producing bacteria (p<0.02). Analyses of the gut-lung axis are ongoing. <bold>Conclusion:</bold> Our results support the contribution of the microbiota to lung function recovery after severe COVID-19, revealing its possible role as a prognostic biomarker.