Respiratory and Gut Microbiota Correlate with Lung Function Recovery after Severe COVID-19

RationaleSevere SARS-CoV-2 infection induces disrupted oropharyngeal and gut microbiota during acute disease which may persist and contribute to the development of post-acute pulmonary sequelae. To date, it is unclear whether dysbiosis following severe disease is linked to long-term pulmonary function impairment. ObjectivesTo determine associations between oropharyngeal and gut microbiota composition with lung function after severe COVID-19. Methods16S and internal transcribed spacer (ITS) rRNA amplicon sequencing were performed on oropharyngeal (16S and ITS) and rectal (16S) swabs at 3-, 6- and 12-months post-hospitalisation from 83 subjects previously admitted to the ICU with severe COVID-19 (Swiss COVIDlung study, NCT04581135). Subjects underwent 1-3 follow-up visits during which lung function testing was performed to investigate associations with microbiota composition. Measurements and Main ResultsThe oropharyngeal microbiota of subjects having suffered from COVID-19-related-severe acute non-cardiogenic hypoxemic respiratory failure with bilateral lung infiltrates (AHRF-BLI) was characterized by decreased -diversity and the presence of differentially abundant taxa. Subjects who recovered in lung function (TLC, FVC, FEV1 and DLCO >Lower Limit of Normal) had a distinct oropharyngeal and gut microbiota composition compared to those whose lung function never recovered. Fungal analysis of oropharyngeal samples revealed the presence of three distinct clusters which were characterized by distinct lung-function associated bacterial-fungal co-occurrence. ConclusionsThis study provide first insights into the role of the airway and gut microbiota in the development of long-term pulmonary sequelae after severe SARS-CoV-2 infection, shedding the light on the potential of the microbiota for preventive and therapeutic strategies in severe COVID-19.