Abstract
Background: Although coronavirus disease 2019 (COVID-19) is primarily a respiratory infection, mounting evidence suggests that the gastrointestinal tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and are related to long-term respiratory dysfunction remains unknown.
Methods: Plasma was collected during hospital admission and after 3 months from the NOR-Solidarity trial (n = 181) and analyzed for markers of gut barrier dysfunction and inflammation. At the 3-month follow-up, pulmonary function was assessed by measuring the diffusing capacity of the lungs for carbon monoxide (DL CO ). Rectal swabs for gut microbiota analyses were collected (n = 97) and analyzed by sequencing the 16S rRNA gene.
Results: Gut microbiota diversity was reduced in COVID-19 patients with respiratory dysfunction, defined as DL CO below the lower limit of normal 3 months after hospitalization. These patients also had an altered global gut microbiota composition, with reduced relative abundance of 20 bacterial taxa and increased abundance of five taxa, including Veillonella, potentially linked to fibrosis. During hospitalization, increased plasma levels of lipopolysaccharide-binding protein (LBP) were strongly associated with respiratory failure, defined as pO 2 /fiO 2 (P/F ratio) <26.6 kPa. LBP levels remained elevated during and after hospitalization and were associated with low-grade inflammation and respiratory dysfunction after 3 months.
Conclusion: Respiratory dysfunction after COVID-19 is associated with altered gut microbiota and persistently elevated LBP levels. Our results should be regarded as hypothesis generating, pointing to a potential gut-lung axis that should be further investigated in relation to long-term pulmonary dysfunction and long COVID.
Keywords: SARS-CoV-2; microbiome; pulmonary function.
【저자키워드】 SARS-CoV-2, Microbiome, pulmonary function., 【초록키워드】 COVID-19, coronavirus disease, Inflammation, Coronavirus disease 2019, Respiratory failure, Trial, Hospitalization, disease severity, Sequencing, gut-lung axis, lung, fibrosis, COVID, 16S rRNA, Protein, Pulmonary function, respiratory infection, microbiota, Lungs, carbon monoxide, Patient, Rectal swabs, plasma, gut microbiota, Hospital admission, Follow-up, Swab, respiratory, gastrointestinal tract, lipopolysaccharide, rRNA, Bacterial, marker, low-grade inflammation, Evidence, Hypothesis, COVID-19 patient, Gut, diffusing capacity, dysfunction, alteration, P/F ratio, 16S rRNA gene, gut microbiota composition, pulmonary dysfunction, FIVE, limit, defined, analyzed, collected, involved, investigated, remained, the disease, elevated, was collected, reduced, analysis, was reduced, diffusing, kPa, LBP, 【제목키워드】 severe COVID-19, gut microbiota, respiratory, dysfunction, alteration,