Gut microbiota alterations in patients with persistent respiratory dysfunction three months after severe COVID-19

Abstract

Objective: Although COVID-19 is primarily a respiratory infection, mounting evidence suggests that the GI tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and could be related to long-term respiratory dysfunction is unknown. Design: From the NOR-Solidarity trial (n=181), plasma was collected during hospital admission and after three months, and analyzed for markers of gut barrier dysfunction and inflammation. At the three-month follow-up, pulmonary function was assessed by measuring diffusing capacity of the lungs for carbon monoxide (DLCO), and rectal swabs for gut microbiota analyses were collected (n= 97) and analysed by sequencing of the 16S rRNA gene. Results: Gut microbiota diversity was reduced in COVID-19 patients with persistent respiratory dysfunction, defined as DLCO below lower limit of normal three months after hospitalization. These patients also had an altered global gut microbiota composition, with reduced abundance of Erysipelotrichaceae UCG-003 and increased abundance of Flavonifractor and Veillonella, the latter potentially being linked to fibrosis. During hospitalization, increased plasma levels of lipopolysaccharide-binding protein (LBP) were strongly associated with respiratory failure, defined as pO2/fiO2-(P/F-ratio)<26.6 kPa. LBP levels remained elevated during and after hospitalization, and was associated with low-grade inflammation and persistent respiratory dysfunction after three months. Conclusion: Persistent respiratory dysfunction after COVID-19 is associated with reduced biodiversity and gut microbiota alterations, along with persistently elevated LBP levels. Our results point to a potential gut-lung axis that should be further investigated in relation to long-term pulmonary dysfunction and long COVID.

Alterations in the Composition of Intestinal DNA Virome in Patients With COVID-19

“…Microbial diversity analysis revealed a significant decrease in diversity of the gut DNA virome in COVID-19 patients compared to healthy controls, which in accordance with similar recent studies (Cao et al, 2021;Zuo et al, 2021). A low diversity of gut microbiota in patients with COVID-19 compared to that in healthy individuals has also been reported earlier (Gu et al, 2020;Zuo et al, 2020;Chen et al, 2021;Vestad et al, 2021). These evidences above supporting the hypothesis that the infection of SARS-CoV-2 impacts the microbial composition and immunity of the host.…”

Long COVID and its Management

“…Upon viral clearance, prior hyperinflammatory state and microbiome imbalance may damage gastrointestinal integrity and function [47]. Current findings have emphasized changes in the gut microbiota in patients following COVID-19 infection [48][49][50].…”

“…SARS-CoV-2 RNA can be detected from fecal samples during acute stage, indicating gastrointestinal (GI) involvement in COVID-19 pathology [46,76]. Recent studies reveal that gut microbiome diversity and composition are changed post COVID-19 infection [48][49][50]. Increase in viral-induced cytokines may compromise intestinal integrity, facilitating the entry of bacteria and metabolites into circulation.…”