• Beate Vestad, Thor Ueland, Tøri Vigeland Lerum, Tuva Børresdatter Dahl, Kristian Holm, Andreas Barratt-Due, Trine Kåsine, Anne Ma Dyrhol-Riise, Birgitte Stiksrud, Kristian Tonby, Hedda Hoel, Inge Christoffer Olsen, Katerina Nezvalova Henriksen, Anders Tveita, Ravinea Manotheepan, Mette Haugli, Ragnhild Eiken, Åse Berg, Bente Halvorsen, Tove Lekva, Trine Ranheim, Annika Elisabeth Michelsen, Anders Benjamin Kildal, Asgeir Johannessen, Lars Thoresen, Hilde Skudal, Bård Reiakvam Kittang, Roy Bjørkholt Olsen, Carl Magnus Ystrøm, Nina Vibeche Skei, Raisa Hannula, Saad Aballi, Reidar Kvåle, Ole Henning Skjønsberg, Pål Aukrust, Johannes Roksund Hov, Marius Trøseid, and NOR-Solidarity study group.
• Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.
• J. Intern. Med. 2022 Jun 1; 291 (6): 801-812.

BackgroundAlthough 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.MethodsPlasma 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 (DLCO ). Rectal swabs for gut microbiota analyses were collected (n = 97) and analyzed by sequencing the 16S rRNA gene.ResultsGut microbiota diversity was reduced in COVID-19 patients with respiratory dysfunction, defined as DLCO 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 pO2 /fiO2 (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.ConclusionRespiratory 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.© 2022 The Association for the Publication of the Journal of Internal Medicine.

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