• Marius Trøseid, Jan Cato Holter, Kristian Holm, Beate Vestad, Taisiia Sazonova, Beathe K Granerud, Anne Ma Dyrhol-Riise, Aleksander R Holten, Kristian Tonby, Anders Benjamin Kildal, Lars Heggelund, Anders Tveita, Simen Bøe, Karl Erik Müller, Synne Jenum, Johannes R Hov, Thor Ueland, and Norwegian SARS-CoV-2 study group.
• Research Institute of Internal Medicine, Oslo University Hospital, 0424, Oslo, Norway. marius.troseid@medisin.uio.no.
• Crit Care. 2023 Feb 23; 27 (1): 6969.

BackgroundGut microbiota alterations have been reported in hospitalized COVID-19 patients, with reduced alpha diversity and altered microbiota composition related to respiratory failure. However, data regarding gut microbiota and mortality are scarce.MethodsRectal swabs for gut microbiota analyses were collected within 48 h after hospital admission (baseline; n = 123) and three-month post-admission (n = 50) in a subset of patients included in the Norwegian SARS-CoV2 cohort study. Samples were analysed by sequencing the 16S rRNA gene. Gut microbiota diversity and composition at baseline were assessed in relation to need for intensive care unit (ICU) admission during hospitalization. The primary objective was to investigate whether the ICU-related gut microbiota was associated with 60-day mortality.ResultsGut microbiota diversity (Shannon index) at baseline was lower in COVID-19 patients requiring ICU admission during hospitalization than in those managed in general wards. A dysbiosis index representing a balance of enriched and reduced taxa in ICU compared with ward patients, including decreased abundance of butyrate-producing microbes and enrichment of a partly oral bacterial flora, was associated with need of ICU admission independent of antibiotic use, dexamethasone use, chronic pulmonary disease, PO2/FiO2 ratio, C-reactive protein, neutrophil counts or creatinine levels (adjusted p < 0.001). The ICU-related dysbiosis index at baseline correlated with systemic inflammation and was associated with 60-day mortality in univariate analyses (Hazard ratio 3.70 [2.00-8.6], p < 0.001), as well as after separate adjustment for covariates. At the three-month follow-up, the dysbiosis index remained elevated in ICU patients compared with ward patients (adjusted p = 0.007).ConclusionsAlthough our data should be regarded as exploratory due to low number of clinical end points, they suggest that gut microbiota alterations during hospitalization could be related to poor prognosis after severe COVID-19. Larger studies of gut involvement during COVID-19 in relation to long-term clinical outcome are warranted. Trial registration NCT04381819 . Retrospectively registered May 11, 2020.© 2023. The Author(s).

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