The study investigates the microbiota configurations associated with a fatal hyperinflammatory immune and metabolic response observed in SARS-CoV-2 patients from different hospital cohorts in Switzerland and Ireland.. A high-risk gut microbiota configuration associates with fatal hyperinflammatory immune and metabolic responses to SARS-CoV-2

Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated clinical sequelae requires well-coordinated immune and metabolic responses that limit viral spread and promote recovery. In order to understand potential mechanisms and interactions that influence coronavirus disease 2019 (COVID-19) outcomes, we compared hospitalised COVID-19 patients with the most severe outcome (i.e. death, n=41) to those with severe non-fatal disease (n=89), or mild/moderate disease (n=42). Severity-associated cytokines, tryptophan metabolism, coagulation-linked fibrinopeptides, and bile acids were associated with multiple pathobionts in the most severely ill patients. In contrast, less severe clinical outcomes associated with clusters of anti-inflammatory microbes such as Bifidobacterium or Ruminococcus, short chain fatty acids (SCFAs) and IL-17A. Distinct mechanistic modules link host and microbiome processes with fatal outcomes to SARS-CoV-2 infection. These features may be useful to identify at risk individuals, but also highlight a role for the microbiome in modifying hyperinflammatory responses to SARS-CoV-2.