Excessive inflammatory and metabolic responses to acute SARS-CoV-2 infection are associated with a distinct gut microbiota composition

Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated clinical sequelae requires well-coordinated metabolic and immune responses that limit viral spread and promote recovery of damaged systems. In order to understand potential mechanisms and interactions that influence coronavirus disease 2019 (COVID-19) outcomes, we performed a multi-omics analysis on hospitalised COVID-19 patients and compared those with the most severe outcome (i.e. death) to those with severe non-fatal disease, or mild/moderate disease, that recovered. A distinct subset of 8 cytokines and 140 metabolites in sera identified those with a fatal outcome to infection. In addition, elevated levels of multiple pathobionts and lower levels of protective or anti-inflammatory microbes were observed in the faecal microbiome of those with the poorest clinical outcomes. Weighted gene correlation network analysis (WGCNA) identified modules that associated severity-associated cytokines with tryptophan metabolism, coagulation-linked fibrinopeptides, and bile acids with multiple pathobionts. 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. Our study uncovered distinct mechanistic modules that 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 and other infectious agents.

Risk of adverse outcomes with COVID-19 in the Republic of Ireland

AimsTo compare the risk of adverse outcomes (i.e. hospital/intensive care admission, death) in population sub-groups during two periods of the COVID-19 pandemic in the Republic of Ireland. MethodsWe analysed routinely-collected, publicly-available data on 67,900 people with laboratory confirmed COVID-19 infection between 29th Feb to 14th Nov 2020. This period encompassed two waves of infection and two corresponding national lockdowns. For two observational periods covering each wave (W1, W2), each ending 17-19 days before implementation of high-level national restrictions, we segmented the population based on age and underlying clinical conditions. ResultsThe prevalence of laboratory confirmed COVID-19 was 1.4%. The risk of admission to hospital, admission to intensive care, and death was 7.2%, 0.9%, and 2.5%, respectively. Compared to younger confirmed cases, those aged [≥]65 y had increased risk of hospital admission (RR 5.61), ICU admission (RR 3.56), and death (RR 60.8). W2 was associated with more cases and fewer adverse events than W1. The risk of all adverse outcomes was reduced in W2 than in W1. ConclusionsOngoing responses should consider the variation in risk of adverse outcomes between specific sub-groups. These findings indicate the need to sustain the prevention, identification and management of noncommunicable diseases to reduce the burden of COVID-19.