Guild-Level Microbiome Signature Associated with COVID-19 Severity and Prognosis

Abstract

Previous reports on the associations between COVID-19 and gut microbiome have been constrained by taxonomic-level analysis and overlook the interaction between microbes. By applying a genome-resolved, reference-free, guild-based metagenomic analysis, we demonstrated that the relationship between gut microbiota and COVID-19 is genome-specific instead of taxon-specific or even species-specific. Moreover, the COVID-19-associated genomes were not independent but formed two competing guilds, with Guild 1 potentially beneficial and Guild 2 potentially more detrimental to the host based on comparative genomic analysis. The dominance of Guild 2 over Guild 1 at time of admission was associated with hospitalized COVID-19 patients at high risk for more severe outcomes. Moreover, the guild-level microbiome signature is not only correlated with the symptom severity of COVID-19 patients, but also differentiates COVID-19 patients from pneumonia controls and healthy subjects across different studies. Here, we showed the possibility of using genome-resolved and guild-level microbiome signatures to identify hospitalized COVID-19 patients with a high risk of more severe outcomes at the time of admission.