Fig. 2: Microbiota compositional changes are associated with COVID-19 severity, hospitalization, and/or antibiotics.

a Alpha diversity (measured as Shannon entropy) of stool and oropharyngeal samples remaining after rarefaction (see “Methods” and Supplementary Figure 1a, b), separated by disease status and severity (measured by OSCI). Box plots display the median (center line), interquartile range (box bounds), and 1.5 times the interquartile range (whiskers). b Beta diversity (principal coordinates analysis, PCoA) on rarefied species abundances, colored to denote disease status and severity as well as any recent or current antibiotic (Abx) intake. c Subset of significant results from our differential abundance and confounder testing of the gut microbiota, comparing uninfected controls to mild disease (i.e., status) and mild to severe disease (i.e., severity; see “Methods”, Supplementary Fig. 1c for the throat microbiota, and Supplementary Table 6 for the full results). Standardized, non-parametric effect sizes were calculated between bacterial abundances and clinical covariates (Spearman for continuous or Cliff’s delta/Wilcoxon for binary variables), and tested for significance. Nested linear models and likelihood ratio tests were then used to disentangle the potentially confounding effects of clinical variables from the disease status or severity (on “naively” disease-associated bacterial taxa from the first step), if possible (see “Methods”). Taxa in bold showed a unique association to the group (control, mild or severe COVID-19) which could be disentangled from covariates. “Antibiotics” refers to any recent or current use and “Medication” is a sum of current medications excluding antibiotics. OSCI ordinal scale for clinical improvement, HAP hospital-acquired pneumonia, VAP ventilator-associated pneumonia, CCI Charlson Comorbidity Index, CRP C-reactive protein, IL-6 interleukin 6, FDR false discovery rate (adjusted).