Deyvid Amgarten, Fernanda de Mello Malta, Raquel Riyuzo de Almeida Franco, Ana Laura Boechat, Ana Carolina Soares, Erick Gustavo Dorlass, Ana Paula Moreira Salles, Pedro Henrique Sebe Rodrigues, Noelly Maria Zimpel Trecenti, Tânia Girão Mangolini, Bruno Martinez de Farias, Raquel Emma Hurtado Castillo, Rodrigo de Souza Reis, Welliton Souza, Ketti Gleyzer de Oliveira, Roberta Sitnik, Fernando Rosado Spilki, Arlene dos Santos Pinto, Alexandre R. Marra, Tatiana Ferreira de Almeida, Murilo Castro Cervato, João Renato Rebello Pinho
The airway microbial community may shape the variable outcomes of COVID-19, but its role is poorly understood. We profiled naso-oropharyngeal swab samples from 561 people using marker-gene amplicon sequencing, total-RNA metatranscriptomics, and shotgun DNA metagenomics, which together tracked SARS-CoV-2 lineages, detected respiratory co-infections, and recovered 190 microbial genomes including candidate previously undescribed species. Here we show that increasing COVID-19 severity is associated with a reproducible depletion of oral commensal bacteria — most consistently Gemella, with Rothia, Haemophilus and related genera — concordant across all three sequencing approaches and robust to sensitivity analyses, and accompanied by shifts in microbial metabolic and stress-response functions. In contrast, bacterial resistance-gene burden did not increase with antibiotic use or severity, host gene-expression changes were limited, and bacteria enriched in severely ill patients were largely environmental, consistent with low-biomass artifacts. These findings define a commensal-depletion signature of COVID-19 severity. High-resolution multi-omics of naso-oropharyngeal swabs defines a respiratory microbiome signature of COVID-19 severity: a reproducible, cross-platform depletion of oral commensal bacteria, most consistently Gemella.