High-resolution multi-omics defines respiratory microbiome and host signatures of COVID-19 severity

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.

Authors

Institutions

Publication Details

Journal
Communications Biology
Published
2026-08-20
DOI
https://doi.org/10.1038/s42003-026-10774-z
Primary Topic
Gut microbiota and health
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

High-resolution multi-omics defines respiratory microbiome and host signatures of COVID-19 severity

João Renato Rebello Pinho, Roberta Sitnik, Ana Laura Boechat, Tatiana Ferreira de Almeida et al.
Communications Biology
Gut microbiota and health
article

High-resolution multi-omics defines respiratory microbiome and host signatures of COVID-19 severity

João Renato Rebello Pinho, Roberta Sitnik, Ana Laura Boechat, Tatiana Ferreira de Almeida, Fernanda de Mello Malta, Deyvid Amgarten, Murilo Castro Cervato, Fernando Rosado Spilki, Tânia Girão Mangolini, Pedro Henrique Sebe Rodrigues, Erick Gustavo Dorlass, Raquel Riyuzo de Almeida Franco, Ana Carolina Soares, Welliton Souza, Alexandre R. Marra, Bruno Martinez de Farias, Ana Paula Moreira Salles, Raquel Emma Hurtado Castillo, Ketti Gleyzer de Oliveira, Arlene dos Santos Pinto, Noelly Maria Zimpel Trecenti, Rodrigo de Souza Reis
article en

Abstract

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.

Communications Biology
Universidade Feevale (BR), Hospital Israelita Albert Einstein (BR), Fundação de Medicina Tropical (BR), ID Genomics (United States) (US), University of Iowa Health Care (US), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (BR), Stanford University (US)
Ministério da Ciência, Tecnologia e Inovação, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Sociedade Beneficente Israelita Brasileira Albert Einstein, Ministério da Ciência, Tecnologia, Inovações e Comunicações
Life in Land
Openalex Percentile: Top 17%
Gut microbiota and health
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.