SARS-CoV-2 Infection Disrupts Lower Respiratory Tract Microbiome Function and Interactions

The respiratory microbiome plays a critical role in host defense and disease outcomes, but the effects of SARS-CoV-2 infection across respiratory compartments remain unclear. Here we show that SARS-CoV-2 infection does not significantly alter alpha or beta diversity in the upper respiratory tract (URT) or lower respiratory tract (LRT), but network analysis revealed a loss of complexity in the URT and novel infection-associated interactions in the LRT. Using shotgun metagenomics, we analyzed 127 retrospective samples from SARS-CoV-2-positive and negative patients in Southern Brazil, including nasopharyngeal swabs from the URT and LRT samples from Severe Acute Respiratory Infection (SARI) patients. LRT composition shifted, with decreased Stenotrophomonas and Pseudomonas and increased Prevotella and Alloprevotella. Functional profiling showed enrichment of metabolic pathways in SARS-CoV-2-positive LRT, while SARS-CoV-2-negative LRT exhibited virulence pathways. Resistome analyses revealed minimal differences but higher antimicrobial resistance gene abundance in SARS-CoV-2-negative LRT. These findings highlight compartment-specific SARS-CoV-2 impacts on the respiratory microbiome.