SARS-CoV-2 Infection disrupts lower respiratory tract microbiome function and interactions

The respiratory microbiome plays a critical role in host defense mechanisms and influences disease outcomes. However, the impact of SARS-CoV-2 infection on microbial community composition, function, and resistance potential across different respiratory tract compartments remains incompletely understood. To address this, we analyzed 127 retrospective respiratory samples from SARS-CoV-2-positive and negative patients from Southern Brazil. The dataset included nasopharyngeal swabs from the upper respiratory tract (URT) and samples from the lower respiratory tract (LRT) of patients with Severe Acute Respiratory Infection (SARI). Microbial taxonomic profiles, diversity, co-occurrence networks, functional pathways, and antibiotic resistance genes (ARGs) were assessed through shotgun metagenomic sequencing. SARS-CoV-2 infection did not affect diversity in the URT, but was associated with altered bacterial beta diversity in the LRT. The LRT microbial composition was markedly altered in SARS-CoV-2-positive cases, with reduced abundance of pathogens such as Stenotrophomonas and Pseudomonas and an increased prevalence of Prevotella and Alloprevotella. Co-occurrence network analysis uncovered a loss of complexity in SARS-CoV-2-positive URT samples and the emergence of novel interactions associated with infection in the LRT. Functional profiling demonstrated that SARS-CoV-2-positive LRT samples were enriched in metabolic pathways, whereas SARS-CoV-2-negative LRT samples were enriched in virulence pathways. Resistome profiling indicated minimal differences in ARG diversity and mechanism distribution, although SARS-CoV-2-negative LRT samples exhibited higher ARG abundance. SARS-CoV-2 infection reshapes the composition, interactions, and functional potential of the LRT microbiome, while the URT remains relatively stable. These findings underscore the compartment-specific impact of SARS-CoV-2 infection on the respiratory microbiome.