Our study maps the impact of SARS-CoV-2 across gut, nasal, and environmental microbiomes alongside host immune responses. Distinct microbial signatures and altered diversity differentiated symptomatic, asymptomatic, and exposed individuals, including children. Elevated inflammatory cytokines in symptomatic cases and early links between gut microbes and immune responses highlight a gut–immune–lung axis. These findings reveal promising microbial and immune biomarkers and demonstrate the potential of microbiome-based community surveillance.