AUTHOR=von Ameln Lovison Otávio , Zempulski Volpato Fabiana Caroline , Weber Lorenzo Gómez , Barth Afonso Luis , Simon Coitinho Adriana , Martins Andreza Francisco TITLE=Unveiling the role of the upper respiratory tract microbiome in susceptibility and severity to COVID-19 JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=Volume 15 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1531084 DOI=10.3389/fcimb.2025.1531084 ISSN=2235-2988 ABSTRACT=It is argued that commensal bacteria in the upper respiratory tract (URT) protect against pathogen colonization and infection, including respiratory viruses. Given that the microbiome can mediate immune modulation, a link between the URT microbiome (URTM) and COVID-19 susceptibility and severity is expected. This 16S metagenomics cross-sectional study assessed URTM composition, metabolic prediction, and association with laboratory biomarkers in non-COVID-19 pneumonia (NO-CoV), moderate (M-CoV), severe (S-CoV) COVID-19 patients, as well as COVID-19-negative, asymptomatic (NC) patients. The S-CoV group exhibited reduced URTM diversity, primarily due to a decreased abundance of eubiotic taxa. Some of these taxa (e.g., Haemophilus sp., Neisseria sp.) were also associated with inflammatory biomarkers. Multiple metabolic pathways (e.g., short-chain fatty acids, vitamin B12) linked to immune response, antiviral activity, and host susceptibility showed decreased abundance in S-CoV. These pathways could suggest potential alternatives for the therapeutic arsenal against COVID-19, providing reassurance about the progress in understanding and treating this disease.