The nasal microbiome modulates risk for SARS-CoV-2 infection

作者：Daniel E. Park, Maliha Aziz, Juan E. Salazar, Tony Pham, Sydney G. Nelson, Jack Villani, Nathan O Weber, Lance B. Price, Bruce A. Hungate, Cindy M. Liu · 发表于：EBioMedicine · 年份：2025 · DOI：10.1016/j.ebiom.2025.105660 · 被引用次数：5 · 研究领域：Sinusitis and nasal conditions、Respiratory viral infections research、SARS-CoV-2 detection and testing

BACKGROUND: The nasal microbiome may influence host risk for COVID-19 by modulating the expression of key proteins that facilitate SARS-CoV-2 entry, including angiotensin-converting enzyme 2 (ACE2), which binds the virus, and transmembrane serine protease 2 (TMPRSS2), which activates viral entry into nasal epithelial cells. This study examined whether the expression levels of ACE2 and TMPRSS2 in the nasal cavity predict the risk of SARS-CoV-2 infection and whether the host nasal microbiome modulates their expression. METHODS: Using 1548 self-collected nasal swabs from a population-based surveillance testing of community-dwelling adults in Washington D.C., we conducted two retrospective case-control studies (cross-sectional: n = 111 cases and 343 controls; longitudinal: n = 97 cases, 286 controls) and a nasal microbiome study (n = 428). Cases, defined as individuals with a positive SARS-CoV-2 test, were matched with controls based on age and test date. Pre-infection samples were analysed. We measured nasal ACE2/TMPRSS2 expression using RT-qPCR and characterized the nasal microbiome using 16S rRNA gene-based qPCR and sequencing. We used machine learning and regression analysis to determine if nasal ACE2/TMPRSS2 expression predicts SARS-CoV-2 infection and whether the nasal microbiome influences their expression. FINDINGS: Elevated nasal ACE2/TMPRSS2 expression was associated with 3.6-fold increased risk of contracting COVID-19 (95% CI = 1.71-7.47) compared to those with no dete...