Alterations of the oral microbiome in patients reinfected with SARS‐CoV‐2 omicron variants

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection induces perturbations in the human oral microbiome. However, alterations of the oral microbiome in patients reinfected with SARS‐CoV‐2 omicron variant (ORs) remain uncharacterized. We enrolled 2046 participants providing tongue‐coating specimens, with 1637 samples meeting inclusion criteria for sequencing and analysis, including 702 ORs, 184 OR primary‐infected patients, 50 wild‐type strain primary‐infected patients (WTPs), 154 common cold patients, and 547 heathy controls (HCs). While α‐diversity showed no significant differences between OR and HC groups, compositional analysis revealed notable taxonomic shifts: ORs exhibited elevated abundance of 13 genera (including Veillonella and Prevotella ) alongside depletion of 12 genera (e.g., Actinomyces and Neisseria ) relative to HCs. Across SARS‐CoV‐2 evolutionary progression and host infection stages, maximal microbial dysbiosis was observed in WTPs, contrasting with minimal perturbation in ORs. The abundance of Fusobacterium and Porphyromonas gradually increased during this process, while Parascardovia and Pyramidobacter gradually decreased. Furthermore, a diagnostic model for OR was constructed. High AUC values were obtained in discovery phase (97.25%, 97.07%) and independent validation phase (89.61%). Importantly, two cross‐regional validation phases (70.90%, 73.97%) also showed high efficiency, and three cross‐disease validation phases (92.34, 95.46, and 85.10%) also revealed good disease specificity. This study is the first to characterize the oral microbiome of ORs. Our findings indicate that dynamic alterations of oral microbiome were closely associated with the severity of COVID‐19. Moreover, oral microbiome analysis contributes to diagnosis for ORs.