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Multiomics Analysis Reveals Microbiota, Immune and Metabolomics Characteristics in COVID-19 Patients with Differing Severity: A Retrospective Study

Year: 2026

Type: article

Abstract: Background & aims: The COVID-19 pandemic remains a significant clinical challenge compounded by the emergence of new variants with heightened pathogenicity. This study aimed to characterize multiomics alterations in COVID-19 patients and establish an early predictive model for disease progression. Methods: We retrospectively analyzed the oral and gut microbiomes, serum metabolome and immune cell profiles in 35 healthy controls and 101 COVID-19 patients with varying severity. Results: COVID-19 patients showed significant reductions in oral and gut microbial diversity, with depletion of beneficial butyrate-producing bacteria and enrichment of opportunistic pathogens like Enterococcus and Streptococcaceae. While overall microbial community structures between severity groups were similar, specific taxonomic and functional shifts were evident, such as an enrichment of oral Helicobacter ganmani and a depletion of gut Gordonibacter pamelaeae in the severe group. Serum metabolomics revealed distinct profiles, with altered lysine degradation in severe cases. Crucially, immune phenotyping demonstrated that severely ill patients had a significantly lower frequency of CD4 + PD-1 + CD69 − T cells, a subset critical for early immune homeostasis, early in the infection. In addition, a preliminary integrated predictive model integrating age, CD4 + PD-1 + CD69 − T cells and oral H. ganmani demonstrated superior discriminatory power for predicting nonsevere COVID-19 cases in the early stage with a risk of progressing to the severe stage. Conclusions: These findings highlight the critical role of early immune dysregulation and suggest that a combined microbial and immune marker approach holds significant potential for timely risk stratification in COVID-19.

Source: Infectious Microbes & Diseases

DOI: 10.1097/im9.0000000000000215