Multiomics Analysis Identifies Microbiota, Immune and Metabolomics Changes Across Disease Stages of COVID-19: A Retrospective Study

The COVID-19 pandemic remains a significant clinical challenge compounded by the emergence of new variants with heightened pathogenicity. This study aimed to characterize multi-omics alterations in COVID-19 patients and establish an early predictive model for disease progression. We analyzed the oral and gut microbiomes, serum metabolome and immune cell profiles in 35 healthy controls and 101 COVID-19 patients with varying severity. 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 sp. and a depletion of gut Gordonibacter sp. 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 + PD1 + CD69 - T cells and oral Helicobacter sp. demonstrate superior discriminatory power for predicting non-severe COVID-19 cases in the early stage with a risk of progressing to the severe stage. 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.