Correlation Study of Immune Functions, Gut Microbiota, and Metabolites with the Severity of Omicron in Patients

Background: COVID-19 is associated with multifactorial interactions, including metabolic and microbial dysbiosis in the host. However, studies on biomarkers of COVID-19 severity remain incomplete, with limited studies on associated cytokines, microecologies, and metabolism processes.Methods: Sixty-three patients with confirmed Omicron infection were collected and categorized into the non-severe group (30 cases), Non-severe-to-severe group (Non-severe converting to severe cases) (5), and severe group (28 cases). Differences and correlations in the serum cytokine, fecal flora and metabolites were analyzed among groups.Findings: Non-severe-to-severe patients had the highest probability of elevated blood lactic acid (blood lactic acid > 1.7 mmol/L) and blood D-dimer levels (blood D-D > 0.2 mg/L), along with the highest rates of ventilator application, organ failure, shock, the longest length of stay (LOS), and the highest mortality rate. The levels of IL-5, IL-8, IL-18, IL-IRA, MIP-1β, GM-CSF, EGF, HGF, PDGF-BB, and VEGF-A were the highest in the Non-severe-to-severe group. The critical flora in the Non-severe-to-severe group were Clostridiales_vadinBB60_group and Odoribacter. Notably, oleamide was associated with Clostridiales_vadinBB60_group and Odoribacter in the Non-severe-to-severe group. Through intestinal flora and cytokine correlation analyses, Clostridiales_vadinBB60_group_norank was found to have the strongest correlation with IL-5, IL-8, and HGF. Additionally, Spearman correlation and regression analyses preliminarily verified that the biomarkers selected in this study were correlated with the clinical indicators of patients with Omicron infection.Interpretation : In comparison to both the Non-severe and Severe groups, the high-expression factors in the Non-severe-to-severe group were IL-5, IL-8, HGF, Clostridiales_vadinBB60_group_norank, and low-expression was oleamide, respectively. These observations suggest that the cytokines IL-5, IL-8, and HGF, the gut bacteria Clostridiales_vadinBB60_group_norank, and the gut metabolite oleamide may be valuable biological markers for therapeutic and preventive interventions in COVID-19 patients with Non-severe to Severe phenotypes.Funding: This work was supported by the National Multidisciplinary Innovation Team Project of Traditional Chinese Medicine (No. ZYYCXTD-D-202201) and the National Natural Science Foundation of China (No. 82141202).Declaration of Interest: All authors declare that they have no competing interestsEthical Approval: The Medical Ethics Committee of Beijing Hospital of Traditional Chinese Medicine, Capital Medical University approved the study protocol of this experiment. The ethical approval number is 2023BL02-016-01. The subjects were ethically cleared, and all recruited patients signed an informed consent form