Early Metabolomic and Immunologic Biomarkers as Prognostic Indicators for COVID-19

• Published in: Metabolites
• Main Authors: Zigui Chen, Erik Fung, Chun-Kwok Wong, Lowell Ling, Grace Lui, Christopher K. C. Lai, Rita W. Y. Ng, Ryan K. H. Sze, Wendy C. S. Ho, David S. C. Hui, Paul K. S. Chan
• Format: Article
• Language: English
• Published: MDPI AG 2024-07-01
• Subjects: metabolome; chemokine; cytokine; COVID; coronavirus; SARS-CoV-2
• Online Access: https://www.mdpi.com/2218-1989/14/7/380

This prospective study in Hong Kong aimed at identifying prognostic metabolomic and immunologic biomarkers for Coronavirus Disease 2019 (COVID-19). We examined 327 patients, mean age 55 (19–89) years, in whom 33.6% were infected with Omicron and 66.4% were infected with earlier variants. The effect size of disease severity on metabolome outweighed others including age, gender, peak C-reactive protein (CRP), vitamin D and peak viral levels. Sixty-five metabolites demonstrated strong associations and the majority (54, 83.1%) were downregulated in severe disease (z score: −3.30 to −8.61). Ten cytokines/chemokines demonstrated strong associations (<i>p</i> < 0.001), and all were upregulated in severe disease. Multiple pairs of metabolomic/immunologic biomarkers showed significant correlations. Fourteen metabolites had the area under the receiver operating characteristic curve (AUC) > 0.8, suggesting a high predictive value. Three metabolites carried high sensitivity for severe disease: triglycerides in medium high-density lipoprotein (MHDL) (sensitivity: 0.94), free cholesterol-to-total lipids ratio in very small very-low-density lipoprotein (VLDL) (0.93), cholesteryl esters-to-total lipids ratio in chylomicrons and extremely large VLDL (0.92);whereas metabolites with the highest specificity were creatinine (specificity: 0.94), phospholipids in large VLDL (0.94) and triglycerides-to-total lipids ratio in large VLDL (0.93). Five cytokines/chemokines, namely, interleukin (IL)-6, IL-18, IL-10, macrophage inflammatory protein (MIP)-1b and tumour necrosis factor (TNF)-a, had AUC > 0.8. In conclusion, we demonstrated a tight interaction and prognostic potential of metabolomic and immunologic biomarkers enabling an outcome-based patient stratification.