Metabolic features of patients with repeated Omicron infections highlight new targets for therapeutic intervention
Abstract Emerging evidence underscores the role of metabolites in immunomodulation. We surmise that specific metabolic signatures might be conserved during repeated Omicron infections. To verify our hypothesis, patients with first (n = 28) and repeated Omicron infections (n = 38) between November 20...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-04745-3 |
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| author | Jiaying Zhang Sin Man Lam Shan Ji Longyu Zhang Jiming Yin Haiqing Sun Danlei Mou Lianchun Liang Qinghua Meng Guanghou Shui Yingmei Feng |
| author_facet | Jiaying Zhang Sin Man Lam Shan Ji Longyu Zhang Jiming Yin Haiqing Sun Danlei Mou Lianchun Liang Qinghua Meng Guanghou Shui Yingmei Feng |
| author_sort | Jiaying Zhang |
| collection | DOAJ |
| description | Abstract Emerging evidence underscores the role of metabolites in immunomodulation. We surmise that specific metabolic signatures might be conserved during repeated Omicron infections. To verify our hypothesis, patients with first (n = 28) and repeated Omicron infections (n = 38) between November 2023 to April 2024 were recruited into this study. Healthy controls (n = 20) were enrolled in the same period. Comprehensive serum metabolome and lipidome were quantitated using mass spectrometric approaches. The neutralizing activity of sera against the pseudotyped Omicron variant JN.1 was determined. Circulating cytokines/chemokines were quantified using a Bioplex Kit Assay. The proportion of severe/moderate infections was 2.9-fold higher in first infection patients compared to reinfection patients (67.9% vs. 23.7%, p = 0.004). Geometric mean titers (GMT) for the Omicron variant JN.1 were higher in moderate/severe infections than mild infections, but non-significant between first and repeated infections. We observed perturbed coregulation between plasma indoles and circulating plasmalogen phospholipids in Omicron-infected patients, while disrupted histidine-triacylglycerol coregulation was specific to first-infections. A panel of three lasso-selected metabolites (SL d18:1/22:0 h, tetra-peptide Pro Tyr Tyr Val, and 1,2,3,4-Tetrahydroisoquinoline) effectively differentiated moderate/severe Omicron infections from mild ones (AUROC at 0.917, 95% CI 0.793-1.000). Our findings highlight modifiable metabolic signatures as possibly new therapeutic interventions against rapidly evolving variants of SARS-CoV-2. |
| format | Article |
| id | doaj-art-f649e983232e4fd1a9fc8ed5ea7c229d |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-f649e983232e4fd1a9fc8ed5ea7c229d2025-08-20T03:38:12ZengNature PortfolioScientific Reports2045-23222025-07-0115111610.1038/s41598-025-04745-3Metabolic features of patients with repeated Omicron infections highlight new targets for therapeutic interventionJiaying Zhang0Sin Man Lam1Shan Ji2Longyu Zhang3Jiming Yin4Haiqing Sun5Danlei Mou6Lianchun Liang7Qinghua Meng8Guanghou Shui9Yingmei Feng10Department of Infectious Diseases, Beijing Youan Hospital, Capital Medical UniversityState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of SciencesDepartment of Infectious Diseases, Beijing Youan Hospital, Capital Medical UniversityDepartment of Infectious Diseases, Beijing Youan Hospital, Capital Medical UniversityBeijing Youan Hospital, Beijing Institute of Hepatology, Capital Medical UniversityDepartment of Clinical Laboratory Centre, Beijing Youan Hospital, Capital Medical UniversityDepartment of Infectious Diseases, Beijing Youan Hospital, Capital Medical UniversityDepartment of Infectious Diseases, Beijing Youan Hospital, Capital Medical UniversityDepartment of Infectious Diseases, Beijing Youan Hospital, Capital Medical UniversityState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of SciencesBeijing Youan Hospital, Beijing Institute of Hepatology, Capital Medical UniversityAbstract Emerging evidence underscores the role of metabolites in immunomodulation. We surmise that specific metabolic signatures might be conserved during repeated Omicron infections. To verify our hypothesis, patients with first (n = 28) and repeated Omicron infections (n = 38) between November 2023 to April 2024 were recruited into this study. Healthy controls (n = 20) were enrolled in the same period. Comprehensive serum metabolome and lipidome were quantitated using mass spectrometric approaches. The neutralizing activity of sera against the pseudotyped Omicron variant JN.1 was determined. Circulating cytokines/chemokines were quantified using a Bioplex Kit Assay. The proportion of severe/moderate infections was 2.9-fold higher in first infection patients compared to reinfection patients (67.9% vs. 23.7%, p = 0.004). Geometric mean titers (GMT) for the Omicron variant JN.1 were higher in moderate/severe infections than mild infections, but non-significant between first and repeated infections. We observed perturbed coregulation between plasma indoles and circulating plasmalogen phospholipids in Omicron-infected patients, while disrupted histidine-triacylglycerol coregulation was specific to first-infections. A panel of three lasso-selected metabolites (SL d18:1/22:0 h, tetra-peptide Pro Tyr Tyr Val, and 1,2,3,4-Tetrahydroisoquinoline) effectively differentiated moderate/severe Omicron infections from mild ones (AUROC at 0.917, 95% CI 0.793-1.000). Our findings highlight modifiable metabolic signatures as possibly new therapeutic interventions against rapidly evolving variants of SARS-CoV-2.https://doi.org/10.1038/s41598-025-04745-3OmicronReinfectionMetabolitesSeverityHost-microbe interactions |
| spellingShingle | Jiaying Zhang Sin Man Lam Shan Ji Longyu Zhang Jiming Yin Haiqing Sun Danlei Mou Lianchun Liang Qinghua Meng Guanghou Shui Yingmei Feng Metabolic features of patients with repeated Omicron infections highlight new targets for therapeutic intervention Scientific Reports Omicron Reinfection Metabolites Severity Host-microbe interactions |
| title | Metabolic features of patients with repeated Omicron infections highlight new targets for therapeutic intervention |
| title_full | Metabolic features of patients with repeated Omicron infections highlight new targets for therapeutic intervention |
| title_fullStr | Metabolic features of patients with repeated Omicron infections highlight new targets for therapeutic intervention |
| title_full_unstemmed | Metabolic features of patients with repeated Omicron infections highlight new targets for therapeutic intervention |
| title_short | Metabolic features of patients with repeated Omicron infections highlight new targets for therapeutic intervention |
| title_sort | metabolic features of patients with repeated omicron infections highlight new targets for therapeutic intervention |
| topic | Omicron Reinfection Metabolites Severity Host-microbe interactions |
| url | https://doi.org/10.1038/s41598-025-04745-3 |
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