Plasma metabolic shifts link to T-cell senescence and mortality in older COVID-19 patients
Dysregulated phospholipid and bile acid metabolism tracked with cytokine spikes and 180-day mortality, while a specific lipid attenuated senescent markers in cell tests.
Researchers profiled the plasma metabolome of elderly COVID-19 patients and healthy controls to examine links between circulating metabolites, immune dysfunction, and survival. Machine learning revealed 24 key metabolites linked to 180-day mortality, mainly involving bile acid metabolism, fatty acid oxidation, and phospholipid pathways. Non-survivors showed higher levels of PE 36:3, glycochenodeoxycholic acid, and deoxycholic acid, alongside elevated levels of five cytokines: GRO-α, IL-6, IL-8, IP-10, and TSLP. Dysregulated phospholipids, including PC, LPC, PE, and LPE, correlated with T-cell senescence. In vitro tests showed that exogenous LPE 18:1 attenuated selected markers of T-cell senescence. Furthermore, altered metabolites correlated with inflammatory cytokine profiles.
Why it matters
The findings suggest that circulating metabolic disturbances may actively drive immune aging and heightened vulnerability to severe infections in older adults. Targeting specific lipid pathways could offer new avenues to manage age-related immune decline.
Caveats
The primary clinical findings are based on observational data, and cohort sizes were not disclosed in the abstract. Additionally, the restorative effects of LPE 18:1 were observed solely in cell culture models rather than in vivo.
- Lysophosphatidylethanolamine 18:1
- Cellular senescence
- Chronic inflammation
- Lipid and ceramide metabolism
- CXCL1
- CXCL10
- CXCL8
- IL6
- TSLP
- Covid-19
- IL-6
- IL-8
The paper
Plasma Metabolomic Alterations Are Associated with T-Cell Senescence, Cytokine Dysregulation, and Prognosis in Elderly COVID-19 Patients
Shang Y, Zhang H, Lang Y et al.
Biomedicines · 19 Sep 2026