Proteomics and Metabolomics Profiles of Unvaccinated Nonagenarian Patients with Severe SARS-CoV-2 Infection

The mortality rate of COVID-19 increases significantly in patients over the age of 90, although some elderly people in this category have experienced mild disease or have been asymptomatic. In this context, we aim to analyze the plasma proteomic and metabolomic profiles of unvaccinated nonagenarian patients who had severe manifestations of COVID-19 and either recovered or died and compare them with noninfected control subjects. Compared with healthy individuals, nonsurviving patients showed a reduced abundance of specific lipid-related proteins and metabolites, including APOH, APOC1, LCAT, 7-α-25-dihydroxycholesterol, 7-dehydrocholesterol, and phosphatidylethanolamine, which may serve as indicative markers of severity. Acute phase response, complement activation, and sphingolipids and phospholipids remain altered in recovered patients, indicating possible persistent effects of COVID-19. This study employs a multiomics approach to unveil key immune alterations in unvaccinated nonagenarians, shedding light on molecular signatures that may serve as predictive markers for disease severity and recovery in the elderly population.