The emergence of the coronavirus, SARS-CoV-2, in late 2019 led to a global pandemic with millions of confirmed cases and fatalities. The mortality rate rises significantly in patients over 90 years old; however, there are cases of older adults who survived or were not even infected despite being exposed. In this context, we aim to analyze the plasma proteomic and metabolomic profiles of nonagenarian patients who recovered (Group R) or died (Group D) from severe COVID-19 and compare them with non-infected control subjects (Group C). Plasma samples from the deceased group were collected days before the patients died, whereas plasma from survivors and non-infected individuals exposed to SARS-CoV-2 was collected 1-3 months after the reported infection or exposure. When compared to the control group, non-survivors 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. These patients also exhibited elevated levels of N-heterocyclic compounds, potentially indicating an antiviral response. Recovered patients showed minimal differences compared to healthy non-infected subjects, indicating restoration of disrupted metabolic and proteomic profiles. However, proteins associated with acute phase response and complement activation did not return to normal levels. Also, specific metabolites, such as sphingolipids and phospholipids, remain altered in survival nonagenarians even after recovery, indicating persistent effects of COVID-19 infection. Alterations in proteins associated with neuronal function indicate possible brain damage and long-term neurological effects of COVID-19 infection.