COVID19 ICU immune and vascular biomarkers of mortality

Biomarkers predicting mortality among critical Coronavirus disease 2019 (COVID-19) patients provide insight into the underlying pathophysiology of fatal disease and may identify targets for host directed therapy. However, data that describe these biomarkers in the African populations are sparse. We collected serum samples and corresponding clinical data from 87 patients with critical COVID-19 on day 1 of admission to the intensive care unit (ICU) of a tertiary hospital in Cape Town, South Africa, during the second wave of the COVID-19 pandemic. A second sample from the same patients was collected on day 7 of ICU admission, and patients were followed up until death or hospital discharge. A custom-designed biomarker panel was performed on the Luminex® platform. Data were analyzed for any association between specific biomarkers and mortality based on pre-determined functional groups and individual analytes. Of 87 patients, 55 (63.2%) died and 32 (36.8%) survived to hospital discharge. We found a dysregulated cytokine response in patients who died, with elevated levels of type-1 and type-2 cytokines and chemokines, acute phase reactants, and reduced levels of regulatory T cell cytokines. This suggests that fatal COVID-19 among these patients involved excessive activation of cytotoxic cells and the NLRP3 inflammasome. Possible superinfection from immune dysregulation and suppression, and endothelial dysfunction with thrombosis might have contributed to death. Furthermore, the study showed that HIV infection did not affect the outcome, in this selected group of patients on antiretroviral therapy. We developed regression predictive models with metrics evaluating performance in predicting the actual outcome, including a clinically relevant biosignature with an 84.8% sensitivity.