Immunologic and vascular biomarkers of mortality in critical COVID-19 in a South African cohort

• Published in: Frontiers in immunology 2023-07, Vol.14, p.1219097-1219097
• Main Authors: Shaw, Jane Alexandra, Meiring, Maynard, Snyders, Candice, Everson, Frans, Sigwadhi, Lovemore Nyasha, Ngah, Veranyay, Tromp, Gerard, Allwood, Brian, Koegelenberg, Coenraad F N, Irusen, Elvis M, Lalla, Usha, Baines, Nicola, Zemlin, Annalise E, Erasmus, Rajiv T, Chapanduka, Zivanai C, Matsha, Tandi E, Walzl, Gerhard, Strijdom, Hans, du Plessis, Nelita, Zumla, Alimuddin, Chegou, Novel, Malherbe, Stephanus T, Nyasulu, Peter S
• Format: Article
• Language: English
• Subjects: Biomarkers; COVID-19; Cytokines; HIV Infections; Hospital Mortality; Humans; Immunology; mortality; Pandemics; Procalcitonin; prognostic; SARS-CoV-2; South Africa - epidemiology
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1219097

Biomarkers predicting mortality among critical Coronavirus disease 2019 (COVID-19) patients provide insight into the underlying pathophysiology of fatal disease and assist with triaging of cases in overburdened settings. However, data describing these biomarkers in Sub-Saharan 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. Patients were followed up until in-hospital death or hospital discharge. A custom-designed 52 biomarker panel was performed on the Luminex® platform. Data were analyzed for any association between biomarkers and mortality based on pre-determined functional groups, and individual analytes. Of 87 patients, 55 (63.2%) died and 32 (36.8%) survived. We found a dysregulated cytokine response in patients who died, with elevated levels of type-1 and type-2 cytokines, chemokines, and acute phase reactants, as well as reduced levels of regulatory T cell cytokines. Interleukin (IL)-15 and IL-18 were elevated in those who died, and levels reduced over time in those who survived. Procalcitonin (PCT), C-reactive protein, Endothelin-1 and vascular cell adhesion molecule-1 were elevated in those who died. These results show the pattern of dysregulation in critical COVID-19 in a Sub-Saharan African cohort. They suggest that fatal COVID-19 involved excessive activation of cytotoxic cells and the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3) inflammasome. Furthermore, superinfection and endothelial dysfunction with thrombosis might have contributed to mortality. HIV infection did not affect the outcome. A clinically relevant biosignature including PCT, pH and lymphocyte percentage on differential count, had an 84.8% sensitivity for mortality, and outperformed the Luminex-derived biosignature.