Shaw, JA; Meiring, M; Snyders, C; Everson, F; Sigwadhi, LN; Ngah, V; Tromp, G; ... Nyasulu, PS; + view all Shaw, JA; Meiring, M; Snyders, C; Everson, F; Sigwadhi, LN; Ngah, V; Tromp, G; Allwood, B; Koegelenberg, CFN; Irusen, EM; Lalla, U; Baines, N; Zemlin, AE; Erasmus, RT; Chapanduka, ZC; Matsha, TE; Walzl, G; Strijdom, H; du Plessis, N; Zumla, A; Chegou, N; Malherbe, ST; Nyasulu, PS; - view fewer (2023) Immunologic and vascular biomarkers of mortality in critical COVID-19 in a South African cohort. Frontiers in Immunology , 14 , Article 1219097. 10.3389/fimmu.2023.1219097.

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Abstract

Introduction: 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. Methods: 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. Results: 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. Discussion: 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.

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