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

tetano

Editor, Senior Moderator
Front Immunol


. 2023 Jul 3;14:1219097.
doi: 10.3389/fimmu.2023.1219097. eCollection 2023. Immunologic and vascular biomarkers of mortality in critical COVID-19 in a South African cohort

Jane Alexandra Shaw[SUP] 1 [/SUP], Maynard Meiring[SUP] 1 [/SUP], Candice Snyders[SUP] 1 [/SUP], Frans Everson[SUP] 2 [/SUP], Lovemore Nyasha Sigwadhi[SUP] 3 [/SUP], Veranyay Ngah[SUP] 3 [/SUP], Gerard Tromp[SUP] 1 4 5 [/SUP], Brian Allwood[SUP] 6 [/SUP], Coenraad F N Koegelenberg[SUP] 6 [/SUP], Elvis M Irusen[SUP] 6 [/SUP], Usha Lalla[SUP] 6 [/SUP], Nicola Baines[SUP] 6 [/SUP], Annalise E Zemlin[SUP] 7 [/SUP], Rajiv T Erasmus[SUP] 7 [/SUP], Zivanai C Chapanduka[SUP] 8 [/SUP], Tandi E Matsha[SUP] 9 [/SUP], Gerhard Walzl[SUP] 1 [/SUP], Hans Strijdom[SUP] 2 [/SUP], Nelita du Plessis[SUP] 1 [/SUP], Alimuddin Zumla[SUP] 10 11 [/SUP], Novel Chegou[SUP] 1 [/SUP], Stephanus T Malherbe[SUP] 1 [/SUP], Peter S Nyasulu[SUP] 3 12 [/SUP]



Affiliations
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.

Keywords: COVID-19; SARS-CoV-2; biomarkers; cytokines; mortality; prognostic.

 
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