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

Frontiers in Immunology

Immunology

Frans Everson¹  Hans Strijdom¹  Nelita du Plessis²  Jane Alexandra Shaw²  Maynard Meiring²  Novel Chegou²  Stephanus T. Malherbe²  Candice Snyders²  Gerhard Walzl²  Gerard Tromp³  Annalise E. Zemlin⁴  Rajiv T. Erasmus⁴  Lovemore Nyasha Sigwadhi⁵  Veranyay Ngah⁵  Peter S. Nyasulu⁶  Zivanai C. Chapanduka⁷  Alimuddin Zumla⁸  Nicola Baines⁹  Coenraad F. N. Koegelenberg⁹  Usha Lalla⁹  Brian Allwood⁹  Elvis M. Irusen⁹  Tandi E. Matsha^1,10 

[1] Centre for Cardiometabolic Research in Africa, Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa;Department of Science and Technology/National Research Foundation (DST-NRF) Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Biomedical Research Institute, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa;Department of Science and Technology/National Research Foundation (DST-NRF) Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Biomedical Research Institute, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa;South African Tuberculosis Bioinformatics Initiative, Stellenbosch University, Cape Town, South Africa;Centre for Bioinformatics and Computational Biology, Stellenbosch University, Stellenbosch, South Africa;Division of Chemical Pathology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University and National Health Laboratory Service, Tygerberg Hospital, Cape Town, South Africa;Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa;Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa;Division of Epidemiology and Biostatistics, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;Division of Haematological Pathology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University and National Health Laboratory Service (NHLS) Tygerberg Hospital, Cape Town, South Africa;Division of Infection and Immunity, Centre for Clinical Microbiology, University College London, London, United Kingdom;National Institute for Health Care Research (NIHR) Biomedical Research Centre, University College London (UCL) Hospitals National Health Service (NHS) Foundation Trust, London, United Kingdom;Division of Pulmonology, Department of Medicine, Stellenbosch University and Tygerberg Hospital, Cape Town, South Africa;Sefako Makgatho University of Health Sciences, Ga-Rankuwa, South Africa;

关键词: biomarkers;    cytokines;    COVID-19;    SARS-CoV-2;    prognostic;    mortality;   

DOI  :  10.3389/fimmu.2023.1219097

 received in 2023-05-08, accepted in 2023-06-12,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionBiomarkers 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.MethodsWe 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.ResultsOf 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.DiscussionThese 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.

【 授权许可】

Unknown   
Copyright © 2023 Shaw, Meiring, Snyders, Everson, Sigwadhi, Ngah, Tromp, Allwood, Koegelenberg, Irusen, Lalla, Baines, Zemlin, Erasmus, Chapanduka, Matsha, Walzl, Strijdom, du Plessis, Zumla, Chegou, Malherbe and Nyasulu