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dc.contributor.author | Van der Mescht, Mieke Adri![]() |
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dc.contributor.author | De Beer, Zelda![]() |
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dc.contributor.author | Steel, Helen C.![]() |
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dc.contributor.author | Anderson, Ronald![]() |
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dc.contributor.author | Masenge, Andries![]() |
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dc.contributor.author | Moore, Penny L.![]() |
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dc.contributor.author | Bastard, Paul![]() |
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dc.contributor.author | Casanova, Jean-Laurent![]() |
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dc.contributor.author | Abdullah, Fareed![]() |
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dc.contributor.author | Ueckermann, Veronica![]() |
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dc.contributor.author | Rossouw, Theresa M.![]() |
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dc.date.accessioned | 2024-08-28T07:52:25Z | |
dc.date.available | 2024-08-28T07:52:25Z | |
dc.date.issued | 2024-09 | |
dc.description | DATA AVAILABILITY : The datasets analyzed for this study can be made available on request. | en_US |
dc.description.abstract | The African continent reported the least number of COVID-19 cases and deaths of all the continents, although the exact reasons for this are still unclear. In addition, little is known about the immunological profiles associated with COVID-19 mortality in Africa. The present study compared clinical and immunological parameters, as well as treatment outcomes in patients admitted with COVID-19 in Pretoria, South Africa, to determine if these parameters correlated with mortality in this population. The in-hospital mortality rate for the cohort was 15.79%. The mortality rate in people living with HIV (PLWH) was 10.81% and 17.16% in people without HIV (p = 0.395). No differences in age (p = 0.099), gender (p = 0.127) or comorbidities were found between deceased patients and those who survived. All four of the PLWH who died had a CD4+ T-cell count <200 cells/mm3, a significantly higher HIV viral load than those who survived (p = 0.009), and none were receiving antiretroviral therapy. Seven of 174 (4%) patients had evidence of auto-antibodies neutralizing Type 1 interferons (IFNs). Two of the them died, and their presence was significantly associated with mortality (p = 0.042). In the adjusted model, the only clinical parameters associated with mortality were: higher fraction of inspired oxygen (FiO2) (OR: 3.308, p = 0.011) indicating a greater need for oxygen, high creatinine (OR: 4.424, p = 0.001) and lower platelet counts (OR: 0.203, p = 0.009), possibly secondary to immunothrombosis. Overall, expression of the co-receptor CD86 (p = 0.021) on monocytes and percentages of CD8+ effector memory 2 T-cells (OR: 0.45, p = 0.027) was lower in deceased patients. Decreased CD86 expression impairs the development and survival of effector memory T-cells. Deceased patients had higher concentrations of RANTES (p = 0.003), eotaxin (p = 0.003) and interleukin (IL)-8 (p < 0.001), all involved in the activation and recruitment of innate immune cells. They also had lower concentrations of transforming growth factor (TGF)-β1 (p = 0.40), indicating an impaired anti-inflammatory response. The immunological profile associated with COVID-19 mortality in South Africa points to the role of aberrate innate immune responses. | en_US |
dc.description.department | Immunology | en_US |
dc.description.department | Internal Medicine | en_US |
dc.description.department | School of Health Systems and Public Health (SHSPH) | en_US |
dc.description.department | Statistics | en_US |
dc.description.librarian | hj2024 | en_US |
dc.description.sdg | SDG-03:Good heatlh and well-being | en_US |
dc.description.sponsorship | The South African Medical Research Council Self-Initiated Research Grant (SAMRC SIR) funded the project. The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) and R21AI160576), the National Center for Advancing Translational Sciences (NCATS), the NIH Clinical and Translational Science Award (CTSA) program, the Fisher Center for Alzheimer's Research Foundation, the Meyer Foundation, the JPB Foundation, the Stavros Niarchos Foundation (SNF) as part of its grant to the SNF Institute for Global Infectious Disease Research at the Rockefeller University, the “Investissement d'Avenir” program launched by the French Government and implemented by the Agence Nationale de la Recherche (ANR), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence, the French Foundation for Medical Research (FRM), the European Union's Horizon 2020 research and innovation program, the Square Foundation, Grandir - Fonds de solidarité pour l'enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, Battersea & Bowery Advisory Group, The French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, Paris Cité University, Imagine Institute and William E. Ford, General Atlantic's Chairman and Chief Executive Officer, Gabriel Caillaux, General Atlantic's Co-President, Managing Director and Head of Business in EMEA, and the General Atlantic Foundation. A.-L.N. was supported by the Imagine Institute international PhD program (with the support of the Fondation Bettencourt-Schueller) and the FRM, the French Foundation for Medical Research, the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller), and a “Poste CCA-INSERM-Bettencourt” (with the support of the Fondation Bettencourt-Schueller). | en_US |
dc.description.uri | https://www.elsevier.com/locate/yclim | en_US |
dc.identifier.citation | Van der Mescht, M.A., D Beer, Z., Steel, H.C. et al. 2024, 'Aberrant innate immune profile associated with COVID-19 mortality in Pretoria, South Africa', Clinical Immunology, vol. 266, art. 110323, pp. 1-11, doi : 10.1016/j.clim.2024.110323. | en_US |
dc.identifier.issn | 1521-6616 | |
dc.identifier.other | 10.1016/j.clim.2024.110323 | |
dc.identifier.uri | http://hdl.handle.net/2263/97902 | |
dc.language.iso | en | en_US |
dc.publisher | Elsevier | en_US |
dc.rights | © 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC license. | en_US |
dc.subject | COVID-19 pandemic | en_US |
dc.subject | Coronavirus disease 2019 (COVID-19) | en_US |
dc.subject | Mortality | en_US |
dc.subject | People living with HIV (PLWHIV) | en_US |
dc.subject | CD86 | en_US |
dc.subject | Cytokines | en_US |
dc.subject | Type 1 IFN antibodies | en_US |
dc.subject | Type 1 interferons (IFNs) | en_US |
dc.subject | SDG-03: Good health and well-being | en_US |
dc.title | Aberrant innate immune profile associated with COVID-19 mortality in Pretoria, South Africa | en_US |
dc.type | Article | en_US |