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Immunological profiles, disease severity and clinical outcomes of HIV-infected and -uninfected patients admitted with COVID-19 in Tshwane
Thesis (PhD (Medical Immunology))--University of Pretoria, 2024.
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| Language: | English |
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University of Pretoria
2025
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| _version_ | 1867613595965063168 |
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| access_status_str | Open Access |
| author2 | Rossouw, Theresa M. |
| author_browse | Rossouw, Theresa M. |
| author_facet | Rossouw, Theresa M. |
| collection | Thesis |
| dc_rights_str_mv | © 2023 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. |
| description | Thesis (PhD (Medical Immunology))--University of Pretoria, 2024. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/101332 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:38:39.160Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | University of Pretoria |
| publisherStr | University of Pretoria |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/101332 Immunological profiles, disease severity and clinical outcomes of HIV-infected and -uninfected patients admitted with COVID-19 in Tshwane Rossouw, Theresa M. u14033692@tuks.co.za Steel, Helen Carolyn Van der Mescht, Mieke Adri UCTD Sustainable Development Goals (SDGs) T-cells People without HIV (PLWH) Cytokines Mortality COVID-19 Monocytes Thesis (PhD (Medical Immunology))--University of Pretoria, 2024. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease (COVID-19). Due to persistent immune deficiency and dysregulation, including systemic immune activation and inflammation leading to immune exhaustion, people living with human immunodeficiency virus (HIV) (PLWH) might be expected to have an increased risk of SARS-CoV-2 infection and worse COVID-19 outcomes. This study aimed to determine if PLWH have different immunological profiles and are at higher risk for severe disease or worse clinical outcomes due to their HIV status. The innate and adaptive immunological profiles of patients with and without HIV admitted to the Steve Biko Academic/Tshwane District Hospital complex with COVID-19 were characterised using flow cytometric and cytokine analysis. Sub-objectives included: 1) Comparing T-cell flow cytometric profiles on day 1 and day 7 of admission; 2) Comparing pro- and anti-inflammatory cytokine and chemokine profiles; and 3) Comparing clinical outcomes of both cohorts. Relevant associations among immunological profiles and clinical outcomes in patients with COVID-19 with or without HIV infection were also assessed. In the context of co-infection with SARS-CoV-2, after approximately 7 days of hospital admission, PLWH had lower percentages of CD8+ effector memory (EM) T-cells compared to those without HIV. This may indicate suppressive T-regulatory (Treg) cell mechanisms inhibiting EM T-cell survival, as suggested by the higher expression of interleukin (IL)-35 found on the day of hospitalisation with COVID-19 in PLWH. PLWH showed a pattern of CD8+ T-cell maturation arrest, evidenced by increased percentages of CD8+ EM2 on day one. This is reflected in the mortality data, which showed that higher percentages of CD8+ EM2 T-cells were associated with survival. PLWH with a CD4+ T-cell count <200 cells/mm³ had lower survival rates. No significant differences were observed in the cytokine, chemokine, and growth factor levels for platelet- and endothelial-associated markers between patients with and without HIV, except for higher vascular endothelial growth factor (VEGF) in PLWH. VEGF, a potent angiogenic factor, could be advantageous under hypoxic conditions, reflected in the clinical profile of PLWH, who had less inflammation and reduced oxygen therapy requirements. No significant difference was found in outcomes between patients with and without HIV. Clinical factors most associated with mortality included lower platelet count, increased creatinine, and a greater need for oxygen therapy. Immunological factors associated with mortality were increased concentrations of Regulated on activation, normal T-cell expressed and secreted (RANTES), IL-8, and eotaxin, all of which are involved in the activation and recruitment of immune cells, with decreased transforming growth factor (TGF)-β1 indicating an impaired anti-inflammatory response. The study of hospitalised patients with moderate-to-severe COVID-19 showed low mortality and good outcomes for both people with and without HIV. Virally suppressed PLWH co-infected with SARS-CoV-2 were not at higher risk of morbidity and mortality compared to those without HIV. Immune dysregulation in these individuals might protect against the hyperinflammatory response to SARS-CoV-2. However, PLWH with a CD4 T-cell count <200 cells/mm³ are at higher risk of COVID-19 mortality due to impaired immune responses. This study emphasises prioritising treatment for PLWH with a CD4 T-cell count <200 cells/mm³ hospitalised with COVID-19. Poliomyelitis Research Fund (PRF) South African Medical Research Council Self-Initiated Research Grant (SAMRC SIR) Immunology PhD (Medical Immunology) Unrestricted Faculty of Health Sciences SDG-03: Good health and well-being 2025-03-04T13:54:17Z 2025-03-04T13:54:17Z 2025-04 2024-09 Thesis * A2025 http://hdl.handle.net/2263/101332 https://doi.org/10.25403/UPresearchdata.28510103 en © 2023 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria |
| spellingShingle | UCTD Sustainable Development Goals (SDGs) T-cells People without HIV (PLWH) Cytokines Mortality COVID-19 Monocytes Immunological profiles, disease severity and clinical outcomes of HIV-infected and -uninfected patients admitted with COVID-19 in Tshwane |
| title | Immunological profiles, disease severity and clinical outcomes of HIV-infected and -uninfected patients admitted with COVID-19 in Tshwane |
| title_full | Immunological profiles, disease severity and clinical outcomes of HIV-infected and -uninfected patients admitted with COVID-19 in Tshwane |
| title_fullStr | Immunological profiles, disease severity and clinical outcomes of HIV-infected and -uninfected patients admitted with COVID-19 in Tshwane |
| title_full_unstemmed | Immunological profiles, disease severity and clinical outcomes of HIV-infected and -uninfected patients admitted with COVID-19 in Tshwane |
| title_short | Immunological profiles, disease severity and clinical outcomes of HIV-infected and -uninfected patients admitted with COVID-19 in Tshwane |
| title_sort | immunological profiles disease severity and clinical outcomes of hiv infected and uninfected patients admitted with covid 19 in tshwane |
| topic | UCTD Sustainable Development Goals (SDGs) T-cells People without HIV (PLWH) Cytokines Mortality COVID-19 Monocytes |
| url | http://hdl.handle.net/2263/101332 https://doi.org/10.25403/UPresearchdata.28510103 |