Effect of HIV status and suppression on SARS-CoV-2 disease severity, vaccine response, and evolution=Umthelela wesifo sesandulela-ngculazi nokucindezelwa kwaso yi-SARS-CoV-2 ubunzima besifo, ukusebenza kwekhambi kanye nokuthuthuka.

Abstract

Abstract SARS-CoV-2 is a global pandemic that has infected 672,115,430 people globally (https://coronavirus.jhu.edu/map.html, accessed 08.02.2023). SARS-CoV-2 is continuously evolving, and new variants pose a continuous threat to curbing this pandemic. Simultaneously, South Africa still struggles to control and manage an enduring HIV pandemic. The synergistic interplay between these two pandemics has necessitated an understanding of how these two viruses interact with each other to tailor an intervention. This thesis investigated the effect of SARS-CoV-2 infection on disease dynamics, differential disease outcomes, vaccine response, as well as SARSCoV- 2 evolution in people living with HIV (PLWH) with different levels of HIV suppression and differing HIV suppression history. The first study investigated the difference in disease severity amongst PLWH in the first and second infection waves in South Africa. COVID-19. Thereafter, we explored persistent SARS-CoV-2 infection in immunocompromised individuals and intra-host evolution in a case study of a participant with advanced HIV infection. Here, we illustrated that advanced HIV disease may lead to prolonged SARS-CoV-2 infection and shedding of infectious virus and results in intra-host evolution of variant mutations, making intra-host evolution in advanced HIV individuals a particular concern within the South African context. Finally, we observed that effectively controlling HIV through ART facilitates SARS-CoV-2 clearance. The last study widened the observations to five participants with advanced HIV disease and showed that vaccination does induce a potent neutralizing antibody response in this group, but only if HIV viremia is first effectively suppressed with antiretroviral therapy. These findings highlight the importance of suppressing HIV infection in eliciting an effective immune response against, and preventing evolution of SARS-CoV-2.

Iqoqa

I-SARS-CoV-2 yisifo esesigulise umhlaba wonke sase sigulisa inani elingama 672,115,430 abantu emhlabeni jikelele (https://coronavirus.jhu.edu/map.html, accessed 08.02.2023). I-SARS-CoV-2 isaqhubeka nokusabalala kanti izinhlobo zayo ezinye zisaqhubeka nokuba yingozi ukuba isifo singanqandeka. Khona-manjalo, iNingizimu Afrikha isathwele kanzima ukulawula isifo sesandulela-ngculazi. Ukuthelelana nokuxhumana phakathi kwalezi zifo kwenze kwanesidingo sokuqonda ukuthi zidlelana kanjani ukwenzela ukuphuma nekhambi. Lolu cwaningo lucwaninge umthelela we SARS-CoV-2 nezinkinga ezikhona ngenxa yazo, imiphumela ehlukene yesifo, ukusebenza kwekhambi, kanjalo nokukhula kwe SARS-CoV-2 ebantwini abaphila naso lesi sifo bebe benesandulela-ngculazi benezinga lesandulela-ngculazi elehlukile kanye nomlando owehlukile. Ucwaningo lokuqala lucubungule umehluko wesankahlu sesifo ezifweni ze-PLWH esiwombeni sokuqala nesesibili salesi sifo eNingizimu Afrikha. Ngakho-ke iye yahlolwa kwalendela umthelela we-SARS-CoV-2 kubantu abanamasosha aphansi omzimba kanye nalokhu esikubiza nge-intra-host evolution ocwaningweni lwesimo kubabambi-qhaza abanesandulela-ngculazi esisezingeni eliphezulu. Lapha kutholakale ukuthi isandulela-ngculazi esisezingeni eliphezulu singaholela ekuguleni isikhathi eside uma unesifo seSARS-CoV-2 kanye nokuthola ezinye izifo ezithelelanayo kanti imiphumela ye-intra-host evolution of variant mutations, okwenza ukukhula kwe-intra-host kulabo abanesandulela-ngculazi ephezulu kusabise isimo saseNingizimu Afrikha. Isiphetho, kutholakale ukuthi ukulawula isandulela-ngculazi nge-ART kwenza iSARS-CoV-2 idambe. Ucwaningo lokugcina luveze ngokubanzi obekubukelwe kubabambiqhaza abanesandulela-ngculazi esiphezulu ngokuthi kuvele ukuthi ikhambi lenza kudambe ukugula kuleli qoqo, kodwa kuphela uma isandulela-ngculazi siqale sacindezelwa nge-antiretroviral therapy. Lemiphumela iveza ukubaluleka kokucindezelwa kwesandulela-ngculazi ukulwa kanye nokucindezela isifo seSARS-CoV-2.