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SARS-CoV-2 clearance requires adaptive immunity but the contribution of neutralizing antibodies and T cells in different immune states is unclear. Here we ask which adaptive immune responses associate with clearance of long-term SARS-CoV-2 infection in HIV-mediated immunosuppression after suppressive antiretroviral therapy (ART) initiation. We assembled a cohort of SARS-CoV-2 infected people in South Africa (n = 994) including participants with advanced HIV disease characterized by immunosuppression due to T cell depletion. Fifty-four percent of participants with advanced HIV disease had prolonged SARS-CoV-2 infection (>1 month). In the five vaccinated participants with advanced HIV disease tested, SARS-CoV-2 clearance associates with emergence of neutralizing antibodies but not SARS-CoV-2 specific CD8 T cells, while CD4 T cell responses were not determined due to low cell numbers. Further, complete HIV suppression is not required for clearance, although it is necessary for an effective vaccine response. Persistent SARS-CoV-2 infection led to SARS-CoV-2 evolution, including virus with extensive neutralization escape in a Delta variant infected participant. The results provide evidence that neutralizing antibodies are required for SARS-CoV-2 clearance in HIV-mediated immunosuppression recovery, and that suppressive ART is necessary to curtail evolution of co-infecting pathogens to reduce individual health consequences as well as public health risk linked with generation of escape mutants., (© 2024. The Author(s).)

There are few data on the real-world effectiveness of COVID-19 vaccines and boosting in Africa, which experienced widespread SARS-CoV-2 infection before vaccine availability. We assessed the association between vaccination and severe COVID-19 in the Western Cape, South Africa, in an observational cohort study of >2 million adults during 2020–2022. We described SARS-CoV-2 testing, COVID-19 outcomes, and vaccine uptake over time. We used multivariable cox models to estimate the association of BNT162b2 and Ad26.COV2.S vaccination with COVID-19-related hospitalization and death, adjusting for demographic characteristics, underlying health conditions, socioeconomic status proxies, and healthcare utilization. We found that by the end of 2022, 41% of surviving adults had completed vaccination and 8% had received a booster dose. Recent vaccination was associated with notable reductions in severe COVID-19 during periods dominated by Delta, and Omicron BA.1/2 and BA.4/5 (sub)lineages. During the latest Omicron BA.4/5 wave, within 3 months of vaccination or boosting, BNT162b2 and Ad26.COV2.S were each 84% effective against death (95% CIs: 57–94 and 49–95, respectively). However, distinct reductions of effectiveness occurred at longer times post completing or boosting vaccination. Results highlight the importance of continued emphasis on COVID-19 vaccination and boosting for those at high risk of severe COVID-19, even in settings with widespread infection-induced immunity. [ABSTRACT FROM AUTHOR]