Unsuppressed HIV infection impairs T cell responses to SARS-CoV-2 infection and abrogates T cell cross-recognition
In some instances, unsuppressed HIV has been associated with severe COVID-19 disease, but the mechanisms underpinning this susceptibility are still unclear. Here, we assessed the impact of HIV infection on the quality and epitope specificity of SARS-CoV-2 T cell responses in the first wave and second wave of the COVID-19 epidemic in South Africa. Flow cytometry was used to measure T cell responses following PBMC stimulation with SARS-CoV-2 peptide pools. Culture expansion was used to determine T cell immunodominance hierarchies and to assess potential SARS-CoV-2 escape from T cell recognition. HIV-seronegative individuals had significantly greater CD4+T cell responses against the Spike protein compared to the viremic PLWH. Absolute CD4 count correlated positively with SARS-CoV-2 specific CD4+ and CD8+ T cell responses (CD4 r= 0.5, p=0.03; CD8 r=0.5, p=0.001), whereas T cell activation was negatively correlated with CD4+ T cell responses (CD4 r= -0.7, p=0.04). There was diminished T cell cross-recognition between the two waves, which was more pronounced in individuals with unsuppressed HIV infection. Importantly, we identify four mutations in the Beta variant that resulted in abrogation of T cell recognition. Together, we show that unsuppressed HIV infection markedly impairs T cell responses to SARS-Cov-2 infection and diminishes T cell cross-recognition. These findings may partly explain the increased susceptibility of PLWH to severe COVID-19 and also highlights their vulnerability to emerging SARS-CoV-2 variants of concern.
Responses: All source data files for the figures are now publicly available on our institutional website (Africa Health Research Institute database). The data can be accessed using this link: https://doi.org/10.23664/AHRI.SARS.CoV.2
Article and author information
Howard Hughes Medical Institute (55008743)
- Zaza M Ndhlovu
Bill and Melinda Gates Foundation (INV-018944)
- Alex Sigal
South Africa Medical Research Council (31026)
- Willem Hanekom
Sub-Sahara African Network for TB and HIV Research Excellence (COL016)
- Zaza M Ndhlovu
Africa Health Research Institute (LoA R82)
- Zaza M Ndhlovu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Human subjects: Ethical Declaration: The study protocol was approved by the University of KwaZulu-Natal Biomedical Research Ethics Committee (BREC) (approval BREC/00001275/2020). Consenting adult patients (>18 years old) presenting at King Edward VIII, Inkosi Albert Luthuli Central Hospital, and Clairwood Hospital in Durban, South Africa, between 29 July to August November 2021 with PCR confirmed SARS-CoV-2 infection were enrolled into the study.
- Joshua T Schiffer, Fred Hutchinson Cancer Research Center, United States
- Received: March 4, 2022
- Preprint posted: April 6, 2022 (view preprint)
- Accepted: July 20, 2022
- Accepted Manuscript published: July 26, 2022 (version 1)
- Version of Record published: August 5, 2022 (version 2)
© 2022, Nkosi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Funding: Key Research and Development Program of Zhejiang Province; Key Program of Health Commission of Zhejiang Province/ Science Foundation of National Health Commission; Major Program of Zhejiang Municipal Natural Science Foundation; Explorer Program of Zhejiang Municipal Natural Science Foundation.