Unsuppressed HIV infection impairs T cell responses to SARS-CoV-2 infection and abrogates T cell cross-recognition

  1. Thandeka Nkosi
  2. Caroline Chasara
  3. Andrea O Papadopoulos  Is a corresponding author
  4. Tiza L Nguni
  5. Farina Karim
  6. Mahomed-Yunus S Moosa
  7. Inbal Gazy
  8. Kondwani Jambo
  9. COMMIT-KZN
  10. Willem Hanekom
  11. Alex Sigal
  12. Zaza M Ndhlovu  Is a corresponding author
  1. University of KwaZulu-Natal, South Africa
  2. Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Malawi

Abstract

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.

Data availability

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

Author details

  1. Thandeka Nkosi

    Africa Health Research Institute, University of KwaZulu-Natal, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  2. Caroline Chasara

    Africa Health Research Institute, University of KwaZulu-Natal, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6860-6111
  3. Andrea O Papadopoulos

    Africa Health Research Institute, University of KwaZulu-Natal, Durban, South Africa
    For correspondence
    andrea.papadopoulos@ahri.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5317-1418
  4. Tiza L Nguni

    Africa Health Research Institute, University of KwaZulu-Natal, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  5. Farina Karim

    Africa Health Research Institute, University of KwaZulu-Natal, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9698-016X
  6. Mahomed-Yunus S Moosa

    Department of Infectious Diseases, University of KwaZulu-Natal, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6191-4023
  7. Inbal Gazy

    KwaZulu-Natal Research Innovation and Sequencing Platform, University of KwaZulu-Natal, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  8. Kondwani Jambo

    Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi
    Competing interests
    The authors declare that no competing interests exist.
  9. COMMIT-KZN

    Africa Health Research Institute, University of KwaZulu-Natal, Durban, South Africa
  10. Willem Hanekom

    Africa Health Research Institute, University of KwaZulu-Natal, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  11. Alex Sigal

    Africa Health Research Institute, University of KwaZulu-Natal, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8571-2004
  12. Zaza M Ndhlovu

    Africa Health Research Institute, University of KwaZulu-Natal, Durban, South Africa
    For correspondence
    zndhlovu@mgh.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2708-3315

Funding

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.

Ethics

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.

Reviewing Editor

  1. Joshua T Schiffer, Fred Hutchinson Cancer Research Center, United States

Publication history

  1. Received: March 4, 2022
  2. Preprint posted: April 6, 2022 (view preprint)
  3. Accepted: July 20, 2022
  4. Accepted Manuscript published: July 26, 2022 (version 1)
  5. Version of Record published: August 5, 2022 (version 2)

Copyright

© 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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  1. Thandeka Nkosi
  2. Caroline Chasara
  3. Andrea O Papadopoulos
  4. Tiza L Nguni
  5. Farina Karim
  6. Mahomed-Yunus S Moosa
  7. Inbal Gazy
  8. Kondwani Jambo
  9. COMMIT-KZN
  10. Willem Hanekom
  11. Alex Sigal
  12. Zaza M Ndhlovu
(2022)
Unsuppressed HIV infection impairs T cell responses to SARS-CoV-2 infection and abrogates T cell cross-recognition
eLife 11:e78374.
https://doi.org/10.7554/eLife.78374
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