HIV status alters disease severity and immune cell responses in beta variant SARS-CoV-2 infection wave

  1. Farina Karim
  2. Inbal Gazy
  3. Sandile Cele
  4. Yenzekile Zungu
  5. Robert Krause
  6. Mallory Bernstein
  7. Khadija Khan
  8. Yashica Ganga
  9. Hylton Errol Rodel
  10. Ntombifuthi Mthabela
  11. Matilda Mazibuko
  12. Daniel Muema
  13. Dirhona Ramjit
  14. Thumbi Ndung'u
  15. Willem Hanekom
  16. Bernadett Gosnell
  17. Richard J Lessells
  18. Emily B Wong
  19. Tulio de Oliveira
  20. Yunus Moosa
  21. Gil Lustig
  22. Alasdair Leslie  Is a corresponding author
  23. Henrik Kløverpris  Is a corresponding author
  24. Alex Sigal  Is a corresponding author
  1. Africa Health Research Institute, South Africa
  2. University of KwaZulu-Natal, South Africa
  3. Africa Health Research Institute; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, South Africa
  4. Africa Health Research Institute; Division of Infection and Immunity, University College London, South Africa
  5. Department of Infectious Diseases, Nelson R. Mandela School of Clinical Medicine, University of KwaZulu-Natal, South Africa
  6. KwaZulu-Natal Research Institute for TB-HIV, South Africa
  7. University of KwaZulu-Natal,SA, South Africa
  8. Centre for the AIDS Programme of Research in South Africa, South Africa
  9. African Health Research Institute, South Africa
  10. Africa Health Research Institute, University of KwaZulu-Natal, South Africa

Abstract

There are conflicting reports on the effects of HIV on COVID-19. Here we analyzed disease severity and immune cell changes during and after SARS-CoV-2 infection in 236 participants from South Africa, of which 39% were people living with HIV (PLWH), during the first and second (beta dominated) infection waves. The second wave had more PLWH requiring supplemental oxygen relative to HIV negative participants. Higher disease severity was associated with low CD4 T cell counts and higher neutrophil to lymphocyte ratios (NLR). Yet, CD4 counts recovered and NLR stabilized after SARS-CoV-2 clearance in wave 2 infected PLWH, arguing for an interaction between SARS-CoV-2 and HIV infection leading to low CD4 and high NLR. The first infection wave, where severity in HIV negative and PLWH was similar, still showed some HIV modulation of SARS-CoV-2 immune responses. Therefore, HIV infection can synergize with the SARS-CoV-2 variant to change COVID-19 outcomes.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files

Article and author information

Author details

  1. Farina Karim

    Division of Clinical Studies, Africa Health Research Institute, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  2. Inbal Gazy

    University of KwaZulu-Natal, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  3. Sandile Cele

    Systems Infection Biology, Africa Health Research Institute, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  4. Yenzekile Zungu

    Africa Health Research Institute, Africa Health Research Institute, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  5. Robert Krause

    Africa Health Research Institute, Africa Health Research Institute; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  6. Mallory Bernstein

    Africa Health Research Institute, Africa Health Research Institute, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  7. Khadija Khan

    Division of Clinical Studies, Africa Health Research Institute, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  8. Yashica Ganga

    Africa Health Research Institute, Africa Health Research Institute, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  9. Hylton Errol Rodel

    Systems Infection Biology, Africa Health Research Institute, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  10. Ntombifuthi Mthabela

    Africa Health Research Institute, Africa Health Research Institute, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  11. Matilda Mazibuko

    Africa Health Research Institute, Africa Health Research Institute, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  12. Daniel Muema

    Africa Health Research Institute; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Africa Health Research Institute; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  13. Dirhona Ramjit

    Africa Health Research Institute, Africa Health Research Institute, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  14. Thumbi Ndung'u

    Africa Health Research Institute, Africa Health Research Institute, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2962-3992
  15. Willem Hanekom

    Africa Health Research Institute; Division of Infection and Immunity, University College London, Africa Health Research Institute; Division of Infection and Immunity, University College London, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  16. Bernadett Gosnell

    Department of Infectious Diseases, Nelson R. Mandela School of Clinical Medicine, University of KwaZulu-Natal, Department of Infectious Diseases, Nelson R. Mandela School of Clinical Medicine, University of KwaZulu-Natal, Durbans, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  17. Richard J Lessells

    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:" 0000-0003-0926-710X
  18. Emily B Wong

    KwaZulu-Natal Research Institute for TB-HIV, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  19. Tulio de Oliveira

    School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal,SA, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  20. Yunus Moosa

    Department of Infectious Diseases, Nelson R. Mandela School of Clinical Medicine, University of KwaZulu-Natal, Department of Infectious Diseases, Nelson R. Mandela School of Clinical Medicine, University of KwaZulu-Natal, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  21. Gil Lustig

    Centre for the AIDS Programme of Research in South Africa, Centre for the AIDS Programme of Research in South Africa, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  22. Alasdair Leslie

    African Health Research Institute, Durban, South Africa
    For correspondence
    Al.Leslie@ahri.org
    Competing interests
    The authors declare that no competing interests exist.
  23. Henrik Kløverpris

    Africa Health Research Institute, Africa Health Research Institute, Durban, South Africa
    For correspondence
    Henrik.Kloverpris@ahri.org
    Competing interests
    The authors declare that no competing interests exist.
  24. Alex Sigal

    School of Laboratory Medicine and Medical Sciences, Africa Health Research Institute, University of KwaZulu-Natal, Durban, South Africa
    For correspondence
    alex.sigal@ahri.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8571-2004

Funding

Bill and Melinda Gates Foundation (INV-018944)

  • Alex Sigal

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The study protocol was approved by the University of KwaZulu-Natal Institutional Review Board (approval BREC/00001275/2020). Adult patients ($>$18 years old) presenting either at King Edward VIII or Clairwood Hospitals in Durban, South Africa, between 8 June to 25 September 2020, diagnosed to be SARS-CoV-2 positive as part of their clinical workup and able to provide informed consent were eligible for the study. Written informed consent was obtained for all enrolled participants.

Reviewing Editor

  1. Lishomwa Ndhlovu

Publication history

  1. Received: February 9, 2021
  2. Accepted: September 7, 2021
  3. Accepted Manuscript published: October 5, 2021 (version 1)
  4. Accepted Manuscript updated: October 6, 2021 (version 2)
  5. Version of Record published: December 16, 2021 (version 3)

Copyright

© 2021, Karim 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. Farina Karim
  2. Inbal Gazy
  3. Sandile Cele
  4. Yenzekile Zungu
  5. Robert Krause
  6. Mallory Bernstein
  7. Khadija Khan
  8. Yashica Ganga
  9. Hylton Errol Rodel
  10. Ntombifuthi Mthabela
  11. Matilda Mazibuko
  12. Daniel Muema
  13. Dirhona Ramjit
  14. Thumbi Ndung'u
  15. Willem Hanekom
  16. Bernadett Gosnell
  17. Richard J Lessells
  18. Emily B Wong
  19. Tulio de Oliveira
  20. Yunus Moosa
  21. Gil Lustig
  22. Alasdair Leslie
  23. Henrik Kløverpris
  24. Alex Sigal
(2021)
HIV status alters disease severity and immune cell responses in beta variant SARS-CoV-2 infection wave
eLife 10:e67397.
https://doi.org/10.7554/eLife.67397
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