1. Microbiology and Infectious Disease
Download icon

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
Research Article
  • Cited 1
  • Views 398
  • Annotations
Cite this article as: eLife 2021;10:e67397 doi: 10.7554/eLife.67397

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)

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.

Metrics

  • 398
    Page views
  • 104
    Downloads
  • 1
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

  1. Further reading

Further reading

    1. Evolutionary Biology
    2. Microbiology and Infectious Disease
    Erik Bakkeren et al.
    Research Article

    Many plasmids encode antibiotic resistance genes. Through conjugation, plasmids can be rapidly disseminated. Previous work identified gut luminal donor/recipient blooms and tissue-lodged plasmid-bearing persister cells of the enteric pathogen Salmonella enterica serovar Typhimurium (S.Tm) that survive antibiotic therapy in host tissues, as factors promoting plasmid dissemination among Enterobacteriaceae. However, the buildup of tissue reservoirs and their contribution to plasmid spread await experimental demonstration. Here, we asked if re-seeding-plasmid acquisition-invasion cycles by S.Tm could serve to diversify tissue-lodged plasmid reservoirs, and thereby promote plasmid spread. Starting with intraperitoneal mouse infections, we demonstrate that S.Tm cells re-seeding the gut lumen initiate clonal expansion. Extended spectrum beta-lactamase (ESBL) plasmid-encoded gut luminal antibiotic degradation by donors can foster recipient survival under beta-lactam antibiotic treatment, enhancing transconjugant formation upon re-seeding. S.Tm transconjugants can subsequently re-enter host tissues introducing the new plasmid into the tissue-lodged reservoir. Population dynamics analyses pinpoint recipient migration into the gut lumen as rate-limiting for plasmid transfer dynamics in our model. Priority effects may be a limiting factor for reservoir formation in host tissues. Overall, our proof-of-principle data indicates that luminal antibiotic degradation and shuttling between the gut lumen and tissue-resident reservoirs can promote the accumulation and spread of plasmids within a host over time.

    1. Microbiology and Infectious Disease
    Fred D Mast et al.
    Research Article

    The emergence of SARS-CoV-2 variants threatens current vaccines and therapeutic antibodies and urgently demands powerful new therapeutics that can resist viral escape. We therefore generated a large nanobody repertoire to saturate the distinct and highly conserved available epitope space of SARS-CoV-2 spike, including the S1 receptor binding domain, N-terminal domain, and the S2 subunit, to identify new nanobody binding sites that may reflect novel mechanisms of viral neutralization. Structural mapping and functional assays show that indeed these highly stable monovalent nanobodies potently inhibit SARS-CoV-2 infection, display numerous neutralization mechanisms, are effective against emerging variants of concern, and are resistant to mutational escape. Rational combinations of these nanobodies that bind to distinct sites within and between spike subunits exhibit extraordinary synergy and suggest multiple tailored therapeutic and prophylactic strategies.