1. Microbiology and Infectious Disease
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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
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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.

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  1. Further reading

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    Background:

    Early identification of severe dengue patients is important regarding patient management and resource allocation. We investigated the association of 10 biomarkers (VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, CRP) with the development of severe/moderate dengue (S/MD).

    Methods:

    We performed a nested case-control study from a multi-country study. A total of 281 S/MD and 556 uncomplicated dengue cases were included.

    Results:

    On days 1–3 from symptom onset, higher levels of any biomarker increased the risk of developing S/MD. When assessing together, SDC-1 and IL-1RA were stable, while IP-10 changed the association from positive to negative; others showed weaker associations. The best combinations associated with S/MD comprised IL-1RA, Ang-2, IL-8, ferritin, IP-10, and SDC-1 for children, and SDC-1, IL-8, ferritin, sTREM-1, IL-1RA, IP-10, and sCD163 for adults.

    Conclusions:

    Our findings assist the development of biomarker panels for clinical use and could improve triage and risk prediction in dengue patients.

    Funding:

    This study was supported by the EU's Seventh Framework Programme (FP7-281803 IDAMS), the WHO, and the Bill and Melinda Gates Foundation.

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    The influenza A virus (IAV) genome consists of eight negative-sense viral RNA (vRNA) segments that are selectively assembled into progeny virus particles through RNA-RNA interactions. To explore putative intersegmental RNA-RNA relationships, we quantified similarity between phylogenetic trees comprising each vRNA segment from seasonal human IAV. Intersegmental tree similarity differed between subtype and lineage. While intersegmental relationships were largely conserved over time in H3N2 viruses, they diverged in H1N1 strains isolated before and after the 2009 pandemic. Surprisingly, intersegmental relationships were not driven solely by protein sequence, suggesting that IAV evolution could also be driven by RNA-RNA interactions. Finally, we used confocal microscopy to determine that colocalization of highly coevolved vRNA segments is enriched over other assembly intermediates at the nuclear periphery during productive viral infection. This study illustrates how putative RNA interactions underlying selective assembly of IAV can be interrogated with phylogenetics.