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

Author:

Karim Farina12ORCID,Gazy Inbal23,Cele Sandile12,Zungu Yenzekile1,Krause Robert12ORCID,Bernstein Mallory1,Khan Khadija12,Ganga Yashica1,Rodel Hylton14,Mthabela Ntombifuthi1,Mazibuko Matilda1,Muema Daniel12,Ramjit Dirhona1,Ndung'u Thumbi1456ORCID,Hanekom Willem14,Gosnell Bernadett7,Archary Moherndran8,Dullabh Kaylesh J9,Giandhari Jennifer3,Goulder Philip10,Harling Guy11,Harrichandparsad Rohen12,Herbst Kobus13,Jeena Prakash8,Khoza Thandeka1,Klein Nigel14,Madansein Rajhmun9,Marakalala Mohlopheni15,Moshabela Mosa16,Naidoo Kogie17,Ndhlovu Zaza18,Nyamande Kennedy19,Padayatchi Nesri17,Patel Vinod20,Smit Theresa1,Steyn Adrie21,Lessells Richard J2317ORCID,Wong Emily B122,de Oliveira Tulio23172324,Moosa Mahomed-Yunus S7,Lustig Gil17,Leslie Alasdair124,Kløverpris Henrik12425,Sigal Alex126ORCID,

Affiliation:

1. Africa Health Research Institute

2. School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal

3. KwaZulu-Natal Research Innovation and Sequencing Platform

4. Division of Infection and Immunity, University College London

5. HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal

6. Max Planck Institute for Infection Biology

7. Department of Infectious Diseases, Nelson R. Mandela School of Clinical Medicine, University of KwaZulu-Natal

8. Department of Paediatrics and Child Health, University of KwaZulu-Natal

9. Department of Cardiothoracic Surgery, University of KwaZulu-Natal

10. Africa Health Research Institute and Department of Paediatrics, University of Oxford

11. Africa Health Research Institute and the Institute for Global Health, University College London

12. Department of Neurosurgery, University of KwaZulu-Natal

13. Africa Health Research Institute and the South African Population Research Infrastructure Network

14. Africa Health Research Institute and the Institute of Child Health, University College London

15. Africa Health Research Institute and Division of Infection and Immunity, University College London

16. College of Health Sciences, University of KwaZulu-Natal

17. Centre for the AIDS Programme of Research in South Africa

18. Africa Health Research Institute and the Ragon Institute of MGH, MIT and Harvard

19. Department of Pulmonology and Critical Care, University of KwaZulu-Natal

20. Department of Neurology, University of KwaZulu-Natal

21. Africa Health Research Institute and Division of Infectious Diseases, University of Alabama at Birmingham

22. Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham

23. Centre for Epidemic Response and Innovation, School of Data Science and Computational Thinking, Stellenbosch University

24. Department of Global Health, University of Washington

25. Department of Immunology and Microbiology, University of Copenhagen

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.

Funder

Bill and Melinda Gates Foundation

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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