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

Farina Karim; Inbal Gazy; Sandile Cele; Yenzekile Zungu; Robert Krause; Mallory Bernstein; Khadija Khan; Yashica Ganga; Hylton Rodel; Ntombifuthi Mthabela; Matilda Mazibuko; Daniel Muema; Dirhona Ramjit; Thumbi Ndung'u; Willem Hanekom; Bernadett Gosnell; COMMIT-KZN Team; Richard J Lessells; Emily B Wong; Tulio de Oliveira; Mahomed-Yunus S Moosa; Gil Lustig; Alasdair Leslie; Henrik Kløverpris; Alex Sigal

doi:10.7554/eLife.67397

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

Elife. 2021 Oct 5:10:e67397. doi: 10.7554/eLife.67397.

Authors

Farina Karim^{1

2}, Inbal Gazy^{2

3}, Sandile Cele^{1

2}, Yenzekile Zungu¹, Robert Krause^{1

2}, Mallory Bernstein¹, Khadija Khan^{1

2}, Yashica Ganga¹, Hylton Rodel^{1

4}, Ntombifuthi Mthabela¹, Matilda Mazibuko¹, Daniel Muema^{1

2}, Dirhona Ramjit¹, Thumbi Ndung'u^{1

4

5

6}, Willem Hanekom^{1

4}, Bernadett Gosnell⁷; COMMIT-KZN Team; Richard J Lessells^{2

3

17}, Emily B Wong^{1

22}, Tulio de Oliveira^{2

3

17

23

24}, Mahomed-Yunus S Moosa⁷, Gil Lustig¹⁷, Alasdair Leslie^{1

2

4}, Henrik Kløverpris^{1

2

4

25}, Alex Sigal^{1

2

6}

Collaborators

COMMIT-KZN Team:
Moherndran Archary⁸, Kaylesh J Dullabh⁹, Jennifer Giandhari³, Philip Goulder¹⁰, Guy Harling¹¹, Rohen Harrichandparsad¹², Kobus Herbst¹³, Prakash Jeena⁸, Thandeka Khoza¹, Nigel Klein¹⁴, Rajhmun Madansein⁹, Mohlopheni Marakalala¹⁵, Mosa Moshabela¹⁶, Kogie Naidoo¹⁷, Zaza Ndhlovu¹⁸, Kennedy Nyamande¹⁹, Nesri Padayatchi¹⁷, Vinod Patel²⁰, Theresa Smit¹, Adrie Steyn²¹

Affiliations

¹ Africa Health Research Institute, Durban, South Africa.
² School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
³ KwaZulu-Natal Research Innovation and Sequencing Platform, Durban, South Africa.
⁴ Division of Infection and Immunity, University College London, London, United Kingdom.
⁵ HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
⁶ Max Planck Institute for Infection Biology, Berlin, Germany.
⁷ Department of Infectious Diseases, Nelson R. Mandela School of Clinical Medicine, University of KwaZulu-Natal, Durban, South Africa.
⁸ Department of Paediatrics and Child Health, University of KwaZulu-Natal, Durban, South Africa.
⁹ Department of Cardiothoracic Surgery, University of KwaZulu-Natal, Durban, South Africa.
¹⁰ Africa Health Research Institute and Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
¹¹ Africa Health Research Institute and the Institute for Global Health, University College London, London, United Kingdom.
¹² Department of Neurosurgery, University of KwaZulu-Natal, Durban, South Africa.
¹³ Africa Health Research Institute and the South African Population Research Infrastructure Network, Durban, South Africa.
¹⁴ Africa Health Research Institute and the Institute of Child Health, University College London, London, United Kingdom.
¹⁵ Africa Health Research Institute and Division of Infection and Immunity, University College London, London, United Kingdom.
¹⁶ College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
¹⁷ Centre for the AIDS Programme of Research in South Africa, Durban, South Africa.
¹⁸ Africa Health Research Institute and the Ragon Institute of MGH, MIT and Harvard, Cambridge, United States.
¹⁹ Department of Pulmonology and Critical Care, University of KwaZulu-Natal, Durban, South Africa.
²⁰ Department of Neurology, University of KwaZulu-Natal, Durban, South Africa.
²¹ Africa Health Research Institute and Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, United States.
²² Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, United States.
²³ Centre for Epidemic Response and Innovation, School of Data Science and Computational Thinking, Stellenbosch University, Stellenbosch, South Africa.
²⁴ Department of Global Health, University of Washington, Seattle, United States.
²⁵ Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.

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.

Keywords: COVID-19; HIV; SARS-CoV-2; antiretroviral therapy; beta variant; infectious disease; microbiology; virus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
CD4 Lymphocyte Count
COVID-19 / complications*
COVID-19 / immunology*
Female
HIV Infections / complications*
HIV Infections / immunology*
Humans
Immunity, Cellular*
Male
Middle Aged
SARS-CoV-2
Severity of Illness Index*
South Africa

Supplementary concepts

SARS-CoV-2 variants

Abstract

Publication types

MeSH terms

Supplementary concepts

Grants and funding