HIV Status Alters Disease Severity and Immune Cell Responses in Beta Variant SARS-CoV-2 Infection Wave

Overview

Journal Elife

Specialty Biology

Date 2021 Oct 5

PMID 34608862

Citations 29

Authors

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 Ndungu

Willem Hanekom

Bernadett Gosnell

Richard J Lessells

Emily B Wong

Tulio de Oliveira

Mahomed-Yunus S Moosa

Gil Lustig

Alasdair Leslie

Henrik Kloverpris

Alex Sigal

Affiliations

Soon will be listed here.

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.

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References

Mavigner M, Cazabat M, Dubois M, LFaqihi F, Requena M, Pasquier C . Altered CD4+ T cell homing to the gut impairs mucosal immune reconstitution in treated HIV-infected individuals. J Clin Invest. 2011; 122(1):62-9. PMC: 3248296. DOI: 10.1172/JCI59011. View

Geretti A, Stockdale A, Kelly S, Cevik M, Collins S, Waters L . Outcomes of Coronavirus Disease 2019 (COVID-19) Related Hospitalization Among People With Human Immunodeficiency Virus (HIV) in the ISARIC World Health Organization (WHO) Clinical Characterization Protocol (UK): A Prospective Observational Study. Clin Infect Dis. 2020; 73(7):e2095-e2106. PMC: 7665382. DOI: 10.1093/cid/ciaa1605. View

Liu J, Li S, Liu J, Liang B, Wang X, Wang H . Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine. 2020; 55:102763. PMC: 7165294. DOI: 10.1016/j.ebiom.2020.102763. View

Dandachi D, Geiger G, Montgomery M, Karmen-Tuohy S, Golzy M, Antar A . Characteristics, Comorbidities, and Outcomes in a Multicenter Registry of Patients With Human Immunodeficiency Virus and Coronavirus Disease 2019. Clin Infect Dis. 2020; 73(7):e1964-e1972. PMC: 7499544. DOI: 10.1093/cid/ciaa1339. View

Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H . Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020; 8(5):475-481. PMC: 7102538. DOI: 10.1016/S2213-2600(20)30079-5. View

Madhi S, Baillie V, Cutland C, Voysey M, Koen A, Fairlie L . Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant. N Engl J Med. 2021; 384(20):1885-1898. PMC: 7993410. DOI: 10.1056/NEJMoa2102214. View

Robbiani D, Gaebler C, Muecksch F, Lorenzi J, Wang Z, Cho A . Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature. 2020; 584(7821):437-442. PMC: 7442695. DOI: 10.1038/s41586-020-2456-9. View

Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H . Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020; 130(5):2620-2629. PMC: 7190990. DOI: 10.1172/JCI137244. View

Ryscavage P, Kelly S, Li J, Harrigan P, Taiwo B . Significance and clinical management of persistent low-level viremia and very-low-level viremia in HIV-1-infected patients. Antimicrob Agents Chemother. 2014; 58(7):3585-98. PMC: 4068602. DOI: 10.1128/AAC.00076-14. View

10.

Fuster F, Vargas J, Jensen D, Sarmiento V, Acuna P, Peirano F . CD4/CD8 ratio as a predictor of the response to HBV vaccination in HIV-positive patients: A prospective cohort study. Vaccine. 2016; 34(16):1889-95. DOI: 10.1016/j.vaccine.2016.02.055. View

11.

Cooper C, Thorne A, Klein M, Conway B, Boivin G, Haase D . Immunogenicity is not improved by increased antigen dose or booster dosing of seasonal influenza vaccine in a randomized trial of HIV infected adults. PLoS One. 2011; 6(3):e17758. PMC: 3064575. DOI: 10.1371/journal.pone.0017758. View

12.

Liu Y, Du X, Chen J, Jin Y, Peng L, Wang H . Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19. J Infect. 2020; 81(1):e6-e12. PMC: 7195072. DOI: 10.1016/j.jinf.2020.04.002. View

13.

Huang J, Xie N, Hu X, Yan H, Ding J, Liu P . Epidemiological, Virological and Serological Features of Coronavirus Disease 2019 (COVID-19) Cases in People Living With Human Immunodeficiency Virus in Wuhan: A Population-based Cohort Study. Clin Infect Dis. 2020; 73(7):e2086-e2094. PMC: 7454403. DOI: 10.1093/cid/ciaa1186. View

14.

Dalgleish A, Beverley P, Clapham P, Crawford D, Greaves M, Weiss R . The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984; 312(5996):763-7. DOI: 10.1038/312763a0. View

15.

Cele S, Gazy I, Jackson L, Hwa S, Tegally H, Lustig G . Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma. Nature. 2021; 593(7857):142-146. PMC: 9867906. DOI: 10.1038/s41586-021-03471-w. View

16.

Hadi Y, Naqvi S, Kupec J, Sarwari A . Characteristics and outcomes of COVID-19 in patients with HIV: a multicentre research network study. AIDS. 2020; 34(13):F3-F8. PMC: 8407436. DOI: 10.1097/QAD.0000000000002666. View

17.

Sekine T, Perez-Potti A, Rivera-Ballesteros O, Stralin K, Gorin J, Olsson A . Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19. Cell. 2020; 183(1):158-168.e14. PMC: 7427556. DOI: 10.1016/j.cell.2020.08.017. View

18.

Tegally H, Wilkinson E, Giovanetti M, Iranzadeh A, Fonseca V, Giandhari J . Detection of a SARS-CoV-2 variant of concern in South Africa. Nature. 2021; 592(7854):438-443. DOI: 10.1038/s41586-021-03402-9. View

19.

Westendorp M, Frank R, Ochsenbauer C, Stricker K, Dhein J, Walczak H . Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120. Nature. 1995; 375(6531):497-500. DOI: 10.1038/375497a0. View

20.

Wibmer C, Ayres F, Hermanus T, Madzivhandila M, Kgagudi P, Oosthuysen B . SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma. Nat Med. 2021; 27(4):622-625. DOI: 10.1038/s41591-021-01285-x. View