Unsuppressed HIV infection impairs T cell responses to SARS-CoV-2 infection and abrogates T cell cross-recognition

Nkosi, Thandeka, Chasara, Caroline, Papadopoulos, Andrea O, Nguni, Tiza L, Karim, Farina, Moosa, Mahomed-Yunus S, Gazy, Inbal, Jambo, Kondwani ORCID: https://orcid.org/0000-0002-3195-2210, Hanekom, Willem, Sigal, Alex and Ndhlovu, Zaza M (2022) 'Unsuppressed HIV infection impairs T cell responses to SARS-CoV-2 infection and abrogates T cell cross-recognition'. eLife, Vol 11, e78374.

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Abstract

In some instances, unsuppressed HIV has been associated with severe COVID-19 disease, but the mechanisms underpinning this susceptibility are still unclear. Here, we assessed the impact of HIV infection on the quality and epitope specificity of SARS-CoV-2 T cell responses in the first wave and second wave of the COVID-19 epidemic in South Africa. Flow cytometry was used to measure T cell responses following peripheral blood mononuclear cell stimulation with SARS-CoV-2 peptide pools. Culture expansion was used to determine T cell immunodominance hierarchies and to assess potential SARS-CoV-2 escape from T cell recognition. HIV-seronegative individuals had significantly greater CD4+ T cell responses against the Spike protein compared to the viremic people living with HIV (PLWH). Absolute CD4 count correlated positively with SARS-CoV-2-specific CD4+ and CD8+ T cell responses (CD4 r=0.5, p=0.03; CD8 r=0.5, p=0.001), whereas T cell activation was negatively correlated with CD4+ T cell responses (CD4 r=−0.7, p=0.04). There was diminished T cell cross-recognition between the two waves, which was more pronounced in individuals with unsuppressed HIV infection. Importantly, we identify four mutations in the Beta variant that resulted in abrogation of T cell recognition. Taken together, we show that unsuppressed HIV infection markedly impairs T cell responses to SARS-Cov-2 infection and diminishes T cell cross-recognition. These findings may partly explain the increased susceptibility of PLWH to severe COVID-19 and also highlights their vulnerability to emerging SARS-CoV-2 variants of concern.

Item Type:	Article
Corporate Authors:	COMMIT-KZN-Team
Subjects:	QU Biochemistry > Cells and Genetics > QU 350 Cellular structures WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503.5 Complications WC Communicable Diseases > Virus Diseases > Viral Respiratory Tract Infections. Respirovirus Infections > WC 506 COVID-19
Faculty: Department:	Clinical Sciences & International Health > Malawi-Liverpool-Wellcome Programme (MLW)
Digital Object Identifer (DOI):	https://doi.org/10.7554/elife.78374
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	06 Oct 2022 09:11
Last Modified:	06 Oct 2022 09:11
URI:	https://archive.lstmed.ac.uk/id/eprint/20937

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