TY - JOUR TI - Unsuppressed HIV infection impairs T cell responses to SARS-CoV-2 infection and abrogates T cell cross-recognition AU - Nkosi, Thandeka AU - Chasara, Caroline AU - Papadopoulos, Andrea O AU - Nguni, Tiza L AU - Karim, Farina AU - Moosa, Mahomed-Yunus S AU - Gazy, Inbal AU - Jambo, Kondwani AU - COMMIT-KZN-Team AU - Hanekom, Willem AU - Sigal, Alex AU - Ndhlovu, Zaza M A2 - Schiffer, Joshua T A2 - Taniguchi, Tadatsugu A2 - Schiffer, Joshua T VL - 11 PY - 2022 DA - 2022/07/26 SP - e78374 C1 - eLife 2022;11:e78374 DO - 10.7554/eLife.78374 UR - https://doi.org/10.7554/eLife.78374 AB - 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. KW - SARS-CoV-2 KW - HIV KW - T cell responses KW - SARS-CoV-2 variants JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -