Relationship of SARS-CoV-2–specific CD4 response to COVID-19 severity and impact of HIV-1 and tuberculosis coinfection
Catherine Riou, … , Robert J. Wilkinson, on behalf of the HIATUS consortium
Catherine Riou, … , Robert J. Wilkinson, on behalf of the HIATUS consortium
Published May 4, 2021
Citation Information: J Clin Invest. 2021;131(12):e149125. https://doi.org/10.1172/JCI149125.
View: Text | PDF
Research Article AIDS/HIV COVID-19

Relationship of SARS-CoV-2–specific CD4 response to COVID-19 severity and impact of HIV-1 and tuberculosis coinfection

Abstract

T cells are involved in control of coronavirus disease 2019 (COVID-19), but limited knowledge is available on the relationship between antigen-specific T cell response and disease severity. Here, we used flow cytometry to assess the magnitude, function, and phenotype of SARS coronavirus 2–specific (SARS-CoV-2–specific) CD4+ T cells in 95 hospitalized COVID-19 patients, 38 of them being HIV-1 and/or tuberculosis (TB) coinfected, and 38 non–COVID-19 patients. We showed that SARS-CoV-2–specific CD4+ T cell attributes, rather than magnitude, were associated with disease severity, with severe disease being characterized by poor polyfunctional potential, reduced proliferation capacity, and enhanced HLA-DR expression. Moreover, HIV-1 and TB coinfection skewed the SARS-CoV-2 T cell response. HIV-1–mediated CD4+ T cell depletion associated with suboptimal T cell and humoral immune responses to SARS-CoV-2, and a decrease in the polyfunctional capacity of SARS-CoV-2–specific CD4+ T cells was observed in COVID-19 patients with active TB. Our results also revealed that COVID-19 patients displayed reduced frequency of Mycobacterium tuberculosis–specific CD4+ T cells, with possible implications for TB disease progression. These results corroborate the important role of SARS-CoV-2–specific T cells in COVID-19 pathogenesis and support the concept of altered T cell functions in patients with severe disease.

Authors

Catherine Riou, Elsa du Bruyn, Cari Stek, Remy Daroowala, Rene T. Goliath, Fatima Abrahams, Qonita Said-Hartley, Brian W. Allwood, Nei-Yuan Hsiao, Katalin A. Wilkinson, Cecilia S. Lindestam Arlehamn, Alessandro Sette, Sean Wasserman, Robert J. Wilkinson, on behalf of the HIATUS consortium

×

Figure 7

Impact of COVID-19 on M.

Options: View larger image (or click on image) Download as PowerPoint
Impact of COVID-19 on M. tuberculosis–specific CD4+ T cell response. (A...
tuberculosis–specific CD4+ T cell response. (A) Representative examples of flow cytometry plots of SARS-CoV-2– and M. tuberculosis–specific CD4+ T cell responses in 3 COVID-19 patients (1 HIV–/aTB–, 1 HIV+/aTB–, and 1 HIV+/aTB+). (B) Comparison of the prevalence and frequencies of SARS-CoV-2– and M. tuberculosis–specific CD4+ T cells in COVID-19 patients stratified by HIV or aTB coinfection. The proportion of responders to each pathogen (S: SARS-CoV-2 and M: M. tuberculosis) is presented with pies at the top of the graph. Statistical comparisons were performed using the χ2 test. Participants were grouped according to their HIV and/or TB status. Black bars represent the medians. (C) Comparisons of the frequencies of M. tuberculosis–specific CD4+ T cells in a cohort recruited before the emergence of COVID-19 (2018, n = 114), SARS-CoV-2–uninfected hospitalized controls (n = 29), and COVID-19 cases (n = 76). Participants were stratified according to their HIV and/or TB status. Statistical comparisons were defined using a Kruskal-Wallis test adjusted for multiple comparisons (Dunn’s test) for each subgroup. (D) Representative flow cytometry plots of HLA-DR expression on TNF-α–producing M. tuberculosis–specific CD4+ T cells in 3 COVID-19 patients (1 HIV–/aTB–, 1 HIV+/aTB–, and 1 HIV+/aTB+). (E) Summary graph of HLA-DR expression on M. tuberculosis–specific CD4+ T cells in a cohort recruited before the emergence of COVID-19 (2018), SARS-CoV-2–uninfected hospitalized controls, and COVID-19 cases stratified according to HIV and TB status. The phenotype of M. tuberculosis–specific CD4+ T cells was assessed only in those with response greater than 20 events.