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

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

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Figure 3

Memory and activation profile of SARS-CoV-2–specific CD4+ T cells between COVID-19 cases and SARS-CoV-2–uninfected hospitalized patients.

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Memory and activation profile of SARS-CoV-2–specific CD4+ T cells betwee...
(A) Overlay flow plots of CD45RA, CD27, PD-1, GrB, CD38, and HLA-DR expression. Dots depict SARS-CoV-2–specific CD4+ T cells and density plots depict total CD4+ T cells. Four memory subsets can be delineated: naive (CD45RA+CD27+), early differentiated (ED, CD45RA–CD27+), late differentiated (LD, CD45RA–CD27–), and effector (Eff, CD45RA+CD27–). (B) Summary graphs of the expression of each marker in SARS-CoV-2–specific CD4+ T cells (n = 75 COVID-19 patients and n = 12 hospitalized controls). The phenotype of SARS-CoV-2–specific CD4+ T cells was assessed only in those with response greater than 20 events. Bars represent medians. Statistical comparisons were calculated using the nonparametric Mann-Whitney U test. (C) Heatmap of pairwise Spearman’s correlations between phenotypical and functional traits of SARS-CoV-2–specific CD4+ T cells. Spearman’s rank r correlation values are shown from blue, –1, to yellow, 1. The red box identifies the profile of ED SARS-CoV-2–specific CD4+ T cells and the blue box the profile of LD cells enriched in hospitalized controls. (D) PCA (left) based on the 8 phenotypical and functional attributes of SARS-CoV-2–specific CD4+ T cells (LD, GrB, HLA-DR, Ki67, CD38 and the proportion of IFN-γ+IL-2+TNF-α+, IFN-γ+IL-2–TNF-α+, and IFN-γ–IL-2–TNF-α+ cells) and corresponding loading plot (right).