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.
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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).