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 5

Relationship between COVID-19 severity and functional and phenotypical traits of SARS-CoV-2–specific CD4+ T cells.

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Relationship between COVID-19 severity and functional and phenotypical t...
(A) Spearman’s correlation r values between indicated SARS-CoV-2–specific CD4+ T cell features and COVID-19 severity (defined by the composite analysis of clinical parameters, PC1 severity). Negative associations are represented in blue and positive associations in yellow. P values are indicated for each comparison. (B) Comparison of the overall profile of SARS-CoV-2–specific CD4+ T cells (PC2 phenotype) in COVID-19 cases (n = 74) stratified by WHO ordinal score and outcome. Statistical comparisons were defined using a Kruskal-Wallis test, adjusted for multiple comparisons (Dunn’s test) for the different WHO groups and the Mann-Whitney U test to compare COVID-19 patients who survived or died. (C) Association between COVID-19 severity (PC1 severity) and the overall profile of SARS-CoV-2–specific CD4+ T cells (PC2 phenotype). COVID-19 survivors are depicted in gray and patients who died in black. Correlation was tested by a 2-tailed nonparametric Spearman’s rank test.