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 6

Impact of HIV, aTB, and HIV/aTB coinfection on SARS-CoV-2–specific CD4+ T cell response.

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Impact of HIV, aTB, and HIV/aTB coinfection on SARS-CoV-2–specific CD4+ ...
(A) Comparison of COVID-19 severity (defined by the composite analysis of clinical parameters, PC1 severity) between patients grouped according to HIV and/or aTB coinfection. (B) Prevalence and frequencies of SARS-CoV-2–specific CD4+ T cells in COVID-19 patients stratified by HIV and/or aTB coinfection. Statistical comparisons were defined using a Kruskal-Wallis test adjusted for multiple comparisons (Dunn’s test). (C) Comparison of the frequency of total CD4+ T cells between SARS-CoV-2 CD4 responders and nonresponders. Dots are color-coded according to patient’s HIV and TB status. Statistical comparison was performed using the Mann-Whitney U test. (D) Association between the frequency of SARS-CoV-2–specific CD4+ T cells and total CD4+ T cells in HIV-infected COVID-19 patients. Correlation was tested by a 2-tailed nonparametric Spearman’s rank test. (E) Prevalence and magnitude of SARS-CoV-2–specific serological response (defined using the Roche Elecsys assay) in COVID-19 patients stratified by HIV and/or aTB coinfection. (F) Association between the magnitude of SARS-CoV-2–specific serological response and the frequency of total CD4+ T cells in HIV-infected COVID-19 patients. Correlation was tested by a 2-tailed nonparametric Spearman’s rank test. (G) Polyfunctional profile of SARS-CoV-2–specific CD4+ T cells in COVID-19 cases stratified by HIV or aTB coinfection. For this analysis, HIV–/aTB+ and HIV+/aTB+ patients were combined in 1 group (aTB). Dots are color-coded according to patients’ HIV and TB status. Wilcoxon’s rank test was used to compare response patterns between groups (**P < 0.01). Statistical differences between pie charts were defined using a permutation test. (H) Comparison of the overall profile of SARS-CoV-2–specific CD4+ T cells (PC2 phenotype) in COVID-19 cases stratified by HIV or aTB coinfection. Statistical comparisons were defined using a Kruskal-Wallis test adjusted for multiple comparisons (Dunn’s test).