Evolution of SARS-CoV-2-specific T cell responses from acute COVID-19 infection through convalescence

Authors

• JD Webber
• PA Przygonska
• CR Sclafani
• PF Pryal
• BG Leach
• CS Abdeen
• RA Davey
• J Voell
• M Sneller
• I Sereti
• AF Suffredini
• M Connors
• SA Migueles

Abstract

The T cell response to SARS-CoV-2 is essential for viral clearance and providing a long-term, cross reactive response to other SARS-CoV-2 variants. While a significant amount of information is known about the T cell response to SARS-CoV-2 during convalescence, little is known of the evolution of the T cell response. We studied 20 unvaccinated patients with varying clinical courses from acute infection to convalescence. Clinical course was categorized as mild/moderate or severe based on hospitalization and oxygen requirements. To investigate the T cell response, peripheral blood mononuclear cells were stimulated for 18 hours with either SARS-CoV-2 spike (S), membrane (M), or nucleocapsid (N) peptide pools with flow analysis focusing on the virus-specific (IFN-+ and/or TNF-+) CD4+ or CD8+ T cells. This analysis revealed that the median frequency of virus-specific CD4+ T cells was 2.5-fold higher than the CD8+ T cell response. Individuals with mild/moderate disease tended to have a higher frequency of virus-specific CD4+ T cells compared to those with severe disease from acute infection through convalescence. Furthermore, patients with mild/moderate disease tended to have lower virus-specific CD8+ T cells compared to those with severe disease. Additionally, markers of T cell activation (Ki67, CD38, and PD-1) on virus-specific T cells decreased over time. These results are consistent with previous studies of bronchoalveolar lavage fluid and suggest that measures of T cell activation are the consequence of recent antigen exposure. Understanding the cellular immunologic differences between clinical courses may inform correlates of protection which aid in the development of new vaccines.

Scientific Focus Area: Immunology

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