T cell phenotypes in COVID-19

Hanna, Stephanie J; Codd, Amy S; Gea-Mallorqui, Ester; Scourfield, D Oliver; Richter, Felix C; Ladell, Kristin; Borsa, Mariana; Compeer, Ewoud B; Moon, Owen R; Galloway, Sarah A E; Dimonte, Sandra; Capitani, Lorenzo; Shepherd, Freya R; Wilson, Joseph D; Uhl, Lion F K; Gallimore, Awen M; Milicic, Anita

COVID-19 is characterised by profound lymphopenia in the peripheral blood, and the remaining T cells display altered phenotypes, characterised by a spectrum of activation and exhaustion. However, antigen-specific T cell responses are emerging as a crucial mechanism for both clearance of the virus and as the most likely route to long-lasting immune memory that would protect against re-infection. Therefore, T cell responses are also of considerable interest in vaccine development. Furthermore, persistent alterations in T cell subset composition and function post-infection have important implications for patients’ long-term immune function. In this review, we examine T cell phenotypes, including those of innate T cells, in both peripheral blood and lungs, and consider how key markers of activation and exhaustion correlate with, and may be able to predict, disease severity. We focus on SARS-CoV-2 specific T cells to elucidate markers which may indicate formation of antigen-specific T cell memory. We also examine peripheral T cell phenotypes in recovery and the likelihood of long-lasting immune disruption. Finally, we discuss T cell phenotypes in the lung as important drivers of both virus clearance and tissue damage. As our knowledge of the adaptive immune response to COVID-19 rapidly evolves, it has become clear that whilst some areas of the T cell response have been investigated in some detail, others, such as the T cell response in children remain largely unexplored. Therefore, this review will also highlight areas where T cell phenotypes require urgent characterisation.