T cell phenotypes in COVID-19 - a living review
Stephanie Hanna, Amy Codd, Ester Gea‐Mallorquí, David Oliver Scourfield, Felix Clemens Richter, Kristin Ladell, Mariana Borsa, Ewoud B. Compeer, Owen Moon, Sarah A. E. Galloway, Sandra Dimonte, Lorenzo Capitani, Freya R Shepherd, Joseph D. Wilson, Lion F. K. Uhl, David Ahern, Hannah Almuttaqi, Dominic S. Alonzi, Aljawharah Alrubayyi, Ghada Alsaleh, Valentina M T Bart, Vicky Batchelor, R. Bayliss, Dorothée L. Berthold, Jelena S. Bezbradica, Tehmina Bharuchq, Helene Borrmann, Mariana Borsa, Rowie Borst, Juliane Brun, Stephanie Burnell, Lorenzo Capitani, Athena Cavounidis, Lucy Chapman, Anne Chauveau, Liliana Cifuentes, Amy Codd, Ewoud B. Compeer, Clarissa Coveney, Amy Cross, Sara Danielli, Luke C. Davies, Calliope A. Dendrou, Sandra Dimonte, Ruban Rex Peter Durairaj, Lynn B. Dustin, Arthur Dyer, Ceri A. Fielding, Fabian Fischer, Awen Gallimore, Sarah A. E. Galloway, Anís N. Gammage, Ester Gea‐Mallorquí, Andrew Godkin, Stephanie Hanna, Cornelia Heuberger, Sarah L. Hulin-Curtis, Fadi Issa, Emma Jones, Ruth Jones, Kristin Ladell, Sarah N. Lauder, Kate Liddiard, Petros Ligoxygakis, Fangfang Lu, Bruce J. MacLachlan, Shayda Maleki-Toyserkani, Elizabeth H. Mann, Anna M. Marzeda, R. James Matthews, Julie M. Mazet, Anita Milicic, Emma Mitchell, Owen Moon, Van Dien Nguyen, Miriam O’Hanlon, Clara Eléonore Pavillet, Dimitra Peppa, Ana Pires, Eleanor Pring, Max Quastel, Sophie Reed, Jan Rehwinkel, Niamh Richmond, Felix Clemens Richter, Alice Robinson, Patrícia R S Rodrigues, Pragati Sabberwal, Arvind Sami, Raphael Sanches Peres, Quentin J. Sattentau, Barbora Schonfeldova, David Oliver Scourfield, T. Selvakumar, Freya R Shepherd, Cariad Shorten, Anna Katharina Simon, Adrian L. Smith, Alicia Teijeira Crespo, Michael Tellier
Abstract
COVID-19 is characterized by profound lymphopenia in the peripheral blood, and the remaining T cells display altered phenotypes, characterized 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 that 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 while 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.