T cell phenotypes in COVID-19 - a living review
Hanna SJ., Codd AS., Gea-Mallorqui E., Scourfield DO., Richter FC., Ladell K., Borsa M., Compeer EB., Moon OR., Galloway SAE., Dimonte S., Capitani L., Shepherd FR., Wilson JD., Uhl LFK., Ahern DJ., Almuttaqi H., Alonzi DS., Alrubayyi A., Alsaleh G., Bart VMT., Batchelor V., Bayliss R., Berthold DL., Bezbradica JS., Bharuchq T., Borrmann H., Borsa M., Borst R., Brun J., Burnell S., Capitani L., Cavounidis A., Chapman L., Chauveau A., Cifuentes L., Codd AS., Compeer EB., Coveney C., Cross A., Danielli S., Davies LC., Dendrou CA., Dimonte S., Peter Durairaj RR., Dustin LB., Dyer A., Fielding C., Fischer F., Gallimore A., Galloway S., Gammage A., Gea-Mallorquí E., Godkin A., Hanna SJ., Heuberger C., Hulin-Curtis S., Issa F., Jones E., Jones R., Ladell K., Lauder SN., Liddiard K., Ligoxygakis P., Lu F., MacLachlan B., Maleki-Toyserkani S., Mann EH., Marzeda AM., Matthews RJ., Mazet JM., Milicic A., Mitchell E., Moon O., Nguyen VD., O'Hanlon M., Eléonore Pavillet C., Peppa D., Pires A., Pring E., Quastel M., Reed S., Rehwinkel J., Richmond N., Richter FC., Robinson AJB., Rodrigues PRS., Sabberwal P., Sami A., Peres RS., Sattentau Q., Schonfeldova B., Scourfield DO., Selvakumar TA., Shepherd FR., Shorten C., Simon AK., Smith AL., Crespo AT., Tellier M., Thornton E., Uhl LFK., van Grinsven E., Wann AKT., Williams R., Wilson JD., Zhou D., Zhu Z., Gallimore AM., Milicic A.
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.