Gamma Delta T Cells and Their Involvement in COVID-19 Virus Infections

The global outbreak of the SARS-Cov-2 virus in 2020 has killed millions of people worldwide and forced large parts of the world into lockdowns. While multiple vaccine programs are starting to immunize the global population, there is no direct cure for COVID-19, the disease caused by the SARS-Cov-2 infection. A common symptom in patients is a decrease in T cells, called lymphopenia. It is as of yet unclear what the exact role of T cells are in the immune response to COVID-19. The research so far has mainly focused on the involvement of classical alpha beta T cells. However, another subset of T cells called gamma delta T cells could have an important role to play. As part of the innate immune system, gamma delta T cells respond to inflammation and stressed or infected cells. The gamma delta T cell subset appears to be particularly affected by lymphopenia in COVID-19 patients and commonly express activation and exhaustion markers. Particularly in children, this subset of T cells seems to be most affected. This is interesting and relevant because gamma delta T cells are more prominent and active in early life. Their specific involvement in this group of patients could indicate a significant role for gamma delta T cells in this disease. Furthermore, they seem to be involved in other viral infections and were able to kill SARS infected cells in vitro. gamma delta T cells can take up, process and present antigens from microbes and human cells. As e.g. tumour-associated antigens are presented by MHC on gamma delta T cells to classical T-cells, we argue here that it stands to reason that also viral antigens, such as SARS-Cov-2-derived peptides, can be presented in the same way. gamma delta T cells are already used for medical purposes in oncology and have potential in cancer therapy. As gamma delta T cells are not necessarily able to distinguish between a transformed and a virally infected cell it could therefore be of great interest to investigate further the relationship between COVID-19 and gamma delta T cells.