Cellular immunity in patients with COVID-19: molecular biology, pathophysiology, and clinical implications

The COVID-19 pandemic is caused by the SARS-CoV-2 coronavirus. From the viewpoint of factors critical to contain the virus, the neutralizing antibodies to SARS-CoV-2 garner most of the attention, however, it is essential to acknowledge that it is the level of the virus-specific T cell and B cell response that forms a basis for an effective neutralizing antibody response. T cell responses develop early and correlate with the protection, but they are relatively attenuated in the severe disease, in part due to lymphopenia. Understanding the role of different T cell subpopulations in the protection or the COVID-19 pathogenesis is critical to the prevention and treatment. The expression profile of different T cell subpopulations varies with the COVID-19 severity and is associated with the degree of T cell responses and the disease outcome. The structural changes in the genome, transcriptome, and proteome of SARS-CoV-2 promote the emergence of new variants of the virus and can reduce its interaction with antibodies and result in avoiding the neutralization. There is a strong correlation between the number of virus-specific CD4 T cells and neutralizing IgG antibody titers against SARS-CoV-2. During the primary viral infection, there is a wide variation in the cellular and humoral immune responses, patients with severe and prolonged symptoms showing highly imbalanced cellular and humoral immune responses. This review focuses on the generation and clinical significance of cellular immunity in the protection against severe acute infection and reinfection, as well as the potential involvement of seasonal coronavirus-specific cross-reactive T cells in response to SARS-CoV-2.