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

Abstract

The COVID-19 pandemic is caused by coronavirus SARS-CoV-2. In terms of our understanding of what is critical to contain the virus, neutralizing antibodies to SARS-CoV-2 garner most of the attention, however, it is essential to recognize that it is the quality and the fitness of the virus-specific T cell and B cell response that lays the foundation for an effective neutralizing antibody response. Most people with SARS-CoV-2 infection survive and clear the virus. SARS-CoV-2-specific T cells develop in almost all infected people. The role of the T-cell immune response in disease pathogenesis and long-term protective immunity is currently poorly defined, but the sophistication and variety of scientific tools now at the disposal of the scientific community make it possible to study both the breadth and depth of the immune response. Understanding the role of different T cell subpopulations in the protection or pathogenesis of COVID-19 is critical to prevention and treatment. The broader and stronger SARS-CoV-2-specific T cell response in patients with severe disease may reflect a poorly functioning early T cell response that failed to control the virus. T cell responses develop early and correlate with protection, but are relatively attenuated in severe disease, due in part to lymphopenia. The expression profile of different T-cell subpopulations varies with COVID-19 of varying severity and is associated with the magnitude of T-cell responses and disease outcome. Structural changes of 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 help avoid 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 primary viral infection, there is a wide variation in cellular and humoral immune responses, with patients with severe and prolonged symptoms show highly unbalanced cellular and humoral immune responses. This review focuses on the generation and clinical significance of cellular immunity in 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.