T cell immunity to SARS-CoV-2 following natural infection and vaccination

Conventional T cells are phenotypically and functionally diverse and have a critical role in long-lasting protection conferred by immune memory. CD8⁺ cytotoxic T lymphocytes (CTL) in the respiratory tract blunt virus replication by directly killing infected cells and secrete antiviral cytokines including IFN-γ and TNF-α.

CD4⁺ T helper cells convey a multiplicity of functions key to coordinating and regulating antiviral immunity. CD4⁺ T cells also promote CD8⁺ T cell activation and the formation of memory cells via chemotactic recruitment and CD40-mediated “licensing” of dendritic cells (DC). Memory CD4⁺ T cells in the lung facilitate early virus control through the recruitment of immune effectors. Induced by infection, CD4⁺ ThCTL in the lung exerts MHC class-II restricted cytotoxicity, and IFN-γ-producing, cytotoxic CD4⁺ T cells from circulation have been associated with protection to influenza in humans. Through a wide variety of effector mechanisms, virus-specific CD4⁺ and CD8⁺ T cells eliminate infected cells, control the inflammatory milieu, and facilitate the optimization of the humoral response.

T cell responses to SARS-CoV-2

The significance of T cells in human immunity to SARS-CoV-2 may be inferred from case studies of COVID-19 patients with agammaglobulinemia. Although limited to only a few documented cases, COVID-19 patients with X-linked or autosomal recessive agammaglobulinemia were able to recover from infection without oxygen ventilation or intensive care, suggesting that while B cells and antibodies are critical for preventing infection, T cell responses may be sufficient to clear the infection with minimal disease.

Differences in peripheral blood immune cell composition may be prognostic of severe COVID-19. The clinical relevance of lower T cell counts in circulation across disease states remains unclear and, may in part reflect margination or recruitment and sequestration of activated cells in lung tissue to combat infection, activation-induced cell death in lymphoid organs, or dysregulation of antigen-presenting cells.

Pre-existing, cross-reactive T cells have the capacity for accelerating virus clearance with improved clinical outcomes following infection. In one study, a high degree of epitope homology (~67%) between SARS-CoV-2 and other hCoVs resulted in cross-reactivity in 57% of cases. T cells to SARS-CoV have been detected in humans more than 10 years after infection, demonstrating the capacity for generating virus-specific memory T cells that theoretically could be recruited into the SARS-CoV-2 response following infection.

 Vaccine-elicited T cell responses

Given the relatively high frequency and potential long-term consequences of severe COVID-19, the establishment of herd immunity to SARS-CoV-2 through vaccination is favored.

Correlates of immune protection to COVID-19 is unknown, but the major goal of most vaccines is the induction of neutralizing antibodies due to their potential for protecting the lower airway and reducing disease severity. They may also reduce the duration of virus shedding in the upper airway and limit transmission. However, coordinated and lasting CD4⁺ and CD8⁺ T cell responses with the proper specificity, phenotype, and function are also likely to be critical components, as multiple studies have reported that circulating antibodies to CoVs may be short-lived, or of low magnitude and/or potency. Therefore, the rapid expansion of vaccine-induced memory lymphocytes may be necessary to boost immunity and curtail COVID-19 disease and transmission.

At Diagnostiki Athinon we perform a molecular test for coronavirus (PCR test) with the ability to separate the Omicron and Delta variants,Coronavirus SARS-CoV-2 (COVID-19), Molecular Detection, Coronavirus SARS-CoV-2 (COVID-19), Omicron & Delta Variants, T cell immunity, Coronavirus SARS-CoV-2 (COVID-19), T Cell Immunity, and quantitative measurement of  IgG,Coronavirus SARS-CoV-2 (COVID-19), IgG Antibodies, and IgM antibodies Coronavirus SARS-CoV-2 (COVID-19), IgM Antibodies.

T cell immunity to SARS-CoV-2 following natural infection and vaccination. DiPiazza, A.T et al., Biochemical and biophysical research communications, 2021;538:211-217.