Systematic examination of T cell responses to SARS-CoV-2 versus influenza virus reveals distinct inflammatory profile

The T cell response to SARS-CoV-2 infection is important for clearing virus-infected cells. Why some patients with severe disease are unable to control infection is unknown. Law et al., 2020 furthers knowledge about the immune response to SARS-CoV-2 by characterising the ex vivo T cell response of 13 SARS-CoV-2 convalescent donors with a range of disease severities and compares responses to influenza virus. PBMCs collected between days 27 to 90 post-disease onset were stimulated with SARS-CoV-2 glycosylated S and recombinant N protein, peptide pools from N, M and E proteins. Outputs included cellular phenotype, cytokine production and proliferative response.  

Research Highlights 

1. 92% of SARS-CoV-2 convalescent patients showed lower CD4+ responses to S and N proteins than influenza A virus (PR8) and trivalent influenza vaccine and no CD8+ T cell response. 

2. SARS-CoV-2-specific T cells were less multifunctional than PR8-specific T cells, particularly in severe cases. 

3. High IL-10 production in response to N protein (indicates immunosuppression). 

4. Granzyme B+/IFN-γ+ CD4+ and CD8+ proliferative responses to peptide pools in most patients, with CD4+ responses predominating over CD8+. 

5. Peripheral T follicular helper responses to S or N strongly correlated with serum neutralization assays and RBD-specific IgA. Tfh response to SARS-CoV-2 was weaker than response to influenza virus. 

Impact for COVID-19 research:  

• CD4+ Th1 (pro-inflammatory) response to SARS-CoV-2 is robust and may contribute to COVID-19 pathology. Conversely, these CD4+ T cells are granzyme B+ and IFN-γ+, and may be functionally cytotoxic, thereby contributing to viral clearance via MHC class II expression on epithelial airway cells 

• PBMCs from SARS-CoV-2 convalescent donors secreted high levels of IL-10 in response to N protein which may contribute to impaired antigen presentation and immunosuppression and should be considered in vaccine design 

Methodologies: 

• Study Type: ex vivo 

• Important cell lines/viral models used: Vero E6 cells 

• Key Techniques: Development of recombinant SARS-CoV and SARS-CoV-2 spike and N protein expression in cell culture, 15-mer peptides for S, M, N and E proteins, intracellular cytokine staining, SARS-CoV-2 neutralisation assay, CFSE T cell proliferation assay, multiplex cytokine bead assay 

Limitations: 

• Small sample size (n= 1 asymptomatic, 6 mild, 3 moderate and 3 severe cases)