Study Compares T-cell Response to Coronavirus and Influenza

With the rise of the pandemic, scientists today are focusing on understanding how the host immune system responds to the virus to better shape public health responses and develop effective vaccines. A new study reports the T cell memory response to the SARS-CoV-2 spike protein, recombinant nucleocapsid protein, and other pooled peptides derived from convalescent patients.

This study included 13 and 1 patient who had tested positive for SARS-CoV-2 and SARS-CoV, respectively. The median age of the patients was 53 years, with all participants being within 90 days of the first symptom. Adaptive immunity is vital for viral clearance and protective immunity. Earlier studies show the development of specific antibodies within 2-4 weeks of the infection. Some suggest the antibody response is transient in mild cases but others suggest that the antibody response can be detected for about 3-4 months.

The current research used recombinant proteins to gauge the T cell response to antigens presented by cells and made use of the fully glycosylated spike protein to simulate the natural presentation of this antigen on the virus. The T cell response to infection with coronavirus is strong, with predominating Th1 cell responses. An inflammatory CD4 response contributes to the severity of the disease.

The scientists also found that in some donors, T follicular helper cells in peripheral blood (pTfh) produce IL-2 and express CCR7+CXCR5+ cells in response to SARS-CoV-2 antigens. The frequency of these cells is intensely related to serum neutralization assays as well as to RBD-IgA, but overall, this response is lower than in influenza. The CD4 memory T cell response was intense in over 90% of cases of exposure to the influenza H1N1 strain. It could be because only two SARS-CoV-2 proteins were used.

Secondly, the predominance of IL-2 and TNF-α over IFN-γ in CD4 T cells responses to this virus contradicts with the IFN-γ-dominant response in influenza. This may result in increased inflammation and impaired viral clearance compared to influenza.

Moreover, this pattern is independent of disease severity. Specific T cells secreting multiple cytokines are significantly fewer in severe COVID-19 and may mirror T cell exhaustion irrespective of the duration of exposure. The high IL-10 may cause poor antigen presentation and immunosuppression, and this finding may shape future vaccine design.

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