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

By Jaclyn C Law, Wan Koh, Patrick Budylowski, Jonah Lin, FengYun Yue, Kento T Abe, Bhavisha Rathod, Melanie Girard, Zhijie Li, James M Rini, Samira Mubareka, Allison McGeer, Adrienne K. Chan, Anne-Claude Gingras, Tania H Watts, Mario Ostrowski

Posted 01 Sep 2020
medRxiv DOI: 10.1101/2020.08.27.20183319

There is a pressing need for an in-depth understanding of immunity to SARS-CoV-2. Here we investigated T cell recall responses to fully glycosylated Spike trimer, recombinant N protein as well as to S, N, M and E peptide pools in the early convalescent phase. All subjects showed SARS-CoV-2-specific T cell responses to at least one antigen. SARS-CoV-2-specific CD4+ T cells were primarily of the central memory phenotype and exhibited a lower IFN-[gamma] to TNF-[alpha] ratio compared to influenza-specific responses of the same donors, independent of disease severity. SARS-CoV-2-specific T cells were less multifunctional than influenza-specific T cells, particularly in severe cases, potentially suggesting exhaustion. High IL-10 production was noted in response to N protein, possibly contributing to immunosuppression, with potential implications for vaccine design. We observed granzyme B+/IFN-[gamma] CD4+ and CD8+ proliferative responses to peptide pools in most individuals, with CD4+ responses predominating over CD8+ responses. Peripheral T follicular helper responses to S or N strongly correlated with serum neutralization assays as well as RBD-specific IgA. Overall, T cell responses to SARS-CoV-2 are robust, however, CD4+ Th1 responses predominate over CD8+ responses and are more inflammatory with a weaker Tfh response than influenza-specific CD4+ responses, potentially contributing to COVID-19 disease.

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