Abstract
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.
Competing Interest Statement
QuestCap provided funds to the ACG and SM labs for development of assays used in this project. All other authors have no conflicts of interest to declare.
Funding Statement
This research was funded by a FAST grant from the Thistledown foundation (to T.H.W.) and by a grant VR1-172711 from the Canadian Institutes of Health research to T.H.W., M.O. and A.C.G. M.O. receives funding from the Ontario HIV Treatment Network (OHTN), the Li Ka Shing Knowledge Institute, and the Juan and Stefania fund for COVID-19 and other virus infections. Funding for the development of the assays in the Gingras lab was provided through generous donations from the Royal Bank of Canada (RBC), QuestCap and the Krembil Foundation to the Sinai Health System Foundation; the equipment used is housed in the Network Biology Collaborative Centre at the Lunenfeld-Tanenbaum Research Institute, a facility supported by Canada Foundation for Innovation funding, by the Ontarian Government and by Genome Canada and Ontario Genomics (OGI-139). JCL and KTA were recipients of Ontario Graduate Scholarships.