Preexisting Cross-Reactive T Cells are Boosted and Comprise Significant Immunity in COVID-19 Recovered Patients

Most SARS-CoV-2 infected individuals develop symptoms that do not require medical management. We hypothesized that pre-existing cross-reactive T cell responses could protect the majority from severe disease. Here we found that CTL and Th cells specific for seasonal human coronaviruses (HCoV) were significantly expanded in recovered COVID-19 donors and that CTL responses were significantly higher than responses to private SARS-CoV-2 peptides not shared with seasonal HCoV. A third of the SARS-CoV-2 peptide:HLA ligandome was matched by highly similar peptide mimics from seasonal HCoV, constituting a common HCoV peptide pool. CTL immunity was significantly skewed to the common HCoV peptide pool in age groups 20-70y, but not >70y-old donors. Over 40% of recovered donors lacked neutralizing antibodies, highlighting the role of T cell immunity in COVID-19. Results suggest a protective pre-acquired T cell immunity to SARS-CoV-2 and identify epitopes that may help boost vaccine responses and ensure broad protection against this family of viruses. Trial Registration: ClinicalTrials.gov: NCT04320732. Funding: This study was funded by The Health-South East Health Authority (Project 29286), the Research Council of Norway (Project 312693), the Oslo University Hospital, the KG Jebsen Foundation (grant 19), the University of Oslo, The Norwegian Cancer Society. Conflict of Interest: The authors declare that we have no competing interests.