Using human blood samples obtained from pre-pandemic donors, a recent article by Mateus et al. in Science provided new evidence that SARS-CoV-2-reactive T-cells in unexposed donors are indeed HCoV-specific T-cells. 1 The rapid global spread of coronavirus disease 2019 (COVID-19), caused by the newly-emerged coronavirus SARS-CoV-2, has led to millions of infections with substantial morbidity and mortality. 2Different clinical manifestations of COVID-19 have been observed: asymptomatic infections, mild self-limiting disease, acute respiratory distress syndrome and death.The determinants underlying disease severity currently remain elusive; since severe patients often present with immune hyperresponsiveness, it is speculated that the host' immune response could be a contributing factor to severe disease.Many studies are dissecting the human immune response to SARS-CoV-2 and several groups have reported marked activation of T-cell subsets in acute COVID-19 patients. 3The antigen-specific T-cell response has only been analyzed in a handful of papers, all sharing a common feature: although SARS-CoV-2-specific CD4 + and CD8 + T-cells are consistently detected in peripheral blood mononuclear cells (PBMC) obtained from COVID-19 patients, studies also report activation of T-cells in 20-50% of the people never exposed to SARS-CoV-2. 1,4,5The frequency of these crossreactive responses in pre-pandemic controls is always low.On average 1% of the CD4 + T-cells from acute COVID-19 patients upregulate activation markers upon peptide pool stimulation.If pre-pandemic donors respond to peptide stimulation, the percentage of responding CD4 + T-cells is always <0.1%. 5 Authors of these papers speculate that these-mainly CD4 + -SARS-CoV-2reactive T-cells are probably induced by past infection with one of the endemic "common cold" coronaviruses (HCoVs), which share at least partial sequence homology with SARS-CoV-2.Experimental evidence for this hypothesis was lacking so far.In this recent article in Science, the authors provided new evidence that SARS-CoV-2-reactive T-cells in unexposed donors are indeed HCoV-specific T-cells. 1 The authors relied on an elegant design of peptide "megapools" (MPs) to determine T-cell specificities.Using these peptide pools in combination with human PBMC obtained from donors between 2015 and 2018, the authors identified 142 HLA class II-restricted SARS-CoV-2 T-cell epitopes.Generation of several short-term T-cell lines proved that at least a number of these T-cells recognized peptides derived from HCoVs.