Can the protection be among us? Previous viral contacts and prevalent HLA alleles could be avoiding an even more disseminated COVID-19 pandemic.

COVID-19 is bringing scenes of sci-fi movies into real life, and it seems to be far from over. Infected individuals exhibit variable severity, suggesting the involvement of the genetic constitution of populations and previous cross-reactive immune contacts in the individuals disease outcome. To investigate the participation of MHC alleles in COVID-19 severity, the combined use of HLA-B*07, HLA-B*44, HLA-DRB1*03, and HLA-DRB1*04 grouped affected countries presenting similar death rates, based only on their allele frequencies. To prospect T cell targets in SARS-CoV-2, we modeled 3D structures of HLA-A*02:01 complexed with immunogenic epitopes from SAR-CoV-1 and compared them with models containing the corresponding SARS-CoV-2 peptides. It reveals molecular conservation between SARS-CoV peptides, evidencing that the corresponding current sequences are putative T cell epitopes. These structures were also compared with other HCoVs sequences, and with a panel of epitopes from unrelated viruses, looking for the triggers of cross-protection in asymptomatic and uninfected individuals. 229E, OC43, and impressively, viruses involved in endemic human infections share fingerprints of immunogenicity with SARS-CoV peptides. Wide-scale HLA genotyping in COVID-19 patients shall improve prognosis prediction. Structural identification of previous triggers paves the way for herd immunity examination and wide spectrum vaccine development.