Can the protection be among us? Previous viral contacts and prevalent HLA alleles 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the National Council for Scientific and Technological Development (CNPq) and National Council for the Improvement of Higher Education (CAPES) for their support. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: not applicable All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The structures of pmhcs containing immunogenic epitopes can be found in the CrossTope database. The CoV targets were recovered on the immune epitope database.