AUTHOR=Schetelig Johannes , Heidenreich Falk , Baldauf Henning , Trost Sarah , Falk Bose , Hoßbach Christian , Real Ruben , Roers Axel , Lindemann Dirk , Dalpke Alexander , Kolditz Martin , de With Katja , Bornhäuser Martin , Bonifacio Ezio E. , Rücker-Braun Elke , Lange Vinzenz , Markert Jan , Barth Ralf , Hofmann Jan A. , Sauter Jürgen , Bernas Stefanie N. , Schmidt Alexander H. TITLE=Individual HLA-A, -B, -C, and -DRB1 Genotypes Are No Major Factors Which Determine COVID-19 Severity JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.698193 DOI=10.3389/fimmu.2021.698193 ISSN=1664-3224 ABSTRACT=

HLA molecules are key restrictive elements to present intracellular antigens at the crossroads of an effective T-cell response against SARS-CoV-2. To determine the impact of the HLA genotype on the severity of SARS-CoV-2 courses, we investigated data from 6,919 infected individuals. HLA-A, -B, and -DRB1 allotypes grouped into HLA supertypes by functional or predicted structural similarities of the peptide-binding grooves did not predict COVID-19 severity. Further, we did not observe a heterozygote advantage or a benefit from HLA diplotypes with more divergent physicochemical peptide-binding properties. Finally, numbers of in silico predicted viral T-cell epitopes did not correlate with the severity of SARS-CoV-2 infections. These findings suggest that the HLA genotype is no major factor determining COVID-19 severity. Moreover, our data suggest that the spike glycoprotein alone may allow for abundant T-cell epitopes to mount robust T-cell responses not limited by the HLA genotype.