The high mortality of COVID-19 is related to poor antigen presentation and lymphopenia. In this present study, domain search results showed that many proteins of the SARS-COV-2 virus had MHC-like domains, which were similar to decoys for the human immune system. MHC-like structures could bind to MHC receptors of immune cells, interfering with antigen presentation. Then the oxygen-free radicals generated by E protein destroyed immune cells after MHC-like of S protein could bind to them. Mutations in the MHC-like region of the viral proteins such as S promoted weaker immune resistance and more robust transmission. S 127-194 were the primary reason for the robust transmission of delta variants. The S 144-162 regulated the formation of S trimer. The mutations of RdRP: G671S and N: D63G of delta variant caused high viral load. S 62-80 of alpha, beta, lambda variants were the important factor for fast-spreading. S 616-676 and 1014-1114 were causes of high mortality for gamma variants infections. These sites were in the MHC-like structure regions.