Malaria symptoms are very similar to those of COVID-19, and infections can be symptomatic or asymptomatic. Common immunodominant epitopes exist between the SARS-CoV-2 proteins and the Plasmodium falciparum antigen. We used the domain search method to investigate the mechanism of SARS-CoV-2 protein invasion into red blood cells in this present study. S protein was found to be bind to complement receptor 1 on the red blood cell membrane via the C1q domain. ORF3a EBA-175 domains were attached to glycophorin A on the red blood cell membrane. Both domains contained a high concentration of tryptophan threonine Plasmodium antigens. S, ORF3a were linked to band 4.1 respectively, one erythrocyte membrane skeleton protein. Through the MACPF domain, the S protein formed a fusion channel on the red blood cell membrane. It injected viral genetic material into the mature red blood cell. The S protein's ion channel injected calcium ions into the virus's membrane fusion region. ORF3a is capable of forming not only dimers but also tetramers. ORF3a employed a thiol-activated cytolysin domain to create hemolytic pores in the red blood cell membrane. As with ryanodine receptors, the channel could release calcium ions from the inside of red blood cells. Calcium ion was a factor in blood clotting. As a result, the viral protein penetrated the red blood cell membrane without inducing significant hemolysis. According to the SARS-COV-2 Plasmodium antigen type, the blood cells of individuals with blood types A and Knops were susceptible to the SARS-COV-2 virus protein attack. It was similar to the blood type infection rule of falciparum malaria.