They found that these cross-reactive CoV-2-reactive IgG antibodies largely target the more highly conserved spike S2 domain, not the S1 domain that contains the RBD, while CoV-2 infection induced IgG and IgM antibodies target both S1 and S2 domains, supporting the theory that pre-existing CoV immunity is largely biased towards conserved S2 epitopes. This evidence concerns the gene CD40LG and COVID-19.