CD4 and infection: To determine whether OC43 pre-exposure can protect against SARS-CoV-2, HLA-DRB1*0101 Ifnar1−/− mice were infected with OC43, challenged with SARS-CoV-2 16 days later (SARS-CoV-2 cross-reactive Th1 CD4+ T cell response peaked at 16 days post-OC43 infection; Fig. 4C), and lungs were harvested at 3 days post-challenge (Fig. 6A).