CD40LG and infection: A critical prediction is that the severity of emergent HCoVs once they reach endemicity depends only on the severity of infection in children (Fig. 3), because all available evidence suggests that immunity to HCoVs has short IES and moderate IEI, leading to frequent reinfection throughout adulthood (11, 12), but strong IEP such that childhood infection provides protection from pathology upon reinfection in adulthood, as evidenced by the rarity of severe infections or detectable IgM titers in adults.