Human coronaviruses can infect all age groups [13, 16, 17]. Infections with HCoV-NL63, HCoV-OC43, and HCoV-229E can occur repeatedly throughout a lifetime. Descriptions of the genetic diversity of endemic HCoVs are limited and the factors that allow repeat infections by these viruses are not fully understood. Protective immune responses to HCoVs may be short lived or insufficient to block reinfection. Alternately, the virus may evolve to avoid protective immunity, with reinfection due to immune escape variants.
A better understanding of virus reinfection might reveal features for improving vaccines. The vaccine concept relies on exposure to a subacute dose of a pathogen resulting in protective immune responses [18, 19]. Although it is generally thought that host immune responses are protective against subsequent exposure to a virus, there is evidence from some pathogenic viruses that prior exposure and immune responses to a virus may actually promote greater virus infection or increased pathology in subsequent exposures to the virus [20]. For instance, antibodies were reported to enhance SARS-CoV cell entry [21, 22] and an animal model of SARS-CoV infection in African green monkeys showed increased liver pathology in immunized animals [23]. Antibody enhancement of flavivirus infection occurs in vitro [24] and there is evidence of immune responses to primary infections of dengue virus or feline coronavirus altering secondary infections [25]. For RSV, molecular studies have noted that previously circulating antigenic diversity may influence subsequent group and genotype predominance during the epidemics and this could be responsible for some of the reinfections observed in populations [26].