Abstract Background A notable feature of coronavirus disease 2019 (COVID-19) is that children are less susceptible to severe disease. Children are known to experience more infections with endemic human coronaviruses (HCoVs) compared to adults. Little is known whether HCoV infections lead to cross-reactive anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. Methods We investigated the presence of cross-reactive anti–SARS-CoV-2 IgG antibodies to spike 1 (S1), S1-receptor-binding domain (S1-RBD), and nucleocapsid protein (NP) by enzyme-linked immunosorbent assays, and neutralizing activity by a SARS-CoV-2 pseudotyped virus neutralization assay, in prepandemic sera collected from children (n = 50) and adults (n = 45), and compared with serum samples from convalescent COVID-19 patients (n = 16). Results A significant proportion of children (up to 40%) had detectable cross-reactive antibodies to SARS-CoV-2 S1, S1-RBD, and NP antigens, and the anti-S1 and anti–S1-RBD antibody levels correlated with anti–HCoV-HKU1 and anti–HCoV-OC43 S1 antibody titers in prepandemic samples ( P < .001). There were marked increases of anti–HCoV-HKU1 and - OC43 S1 (but not anti-NL63 and -229E S1-RBD) antibody titers in serum samples from convalescent COVID-19 patients ( P < .001), indicating an activation of cross-reactive immunological memory to β-coronavirus spike. Conclusions We demonstrated cross-reactive anti–SARS-CoV-2 antibodies in prepandemic serum samples from children and young adults. Promoting this cross-reactive immunity and memory response derived from common HCoV may be an effective strategy against SARS-COV-2 and future novel coronaviruses. We demonstrated preexisting cross-reactive anti–SARS-CoV-2 antibodies in prepandemic serum samples from children and young adults, which were likely derived from previous infection with common endemic β-coronaviruses. Promoting this cross-reactive immunity may be an effective strategy against SARS-COV-2 and future novel coronaviruses.
【저자키워드】 SARS, Immunological memory, COVID, HCoV, CoV, NL63, 19, 2, common human coronavirus (HCoV)-HKU1, serum antibody, cross, reactive immunity, 【초록키워드】 COVID-19, coronavirus disease, antibodies, SARS-CoV-2, Coronavirus disease 2019, coronavirus, Immunity, antibody, children, Infection, nucleocapsid protein, Adults, Neutralizing activity, Neutralization assay, IgG antibodies, enzyme-linked immunosorbent assays, sera, HCoV, Antibody titer, antigens, NL63, respiratory, OC43, HKU1, Antibody titers, Anti-S1, convalescent COVID-19 patients, memory response, Endemic, severe disease, cross-reactive, cross-reactive antibody, lead, acute respiratory syndrome, Activation, acute respiratory syndrome coronavirus, serum samples, enzyme, domain, novel coronaviruses, HCoVs, SARS-CoV-2 pseudotyped virus, serum sample, endemic human coronaviruses, SARS-CoV-2 S1, β-coronavirus, β-Coronaviruses, susceptible, effective, Result, collected, proportion, investigated, detectable, increase, less, demonstrated, correlated, notable, Promoting, anti–SARS-CoV-2 IgG antibody, convalescent COVID-19 patient, endemic human coronavirus, 【제목키워드】 SARS-CoV-2, detection, response, Sample,