Detection of serum cross-reactive antibodies and memory response to SARS-CoV-2 in pre-pandemic and post-COVID-19 convalescent samples

Background

A notable feature of 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-SARS-CoV-2 antibodies.

Methods

We investigated the presence of cross-reactive anti-SARS-CoV-2 IgG antibodies (to spike(S)1, S1-receptor-binding receptor (S1-RBD) and nucleocapsid protein(NP)), by enzyme-linked immunosorbent assays, and neutralizing activity by a SARS-CoV-2 pseudotyped virus neutralisation assay, in pre-pandemic 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 -S1-RBD antibody levels correlated with anti-HCoV-HKU1 and -OC43 S1 antibody titers in pre-pandemic samples(p<0.001). There were marked increases of anti-HCoV-HKU1 and -OC43 S1 (but not anti-NL63 and -229E S-RBD) antibody titres in serum samples from convalescent COVID-19 patients(p<0.001), indicating an activation of cross-reactive immunological memory to β-coronavirus spike.

Conclusions

We demonstrated cross-reactive anti-SARS-CoV-2 antibodies in pre-pandemic 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.