Analysis of Serologic Cross-Reactivity Between Common Human Coronaviruses and SARS-CoV-2 Using Coronavirus Antigen Microarray

Saahir Khan; Rie Nakajima; Aarti Jain; Rafael Ramiro de Assis; Al Jasinskas; Joshua M. Obiero; Oluwasanmi Adenaiye; Sheldon Tai; Filbert Hong; Donald K. Milton; Huw Davies; Philip L. Felgner

Overall, the 5 sera tested on the coronavirus antigen microarray all showed high IgG seroreactivity to antigens from common human coronaviruses and other respiratory viruses with known seasonal circulation versus low IgG seroreactivity to antigens from epidemic viruses that were not circulating at time of collection ( Figure 2) . Specifically, 4 of the 5 sera showed high IgG seroreactivity across the 4 common human coronaviruses, while all of the sera showed low IgG seroreactivity to SARS-CoV-2, SARS-CoV, and MERS-CoV. All 5 sera showed high IgG seroreactivity to RSV and parainfluenza viruses, while 3 of the 5 sera showed high IgG seroreactivity to adenoviruses. For influenza, all 5 sera showed high IgG seroreactivity to H1N1 and H3N2 influenza A and influenza B strains but low IgG seroreactivity to H5N1 and H7N9 influenza A strains. With respect to specific antigens, the S1 domain of the spike protein including the receptor-binding domain (RBD) demonstrates very low cross-reactivity between epidemic coronaviruses and common human coronaviruses, whereas the S2 domain of the spike protein and the nucleocapsid protein (NP) show low-level cross-reactivity between these coronavirus subtypes. Similarly, the head domain of influenza hemagglutinin (HA1) is not cross-reactive between seasonal and avian influenza strains, whereas the stalk domain (HA2) is cross-reactive between influenza virus subgroups, as seen between H1N1 and H5N1 influenza viruses.