Mapping SARS-CoV-2 Antibody Epitopes in COVID-19 Patients with a Multi-Coronavirus Protein Microarray

The emergence and rapid worldwide spread of SARS-CoV-2 has accelerated research and development for controlling the pandemic. A multi-coronavirus protein microarray was created containing full-length proteins, overlapping protein fragments of varying lengths and peptide libraries from SARS-CoV-2 and four other human coronaviruses. Sera from confirmed COVID-19 patients as well as unexposed individuals were applied to multi-coronavirus arrays to identify specific antibody reactivity. High level IgG, IgM and IgA reactivity to structural proteins S, M and N, as well as accessory proteins, of SARS-CoV-2 were observed that was specific to COVID-19 patients. Overlapping 100, 50 and 30 amino acid fragments of SARS-CoV-2 proteins identified antigenic regions. Numerous proteins of SARS-CoV, MERS-CoV and the endemic human coronaviruses, HCoV-NL63 and HCoV-OC43 were also more reactive with IgG, IgM and IgA in COVID-19 patient sera than in unexposed control sera, providing further evidence of immunologic cross-reactivity between these viruses. The multi-coronavirus protein microarray is a useful tool for mapping antibody reactivity in COVID-19 patients.