BACKGROUND . The role of humoral immunity in the coronavirus disease 2019 (COVID-19) is not fully understood owing, in large part, to the complexity of antibodies produced in response to the SARS-CoV-2 infection . There is a pressing need for serology tests to assess patient-specific antibody response and predict clinical outcome .
METHODS . Using SARS-CoV-2 proteome and peptide microarrays, we screened 146 COVID-19 patients plasma samples to identify antigens and epitopes . This enabled us to develop a master epitope array and an epitope-specific agglutination assay to gauge antibody responses systematically and with high resolution .
RESULTS . We identified 54 linear epitopes from the Spike (S) and Nucleocapsid (N) protein and showed that epitopes enabled higher resolution antibody profiling than protein antigens . Specifically, we found that antibody responses to the S (811-825), S (881-895) and N (156-170) epitopes negatively or positively correlated with clinical severity or patient survival . Moreover, we found that the P681H and S235F mutations associated with the coronavirus variant B.1.1.7 altered the specificity of the corresponding epitopes .
CONCLUSIONS . Epitope-resolved antibody testing not only offers a high-resolution alternative to conventional immunoassays to delineate the complex humoral immunity to SARS-CoV-2 and differentiate between neutralizing and non-neutralizing antibodies, it may also be used as predictor of clinical outcome . The epitope peptides can be readily modified to detect antibodies against variants in both the peptide array and latex agglutination formats .
FUNDING . Ontario Research Fund (ORF) -COVID-19 Rapid Research Fund, the Toronto COVID-19 Action Fund, Western University, the Lawson Health Research Institute, the London Health Sciences Foundation, and the AMOSO Innovation Fund.