Antibody landscape against SARS-CoV-2 proteome revealed significant differences between non-structural/ accessory proteins and structural proteins

Summary The immunogenicity of SARS-CoV-2 proteome is largely unknown, especially for non-structural proteins and accessory proteins. Here we collected 2,360 COVID-19 sera and 601 control sera. We analyzed these sera on a protein microarray with 20 proteins of SARS-CoV-2, built an antibody response landscape for IgG and IgM. We found that non-structural proteins and accessory proteins NSP1, NSP7, NSP8, RdRp, ORF3b and ORF9b elicit prevalent IgG responses. The IgG patterns and dynamic of non-structural/ accessory proteins are different from that of S and N protein. The IgG responses against these 6 proteins are associated with disease severity and clinical outcome and declined sharply about 20 days after symptom onset. In non-survivors, sharp decrease of IgG antibodies against S1 and N protein before death was observed. The global antibody responses to non-structural/ accessory proteins revealed here may facilitate deeper understanding of SARS-CoV-2 immunology. Highlights An antibody response landscape against SARS-CoV-2 proteome was constructed Non-structural/accessory proteins elicit prevalent antibody responses but likely through a different mechanism to that of structural proteins IgG antibodies against non-structural/accessory proteins are more associated with disease severity and clinical outcome For non-survivors, the levels of IgG antibodies against S1 and N decline significantly before death