Antibody landscape against SARS-CoV-2 reveals significant differences between non-structural/accessory and structural...

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• The immunogenicity of the SARS-CoV-2 proteome, particularly non-structural and accessory proteins, remains largely uncharacterized.
• Understanding the full spectrum of antibody responses is crucial for comprehending SARS-CoV-2 pathogenesis and host immunity.

Purpose of the Study:

• To map the antibody response landscape against SARS-CoV-2 proteins, including non-structural and accessory proteins.
• To investigate the association of these antibody responses with COVID-19 disease severity and clinical outcomes.

Main Methods:

• Analysis of 2,360 COVID-19 patient sera and 601 control sera using a protein microarray.
• Detection of immunoglobulin (Ig)G and IgM antibody responses against 20 SARS-CoV-2 proteins.

Main Results:

• Prevalent IgG responses were observed against non-structural and accessory proteins NSP1, NSP7, NSP8, RdRp, ORF3b, and ORF9b.
• Antibody response patterns and dynamics differed between non-structural/accessory proteins and the S and N proteins.
• IgG responses against these six proteins correlated with disease severity and clinical outcomes, declining sharply around 20 days post-symptom onset.
• A notable decrease in IgG against S1 and N proteins was observed in non-survivors prior to death.

Conclusions:

• Non-structural and accessory proteins of SARS-CoV-2 elicit significant and distinct antibody responses.
• These antibody profiles provide insights into SARS-CoV-2 immunology, disease progression, and potential prognostic markers.