ORF8 and ORF3b antibodies are accurate serological markers of early and late SARS-CoV-2 infection

Nat Immunol. 2020 Oct;21(10):1293-1301. doi: 10.1038/s41590-020-0773-7. Epub 2020 Aug 17.


The SARS-CoV-2 virus emerged in December 2019 and has caused a worldwide pandemic due to the lack of any pre-existing immunity. Accurate serology testing is urgently needed to help diagnose infection, determine past exposure of populations and assess the response to a future vaccine. The landscape of antibody responses to SARS-CoV-2 is unknown. In this study, we utilized the luciferase immunoprecipitation system to assess the antibody responses to 15 different SARS-CoV-2 antigens in patients with COVID-19. We identified new targets of the immune response to SARS-CoV-2 and show that nucleocapsid, open reading frame (ORF)8 and ORF3b elicit the strongest specific antibody responses. ORF8 and ORF3b antibodies, taken together as a cluster of points, identified 96.5% of COVID-19 samples at early and late time points of disease with 99.5% specificity. Our findings could be used to develop second-generation diagnostic tests to improve serological assays for COVID-19 and are important in understanding pathogenicity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Antibodies, Viral / blood*
  • Antibodies, Viral / immunology
  • Antigens, Viral / immunology
  • Betacoronavirus / immunology*
  • COVID-19
  • COVID-19 Testing
  • Clinical Laboratory Techniques / methods*
  • Coronavirus Infections / blood
  • Coronavirus Infections / diagnosis*
  • Coronavirus Infections / immunology
  • Coronavirus Infections / virology
  • Female
  • Hong Kong
  • Humans
  • Male
  • Middle Aged
  • Pandemics
  • Pneumonia, Viral / blood
  • Pneumonia, Viral / diagnosis*
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Sensitivity and Specificity
  • Time Factors
  • Viral Proteins / immunology*


  • Antibodies, Viral
  • Antigens, Viral
  • ORF8 protein, SARS-CoV-2
  • Viral Proteins