17 Aug 2020

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

A proportion of patients with COVID-19 do not develop a strong antibody response; hence, current serological tests may underestimate asymptomatic and mild infections. Current serology tests are also not suitable for early diagnosis, since they detect spike and nucleocapsid antibodies that are usually produced in the second or third week of infection. In this study, HKUMed researchers reported the use of a luciferase immunoprecipitation system – a rapid, simple and sensitive test to detect antibody response – to detect antibody responses to 15 SARS-CoV-2 antigens (viral proteins to which the body can generate an immune response). Study results were published in Nature Immunology.

Key takeaways from the study:

  • The immune system responded strongly to nucleocapsid and open reading frame (ORF) 8 and ORF3b. Nucleocapsid is a protein shell that contains the virus genes. ORF8 and ORF3b are non-structural proteins and their functions are unknown.
  • Antibody responses to all 15 antigens showed high specificity (ability of a test to correctly identify those without the disease); but only the nucleocapsid, ORF3b and ORF8 antibodies showed high sensitivity (ability of a test to correctly identify those with the disease) with levels of 93.3%, 86.6% and 100%, respectively.
  • Combined use of ORF8 and ORF3b enabled a highly sensitive (96.5%) and specific (99.5%) method to detect patients with COVID-19 at the early and late stage of infection.
  • ORF8 and ORF3b antibodies remained stable over time, making them ideal antibodies to screen for COVID-19.

This study informed the specificity and sensitivity of antibody responses to 15 different antigens from SARS-CoV-2. Both ORF8 and ORF3b antibodies were stable for up to 100 days after the first appearance of symptoms. The diagnosis of COVID-19 in early and late stage was highly accurate when both ORF8 and ORF3b antibodies were analysed together.

To read the original article published in Nature Immunology, click here.