This is a summary, written by members of the CITF Secretariat, of:

Golding L, Watts AW, Shew J, Paramo MV, Mâsse LC, Goldfarb DM, Abu-Raya B, Lavoie PM. A novel anti-nucleocapsid antibody avidity method for identifying SARS-CoV-2 reinfections. J Infect Dis. 2024 March 05. doi:

The results and/or conclusions contained in the research do not necessarily reflect the views of all CITF members.

A CITF-funded proof-of-principle study, published in the Journal of Infectious Diseases, found that high avidity anti-nucleocapsid (anti-N) IgG antibodies detect SARS-CoV-2 reinfections with higher specificity compared to solely measuring anti-N IgG serum levels. The authors believe this to be the first serology method to detect reinfections without the use of longitudinal blood samples, arguing that this could be useful to understand the long-term health burden of COVID-19. This study was led by Liam Golding and CITF-funded researchers Drs. Pascal M. Lavoie and Louise Mâsse (University of British Columbia).

Avidity refers to the overall strength of antibody-antigen binding. Understanding that antibody levels tend to wane, but that antibody avidity increases after reinfection, these researchers used a chemical antibody-antigen bond-breaking agent, to come up with a set of conditions that best identified individuals reinfected by SARS-CoV-2.

To optimize assay performance to detect changes in SARS-CoV-2 N antibody avidity profiles, they used sera from eight uninfected, 27 infected, and 12 reinfected individuals. Using this set of samples, they classified antibody fractions based on their resistance to increasing concentrations of the antibody-antigen bond-breaking agent. After demonstrating the ability of the high avidity fraction to distinguish singly infected from reinfected individuals, they then quantified the accuracy of their anti-N avidity assay using another set of 183 singly infected and 46 reinfected sera.

Key findings:

  • “High” and “very high” avidity anti-N antibodies were significantly increased following reinfection compared to among those who had only been infected once.
  • The high anti-N IgG antibody avidity fraction detected SARS-CoV-2 reinfections with higher specificity (85%) than serum anti-N antibody levels alone (74%).
  • The high anti-N IgG antibody avidity fraction remained stable over time.

As a next step, the researchers plan to use this novel antibody avidity method to investigate the long-term impact of reinfections on the cumulative risk of post-COVID symptoms.