Assessment of anti-nucleocapsid antibodies to indicate SARS-CoV-2 infection in healthcare workers

Overview

This longitudinal study evaluated the presence of anti-nucleocapsid (anti-N) antibodies as markers of SARS-CoV-2 infection among healthcare workers at a Catalonian university hospital. The investigation spanned from June 2020 to November 2021, encompassing pre- and post-vaccination periods, and demonstrated that anti-N antibody detection effectively identified prior infections despite vaccination with spike protein-based vaccines.

Background

Healthcare workers are at elevated risk of SARS-CoV-2 infection due to direct patient exposure, potentially serving as vectors for transmission. SARS-CoV-2 encodes four structural proteins, with the spike (S) and nucleocapsid (N) proteins being primary targets for diagnostic assays. Vaccines administered locally utilize the S protein as the immunogen, making anti-N antibody detection a specific indicator of natural infection rather than vaccination response. Serological testing for anti-N antibodies thus provides a means to confirm infection in vaccinated individuals.

Data Highlights

Key Findings

• Anti-N antibody detection was performed at two time points: P1 (June-July 2020) and P2 (October-November 2021).
• Infection rates were calculated using combined anti-N antibody positivity and PCR/antigen test results.
• Reinfections were identified by increased anti-N antibody titers between P1 and P2.
• All participants were vaccinated with spike protein-based vaccines, allowing anti-N antibodies to specifically indicate natural infection.
• Anti-N antibody testing demonstrated high sensitivity and specificity for detecting prior SARS-CoV-2 infection in this healthcare worker cohort.

Clinical Implications

Detection of anti-nucleocapsid antibodies is a reliable method to confirm SARS-CoV-2 infection in vaccinated healthcare workers, as vaccination does not induce anti-N antibodies. This approach enables accurate assessment of infection prevalence and reinfection rates in high-risk populations despite widespread vaccination. Incorporating anti-N antibody testing into surveillance protocols can improve infection control strategies within healthcare settings.

Conclusion

Anti-nucleocapsid antibody detection serves as a valuable serological marker to identify SARS-CoV-2 infections in vaccinated healthcare workers, facilitating longitudinal monitoring of infection dynamics in this vulnerable group. This method complements direct viral detection and supports informed occupational health decisions.

References

1. Althaia Xarxa Assistencial Universitària Study, 2021 -- Assessment of anti-nucleocapsid antibody presence as an indicator of SARS-CoV-2 infection among healthcare workers