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Using SARS-CoV-2 nucleoprotein antibodies to detect (re)infection
Christel E Hoeve1, Nienke Neppelenbroek1, Eric R A Vos1
1National Institute for Public Health and the Environment, Center for Infectious Disease Control, Bilthoven, The Netherlands.
Epidemiology and Infection
|February 6, 2025
Summary
Serum nucleoprotein antibodies (N-antibodies) effectively identify SARS-CoV-2 reinfections for up to a year, even with limited testing. This supports ongoing COVID-19 monitoring and vaccine effectiveness studies.
Area of Science:
- Immunology
- Infectious Diseases
- Epidemiology
Background:
- Accurate identification of SARS-CoV-2 infections and reinfections is crucial for public health surveillance.
- Nucleoprotein antibodies (N-antibodies) are a key serological marker for SARS-CoV-2 exposure.
- Understanding the persistence and boosting of N-antibody levels is essential for interpreting serological test results.
Purpose of the Study:
- To assess the validity of serum N-antibodies for identifying SARS-CoV-2 (re)infections.
- To estimate the persistence of N-antibody seropositivity and antibody boosting following infection and reinfection.
- To explore determinants influencing N-antibody responses.
Main Methods:
- Prospective cohort study (VASCO) with adult participants providing serial serum samples (4-8 months apart).
- Stratification of sample pairs based on initial N-antibody serostatus and self-reported infection.
- Calculation of N-seroconversion rates and fold-increase in N-antibody concentration over time.
Main Results:
- Among initially seronegative individuals, 89% showed N-seroconversion after reported infection.
- In initially seropositive individuals, reported reinfection led to 82%-65% fold-increase in N-antibody levels.
- After one year, 83% remained N-seropositive post-first infection; 93%-61% showed a 1.5- to 4-fold increase post-reinfection.
- Symptomatic and Omicron variant infections were associated with higher seroconversion and fold-increase odds.
Conclusions:
- Serum N-antibody testing is a valid method for detecting SARS-CoV-2 (re)infections up to one year post-infection.
- N-serology can be utilized in settings with limited PCR or antigen testing availability.
- This approach supports the monitoring of COVID-19 burden and vaccine effectiveness.
