Detection of Nucleocapsid Antibodies Associated with Primary SARS-CoV-2 Infection in Unvaccinated and Vaccinated Blood Donors

• Published in: Emerging infectious diseases 2024-08, Vol.30 (8), p.1621-1630
• Main Authors: Grebe, Eduard, Stone, Mars, Spencer, Bryan R, Akinseye, Akintunde, Wright, David, Di Germanio, Clara, Bruhn, Roberta, Zurita, Karla G, Contestable, Paul, Green, Valerie, Lanteri, Marion C, Saa, Paula, Biggerstaff, Brad J, Coughlin, Melissa M, Kleinman, Steve, Custer, Brian, Jones, Jefferson M, Busch, Michael P
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Antibodies; Antibodies, Viral - blood; Antibodies, Viral - immunology; Blood; Blood & organ donations; Blood Donors; COVID-19; COVID-19 - epidemiology; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 Serological Testing - methods; COVID-19 Vaccines - immunology; Detection of Nucleocapsid Antibodies Associated with Primary SARS-CoV-2 Infection in Unvaccinated and Vaccinated Blood Donors; Female; Health aspects; Humans; Immunization; Immunoassay; Infections; Male; Measurement; Middle Aged; Nucleocapsid - immunology; Regression analysis; respiratory infections; SARS-CoV-2; SARS-CoV-2 - immunology; Self report; Sensitivity and Specificity; Serology; Severe acute respiratory syndrome coronavirus 2; Testing laboratories; Vaccination; vaccine-preventable diseases; Vaccines; Viral antibodies; viruses; Young Adult; zoonoses
• ISSN: 1080-6040; 1080-6059; 1080-6059
• DOI: 10.3201/eid3008.240659

Nucleocapsid antibody assays can be used to estimate SARS-CoV-2 infection prevalence in regions implementing spike-based COVID-19 vaccines. However, poor sensitivity of nucleocapsid antibody assays in detecting infection after vaccination has been reported. We derived a lower cutoff for identifying previous infections in a large blood donor cohort (N = 142,599) by using the Ortho VITROS Anti-SARS-CoV-2 Total-N Antibody assay, improving sensitivity while maintaining specificity >98%. We validated sensitivity in samples donated after self-reported swab-confirmed infections diagnoses. Sensitivity for first infections in unvaccinated donors was 98.1% (95% CI 98.0-98.2) and for infection after vaccination was 95.6% (95% CI 95.6-95.7) based on the standard cutoff. Regression analysis showed sensitivity was reduced in the Delta compared with Omicron period, in older donors, in asymptomatic infections,