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Emerg Infect Dis . Detection of SARS-CoV-2 Reinfections Using Nucleocapsid Antibody Boosting

tetano

Editor, Senior Moderator
Emerg Infect Dis


. 2025 May;31(5):958-966.
doi: 10.3201/eid3105.250021.
Detection of SARS-CoV-2 Reinfections Using Nucleocapsid Antibody Boosting

Eduard Grebe, Daniel Chacreton, Mars Stone, Bryan R Spencer, James Haynes, Akintunde Akinseye, Marion C Lanteri, Valerie Green, Hasan Sulaeman, Roberta Bruhn, Vivian I Avelino-Silva, Paul Contestable, Brad J Biggerstaff, Melissa M Coughlin, Brian Custer, Jefferson M Jones, David Wright, Michael P Busch
Abstract

More than 85% of US adults had been infected with SARS-CoV-2 by the end of 2023. Continued serosurveillance of transmission and assessments of correlates of protection require robust detection of reinfections. We developed a serologic method for identifying reinfections in longitudinal blood donor data by assessing nucleocapsid (N) antibody boosting using a total immunoglobulin assay. Receiver operating characteristic curve analysis yielded an optimal ratio of >1.43 (sensitivity 87.1%, specificity 96.0%). When prioritizing specificity, a ratio of >2.33 was optimal (sensitivity 75.3%, specificity 99.3%). In donors with higher anti-N reactivity levels before reinfection, sensitivity was reduced. Sensitivity could be improved by expanding the dynamic range of the assay through dilutional testing, from 38.8% to 66.7% in the highest reactivity group (signal-to-cutoff ratio before reinfection >150). This study demonstrated that longitudinal testing for N antibodies can be used to identify reinfections and estimate total infection incidence in a blood donor cohort.

Keywords: COVID-19; SARS-CoV-2; blood donors; respiratory infections; serology; serosurveillance; severe acute respiratory syndrome coronavirus 2; viruses; zoonoses.

 
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