Background: In May 2023, the World Health Organization declared COVID-19 no longer a public health emergency. Despite successful vaccination campaigns, vaccines provide limited protection against transmission. Since general testing has been abandoned in most countries, alternative population surveillance methods to assess SARS-CoV-2 exposure are needed.

Methods: N-antigen is a protein of the SARS-CoV-2 virus that is not present in the vaccines and hence may be a useful serological marker of infection. This study evaluated N-antigen antibodies as a marker of SARS-CoV-2 exposure in a vaccinated Swedish cohort. Serum samples were collected and analysed for N-antigen antibodies using the mesoscale system. Nonlinear mixed-effects model accounting for multiple measurements per individual was used to estimate the half-life of N-antigen antibodies.

Results: A total of 3,202 participants (median age 31 years) were recruited from April 2021 to February 2022 from four vaccination centres in Skåne, Sweden. A total of 2,999 participants had at least one valid N-antigen antibody measurement. The estimated half-life of N-antigen antibodies was 59 days (95% CI: 55-64 days). The estimated 95% range of halves-lives were from 24 to 174 days. The repeated measurements of N-antigen antibody levels could accurately detect SARS-CoV-2 infection. A twofold increase had a sensitivity of 91%, whereas a 16-fold increase had a specificity of 91%, respectively. The area under the curve (AUC) for predicting infection was 0.88 [95% C.I. 0.86-0.90].

Conclusion: Repeated monitoring of N-antigen antibody levels may be a valuable tool for assessing SARS-CoV-2 exposure and thus aid in monitoring transmission thereby helping in guiding vaccination strategies.