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Anti-SARS-CoV-2 nucleocapsid antibodies to detect exposure to SARS-CoV-2 : results from a prospective cohort study on COVID-19 vaccination

Rasmussen, Magnus LU orcid ; Neumann, Ariane LU orcid ; Moghaddassi, Mahnaz LU ; Inghammar, Malin LU ; Björk, Jonas LU orcid ; Malmqvist, Ulf LU and Kahn, Fredrik LU (2025) In Infectious Diseases 57(8). p.782-792
Abstract

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... (More)

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.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, COVID-19/diagnosis, Antibodies, Viral/blood, Adult, Female, Male, SARS-CoV-2/immunology, Sweden/epidemiology, Prospective Studies, Middle Aged, COVID-19 Vaccines/immunology, Young Adult, Adolescent, Aged, Coronavirus Nucleocapsid Proteins/immunology, Vaccination, COVID-19 Serological Testing, Phosphoproteins, nucleocapsid antibodies, COVID-19, serology, SARS Cov-2, half-life
in
Infectious Diseases
volume
57
issue
8
pages
11 pages
publisher
Taylor & Francis
external identifiers
  • scopus:105000422864
  • pmid:40100206
ISSN
2374-4235
DOI
10.1080/23744235.2025.2479139
language
English
LU publication?
yes
id
42871ed8-3cfa-4c50-be07-972842c6520d
date added to LUP
2025-09-22 09:07:06
date last changed
2025-09-23 04:04:25
@article{42871ed8-3cfa-4c50-be07-972842c6520d,
  abstract     = {{<p>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.</p><p>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.</p><p>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].</p><p>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.</p>}},
  author       = {{Rasmussen, Magnus and Neumann, Ariane and Moghaddassi, Mahnaz and Inghammar, Malin and Björk, Jonas and Malmqvist, Ulf and Kahn, Fredrik}},
  issn         = {{2374-4235}},
  keywords     = {{Humans; COVID-19/diagnosis; Antibodies, Viral/blood; Adult; Female; Male; SARS-CoV-2/immunology; Sweden/epidemiology; Prospective Studies; Middle Aged; COVID-19 Vaccines/immunology; Young Adult; Adolescent; Aged; Coronavirus Nucleocapsid Proteins/immunology; Vaccination; COVID-19 Serological Testing; Phosphoproteins; nucleocapsid antibodies; COVID-19; serology; SARS Cov-2; half-life}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{8}},
  pages        = {{782--792}},
  publisher    = {{Taylor & Francis}},
  series       = {{Infectious Diseases}},
  title        = {{Anti-SARS-CoV-2 nucleocapsid antibodies to detect exposure to SARS-CoV-2 : results from a prospective cohort study on COVID-19 vaccination}},
  url          = {{http://dx.doi.org/10.1080/23744235.2025.2479139}},
  doi          = {{10.1080/23744235.2025.2479139}},
  volume       = {{57}},
  year         = {{2025}},
}