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Identification of undetected SARS-CoV-2 infections by clustering of Nucleocapsid antibody trajectories

Abstract:
During the COVID-19 pandemic, numerous SARS-CoV-2 infections remained undetected. We combined results from routine monthly nose and throat swabs, and self-reported positive swab tests, from a UK household survey, linked to national swab testing programme data from England and Wales, together with Nucleocapsid (N-)antibody trajectories clustered using a longitudinal variation of K-means (N = 185,646) to estimate the number of infections undetected by either approach. Using N-antibody (hypothetical) infections and swab-positivity, we estimated that 7.4% (95%CI: 7.0–7.8%) of all true infections (detected and undetected) were undetected by both approaches, 25.8% (25.5–26.1%) by swab-positivity-only and 28.6% (28.4–28.9%) by trajectory-based N-antibody-classifications-only. Congruence with swab-positivity was respectively much poorer and slightly better with N-antibody classifications based on fixed thresholds or fourfold increases. Using multivariable logistic regression N-antibody seroconversion was more likely as age increased between 30–60 years, in non-white participants, those less (recently/frequently) vaccinated, for lower cycle threshold values in the range above 30, and in symptomatic and Delta (vs. BA.1) infections. Comparing swab-positivity data sources showed that routine monthly swabs were insufficient to detect infections and incorporating national testing programme/self-reported data substantially increased detection. Overall, whilst N-antibody serosurveillance can identify infections undetected by swab-positivity, optimal use requires fourfold-increase-based or trajectory-based analysis.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41467-025-57370-z

Authors

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Institution:
University of Oxford
Division:
MSD
Department:
NDM
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Role:
Author
ORCID:
0000-0003-3477-8307
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Nuffield Department of Population Health
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
NDM Experimental Medicine
Role:
Author
ORCID:
0000-0002-0412-8509


More from this funder
Funder identifier:
https://ror.org/0187kwz08
Grant:
NIHR200915 - 546912


Publisher:
Springer Nature
Journal:
Nature Communications More from this journal
Volume:
16
Issue:
1
Article number:
4466
Publication date:
2025-05-14
Acceptance date:
2025-02-20
DOI:
EISSN:
2041-1723


Language:
English
Pubs id:
2093040
Local pid:
pubs:2093040
Deposit date:
2025-03-01
ARK identifier:

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