@article{Zwerwer_L-2025_209740,
title = {Identification of undetected SARS-CoV-2 infections by clustering of Nucleocapsid antibody trajectories},
author = {Zwerwer, L. and Pouwels, K. and Walker, A. and Eyre, D. and Stroesser, N. and Matthews, P. and Wei, J. and Diamond, I. and Studley, R. and Taylor, N. and Rourke, E. and Thomas, T. and Pienaar, D. and Preece, J. and Crofts, S. and Lloyd, L. and Bowen, M. and Ayoubkhani, D. and Black, R. and Felton, A. and Crees, M. and Jones, J. and Sutherland, E. and Crook, D. and Pritchard, E. and Vihta, K. and Howarth, A. and Marsden, B. and Chau, K. and Martins Ferreira, L. and Dejnirattisai, W. and Mongkolsapaya, J. and Hoosdally, S. and Cornall, R. and Stuart, D. and Screaton, G. and Lythgoe, K. and Bonsall, D. and Golubchik, T. and Fryer, H. and Newton, J. and Bell, J. and Cox, S. and Paddon, K. and James, T. and House, T. and Robotham, J. and Birrell, P. and Jordan, H. and Sheppard, T. and Athey, G. and Moody, D. and Curry, L. and Brereton, P. and Jarvis, I. and Godsmark, A. and Morris, G. and Mallick, B. and Eeles, P. and Hay, J. and VanSteenhouse, H. and Lee, J. and White, S. and Evans, T. and Bloemberg, L. and Allison, K. and Pandya, A. and Davis, S. and Conway, D. and MacLeod, M. and Cunningham, C. and Peto, T.},
month = {may},
year = {2025},
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.},
volume = {16},
journal = {Nature Communications},
publisher = {Springer Nature},
url = {https://doi.org/10.1038/s41467-025-57370-z},
}
