Identification of undetected SARS-CoV-2 infections by clustering of Nucleocapsid antibody trajectories
Year: 2025
Type: article
Study design: Observational Study
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.
Source: Nature Communications
Authors: Leslie R. Zwerwer, Tim E. A. Peto, Koen B. Pouwels, Ann Sarah Walker, the COVID-19 Infection Survey team, David W. Eyre, Nicole Stroesser, Philippa C. Matthews, Jia Wei, Ian Diamond, Ruth Studley, Nick Taylor, Emma Rourke, Tina Thomas, Dawid Pienaar, Joy Preece, Sarah Crofts, Lina Lloyd, Michelle Bowen, Daniel Ayoubkhani, Russell Black, Antonio Felton, Megan Crees, Joel Jones, Esther Sutherland, Derrick W. Crook, Emma Pritchard, Karina-Doris Vihta, Alison Howarth, Brian D. Marsden, Kevin K. Chau, Lucas Martins Ferreira, Wanwisa Dejnirattisai, Juthathip Mongkolsapaya, Sarah Hoosdally, Richard Cornall, David I. Stuart, Gavin Screaton, Katrina Lythgoe, David Bonsall, Tanya Golubchik, Helen Fryer, John N. Newton, John I. Bell, Stuart Cox, Kevin Paddon, Tim James, Thomas House, Julie Robotham, Paul Birrell, Helena Jordan, Tim Sheppard, Graham Athey, Dan Moody, Leigh Curry, Pamela Brereton, Ian Jarvis, Anna Godsmark, George Morris, Bobby Mallick, Phil Eeles, Jodie Hay, Harper VanSteenhouse, Jessica Lee, Sean White, Tim Evans, Lisa Bloemberg, Katie Allison, Anouska Pandya, Sophie Davis, David I. Conway, Margaret MacLeod, Chris Cunningham
Institutions: University Medical Center Groningen, University of Groningen, University of Oxford, John Radcliffe Hospital, National Institute for Health and Care Research, The Francis Crick Institute, University College London, Office for National Statistics, Oxford University Hospitals NHS Trust, University of Manchester, UK Health Security Agency, IQVIA (United Kingdom), Department of Health and Social Care, Welsh Government, Scottish Government, Public Health Scotland
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W4410370552