Identification of undetected SARS-CoV-2 infections by clustering of Nucleocapsid antibody trajectories
Abstract
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.
Article Details
Authors (72)
Leslie R. Zwerwer
Tim E. A. Peto
Koen B. Pouwels
Ann Sarah Walker
David W. Eyre
Nicole Stroesser
Philippa C. Matthews
Jia Wei
State Key Laboratory of Microbial Technology, Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University
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
Division of Structural Biology, Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford
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
School of Medicine, Dentistry, and Nursing University of Glasgow Glasgow UK
Margaret MacLeod
Chris Cunningham