Probabilistic classification of anti-SARS-CoV-2 antibody responses improves seroprevalence estimates.
Clin Transl Immunology
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Castro Dopico, X., Muschiol, S., Grinberg, N. F., Aleman, S., Sheward, D. J., Hanke, L., Ahl, M., et al. (2022). Probabilistic classification of anti-SARS-CoV-2 antibody responses improves seroprevalence estimates.. Clin Transl Immunology, 11 (3) https://doi.org/10.1002/cti2.1379
Objectives: Population-level measures of seropositivity are critical for understanding the epidemiology of an emerging pathogen, yet most antibody tests apply a strict cutoff for seropositivity that is not learnt in a data-driven manner, leading to uncertainty when classifying low-titer responses. To improve upon this, we evaluated cutoff-independent methods for their ability to assign likelihood of SARS-CoV-2 seropositivity to individual samples. Methods: Using robust ELISAs based on SARS-CoV-2 spike (S) and the receptor-binding domain (RBD), we profiled antibody responses in a group of SARS-CoV-2 PCR+ individuals (n = 138). Using these data, we trained probabilistic learners to assign likelihood of seropositivity to test samples of unknown serostatus (n = 5100), identifying a support vector machines-linear discriminant analysis learner (SVM-LDA) suited for this purpose. Results: In the training data from confirmed ancestral SARS-CoV-2 infections, 99% of participants had detectable anti-S and -RBD IgG in the circulation, with titers differing > 1000-fold between persons. In data of otherwise healthy individuals, 7.2% (n = 367) of samples were of uncertain serostatus, with values in the range of 3-6SD from the mean of pre-pandemic negative controls (n = 595). In contrast, SVM-LDA classified 6.4% (n = 328) of test samples as having a high likelihood (> 99% chance) of past infection, 4.5% (n = 230) to have a 50-99% likelihood, and 4.0% (n = 203) to have a 10-49% likelihood. As different probabilistic approaches were more consistent with each other than conventional SD-based methods, such tools allow for more statistically-sound seropositivity estimates in large cohorts. Conclusion: Probabilistic antibody testing frameworks can improve seropositivity estimates in populations with large titer variability.
Original Article, antibody responses, antibody testing, COVID‐19, probability, SARS‐CoV‐2, serology
Wellcome Trust (107881/Z/15/Z)
National Institute for Health Research (IS-BRC-1215-20014)
Wellcome Trust (220788/Z/20/Z)
External DOI: https://doi.org/10.1002/cti2.1379
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334624