Estimating the cumulative incidence of SARS-CoV-2 with imperfect serological tests: Exploiting cutoff-free approaches.
Details
Serval ID
serval:BIB_BD93B53B74D7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Estimating the cumulative incidence of SARS-CoV-2 with imperfect serological tests: Exploiting cutoff-free approaches.
Journal
PLoS computational biology
ISSN
1553-7358 (Electronic)
ISSN-L
1553-734X
Publication state
Published
Issued date
02/2021
Peer-reviewed
Oui
Volume
17
Number
2
Pages
e1008728
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Abstract
Large-scale serological testing in the population is essential to determine the true extent of the current SARS-CoV-2 pandemic. Serological tests measure antibody responses against pathogens and use predefined cutoff levels that dichotomize the quantitative test measures into sero-positives and negatives and use this as a proxy for past infection. With the imperfect assays that are currently available to test for past SARS-CoV-2 infection, the fraction of seropositive individuals in serosurveys is a biased estimator of the cumulative incidence and is usually corrected to account for the sensitivity and specificity. Here we use an inference method-referred to as mixture-model approach-for the estimation of the cumulative incidence that does not require to define cutoffs by integrating the quantitative test measures directly into the statistical inference procedure. We confirm that the mixture model outperforms the methods based on cutoffs, leading to less bias and error in estimates of the cumulative incidence. We illustrate how the mixture model can be used to optimize the design of serosurveys with imperfect serological tests. We also provide guidance on the number of control and case sera that are required to quantify the test's ambiguity sufficiently to enable the reliable estimation of the cumulative incidence. Lastly, we show how this approach can be used to estimate the cumulative incidence of classes of infections with an unknown distribution of quantitative test measures. This is a very promising application of the mixture-model approach that could identify the elusive fraction of asymptomatic SARS-CoV-2 infections. An R-package implementing the inference methods used in this paper is provided. Our study advocates using serological tests without cutoffs, especially if they are used to determine parameters characterizing populations rather than individuals. This approach circumvents some of the shortcomings of cutoff-based methods at exactly the low cumulative incidence levels and test accuracies that we are currently facing in SARS-CoV-2 serosurveys.
Keywords
Antibodies, Viral/blood, Asymptomatic Infections/epidemiology, COVID-19/diagnosis, COVID-19/epidemiology, COVID-19/immunology, COVID-19 Serological Testing/methods, COVID-19 Serological Testing/statistics & numerical data, Computational Biology, Computer Simulation, Confidence Intervals, False Negative Reactions, False Positive Reactions, Humans, Incidence, Likelihood Functions, Models, Statistical, Pandemics/statistics & numerical data, ROC Curve, Reproducibility of Results, SARS-CoV-2/immunology, Sensitivity and Specificity
Pubmed
Web of science
Open Access
Yes
Create date
11/03/2025 11:31
Last modification date
12/03/2025 8:08