UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Increasing test specificity without impairing sensitivity: lessons learned from SARS-CoV-2 serology

Perkmann, Thomas; Koller, Thomas; Perkmann-Nagele, Nicole; Ozsvar-Kozma, Maria; Eyre, David; Matthews, Philippa; Bown, Abbie; ... Haslacher, Helmuth; + view all (2022) Increasing test specificity without impairing sensitivity: lessons learned from SARS-CoV-2 serology. Journal of Clinical Pathology 10.1136/jcp-2022-208171. (In press). Green open access

[thumbnail of Matthews_J Clin Path Main document.pdf]
Preview
Text
Matthews_J Clin Path Main document.pdf

Download (332kB) | Preview

Abstract

Background: Serological tests are widely used in various medical disciplines for diagnostic and monitoring purposes. Unfortunately, the sensitivity and specificity of test systems are often poor, leaving room for false-positive and false-negative results. However, conventional methods were used to increase specificity and decrease sensitivity and vice versa. Using SARS-CoV-2 serology as an example, we propose here a novel testing strategy: the € sensitivity improved two-test' or € SIT²' algorithm. Methods: SIT² involves confirmatory retesting of samples with results falling in a predefined retesting zone of an initial screening test, with adjusted cut-offs to increase sensitivity. We verified and compared the performance of SIT² to single tests and orthogonal testing (OTA) in an Austrian cohort (1117 negative, 64 post-COVID-positive samples) and validated the algorithm in an independent British cohort (976 negatives and 536 positives). Results: The specificity of SIT² was superior to single tests and non-inferior to OTA. The sensitivity was maintained or even improved using SIT² when compared with single tests or OTA. SIT² allowed correct identification of infected individuals even when a live virus neutralisation assay could not detect antibodies. Compared with single testing or OTA, SIT² significantly reduced total test errors to 0.46% (0.24-0.65) or 1.60% (0.94-2.38) at both 5% or 20% seroprevalence. Conclusion: For SARS-CoV-2 serology, SIT² proved to be the best diagnostic choice at both 5% and 20% seroprevalence in all tested scenarios. It is an easy to apply algorithm and can potentially be helpful for the serology of other infectious diseases.

Type: Article
Title: Increasing test specificity without impairing sensitivity: lessons learned from SARS-CoV-2 serology
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1136/jcp-2022-208171
Publisher version: http://dx.doi.org/10.1136/jcp-2022-208171
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Pathology, serology, allergy and immunology, medical laboratory science
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10161697
Downloads since deposit
10Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item