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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.
- serology
- allergy and immunology
- medical laboratory science
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Data availability statement
Data are available upon reasonable request. Data are available to interested researchers upon request from the corresponding author.
Footnotes
Handling editor Tahir S Pillay.
Contributors TP and TK contributed equally. Conceptualisation: TP, TK, OFW, HH. Methodology: TP, TK, NP-N, HH; investigation: TP, TK, NP-N, MO-K, DWE, PM, AB, NS, M-LB, RB-K, OCB, SH, DA, DS, PQ, RM, PM, AR, MK, MD, BHo, BHa, RS, GL, FG, WG, RG, HH; data curation: TP, TK, DW, PM, AB, NS, M-LB, RB-K, OCB, SH, DA, DS; project administration: PM, AR; formal analysis: HH; validation: DWE, PM, AB, NS; writing—original draft: TP, TK, NP-N, HH; visualisation: HH; supervision: OFW, CJB, HH; resources: DWE, PM, AB, NS, M-LB, RB-K, OCB, SH, DA, DS, PQ, RM, MK, MD, BHo, BHa, RS, GL, FG, WG, RG, OFW, CJB; writing—review and editing: all authors; guarantor: HH.
Funding The MedUni Wien Biobank is funded to participate in the biobank consortium BBMRI.at (www.bbmri.at) by the Austrian Federal Ministry of Science, Research and Technology. There was no external funding received for the work presented. However, test kits for the Technoclone ELISAs were kindly provided by the manufacturer.
Competing interests NP-N received a travel grant from DiaSorin. DWE reports lecture fees from Gilead outside the submitted work. OCB reports grants from GSK, grants from Menarini, grants from Boehringer Ingelheim, grants from Astra, grants from MSD, grants from Pfizer, and grants from Chiesi, outside the submitted work. SH does receive unrestricted research grants (GSK, Boehringer, Menarini, Chiesi, Astra Zeneca, MSD, Novartis, Air Liquide, Vivisol, Pfizer, TEVA) for the Ludwig Boltzmann Institute of COPD and Respiratory Epidemiology, and is on advisory boards for G. SK, Boehringer Ingelheim, Novartis, Menarini, Chiesi, Astra Zeneca, MSD, Roche, Abbvie, Takeda and TEVA for respiratory oncology and COPD. PQ is an advisory board member for Roche Austria and reports personal fees from Takeda outside the submitted work. The Dept. of Laboratory Medicine (Head: OWF) received compensations for advertisement on scientific symposia from Roche, DiaSorin, and Abbott and holds a grant for evaluating an in-vitro diagnostic device from Roche. CJB is a Board Member of Technoclone. HH receives compensations for biobank services from Glock Health Science and Research and BlueSky immunotherapies.
Provenance and peer review Not commissioned; externally peer reviewed.
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