Assessing the Quality of Serological Testing in the COVID-19 Pandemic: Results of a European External Quality Assessment (EQA) Scheme for Anti-SARS-CoV-2 Antibody Detection

Ast, Volker; Costina, Victor; Eichner, Romy; Bode, Anna; Aida, Sihem; Gerhards, Catharina; Thiaucourt, Margot; Dobler, Gerhard; Geilenkeuser, Wolf-Jochen; Wölfel, Roman; Neumaier, Michael; Haselmann, Verena

doi:10.1128/jcm.00559-21

Cited by 10 publications

(8 citation statements)

References 31 publications

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“…Our analysis of multiple large datasets of patients with confirmed SARS-CoV-2 infection suggests that serology tests performed lower than = expected-with PPA ranges (a measure analogous to sensitivity) from 65-90%.-Our results align with results from smaller, detailed laboratory evaluations that suggest a lack of harmonization, including optimization of cut-off values, may contribute to decreased overall performance. Additionally, our results align with studies that include more representative samples of milder or asymptomatic persons [37][38][39]. Two of seven tests…”

Section: Discussionsupporting

confidence: 86%

Real-world performance of SARS-Cov-2 serology tests in the United States, 2020

Rodriguez-Watson

Louder²,

Kabelac³

et al. 2023

PLoS ONE

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Background Real-world performance of COVID-19 diagnostic tests under Emergency Use Authorization (EUA) must be assessed. We describe overall trends in the performance of serology tests in the context of real-world implementation. Methods Six health systems estimated the odds of seropositivity and positive percent agreement (PPA) of serology test among people with confirmed SARS-CoV-2 infection by molecular test. In each dataset, we present the odds ratio and PPA, overall and by key clinical, demographic, and practice parameters. Results A total of 15,615 people were observed to have at least one serology test 14–90 days after a positive molecular test for SARS-CoV-2. We observed higher PPA in Hispanic (PPA range: 79–96%) compared to non-Hispanic (60–89%) patients; in those presenting with at least one COVID-19 related symptom (69–93%) as compared to no such symptoms (63–91%); and in inpatient (70–97%) and emergency department (93–99%) compared to outpatient (63–92%) settings across datasets. PPA was highest in those with diabetes (75–94%) and kidney disease (83–95%); and lowest in those with auto-immune conditions or who are immunocompromised (56–93%). The odds ratios (OR) for seropositivity were higher in Hispanics compared to non-Hispanics (OR range: 2.59–3.86), patients with diabetes (1.49–1.56), and obesity (1.63–2.23); and lower in those with immunocompromised or autoimmune conditions (0.25–0.70), as compared to those without those comorbidities. In a subset of three datasets with robust information on serology test name, seven tests were used, two of which were used in multiple settings and met the EUA requirement of PPA ≥87%. Tests performed similarly across datasets. Conclusion Although the EUA requirement was not consistently met, more investigation is needed to understand how serology and molecular tests are used, including indication and protocol fidelity. Improved data interoperability of test and clinical/demographic data are needed to enable rapid assessment of the real-world performance of in vitro diagnostic tests.

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Section: Discussionsupporting

confidence: 86%

Real-world performance of SARS-Cov-2 serology tests in the United States, 2020

Rodriguez-Watson

Louder²,

Kabelac³

et al. 2023

PLoS ONE

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“…Correct characterisation of the three specificity samples (C, E and F) was more problematic than of the sensitivity samples. Variable test performance for specificity samples has been reported before [ 20 , 21 ]. A likely explanation is potential cross-reactivity with antibodies raised by previous infection with other human coronaviruses causing the common cold [ 13 ], as all samples in the proficiency panel of this EQA also contained antibodies against all other seasonally circulating human coronaviruses ( Supplementary Table S1 ).…”

Section: Discussionmentioning

confidence: 86%

External quality assessment of SARS-CoV-2 serology in European expert laboratories, April 2021

et al. 2022

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Background Countries worldwide are focusing to mitigate the ongoing SARS-CoV-2 pandemic by employing public health measures. Laboratories have a key role in the control of SARS-CoV-2 transmission. Serology for SARS-CoV-2 is of critical importance to support diagnosis, define the epidemiological framework and evaluate immune responses to natural infection and vaccine administration. Aim The aim of this study was the assessment of the actual capability among laboratories involved in sero-epidemiological studies on COVID-19 in EU/EEA and EU enlargement countries to detect SARS-CoV-2 antibodies through an external quality assessment (EQA) based on proficiency testing. Methods The EQA panels were composed of eight different, pooled human serum samples (all collected in 2020 before the vaccine roll-out), addressing sensitivity and specificity of detection. The panels and two EU human SARS-CoV-2 serological standards were sent to 56 laboratories in 30 countries. Results The overall performance of laboratories within this EQA indicated a robust ability to establish past SARS-CoV-2 infections via detection of anti-SARS-CoV-2 antibodies, with 53 of 55 laboratories using at least one test that characterised all EQA samples correctly. IgM-specific test methods provided most incorrect sample characterisations (24/208), while test methods detecting total immunoglobulin (0/119) and neutralising antibodies (2/230) performed the best. The semiquantitative assays used by the EQA participants also showed a robust performance in relation to the standards. Conclusion Our EQA showed a high capability across European reference laboratories for reliable diagnostics for SARS-CoV-2 antibody responses. Serological tests that provide robust and reliable detection of anti-SARS-CoV-2 antibodies are available.

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“…External ring trials show poor comparability of assays from different manufacturers (124,125) and there are significant challenges with the current binding antibody units (BAU) standardization, due to multiple factors, including different assay methods, antibody class(es) detected and target antigen used. Of note, BAU reference materials were derived from UK convalescent individuals infected in 2020 (126) (pre-Omicron), and there are vastly different BAU standardized values (Kroidl et al 2023, submitted).…”

Section: Expert Recommendationsmentioning

confidence: 99%

Clinical and laboratory considerations: Determining an antibody-based composite correlate of risk for reinfection with SARS-CoV-2 or severe COVID-19

Holdenrieder,

Ferreira,

Izopet

et al. 2023

Preprint

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Much of the global population now has some level of adaptive immunity to SARS-CoV-2 induced by exposure to the virus (natural infection), vaccination, or a combination of both (hybrid immunity). Key questions that subsequently arise relate to the duration and the level of protection an individual might expect based on their infection and vaccination history. A multi-component composite correlate of risk (CoR) could inform individuals and stakeholders about protection and aid decision making. This perspective evaluates the various elements that need to be accommodated in the development of an antibody-based composite CoR for reinfection with SARS-CoV-2 or development of severe COVID-19, including variation in exposure dose, transmission route, viral genetic variation, patient factors, and vaccination status. We provide an overview of antibody dynamics to aid exploration of the specifics of SARS-CoV-2 antibody testing. We further discuss anti-SARS-CoV-2 immunoassays, sample matrices, testing formats, frequency of sampling and the optimal time point for such sampling. Whilst the development of a composite CoR is challenging, we provide our recommendations for each of these key areas and highlight areas that require further work to be undertaken.

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Assessing the Quality of Serological Testing in the COVID-19 Pandemic: Results of a European External Quality Assessment (EQA) Scheme for Anti-SARS-CoV-2 Antibody Detection

Cited by 10 publications

References 31 publications

Real-world performance of SARS-Cov-2 serology tests in the United States, 2020

Real-world performance of SARS-Cov-2 serology tests in the United States, 2020

External quality assessment of SARS-CoV-2 serology in European expert laboratories, April 2021

Clinical and laboratory considerations: Determining an antibody-based composite correlate of risk for reinfection with SARS-CoV-2 or severe COVID-19

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