Head-to-head validation of six immunoassays for SARS-CoV-2 in hospitalized patients

Rens Zonneveld; Suzanne Jurriaans; Tom van Gool; Jorrit J Hofstra; Thecla A M Hekker; Pien Defoer; Patricia E Broekhuizen-van Haaften; Ellen M Wentink-Bonnema; Lynn Boonkamp; Charlotte E Teunissen; Annemieke C Heijboer; Frans Martens; Godelieve de Bree; Michele van Vugt; Robin van Houdt; Amsterdam UMC COVID-19 Biobank

doi:10.1016/j.jcv.2021.104821

Head-to-head validation of six immunoassays for SARS-CoV-2 in hospitalized patients

J Clin Virol. 2021 Jun:139:104821. doi: 10.1016/j.jcv.2021.104821. Epub 2021 Apr 18.

Authors

Rens Zonneveld¹, Suzanne Jurriaans², Tom van Gool², Jorrit J Hofstra², Thecla A M Hekker², Pien Defoer², Patricia E Broekhuizen-van Haaften², Ellen M Wentink-Bonnema², Lynn Boonkamp³, Charlotte E Teunissen³, Annemieke C Heijboer⁴, Frans Martens⁴, Godelieve de Bree⁵, Michele van Vugt⁵, Robin van Houdt²; Amsterdam UMC COVID-19 Biobank

Collaborators

Amsterdam UMC COVID-19 Biobank:
Janke Schinkel⁶, Menno D de Jong⁶, M van Agtmael⁶, A G Algera⁷, F van Baarle⁷, D Bax⁸, M Beudel⁹, H J Bogaard¹⁰, M Bomers⁶, L Bos⁷, M Botta⁷, J de Brabander⁶, M C Brouwer⁹, S de Bruin⁷, M Bugiani¹¹, E Bulle⁷, O Chouchane⁶, A Cloherty⁸, P Elbers⁷, L Fleuren⁷, S Geerlings⁶, B Geerts¹², T Geijtenbeek⁸, A Girbes⁷, A Goorhuis⁶, M P Grobusch⁶, F Hafkamp¹³, L Hagens⁷, J Hamann¹⁴, V Harris⁶, R Hemke¹⁵, S M Hermans⁶, L Heunks⁷, M W Hollmann¹², J Horn⁷, J W Hovius⁶, R Koning⁹, N van Mourik⁷, J Nellen⁶, F Paulus⁷, E Peters⁶, T van der Poll⁶, B Preckel¹², J M Prins⁶, J Raasveld⁷, T Reijnders⁶, M Schinkel⁶, M J Schultz⁷, A Schuurman¹⁵, K Sigaloff⁶, M Smit⁷, C S Stijnis⁶, W Stilma⁷, P Thoral⁷, A Tsonas⁷, M van der Valk⁶, D Veelo¹², A P J Vlaar⁷, H de Vries⁷, W J Wiersinga⁶, D Wouters¹⁶, A H Zwinderman¹⁷, D van de Beek⁹

Affiliations

¹ Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Center, University of Amsterdam and VU University Amsterdam, the Netherlands. Electronic address: [email protected].
² Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Center, University of Amsterdam and VU University Amsterdam, the Netherlands.
³ Neurochemical Laboratory, Amsterdam University Medical Center, University of Amsterdam and VU University Amsterdam, the Netherlands.
⁴ Endocrine Laboratory, Amsterdam University Medical Center, University of Amsterdam and VU University Amsterdam, the Netherlands.
⁵ Department of Internal Medicine & Infectious Diseases, Amsterdam University Medical Center, University of Amsterdam and VU University Amsterdam, the Netherlands.
⁶ Departments of Infectious Diseases, the Netherlands.
⁷ Departments of Intensive Care, the Netherlands.
⁸ Departments of Experimental Immunology, the Netherlands.
⁹ Departments of Neurology, the Netherlands.
¹⁰ Departments of Pulmonology, the Netherlands.
¹¹ Departments of Pathology, the Netherlands.
¹² Departments of Anesthesiology, the Netherlands.
¹³ Departments of Amsterdam UMC Biobank Core Facility, the Netherlands.
¹⁴ Departments of Radiology, the Netherlands.
¹⁵ Departments of Internal Medicine, the Netherlands.
¹⁶ Departments of Clinical Chemistry, the Netherlands.
¹⁷ Departments of Clinical Epidemiology, Biostatistics and Bioinformatics, the Netherlands.

Abstract

Background: Detecting SARS-CoV-2 antibodies may help to diagnose COVID-19. Head-to-head validation of different types of immunoassays in well-characterized cohorts of hospitalized patients remains needed.

Methods: We validated three chemiluminescence immunoassays (CLIAs) (Liaison, Elecsys, and Abbott) and one single molecule array assay (SIMOA) (Quanterix) for automated analyzers, one rapid immunoassay RIA (AllTest), and one ELISA (Wantai) in parallel in first samples from 126 PCR confirmed COVID-19 hospitalized patients and 158 pre-COVID-19 patients. Specificity of the AllTest was also tested in 106 patients with confirmed parasitic and dengue virus infections. Specificity of the Wantai assay was not tested due to limitations in sample volumes.

Results: Overall sensitivity in first samples was 70.6 % for the Liaison, 71.4 % for the Elecsys, 75.4 % for the Abbott, 70.6 % for the Quanterix, 77.8 % for the AllTest, and 88.9 % for the Wantai assay, respectively. Sensitivity was between 77.4 % (Liaison) and 94.0 % (Wantai) after 10 dpso. No false positive results were observed for the Elecsys and Abbott assays. Specificity was 91.1 % for the Quanterix, 96.2 % for the Liaison, and 98.1 % for the AllTest assay, respectively.

Conclusion: We conclude that low sensitivity of all immunoassays limits their use early after onset of illness in diagnosing COVID-19 in hospitalized patients. After 10 dpso, the Wantai ELISA has a relatively high sensitivity, followed by the point-of-care AllTest RIA that compares favorably with automated analyzer immunoassays.

Keywords: COVID-19; ELISA; Immunoassay; SARS-CoV-2; Serology.

Publication types

Validation Study

MeSH terms

Adult
Aged
Aged, 80 and over
Antibodies, Viral / blood*
COVID-19 / diagnosis*
COVID-19 Serological Testing
Enzyme-Linked Immunosorbent Assay
Female
Humans
Immunoassay / methods*
Male
Middle Aged
SARS-CoV-2 / immunology*
Sensitivity and Specificity

Substances

Antibodies, Viral