One consequence of the ongoing coronavirus disease pandemic was the rapid development of both in-house and commercial serological assays detecting anti-SARS-CoV-2 antibodies, in an effort to reliably detect acute and past SARS-CoV-2 infections. It is crucial to evaluate the quality of these serological tests and consequently the sero-epidemiological studies that are performed with the respective tests. Here, we describe the set-up and results of a comparative study, in which a laboratory contracted by the European Centre for Disease Prevention and Control offered a centralised service to EU/EEA Member and pre-accession Member States to test representative serum specimens with known serological results, with the gold standard technique (virus neutralisation tests) to determine the presence of neutralising antibodies. Laboratories from 12 European countries shared 719 serum specimens with the contractor laboratory. We found that in-house serological tests detecting neutralising antibodies showed the highest percent agreement, both positive and negative, with the virus neutralisation test results. Despite extensive differences in virus neutralisation protocols neutralisation titres showed a strong correlation. From the commercial assays, the best positive percent agreement was found for SARS-CoV-2 IgG (sCOVG) (Siemens - Atellica IM Analyzer). Despite lower positive percent agreement of LIAISON SARS-CoV-2 TrimericS IgG kit (Diasorin Inc.), the obtained results showed relatively good correlation with neutralisation titres. The set-up of this study allowed for high comparability between laboratories and enabled laboratories that do not have the capacity or capability to perform VNTs themselves. Given the variety of in-house protocols detecting SARS-CoV-2 specific neutralising antibodies, including the virus strain, it could be of interest to select reference isolates for SARS-CoV-2 diagnostic to be made available for interested EU Member States and pre-accession countries.

Austrian Agency for Health and Food Safety GmbH Vienna Austria

Centre for Infectious Disease Control National Institute for Public Health and the Environment Bilthoven the Netherlands

European Centre for Disease Prevention and Control Stockholm Sweden

Finnish Institute for Health and Welfare Helsinki Finland

Institute of Virology Vaccines and Sera Torlak Belgrade Serbia

Laboratoire National de Santé Dudelange Luxembourg

National Institute for Public Health Bucharest Romania

National Institute of Public Health NIH NRI Warsaw Poland

National Laboratory for Health Environment and Food Slovenia

Public Health General Directorate of Turkey Ankara Turkey

Public Health Institute Ostrava Ostrava Czech Republic

Riga East Clinical University Hospital Riga Latvia

Scientific Department Army Medical Center Rome Italy

The National Institute of Health Dr Ricardo Jorge Lisbon Portugal

Zobrazit více v PubMed

Caniels T.G., Bontjer I., van der Straten K., Poniman M., Burger J.A., Appelman B., et al. Emerging SARS-CoV-2 variants of concern evade humoral immune responses from infection and vaccination. Sci. Adv. 2021;7(36) PubMed PMC

Chen Y., Zhao X., Zhou H., Zhu H., Jiang S., Wang P. Broadly neutralizing antibodies to SARS-CoV-2 and other human coronaviruses. Nat. Rev. Immunol. 2022:1–11. PubMed PMC

Eccles R. Why is temperature sensitivity important for the success of common respiratory viruses? Rev. Med. Virol. 2021;31(1):1–8. PubMed PMC

ECDC, 2021. COVID-19 Vaccine rollout overview: ECDC; 27–06-2021 [Available from: 〈https://www.ecdc.europa.eu/en/covid-19/vaccine-roll-out-overview〉.

FIND, 2021. Test directory: FIND; 27–06-2021 [Available from: 〈https://www.finddx.org/test-directory/?_type_of_technology=immunoassay〉.

Fischer C., Pedroso C., Mendrone A., Jr., Bispo de Filippis A.M., Vallinoto A.C.R., Ribeiro B.M., et al. External quality assessment for zika virus molecular diagnostic testing, Brazil. Emerg. Infect. Dis. 2018;24(5) PubMed PMC

Haveri A., Ekstrom N., Solastie A., Virta C., Osterlund P., Isosaari E., et al. Persistence of neutralizing antibodies a year after SARS-CoV-2 infection in humans. Eur. J. Immunol. 2021;51(12):3202–3213. PubMed PMC

Irsara C., Egger A.E., Prokop W., Nairz M., Loacker L., Sahanic S., et al. Clinical validation of the Siemens quantitative SARS-CoV-2 spike IgG assay (sCOVG) reveals improved sensitivity and a good correlation with virus neutralization titers. Clin. Chem. Lab Med. 2021;59(8):1453–1462. PubMed

Ismail A., Shurrab F.M., Al-Jighefee H.T., Al-Sadeq D.W., Qotba H., Al-Shaar I.A., et al. Can commercial automated immunoassays be utilized to predict neutralizing antibodies after SARS-CoV-2 infection? A comparative study between three different assays. Front Biosci. 2021;26(7):198–206. PubMed

Kohmer N., Rabenau H.F., Hoehl S., Kortenbusch M., Ciesek S., Berger A. Comparative analysis of point-of-care, high-throughput and laboratory-developed SARS-CoV-2 nucleic acid amplification tests (NATs) J. Virol. Methods. 2021;291 PubMed PMC

Matheeussen V., Corman V.M., Donoso Mantke O., McCulloch E., Lammens C., Goossens H., et al. International external quality assessment for SARS-CoV-2 molecular detection and survey on clinical laboratory preparedness during the COVID-19 pandemic, April/May 2020. Eur. Surveill. 2020;25(27) PubMed PMC

Nandakumar V., Profaizer T., Lozier B.K., Elgort M.G., Larragoite E.T., Williams E.S.C.P., et al. Evaluation of a surrogate enzyme-linked immunosorbent assay-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cPass neutralization antibody detection assay and correlation with immunoglobulin G commercial serology assays. Arch. Pathol. Lab Med. 2021;145(10):1212–1220. PubMed

Nguyen D., Simmonds P., Steenhuis M., Wouters E., Desmecht D., Garigliany M., et al. SARS-CoV-2 neutralising antibody testing in Europe: towards harmonisation of neutralising antibody titres for better use of convalescent plasma and comparability of trial data. Eur. Surveill. 2021;26(27) PubMed PMC

NIBSC , 2020. WHO International Standard, First WHO International Standard for anti-SARS-CoV-2, immunoglobulin (human) NIBSC code: 20/136: WHO [Available from: 〈https://www.nibsc.org/documents/ifu/20-136.pdf〉.

NIBSC , 2021. Working Standard Working reagent for anti-SARS-CoV-2 immunoglobulin NIBSC code: 21/234. [Available from: 〈https://www.nibsc.org/documents/ifu/21-234.pdf〉.

Perry J., Osman S., Wright J., Richard-Greenblatt M., Buchan S.A., Sadarangani M., et al. Does a humoral correlate of protection exist for SARS-CoV-2? A systematic review. PLOS One. 2022;17(4) PubMed PMC

Reusken C.B., Mogling R., Smit P.W., Grunow R., Ippolito G., Di Caro A., et al. Status, quality and specific needs of Ebola virus diagnostic capacity and capability in laboratories of the two European preparedness laboratory networks EMERGE and EVD-LabNet. Eur. Surveill. 2018;23(19) PubMed PMC

Rijkers G., Murk J.L., Wintermans B., van Looy B., van den Berge M., Veenemans J., et al. Differences in antibody kinetics and functionality between severe and mild severe acute respiratory syndrome coronavirus 2 infections. J. Infect. Dis. 2020;222(8):1265–1269. PubMed PMC

Rychert J., Couturier M.R., Elgort M., Lozier B.K., La’ulu S., Genzen J.R., et al. Evaluation of 3 SARS-CoV-2 IgG antibody assays and correlation with neutralizing antibodies. J. Appl. Lab Med. 2021;6(3):614–624. PubMed PMC

Simanek V., Pecen L., Kratka Z., Furst T., Rezackova H., Topolcan O., et al. Five commercial immunoassays for SARS-CoV-2 antibody determination and their comparison and correlation with the virus neutralization test. Diagnostics. 2021;11(4) PubMed PMC

Sung H., Han M.G., Yoo C.K., Lee S.W., Chung Y.S., Park J.S., et al. Nationwide external quality assessment of SARS-CoV-2 molecular testing, South Korea. Emerg. Infect. Dis. 2020;26(10):2353–2360. PubMed PMC

WHO, 2021a. WHO Coronavirus (COVID-19) Dashboard: WHO; 27–06-2021a [Available from: 〈https://covid19.who.int/〉.

WHO, 2021b. COVID-19 vaccines: WHO; 27–06-2021b [Available from: 〈https://www.who.int/emergencies/diseases/novel-coronavirus-2019/covid-19-vaccines〉.