Serological testing for SARS-CoV-2 antibodies in clinical practice: A comparative diagnostic accuracy study.

Autor: Horn MP; University Institute of Clinical Chemistry, Inselspital University Hospital, Bern, Switzerland., Jonsdottir HR; Department of Rheumatology, Immunology, and Allergology, Inselspital University Hospital, Bern, Switzerland.; Department of BioMedical Research, University of Bern, Bern, Switzerland.; Spiez Laboratory, Federal Office for Civil Protection, Spiez, Switzerland., Brigger D; Department of Rheumatology, Immunology, and Allergology, Inselspital University Hospital, Bern, Switzerland.; Department of BioMedical Research, University of Bern, Bern, Switzerland., Damonti L; Department of Infectious Diseases, Bern University Hospital, and University of Bern, Bern, Switzerland.; Ente Ospedaliero Cantonale, Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland., Suter-Riniker F; Institute for Infectious Diseases, University of Bern, Bern, Switzerland., Endrich O; Medical Directorate, Inselspital, University Hospital of Bern, Berne, Switzerland., Froehlich TK; University Institute of Clinical Chemistry, Inselspital University Hospital, Bern, Switzerland., Fiedler M; University Institute of Clinical Chemistry, Inselspital University Hospital, Bern, Switzerland., Largiadèr CR; University Institute of Clinical Chemistry, Inselspital University Hospital, Bern, Switzerland., Marschall J; Department of Infectious Diseases, Bern University Hospital, and University of Bern, Bern, Switzerland., Weber B; Spiez Laboratory, Federal Office for Civil Protection, Spiez, Switzerland., Eggel A; Department of Rheumatology, Immunology, and Allergology, Inselspital University Hospital, Bern, Switzerland.; Department of BioMedical Research, University of Bern, Bern, Switzerland., Nagler M; University Institute of Clinical Chemistry, Inselspital University Hospital, Bern, Switzerland.; Department of BioMedical Research, University of Bern, Bern, Switzerland.
Jazyk: angličtina
Zdroj: Allergy [Allergy] 2022 Jul; Vol. 77 (7), pp. 2090-2103. Date of Electronic Publication: 2022 Jan 11.
DOI: 10.1111/all.15206
Abstrakt: Background: Serological tests are a powerful tool in the monitoring of infectious diseases and the detection of host immunity. However, manufacturers often provide diagnostic accuracy data generated through biased studies, and the performance in clinical practice is essentially unclear.
Objectives: We aimed to determine the diagnostic accuracy of various serological testing strategies for (a) identification of patients with previous coronavirus disease-2019 (COVID-19) and (b) prediction of neutralizing antibodies against SARS-CoV-2 in real-life clinical settings.
Methods: We prospectively included 2573 consecutive health-care workers and 1085 inpatients with suspected or possible previous COVID-19 at a Swiss University Hospital. Various serological immunoassays based on different analytical techniques (enzyme-linked immunosorbent assays, ELISA; chemiluminescence immunoassay, CLIA; electrochemiluminescence immunoassay, ECLIA; and lateral flow immunoassay, LFI), epitopes of SARS-CoV-2 (nucleocapsid, N; receptor-binding domain, RBD; extended RBD, RBD+; S1 or S2 domain of the spike [S] protein, S1/S2), and antibody subtypes (IgG, pan-Ig) were conducted. A positive real-time PCR test from a nasopharyngeal swab was defined as previous COVID-19. Neutralization assays with live SARS-CoV-2 were performed in a subgroup of patients to assess neutralization activity (n = 201).
Results: The sensitivity to detect patients with previous COVID-19 was ≥85% in anti-N ECLIA (86.8%) and anti-S1 ELISA (86.2%). Sensitivity was 84.7% in anti-S1/S2 CLIA, 84.0% in anti-RBD+LFI, 81.0% in anti-N CLIA, 79.2% in anti-RBD ELISA, and 65.6% in anti-N ELISA. The specificity was 98.4% in anti-N ECLIA, 98.3% in anti-N CLIA, 98.2% in anti-S1 ELISA, 97.7% in anti-N ELISA, 97.6% in anti-S1/S2 CLIA, 97.2% in anti-RBD ELISA, and 96.1% in anti-RBD+LFI. The sensitivity to detect neutralizing antibodies was ≥85% in anti-S1 ELISA (92.7%), anti-N ECLIA (91.7%), anti-S1/S2 CLIA (90.3%), anti-RBD+LFI (87.9%), and anti-RBD ELISA (85.8%). Sensitivity was 84.1% in anti-N CLIA and 66.2% in anti-N ELISA. The specificity was ≥97% in anti-N CLIA (100%), anti-S1/S2 CLIA (97.7%), and anti-RBD+LFI (97.9%). Specificity was 95.9% in anti-RBD ELISA, 93.0% in anti-N ECLIA, 92% in anti-S1 ELISA, and 65.3% in anti-N ELISA. Diagnostic accuracy measures were consistent among subgroups.
Conclusions: The diagnostic accuracy of serological tests for SARS-CoV-2 antibodies varied remarkably in clinical practice, and the sensitivity to identify patients with previous COVID-19 deviated substantially from the manufacturer's specifications. The data presented here should be considered when using such tests to estimate the infection burden within a specific population and determine the likelihood of protection against re-infection.
(© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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