1887

Abstract

A number of seroassays are available for SARS-CoV-2 testing; yet, head-to-head evaluations of different testing principles are limited, especially using raw values rather than categorical data. In addition, identifying correlates of protection is of utmost importance, and comparisons of available testing systems with functional assays, such as direct viral neutralisation, are needed.We analysed 6658 samples consisting of true-positives (=193), true-negatives (=1091), and specimens of unknown status (=5374). For primary testing, we used Euroimmun-Anti-SARS-CoV-2-ELISA-IgA/IgG and Roche-Elecsys-Anti-SARS-CoV-2. Subsequently virus-neutralisation, GeneScriptcPass, VIRAMED-SARS-CoV-2-ViraChip, and Mikrogen-Line-SARS-CoV-2-IgG were applied for confirmatory testing. Statistical modelling generated optimised assay cut-off thresholds. Sensitivity of Euroimmun-anti-S1-IgA was 64.8%, specificity 93.3% (manufacturer’s cut-off); for Euroimmun-anti-S1-IgG, sensitivity was 77.2/79.8% (manufacturer’s/optimised cut-offs), specificity 98.0/97.8%; Roche-anti-N sensitivity was 85.5/88.6%, specificity 99.8/99.7%. In true-positives, mean and median Euroimmun-anti-S1-IgA and -IgG titres decreased 30/90 days after RT-PCR-positivity, Roche-anti-N titres decreased significantly later. Virus-neutralisation was 80.6% sensitive, 100.0% specific (≥1:5 dilution). Neutralisation surrogate tests (GeneScriptcPass, Mikrogen-Line-RBD) were >94.9% sensitive and >98.1% specific. Optimised cut-offs improved test performances of several tests. Confirmatory testing with virus-neutralisation might be complemented with GeneScriptcPass or Line-RBD for certain applications. Head-to-head comparisons given here aim to contribute to the refinement of testing strategies for individual and public health use.

Funding
This study was supported by the:
  • German Ministry for Education and Research
  • Bielefeld University
  • University of Bonn
  • Helmholtz Centre Munich, German Research Center for Environmental Health
  • University Hospital, LMU Munich
  • Bayerisches Staatsministerium für Wissenschaft, Forschung und Kunst
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. The Microbiology Society waived the open access fees for this article.
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001653
2021-10-08
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/102/10/jgv001653.html?itemId=/content/journal/jgv/10.1099/jgv.0.001653&mimeType=html&fmt=ahah

References

  1. Huang C, Wang Y, Li X, Ren L, Zhao J et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet 2020; 395:497–506 [View Article]
    [Google Scholar]
  2. Amanat F, Stadlbauer D, Strohmeier S, Nguyen THO, Chromikova V et al. A serological assay to detect SARS-CoV-2 seroconversion in humans. Nat Med 2020; 26:1033–1036 [View Article] [PubMed]
    [Google Scholar]
  3. Chen X, Pan Z, Yue S, Yu F, Zhang J et al. Disease severity dictates SARS-CoV-2-specific neutralising antibody responses in COVID-19. Signal Transduct Target Ther 2020; 5:180 [View Article] [PubMed]
    [Google Scholar]
  4. Meyer B, Torriani G, Yerly S, Mazza L, Calame A et al. Validation of a commercially available SARS-CoV-2 serological immunoassay. Clin Microbiol Infect 2020; 26:1386–1394 [View Article] [PubMed]
    [Google Scholar]
  5. (FIND) FfIND SARS-CoV-2 diagnostic pipeline; 2020 https://www.finddx.org/covid-19/pipeline
  6. Huang AT, Garcia-Carreras B, Hitchings MDT, Yang B, Katzelnick LC et al. A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection, and association with severity. Nat Commun 2020; 11:4704 [View Article] [PubMed]
    [Google Scholar]
  7. Cheng MP, Yansouni CP, Basta NE, Desjardins M, Kanjilal S et al. Serodiagnostics for severe acute respiratory syndrome-related coronavirus 2: a narrative review. Ann Intern Med 2020; 173:450–460 [View Article] [PubMed]
    [Google Scholar]
  8. Jääskeläinen AJ, Kuivanen S, Kekäläinen E, Ahava MJ, Loginov R et al. Performance of six SARS-CoV-2 immunoassays in comparison with microneutralisation. J Clin Virol 2020; 129:104512 [View Article] [PubMed]
    [Google Scholar]
  9. Kohmer N, Westhaus S, Rühl C, Ciesek S, Rabenau HF. Brief clinical evaluation of six high-throughput SARS-CoV-2 IgG antibody assays. J Clin Virol 2020; 129:104480 [View Article] [PubMed]
    [Google Scholar]
  10. Weidner L, Gänsdorfer S, Unterweger S, Weseslindtner L, Drexler C et al. Quantification of SARS-CoV-2 antibodies with eight commercially available immunoassays. J Clin Virol 2020; 129:104540 [View Article] [PubMed]
    [Google Scholar]
  11. National SARS-CoV-2 Serology Assay Evaluation Group Performance characteristics of five immunoassays for SARS-CoV-2: a head-to-head benchmark comparison. Lancet Infect Dis 2020; 20:1390–1400 [View Article] [PubMed]
    [Google Scholar]
  12. Plebani M, Padoan A, Negrini D, Carpinteri B, Sciacovelli L. Diagnostic performances and thresholds: the key to harmonization in serological SARS-CoV-2 assays?. medRxiv 2020
    [Google Scholar]
  13. Radon K, Saathoff E, Pritsch M, Guggenbühl Noller JM, Kroidl I et al. Protocol of a population-based prospective COVID-19 cohort study Munich, Germany (KoCo19. BMC Public Health 2020; 20:1036 [View Article] [PubMed]
    [Google Scholar]
  14. Pritsch M, Radon K, Bakuli A, Le Gleut R, Olbrich L et al. Prevalence and risk factors of infection in the representative COVID-19 cohort Munich. Int J Environ Res Public Health 2021; 18:3572 [View Article] [PubMed]
    [Google Scholar]
  15. Haselmann V, Özçürümez MK, Klawonn F, Ast V, Gerhards C et al. Results of the first pilot external quality assessment (EQA) scheme for anti-SARS-CoV2-antibody testing. Clin Chem Lab Med 2020; 58:2121–2130 [View Article]
    [Google Scholar]
  16. Benjamini Y, Yekutieli D. The control of the false discovery rate in multiple testing under dependency. Ann Stat 20011165–1188
    [Google Scholar]
  17. Chew KL, Tan SS, Saw S, Pajarillaga A, Zaine S et al. Clinical evaluation of serological IgG antibody response on the Abbott Architect for established SARS-CoV-2 infection. Clinical microbiology and infection: the official publication of the European Society of Clinical Microbiology and Infectious Diseases 2020; 26:
    [Google Scholar]
  18. Eyre DW, Lumley SF, Stoesser NE, Matthews PC et al. Stringent thresholds for SARS-CoV-2 IgG assays result in under-detection of cases reporting loss of taste/smell. medRxiv 2020
    [Google Scholar]
  19. Gudbjartsson DF, Helgason A, Jonsson H, Magnusson OT, Melsted P et al. Spread of SARS-CoV-2 in the Icelandic population. N Engl J Med 2020; 382:2302–2315 [View Article]
    [Google Scholar]
  20. Long QX, Liu BZ, Deng HJ, GC W, Deng K et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med 2020; 26:845–848 [View Article] [PubMed]
    [Google Scholar]
  21. Long Q-X, Tang X-J, Shi Q-L, Li Q, Deng H-J et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med 2020; 26:1200–1204 [View Article] [PubMed]
    [Google Scholar]
  22. Pollán M, Pérez-Gómez B, Pastor-Barriuso R, Oteo J, Hernán MA et al. Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study. The Lancet 2020
    [Google Scholar]
  23. Shakiba M, Hashemi Nazari SS, Mehrabian F, Rezvani SM, Ghasempour Z et al. Seroprevalence of COVID-19 virus infection in Guilan province, Iran. medRxiv 2020
    [Google Scholar]
  24. Streeck H, Schulte B, Kuemmerer B, Richter E, Hoeller T et al. Infection fatality rate of SARS-CoV-2 infection in a German community with a super-spreading event. medRxiv 2020
    [Google Scholar]
  25. Stringhini S, Wisniak A, Piumatti G, Azman AS, Lauer SA et al. Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study. Lancet 2020; 396:313–319 [View Article] [PubMed]
    [Google Scholar]
  26. Mahajan S, Redlich CA, Wisnewski AV, Fazen LE, Rao LV et al. Performance of abbott architect, ortho vitros, and euroimmun assays in detecting prior SARS-CoV-2 infection. medRxiv
    [Google Scholar]
  27. Seow J, Graham C, Merrick B, Acors S, Pickering S et al. Longitudinal observation and decline of neutralising antibody responses in the three months following SARS-CoV-2 infection in humans. Nat Microbiol 2020; 5:1598–1607 [View Article] [PubMed]
    [Google Scholar]
  28. Seow J, Graham C, Merrick B, Acors S, Steel KJA et al. Longitudinal evaluation and decline of antibody responses in SARS-CoV-2 infection. medRxiv 2020
    [Google Scholar]
  29. Long Q-X, Tang X-J, Shi Q-L, Li Q, Deng H-J et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med 20201–5
    [Google Scholar]
  30. Seow J, Graham C, Merrick B, Acors S, Pickering S et al. Longitudinal observation and decline of neutralising antibody responses in the three months following SARS-CoV-2 infection in humans. Nat Microbiol 2020; 5:1598–1607 [View Article] [PubMed]
    [Google Scholar]
  31. Staines HM, Kirwan DE, Clark DJ, Adams ER, Augustin Y et al. Dynamics of IgG seroconversion and pathophysiology of COVID-19 infections. medRxiv 2020
    [Google Scholar]
  32. Chi X, Liu X, Wang C, Zhang X, Li X et al. Humanized single domain antibodies neutralise SARS-CoV-2 by targeting the spike receptor binding domain. Nat Commun 2020; 11:4528 [View Article] [PubMed]
    [Google Scholar]
  33. Tan CW, Chia WN, Qin X, Liu P, Chen MIC et al. A SARS-CoV-2 surrogate virus neutralisation test based on antibody-mediated blockage of ACE2–spike protein–protein interaction. Nat Biotechnol 2020; 38:1073–1078 [View Article] [PubMed]
    [Google Scholar]
  34. Marot S, Malet I, Leducq V, Zafilaza K, Sterlin D et al. Rapid decline of neutralising antibodies against SARS-CoV-2 among infected healthcare workers. Nat Commun 2021; 12:844 [View Article] [PubMed]
    [Google Scholar]
  35. Tuaillon E, Bolloré K, Pisoni A, Debiesse S, Renault C et al. Detection of SARS-CoV-2 antibodies using commercial assays and seroconversion patterns in hospitalized patients. J Infect 2020; 81:e39–e45 [View Article] [PubMed]
    [Google Scholar]
  36. Gallais F, Velay A, Wendling M-J, Nazon C, Partisani M et al. Intrafamilial exposure to SARS-CoV-2 induces cellular immune response without seroconversion. medRxiv 2020
    [Google Scholar]
  37. Okba NM, Müller MA, Li W, Wang C, GeurtsvanKessel CH et al. Severe acute respiratory syndrome coronavirus 2− specific antibody responses in coronavirus disease patients. Emerging Infect Dis 2020; 26:1478–1488 [View Article]
    [Google Scholar]
  38. Ripperger TJ, Uhrlaub JL, Watanabe M, Wong R, Castaneda Y et al. Orthogonal SARS-CoV-2 serological assays enable surveillance of low-prevalence communities and reveal durable humoral immunity. Immunity 2020; 53:e4 [View Article]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001653
Loading
/content/journal/jgv/10.1099/jgv.0.001653
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error