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Abstract

Background

Reliable testing for SARS-CoV-2 is key for the management of the COVID-19 pandemic.

Aim

We estimate diagnostic accuracy for nucleic acid and antibody tests 5 months into the COVID-19 pandemic, and compare with manufacturer-reported accuracy.

Methods

We reviewed the clinical performance of SARS-CoV-2 nucleic acid and antibody tests based on 93,757 test results from 151 published studies and 20,205 new test results from 12 countries in the European Union and European Economic Area (EU/EEA).

Results

Pooling the results and considering only results with 95% confidence interval width ≤ 5%, we found four nucleic acid tests, including one point-of-care test and three antibody tests, with a clinical sensitivity ≥ 95% for at least one target population (hospitalised, mild or asymptomatic, or unknown). Nine nucleic acid tests and 25 antibody tests, 12 of them point-of-care tests, had a clinical specificity of ≥ 98%. Three antibody tests achieved both thresholds. Evidence for nucleic acid point-of-care tests remains scarce at present, and sensitivity varied substantially. Study heterogeneity was low for eight of 14 sensitivity and 68 of 84 specificity results with confidence interval width ≤ 5%, and lower for nucleic acid tests than antibody tests. Manufacturer-reported clinical performance was significantly higher than independently assessed in 11 of 32 and four of 34 cases, respectively, for sensitivity and specificity, indicating a need for improvement in this area.

Conclusion

Continuous monitoring of clinical performance within more clearly defined target populations is needed.

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/content/10.2807/1560-7917.ES.2021.26.45.2001675
2021-11-11
2021-11-29
http://instance.metastore.ingenta.com/content/10.2807/1560-7917.ES.2021.26.45.2001675
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References

  1. United States Food and Drug Administration (FDA). Emergency use authorizations for medical devices. Silver Spring: FDA. [Accessed: 20 Jul 2020]. Available from: https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations-medical-devices#covid19ivd
  2. World Health Organisation (WHO). WHO Emergency Use Listing for In vitro diagnostics (IVDs) Detecting SARS-CoV-2. Geneva: WHO. [Accessed: 31 Oct 2021]. Available from: https://www.who.int/publications/m/item/200922-eul-sars-cov2-product-list
  3. Joint Research Centre of the European Commission. COVID-19 in vitro diagnostic devices and test methods database. Brussels: European Commission. [Accessed: 20 Jul 2020]. Available from: https://covid-19-diagnostics.jrc.ec.europa.eu
  4. Foundation for Innovative Diagnostics (FIND). COVID-19 tests (commercialized & in development). Geneva: FIND. [Accessed: 20 Jul 2020]. Available from: https://www.finddx.org/covid-19/tests
  5. United States Food and Drug Administration (FDA). openFDA COVID-19 serological testing evaluations. Silver Spring: FDA. [Accessed: 20 Jul 2020]. Available from: https://open.fda.gov/apis/device/covid19serology/download
  6. Deeks JJ, Dinnes J, Takwoingi Y, Davenport C, Spijker R, Taylor-Phillips S, et al. Antibody tests for identification of current and past infection with SARS-CoV-2. Cochrane Database Syst Rev. 2020;6:CD013652.  https://doi.org/10.1002/14651858.CD013652  PMID: 32584464 
  7. European Network for Health Technology Assessment (EUnetHTA). Rapid collaborative review on the current role of antibody tests for novel coronavirus SARS-CoV-2 in the management of the pandemic. Diemen: EUnetHTA; 2020. Available from: https://www.eunethta.eu/wp-content/uploads/2020/06/RCR_OT_01-_Antibody-tests-for-SARS-CoV-2_23-06-2020.pdf
  8. Lisboa Bastos M, Tavaziva G, Abidi SK, Campbell JR, Haraoui LP, Johnston JC, et al. Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis. BMJ. 2020;370:m2516.  https://doi.org/10.1136/bmj.m2516  PMID: 32611558 
  9. Dinnes J, Deeks JJ, Adriano A, Berhane S, Davenport C, Dittrich S, et al. Rapid, point-of-care antigen and molecular-based tests for diagnosis of SARS-CoV-2 infection. Cochrane Database Syst Rev. 2020;8(8):CD013705. PMID: 32845525 
  10. Attwood LO, Francis MJ, Hamblin J, Korman TM, Druce J, Graham M. Clinical evaluation of AusDiagnostics SARS-CoV-2 multiplex tandem PCR assay. J Clin Virol. 2020;128:104448.  https://doi.org/10.1016/j.jcv.2020.104448  PMID: 32460173 
  11. Pan Y, Li X, Yang G, Fan J, Tang Y, Zhao J, et al. Serological immunochromatographic approach in diagnosis with SARS-CoV-2 infected COVID-19 patients. J Infect. 2020;81(1):e28-32.  https://doi.org/10.1016/j.jinf.2020.03.051  PMID: 32283141 
  12. Wang P. Combination of serological total antibody and RT-PCR test for detection of SARS-COV-2 infections. J Virol Methods. 2020;283:113919.  https://doi.org/10.1016/j.jviromet.2020.113919  PMID: 32554043 
  13. Zhao J, Yuan Q, Wang H, Liu W, Liao X, Su Y, et al. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clin Infect Dis. 2020;71(16):2027-34.  https://doi.org/10.1093/cid/ciaa344  PMID: 32221519 
  14. Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z, et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N Engl J Med. 2020;382(12):1177-9.  https://doi.org/10.1056/NEJMc2001737  PMID: 32074444 
  15. Green DA, Zucker J, Westblade LF, Whittier S, Rennert H, Velu P, et al. Clinical performance of SARS-CoV-2 molecular tests. J Clin Microbiol. 2020;58(8):e00995-20.  https://doi.org/10.1128/JCM.00995-20  PMID: 32513858 
  16. Kim H, Hong H, Yoon SH. Diagnostic performance of CT and reverse transcriptase polymerase chain reaction for coronavirus disease 2019: a meta-analysis. Radiology. 2020;296(3):E145-55.  https://doi.org/10.1148/radiol.2020201343  PMID: 32301646 
  17. World Health Organization (WHO). Laboratory testing for coronavirus disease (‎‎‎‎COVID-19)‎‎‎‎ in suspected human cases: interim guidance, 19 March 2020. Geneva: WHO; ‎2020. Available from: https://apps.who.int/iris/handle/10665/331501
  18. Viechtbauer W. Conducting meta-analyses in R with the metafor package. J Stat Softw. 2010;36(3):1-48.  https://doi.org/10.18637/jss.v036.i03 
  19. World Health Organization (WHO). COVID-19 target product profiles for priority diagnostics to support response to the COVID-19 pandemic v.0.1. Geneva: WHO; ‎2020. Available from: https://www.who.int/publications/m/item/covid-19-target-product-profiles-for-priority-diagnostics-to-support-response-to-the-covid-19-pandemic-v.0.1
  20. Sethuraman N, Jeremiah SS, Ryo A. Interpreting diagnostic tests for SARS-CoV-2. JAMA. 2020;323(22):2249-51.  https://doi.org/10.1001/jama.2020.8259  PMID: 32374370 
  21. La Marca A, Capuzzo M, Paglia T, Roli L, Trenti T, Nelson SM. Testing for SARS-CoV-2 (COVID-19): a systematic review and clinical guide to molecular and serological in-vitro diagnostic assays. Reprod Biomed Online. 2020;41(3):483-99.  https://doi.org/10.1016/j.rbmo.2020.06.001  PMID: 32651106 
  22. Böger B, Fachi MM, Vilhena RO, Cobre AF, Tonin FS, Pontarolo R. Systematic review with meta-analysis of the accuracy of diagnostic tests for COVID-19. Am J Infect Control. 2021;49(1):21-9.  https://doi.org/10.1016/j.ajic.2020.07.011  PMID: 32659413 
  23. Caini S, Bellerba F, Corso F, Díaz-Basabe A, Natoli G, Paget J, et al. Meta-analysis of diagnostic performance of serological tests for SARS-CoV-2 antibodies up to 25 April 2020 and public health implications. Euro Surveill. 2020;25(23):2000980.  https://doi.org/10.2807/1560-7917.ES.2020.25.23.2000980  PMID: 32553061 
  24. Moura DTH, McCarty TR, Ribeiro IB, Funari MP, Oliveira PVAG, Miranda Neto AA, et al. Diagnostic characteristics of serological-based COVID-19 testing: a systematic review and meta-analysis. Clinics (São Paulo). 2020;75:e2212.  https://doi.org/10.6061/clinics/2020/e2212  PMID: 32785570 
  25. Vermeersch P, André E. How the European in vitro diagnostic regulation could negatively impact the European response to the next pandemic: an urgent call for action before May 2022. Clin Microbiol Infect. 2021;27(8):1074-5.  https://doi.org/10.1016/j.cmi.2021.05.009  PMID: 33979703 
  26. European Commission (EC). Questions and answers on the progressive roll-out of the new In Vitro Diagnostic Medical Devices Regulation. Brussels: EC. [Accessed: 1 Nov 2021]. Available from: https://ec.europa.eu/commission/presscorner/detail/en/qanda_21_5210
  27. Cohen JF, Korevaar DA, Altman DG, Bruns DE, Gatsonis CA, Hooft L, et al. STARD 2015 guidelines for reporting diagnostic accuracy studies: explanation and elaboration. BMJ Open. 2016;6(11):e012799.  https://doi.org/10.1136/bmjopen-2016-012799  PMID: 28137831 
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