False-negative results of initial RT-PCR assays for COVID-19: A systematic review.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
14
05
2020
accepted:
12
11
2020
entrez:
10
12
2020
pubmed:
11
12
2020
medline:
5
1
2021
Statut:
epublish
Résumé
A false-negative case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is defined as a person with suspected infection and an initial negative result by reverse transcription-polymerase chain reaction (RT-PCR) test, with a positive result on a subsequent test. False-negative cases have important implications for isolation and risk of transmission of infected people and for the management of coronavirus disease 2019 (COVID-19). We aimed to review and critically appraise evidence about the rate of RT-PCR false-negatives at initial testing for COVID-19. We searched MEDLINE, EMBASE, LILACS, as well as COVID-19 repositories, including the EPPI-Centre living systematic map of evidence about COVID-19 and the Coronavirus Open Access Project living evidence database. Two authors independently screened and selected studies according to the eligibility criteria and collected data from the included studies. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We calculated the proportion of false-negative test results using a multilevel mixed-effect logistic regression model. The certainty of the evidence about false-negative cases was rated using the GRADE approach for tests and strategies. All information in this article is current up to July 17, 2020. We included 34 studies enrolling 12,057 COVID-19 confirmed cases. All studies were affected by several risks of bias and applicability concerns. The pooled estimate of false-negative proportion was highly affected by unexplained heterogeneity (tau-squared = 1.39; 90% prediction interval from 0.02 to 0.54). The certainty of the evidence was judged as very low due to the risk of bias, indirectness, and inconsistency issues. There is substantial and largely unexplained heterogeneity in the proportion of false-negative RT-PCR results. The collected evidence has several limitations, including risk of bias issues, high heterogeneity, and concerns about its applicability. Nonetheless, our findings reinforce the need for repeated testing in patients with suspicion of SARS-Cov-2 infection given that up to 54% of COVID-19 patients may have an initial false-negative RT-PCR (very low certainty of evidence). Protocol available on the OSF website: https://tinyurl.com/vvbgqya.
Sections du résumé
BACKGROUND
A false-negative case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is defined as a person with suspected infection and an initial negative result by reverse transcription-polymerase chain reaction (RT-PCR) test, with a positive result on a subsequent test. False-negative cases have important implications for isolation and risk of transmission of infected people and for the management of coronavirus disease 2019 (COVID-19). We aimed to review and critically appraise evidence about the rate of RT-PCR false-negatives at initial testing for COVID-19.
METHODS
We searched MEDLINE, EMBASE, LILACS, as well as COVID-19 repositories, including the EPPI-Centre living systematic map of evidence about COVID-19 and the Coronavirus Open Access Project living evidence database. Two authors independently screened and selected studies according to the eligibility criteria and collected data from the included studies. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We calculated the proportion of false-negative test results using a multilevel mixed-effect logistic regression model. The certainty of the evidence about false-negative cases was rated using the GRADE approach for tests and strategies. All information in this article is current up to July 17, 2020.
RESULTS
We included 34 studies enrolling 12,057 COVID-19 confirmed cases. All studies were affected by several risks of bias and applicability concerns. The pooled estimate of false-negative proportion was highly affected by unexplained heterogeneity (tau-squared = 1.39; 90% prediction interval from 0.02 to 0.54). The certainty of the evidence was judged as very low due to the risk of bias, indirectness, and inconsistency issues.
CONCLUSIONS
There is substantial and largely unexplained heterogeneity in the proportion of false-negative RT-PCR results. The collected evidence has several limitations, including risk of bias issues, high heterogeneity, and concerns about its applicability. Nonetheless, our findings reinforce the need for repeated testing in patients with suspicion of SARS-Cov-2 infection given that up to 54% of COVID-19 patients may have an initial false-negative RT-PCR (very low certainty of evidence).
SYSTEMATIC REVIEW REGISTRATION
Protocol available on the OSF website: https://tinyurl.com/vvbgqya.
Identifiants
pubmed: 33301459
doi: 10.1371/journal.pone.0242958
pii: PONE-D-20-14317
pmc: PMC7728293
doi:
Substances chimiques
RNA, Viral
0
Types de publication
Journal Article
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0242958Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Clin Chem Lab Med. 2020 Jun 25;58(7):1070-1076
pubmed: 32172228
J Clin Epidemiol. 2020 Jun;122:142-152
pubmed: 32058069
Euro Surveill. 2020 Jan;25(3):
pubmed: 31992387
Radiology. 2020 Aug;296(2):E72-E78
pubmed: 32216717
Radiol Cardiothorac Imaging. 2020 Apr 06;2(2):e200092
pubmed: 33778564
Int J Infect Dis. 2020 Dec;101:138-148
pubmed: 33007452
Syst Rev. 2015 Mar 11;4:25
pubmed: 25875495
Radiology. 2020 Aug;296(2):E32-E40
pubmed: 32101510
Ann Transl Med. 2020 Jun;8(11):679
pubmed: 32617299
Clin Chem. 2020 Apr 1;66(4):549-555
pubmed: 32031583
Genet Mol Res. 2015 Dec 02;14(4):15634-41
pubmed: 26634531
Clin Infect Dis. 2020 Jul 28;71(15):706-712
pubmed: 32109279
JAMA. 2020 Apr 21;323(15):1437-1438
pubmed: 32150622
Int J Infect Dis. 2020 Jun;95:106-112
pubmed: 32272262
Infection. 2020 Oct;48(5):687-694
pubmed: 32390091
Eur Radiol. 2020 Nov;30(11):6178-6185
pubmed: 32518987
Health Res Policy Syst. 2018 Feb 26;16(1):17
pubmed: 29482643
PLoS Med. 2020 Sep 22;17(9):e1003346
pubmed: 32960881
J Virol Methods. 2020 Sep;283:113919
pubmed: 32554043
JAMA. 2020 May 26;323(20):2052-2059
pubmed: 32320003
JAMA. 2018 Jan 23;319(4):388-396
pubmed: 29362800
J Clin Epidemiol. 2020 Oct;126:172-176
pubmed: 32622902
JCI Insight. 2020 May 21;5(10):
pubmed: 32352933
Swiss Med Wkly. 2020 Jun 22;150:w20304
pubmed: 32580213
Ann Intern Med. 2011 Oct 18;155(8):529-36
pubmed: 22007046
Eur Radiol. 2020 Dec;30(12):6818-6827
pubmed: 32666316
J Med Virol. 2020 Jul;92(7):903-908
pubmed: 32219885
Syst Rev. 2017 Feb 17;6(1):32
pubmed: 28212677
Eur Radiol. 2020 Oct;30(10):5446-5454
pubmed: 32367418
J Clin Virol. 2020 Jun;127:104359
pubmed: 32302956
Radiology. 2020 Jun;295(3):200463
pubmed: 32077789
Lancet Infect Dis. 2020 Jun;20(6):669-677
pubmed: 32240634
Diagn Interv Radiol. 2020 Jul;26(4):308-314
pubmed: 32558645
PLoS One. 2020 Jun 26;15(6):e0235460
pubmed: 32589687
Clin Infect Dis. 2021 Jan 27;72(2):323-326
pubmed: 33501950
J Med Virol. 2021 Jan;93(1):48-50
pubmed: 32484950
Eur Rev Med Pharmacol Sci. 2020 Feb;24(4):2012-2019
pubmed: 32141570
AJR Am J Roentgenol. 2021 Jan;216(1):66-70
pubmed: 32368928
J Clin Epidemiol. 2020 Jun;122:129-141
pubmed: 32060007
Respir Med. 2020 Jul;168:105980
pubmed: 32364959
JAMA. 2020 Feb 25;323(8):707-708
pubmed: 31971553
Eur J Radiol. 2020 May;126:108961
pubmed: 32229322
Clin Infect Dis. 2020 Nov 19;71(16):2246-2248
pubmed: 32306042
JAMA. 2018 Nov 6;320(17):1743-1744
pubmed: 30398590
JAMA. 2020 Apr 21;323(15):1488-1494
pubmed: 32125362
Lancet. 2020 Feb 15;395(10223):497-506
pubmed: 31986264
Ann Intern Med. 2020 Aug 18;173(4):262-267
pubmed: 32422057
BMC Med. 2020 May 6;18(1):123
pubmed: 32370747
Lancet Infect Dis. 2020 Jul;20(7):756-757
pubmed: 32251637
Allergy. 2020 Jul;75(7):1809-1812
pubmed: 32281110
Korean J Radiol. 2020 Apr;21(4):505-508
pubmed: 32174053
Jpn J Radiol. 2020 Jul;38(7):683-690
pubmed: 32458125
J Clin Med. 2020 Feb 26;9(3):
pubmed: 32110875
PLoS One. 2020 Jul 9;15(7):e0235844
pubmed: 32645053
Radiology. 2020 Aug;296(2):E115-E117
pubmed: 32073353
J Med Virol. 2020 Jun;92(6):683-687
pubmed: 32162699
Clin Infect Dis. 2020 Jun 16;:
pubmed: 32556191
Radiology. 2020 Aug;296(2):E41-E45
pubmed: 32049601
Medicine (Baltimore). 2020 Jun 26;99(26):e20837
pubmed: 32590775
Crit Care. 2020 Jul 2;24(1):389
pubmed: 32616077