At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data

被引:122
作者
Mallett, Sue [1 ]
Allen, A. Joy [2 ]
Graziadio, Sara [3 ]
Taylor, Stuart A. [1 ]
Sakai, Naomi S. [1 ]
Green, Kile [2 ]
Suklan, Jana [2 ]
Hyde, Chris [4 ]
Shinkins, Bethany [5 ]
Zhelev, Zhivko [4 ]
Peters, Jaime [4 ]
Turner, Philip J. [6 ]
Roberts, Nia W. [7 ]
di Ruffano, Lavinia Ferrante [8 ]
Wolff, Robert [9 ]
Whiting, Penny [10 ]
Winter, Amanda [3 ]
Bhatnagar, Gauraang [11 ]
Nicholson, Brian D. [6 ]
Halligan, Steve [1 ]
机构
[1] UCL, Ctr Med Imaging, 2nd Floor,Charles Bell House,43-45 Foley St, London W1W 7TS, England
[2] Newcastle Univ, NIHR In Vitro Diagnost Cooperat, Newcastle Upon Tyne NE2 7RU, Tyne & Wear, England
[3] Newcastle Upon Tyne Hosp NHS Fdn Trust, NIHR In Vitro Diagnost Cooperat, Newcastle Upon Tyne NE7 7DN, Tyne & Wear, England
[4] Univ Exeter, Med Sch, Inst Hlth Res, Exeter Test Grp, Coll House,St Lukes Campus, Exeter EX1 2LU, Devon, England
[5] Univ Leeds, Acad Unit Hlth Econ, Leeds Inst Hlth Sci, Test Evaluat Grp, Worsley Bldg,Clarendon Way, Leeds LS2 9LJ, W Yorkshire, England
[6] Univ Oxford, Nuffield Dept Primary Care Hlth Sci, Oxford, England
[7] Univ Oxford, Canc Serv Gastroenterol Populat Hlth & Primary Ca, Bodleian Hlth Care Lib, Oxford OX2 6HT, England
[8] Univ Birmingham, Inst Appl Hlth Res, Test Evaluat Res Grp, Birmingham B15 2TT, W Midlands, England
[9] Kleijnen Systemat Reviews Ltd, York, N Yorkshire, England
[10] Univ Bristol, Bristol Med Sch, Bristol, Avon, England
[11] Frimley Hlth NHS Fdn Trust, Camberley GU16 7UJ, England
关键词
SARS-CoV-2; RT-PCR; COVID-19; QUADAS-2; Diagnostic test; Anatomical sampling; IPD; Duration virus detection; Systematic review; SPECIMENS; RNA;
D O I
10.1186/s12916-020-01810-8
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BackgroundTests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR) are pivotal to detecting current coronavirus disease (COVID-19) and duration of detectable virus indicating potential for infectivity.MethodsWe conducted an individual participant data (IPD) systematic review of longitudinal studies of RT-PCR test results in symptomatic SARS-CoV-2. We searched PubMed, LitCOVID, medRxiv, and COVID-19 Living Evidence databases. We assessed risk of bias using a QUADAS-2 adaptation. Outcomes were the percentage of positive test results by time and the duration of detectable virus, by anatomical sampling sites.ResultsOf 5078 studies screened, we included 32 studies with 1023 SARS-CoV-2 infected participants and 1619 test results, from -6 to 66days post-symptom onset and hospitalisation. The highest percentage virus detection was from nasopharyngeal sampling between 0 and 4days post-symptom onset at 89% (95% confidence interval (CI) 83 to 93) dropping to 54% (95% CI 47 to 61) after 10 to 14days. On average, duration of detectable virus was longer with lower respiratory tract (LRT) sampling than upper respiratory tract (URT). Duration of faecal and respiratory tract virus detection varied greatly within individual participants. In some participants, virus was still detectable at 46days post-symptom onset.ConclusionsRT-PCR misses detection of people with SARS-CoV-2 infection; early sampling minimises false negative diagnoses. Beyond 10days post-symptom onset, lower RT or faecal testing may be preferred sampling sites. The included studies are open to substantial risk of bias, so the positivity rates are probably overestimated.
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