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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.
BMC Med. 2020 11 04; 18(1):346.BM

Abstract

BACKGROUND

Tests 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.

METHODS

We 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.

RESULTS

Of 5078 studies screened, we included 32 studies with 1023 SARS-CoV-2 infected participants and 1619 test results, from - 6 to 66 days post-symptom onset and hospitalisation. The highest percentage virus detection was from nasopharyngeal sampling between 0 and 4 days post-symptom onset at 89% (95% confidence interval (CI) 83 to 93) dropping to 54% (95% CI 47 to 61) after 10 to 14 days. 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 46 days post-symptom onset.

CONCLUSIONS

RT-PCR misses detection of people with SARS-CoV-2 infection; early sampling minimises false negative diagnoses. Beyond 10 days 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.

Authors+Show Affiliations

Centre for Medical Imaging, University College London, 2nd Floor, Charles Bell House, 43-45 Foley Street, London, W1W 7TS, UK. sue.mallett@ucl.ac.uk.NIHR In Vitro Diagnostics Co-operative, Newcastle University, Newcastle upon Tyne, NE2 7RU, UK.NIHR In Vitro Diagnostics Co-operative, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE7 7DN, UK.Centre for Medical Imaging, University College London, 2nd Floor, Charles Bell House, 43-45 Foley Street, London, W1W 7TS, UK.Centre for Medical Imaging, University College London, 2nd Floor, Charles Bell House, 43-45 Foley Street, London, W1W 7TS, UK.NIHR In Vitro Diagnostics Co-operative, Newcastle University, Newcastle upon Tyne, NE2 7RU, UK.NIHR In Vitro Diagnostics Co-operative, Newcastle University, Newcastle upon Tyne, NE2 7RU, UK.Exeter Test Group, Institute of Health Research, University of Exeter Medical School, University of Exeter, College House, St Luke's Campus, Exeter, EX1 2LU, UK.Test Evaluation Group, Academic Unit of Health Economics, Leeds Institute of Health Sciences, University of Leeds, Worsley Building , Clarendon Way, Leeds, LS2 9LJ, UK.Exeter Test Group, Institute of Health Research, University of Exeter Medical School, University of Exeter, College House, St Luke's Campus, Exeter, EX1 2LU, UK.Exeter Test Group, Institute of Health Research, University of Exeter Medical School, University of Exeter, College House, St Luke's Campus, Exeter, EX1 2LU, UK.Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.Cancer Services, Gastroenterology, Population Health & Primary Care, Bodleian Health Care Libraries, University of Oxford, Oxford, OX2 6HT, UK.Test Evaluation Research Group, Institute of Applied Health Research, University of Birmingham, Birmingham, B15 2TT, UK.Kleijnen Systematic Reviews Ltd, York, UK.Bristol Medical School, University of Bristol, Bristol, UK.NIHR In Vitro Diagnostics Co-operative, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE7 7DN, UK.Frimley Health NHS Foundation Trust, Frimley, Camberley, GU16 7UJ, UK.Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.Centre for Medical Imaging, University College London, 2nd Floor, Charles Bell House, 43-45 Foley Street, London, W1W 7TS, UK.

Pub Type(s)

Journal Article
Systematic Review

Language

eng

PubMed ID

33143712

Citation

Mallett, Sue, et al. "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." BMC Medicine, vol. 18, no. 1, 2020, p. 346.
Mallett S, Allen AJ, Graziadio S, et al. 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. BMC Med. 2020;18(1):346.
Mallett, S., Allen, A. J., Graziadio, S., Taylor, S. A., Sakai, N. S., Green, K., Suklan, J., Hyde, C., Shinkins, B., Zhelev, Z., Peters, J., Turner, P. J., Roberts, N. W., di Ruffano, L. F., Wolff, R., Whiting, P., Winter, A., Bhatnagar, G., Nicholson, B. D., & Halligan, S. (2020). 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. BMC Medicine, 18(1), 346. https://doi.org/10.1186/s12916-020-01810-8
Mallett S, et al. 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. BMC Med. 2020 11 4;18(1):346. PubMed PMID: 33143712.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Mallett,Sue, AU - Allen,A Joy, AU - Graziadio,Sara, AU - Taylor,Stuart A, AU - Sakai,Naomi S, AU - Green,Kile, AU - Suklan,Jana, AU - Hyde,Chris, AU - Shinkins,Bethany, AU - Zhelev,Zhivko, AU - Peters,Jaime, AU - Turner,Philip J, AU - Roberts,Nia W, AU - di Ruffano,Lavinia Ferrante, AU - Wolff,Robert, AU - Whiting,Penny, AU - Winter,Amanda, AU - Bhatnagar,Gauraang, AU - Nicholson,Brian D, AU - Halligan,Steve, Y1 - 2020/11/04/ PY - 2020/07/14/received PY - 2020/10/08/accepted PY - 2020/11/4/entrez PY - 2020/11/5/pubmed PY - 2020/11/18/medline KW - Anatomical sampling KW - COVID-19 KW - Diagnostic test KW - Duration virus detection KW - IPD KW - QUADAS-2 KW - RT-PCR KW - SARS-CoV-2 KW - Systematic review SP - 346 EP - 346 JF - BMC medicine JO - BMC Med VL - 18 IS - 1 N2 - BACKGROUND: Tests 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. METHODS: We 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. RESULTS: Of 5078 studies screened, we included 32 studies with 1023 SARS-CoV-2 infected participants and 1619 test results, from - 6 to 66 days post-symptom onset and hospitalisation. The highest percentage virus detection was from nasopharyngeal sampling between 0 and 4 days post-symptom onset at 89% (95% confidence interval (CI) 83 to 93) dropping to 54% (95% CI 47 to 61) after 10 to 14 days. 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 46 days post-symptom onset. CONCLUSIONS: RT-PCR misses detection of people with SARS-CoV-2 infection; early sampling minimises false negative diagnoses. Beyond 10 days 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. SN - 1741-7015 UR - https://www.unboundmedicine.com/medline/citation/33143712/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_ L2 - https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-020-01810-8 DB - PRIME DP - Unbound Medicine ER -