What factors affect sensitivity and specificity of the COVID-19 nasal swab?Posted on by
- NP swabs must have proper technique and reach the nasopharynx for adequate collection.
- Swabs performed closer to the onset of symptoms are generally more accurate.
- Heat may affect test accuracy so samples must be stored properly before shipping to the lab.
- CT Chest has been shown to be more sensitive than RT-PCR and other tests are on the horizon.
I. EVIDENCE FOR COVID-19 NASOPHARYNGEAL SWAB
- While the nasopharyngeal swabs have high specificity, recent low-quality evidence suggests potentially low sensitivity (71-97%), resulting in high rates of false negative tests.
- Xie et. al. evaluated 167 patients treated for COVID-19 and found that 5/167 had initially negative RT-PCR (97% sensitivity) but positive CT Chest (1).
- Fang et. al. studied 51 patients and showed that RT-PCR had a sensitivity of 71% (36/51) (2).
- Finally, Luo et. al. similarly reported that the initial sensitivity of oropharyngeal swabs in close contacts was 71.3% in the first PCR test (92.2% in the second) (3).
- In summary, the COVID-19 RT-PCR is very specific but recent evidence from China suggests that sensitivity may be limited to ~71%.
II. FACTORS AFFECTING ACCURACY
- Swab technique/modality (0-7 days after symptom onset) (4,5)
- Bronchoalveolar lavage fluid: 88.5% of patients tested positive for COVID-19.
- Sputum: 82.2% of patients with mild symptoms and 88.9% with severe tested positive.
- NP: 72.1% with mild symptoms and 73.3% with severe tested positive (you must swab the nasopharynx to obtain an acceptable sample) (6).
- OP: 61.3% with mild symptoms and 60.0% with severe tested positive.
- Swab technique/modality (0-7 days after symptom onset) (4,5)
- Recommendation: although sputum is more sensitive, NP swabs are more accessible and accurate than OP swabs, making it the better choice for outpatient primary care.
- Timing of swab relative to onset of symptoms
- Using NP swabs, Yang et. al. showed that patients with severe symptoms had a 73.3% positive test rate 0-7 days after symptom onset, 72.3% at 8-14 days and 50.0% at 15+ days. They also showed that patients with mild symptoms had a 72.1% positive test rate at 0-7 days, 53.6% at 8-14 days and 54.5% at 15+ days (4).
- Wikramaratna et. al. analyzed publically available data to show that the probability of a positive test decreases through time as the infection progresses (7).
- Recommendation: NP swabs should be performed as early as possible to reduce the probability of false negative testing for COVID-19.
- Storage and transportation
- Pan et. al. showed that 7/15 weakly-positive viral samples to be RT-PCR negative after thermal incubation (56°C water bath for 30 min) (8).
- Recommendation: according to the CDC, NP swabs should be stored in viral media tubes at 2-8°C for up to 72 hours. If delays are expected, store samples at -70°C or below (9).
- Multiple tests
- There is some evidence to suggest that 2 NP swabs for RT-PCR 24 hours apart can increase sensitivity to 92.2% but given the lack of resources in BC, this is not common practice (3).
III. OTHER TESTS
- CT Chest: Ai et. al. suggests that CT chest has a sensitivity of 97% but this is likely an overestimation as it uses RT-PCR as the standard for comparison, which itself is not an entirely reliable testing modality (10).
- COVID-19 Antibody Tests: this detects the presence of COVID-19 antibodies in blood. Recent reports suggest that antibody testing has a sensitivity of 93.8% and a specificity of 96.4% (11). However, there have been a number of reports of faulty test supplies and lower-than-expected antibody production in some patients. The test is also limited in that it shows only previous exposures to COVID-19, not necessarily an active infection. Commercial antibody testing is still under development (12).
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- Xie X, Zhong Z, Zhao W, Zheng C, Wang F, Liu J. Chest CT for Typical 2019-nCoV Pneumonia: Relationship to Negative RT-PCR Testing. Radiology [Internet]. 2020 [cited 17 April 2020];. Available from: https://pubs.rsna.org/doi/10.1148/radiol.2020200343
- Fang Y, Zhang H, Xie J, Lin M, Ying L, Pang P et al. Sensitivity of Chest CT for COVID-19: Comparison to RT-PCR. Radiology [Internet]. 2020 [cited 17 April 2020];. Available from: https://pubs.rsna.org/doi/10.1148/radiol.2020200432
- Luo L, Liu D, Liao X, Wu X, Jing Q, Zheng J et al. Modes of Contact and Risk of Transmission in COVID-19: A Prospective Cohort Study 4950 Close Contact Persons in Guangzhou of China. SSRN Electronic Journal [Internet]. 2020 [cited 17 April 2020];. Available from: https://www.medrxiv.org/content/10.1101/2020.03.24.20042606v1
- Yang Y, Yang M, Shen C, Wang F, Yuan J, Li J. Evaluating the accuracy of different respiratory specimens in the laboratory diagnosis and monitoring the viral shedding of 2019-nCoV infections. [Internet]. 2020 [cited 17 April 2020];. Available from: https://www.medrxiv.org/content/10.1101/2020.02.11.20021493v2.full.pdf
- Wang W, Xu Y, Gao R, Lu R, Han K, Wu G et al. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA [Internet]. 2020 [cited 17 April 2020];. Available from: https://jamanetwork.com/journals/jama/fullarticle/2762997
- How to collect a Nasopharyngeal (NP) swab [Internet]. Ottawa Public Health. 2020 [cited 17 April 2020]. Available from: https://www.ottawapublichealth.ca/en/professionals-and-partners/how-to-collect-a-nasopharyngeal–np–swab.aspx
- Wikramaratna P, Paton R, Ghafari M, Lourenco J. Estimating false-negative detection rate of SARS-CoV-2 by RT-PCR. [Internet]. 2020 [cited 17 April 2020];. Available from: https://www.medrxiv.org/content/medrxiv/early/2020/04/07/2020.04.05.20053355.full.pdf
- Pan Y, Long L, Zhang D, Yan T, Cui S, Yang P et al. Potential false-negative nucleic acid testing results for Severe Acute Respiratory Syndrome Coronavirus 2 from thermal inactivation of samples with low viral loads. Clinical Chemistry [Internet]. 2020 [cited 17 April 2020];. Available from: https://academic.oup.com/clinchem/article/doi/10.1093/clinchem/hvaa091/5815979
- Coronavirus Disease 2019 (COVID-19) [Internet]. Centers for Disease Control and Prevention. 2020 [cited 17 April 2020]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/lab/guidelines-clinical-specimens.html
- Ai T, Yang Z, Hou H, Zhan C, Chen C, Lv W et al. Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases. Radiology [Internet]. 2020 [cited 17 April 2020];. Available from: https://pubs.rsna.org/doi/10.1148/radiol.2020200642
- Cellex. Cellex qSARS-CoV-2 IgG/IgM Rapid test [Internet]. FDA. 2020 [cited 17 April 2020]. Available from: https://www.fda.gov/media/136625/download
- Laboratory testing for 2019 novel coronavirus (2019-nCoV) in suspected human cases [Internet]. World Health Organization. 2020 [cited 17 April 2020]. Available from: https://www.who.int/publications-detail/laboratory-testing-for-2019-novel-coronavirus-in-suspected-human-cases-20200117
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