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. 2020 Aug 17;222(6):899-902.
doi: 10.1093/infdis/jiaa370.

Suboptimal Biological Sampling as a Probable Cause of False-Negative COVID-19 Diagnostic Test Results

Natalie N Kinloch  1   2 , Gordon Ritchie  3   4 , Chanson J Brumme  2   5 , Winnie Dong  2 , Weiyan Dong  2 , Tanya Lawson  3 , R Brad Jones  6 , Julio S G Montaner  2   5 , Victor Leung  3   4 , Marc G Romney  3   4 , Aleksandra Stefanovic  3   4 , Nancy Matic  3   4 , Christopher F Lowe  3   4 , Zabrina L Brumme  1   2
Affiliations

Suboptimal Biological Sampling as a Probable Cause of False-Negative COVID-19 Diagnostic Test Results

Natalie N Kinloch et al. J Infect Dis. .

Erratum in

Abstract

False-negative severe acute respiratory syndrome coronavirus 2 test results can negatively impact the clinical and public health response to coronavirus disease 2019 (COVID-19). We used droplet digital polymerase chain reaction (ddPCR) to demonstrate that human DNA levels, a stable molecular marker of sampling quality, were significantly lower in samples from 40 confirmed or suspected COVID-19 cases that yielded negative diagnostic test results (ie, suspected false-negative test results) compared with a representative pool of 87 specimens submitted for COVID-19 testing. Our results support suboptimal biological sampling as a contributor to false-negative COVID-19 test results and underscore the importance of proper training and technique in the collection of nasopharyngeal specimens.

Keywords: COVID-19; ddPCR; false negative; nasopharyngeal swab; sample quality.

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Figures

Figure 1.
Figure 1.
Suspected false-negative coronavirus disease 2019 test samples contained significantly lower human deoxyribonucleic acid (DNA) levels compared with a representative pool of specimens submitted for testing. Human DNA levels (RPP30 gene target) were measured using droplet digital polymerase chain reaction (ddPCR) in nasopharyngeal extracts as a molecular marker of biological sampling quality. “Suspect false-negatives” included 23 negative samples from individuals who recorded a positive test within ±12 days of the negative test (gray) and 17 samples from individuals with high clinical suspicion of being infected but never molecularly confirmed (white). The comparison dataset was a consecutive set of 87 samples submitted for testing in April 2020 to the same laboratory (black). P values report the significance level between the comparison dataset and the suspect false-negative group as a whole (black), between the comparison dataset and the negative samples from individuals who reported a positive test within ±12 days (gray) and between the comparison dataset and the negative samples from individuals with high clinical suspicion (white).
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References

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