Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Dec:133:104683.
doi: 10.1016/j.jcv.2020.104683. Epub 2020 Oct 29.

A needle in the haystack? Assessing the significance of envelope (E) gene-negative, nucleocapsid (N2) gene-positive SARS-CoV-2 detection by the Cepheid Xpert Xpress SARS-COV-2 assay

Mahdi Khoshchehreh  1 , Noah Wald-Dickler  2 , Paul Holtom  2 , Susan M Butler-Wu  3
Affiliations

A needle in the haystack? Assessing the significance of envelope (E) gene-negative, nucleocapsid (N2) gene-positive SARS-CoV-2 detection by the Cepheid Xpert Xpress SARS-COV-2 assay

Mahdi Khoshchehreh et al. J Clin Virol. 2020 Dec.

Abstract

The clinical significance of high crossing threshold (Ct) detection of SARS-CoV-2 by RT-PCR is inadequately defined. In the course of universal admission screening with the Cepheid Xpert Xpress SARS-CoV-2 assay at our institution, we observed that 3.9 % (44/1123) of SARS-CoV-2 positive results were negative for the envelope (E) gene target but positive for the nucleocapsid (N2) target. The overall SARS-CoV-2 positivity rate during the three-month study period was 15.4 % (1123/7285), spanning April-June 2020. The majority of patients with E-negative, N2-positive results were asymptomatic, with 29.5 % of patients symptomatic for COVID-19 at the time of presentation. Asymptomatic patients with E-negative, N2-positive results were significantly younger than symptomatic patients with the same results (average 37.6 vs. 58.4, p = 0.003). Similar proportions of prior SARS-CoV-2 positivity were noted among symptomatic and asymptomatic individuals (38.5 % vs. 33.3 %, p = 0.82). Among the 16 asymptomatic patients with radiographic imaging performed, four (25 %) had chest radiographic findings concerning for viral pneumonia. Interestingly, we observed an E-negative, N2-positive result in one patient with a previous SARS-CoV-2 by the Xpert Xpress that occurred 71 days prior. Critically, E-negative, N2-positive results were observed in 8 symptomatic patients with a new diagnosis of COVID-19. Thus, though concerns remain about extended SARS-CoV-2 RT-PCR positivity in some patients, the ability of clinical laboratories to detect patients with high Ct values (including E-negative, N2-positive results) is vital for retaining maximal sensitivity for diagnostic purposes. Our data show that a finding of E-positive, N2-negative SARS-CoV-2 should not be used to rule out the presence of subclinical infection.

Keywords: COVID-19; Ct value; RT-PCR; SARS-CoV-2.

PubMed Disclaimer

Conflict of interest statement

SBW has received consulting honoraria from Cepheid. All other authors have no relevant disclosures.

References

    1. Lai C.C., Wang C.Y., Ko W.C., Hsueh P.R. In vitro diagnostics of coronavirus disease 2019: Technologies and application. J. Microbiol. Immunol. Infect. 2020 doi: 10.1016/j.jmii.2020.05.016. Jun 5;S1684-1182(20)30140-7. - DOI - PMC - PubMed
    1. Loeffelholz M.J., Tang Y.W. Laboratory diagnosis of emerging human coronavirus infections - the state of the art. Emerg. Microbes Infect. 2020;9:747–756. - PMC - PubMed
    1. Loeffelholz M.J., Alland D., Butler-Wu S.M., Pandey U., Perno C.F., Nava A., Carroll K.C., Mostafa H., Davies E., McEwan A., Rakeman J.L., Fowler R.C., Pawlotsky J.M., Fourati S., Banik S., Banada P.P., Swaminathan S., Chakravorty S., Kwiatkowski R.W., Chu V.C., Kop J., Gaur R., Sin M.L.Y., Nguyen D., Singh S., Zhang N., Persing D.H. Multicenter Evaluation of the Cepheid Xpert Xpress SARS-CoV-2 Test. J. Clin. Microbiol. 2020:58. - PMC - PubMed
    1. Mandavilli A. 2020. Your Coronavirus Test Is Positive. Maybe It Shouldn’t Be., P in the New York Times.https://www.nytimes.com/2020/08/29/health/coronavirus-testing.html
    1. Magleby R., Westblade L.F., Trzebucki A., Simon M.S., Rajan M., Park J., Goyal P., Safford M.M., Satlin M.J. Impact of SARS-CoV-2 viral load on risk of intubation and mortality among hospitalized patients with coronavirus disease 2019. Clin. Infect. Dis. 2020 doi: 10.1093/cid/ciaa851. Jun 30;ciaa851. Online ahead of print. PMID: 32603425. - DOI - PMC - PubMed

Substances