Nonconcordance of E, N, and RdRp Genes in SARS-Coronavirus-2 Nucleic Acid Amplification Test Among Patients Older than 60 Years

Abstract

Introduction/ObjectiveDuring the COVID-19 pandemic, the FDA authorized emergency use of nucleic acid amplification (NAA) testing. Accurate and rapid testing identifies infected persons, especially among at-risk populations. In our institution, the InGenius platform detects three gene targets of SARS-Coronavirus-2: envelope (E), nucleocapsid (N), and RNA-dependent RNA polymerase (RdRp). Nonconcordance of these components present accuracy or precision errors or may correspond to varying expression of viral genes with disease progression.MethodsWe retrospectively analyzed the result components from 93 nasopharyngeal swabs from 50 patients older than 60 years and positive for SARS-Coronavirus-2 (SARS-CoV-2). The symptom onset date was determined by chart review.ResultsWe found a significant 26% nonconcordance rate, with a predominant pattern demonstrating positive N with negative RdRp and E (χ2 = 27.25, P < 0.0005). This nonconcordant pattern was more prevalent at longer symptom durations. In 7 patients with serial testing, the transition from concordant to nonconcordant results occurred 12 days (95% CI 3.5 – 20.3 days) after symptom onset.ConclusionThis may be caused by several mechanisms. Possibilities include decreased expression of E and RdRp over time, inhibition of expression by treatments or host immune response, or lower viral titers by clearance or migration to the lower respiratory tract. Presence of a different viral strain or systematic processing errors are less likely causes of nonconcordance. Future directions of study would determine whether a similar decline in RdRp and E detection is seen in tracheal samples or if this correlates with changes in symptom severity.