Nosocomial severe acute respiratory coronavirus virus 2 (SARS-CoV-2) transmission arising from a case of N-gene dropout on reverse-transcription polymerase chain reaction (RT-PCR) testing

• Published in: Infection Control & Hospital Epidemiology 2023-01, Vol.44 (1), p.154-156
• Main Authors: Wee, Liang En Ian, Ko, Karrie Kwan-Ki, Conceicao, Edwin Philip, Aung, May Kyawt, Aung, Myat Oo, Yang, Yong, Arora, Shalvi, Suphavilai, Chayaporn, Venkatachalam, Indumathi
• Format: Article
• Language: English
• Subjects: Antigens; Coronaviruses; COVID-19; COVID-19 - diagnosis; COVID-19 Testing; COVID-19 vaccines; Cross Infection - prevention & control; Disease transmission; Epidemics; Genomes; Humans; Infections; Letter to the Editor; Mutation; Nosocomial infection; Polymerase chain reaction; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; SARS-CoV-2 - genetics; Sensitivity and Specificity; Severe acute respiratory syndrome coronavirus 2; Virus Diseases
• ISSN: 0899-823X; 1559-6834
• DOI: 10.1017/ice.2022.170

SARS-CoV-2 RAD testing on admission was negative; SARS-CoV-2 PCR on admission screening via GeneXpert-Xpert-Xpress returned a positive result on the E-gene gene target (cycle-threshold [Ct], 20.7) but a negative result on the N2 gene target. Because our institution had not encountered N-gene dropout cases among hospitalized inpatients prior to January 2022, the practice at that time was to await results of repeated SARS-CoV-2 PCR testing using a different assay (Roche cobas-6800, Roche Diagnostics, Indianapolis, IN) that utilized a separate set of gene targets (ORF-1a and E-gene regions). No additional cases of N-gene dropout were detected amongst inpatients or healthcare workers (HCWs) despite intensive surveillance including weekly, rostered, routine testing.7 This result is likely due to enhanced infection prevention measures in-place during the study period, including universal N95 usage by HCWs and high vaccination-uptake rates (≥80%) among inpatients and HCWs.9 The potential of nosocomial SARS-CoV-2 transmission from cases of N-gene dropout is not purely theoretical. According to the manufacturer instructions for the Cepheid GeneXpert-Xpert-Xpress test kit, cases with discrepant results (negative on the N2-gene gene target but positive on the E-gene gene-target) should have been reported as presumptive positive with a recommendation for repeated testing.10 Had this interpretation been used, the patient would have been isolated upon admission and the additional period of transmission risk would not have occurred, despite the N-gene dropout.