Digital PCR for high sensitivity viral detection in false-negative SARS-CoV-2 patients

• Main Authors: Paolo Poggio, Paola Songia, Chiara Vavassori, Veronica Ricci, Cristina Banfi, Silvia Stella Barbieri, Gloria Garoffolo, Veronika A. Myasoedova, Luca Piacentini, Angela Raucci, Alessandro Scopece, Elena Sommariva, Maria Cristina Vinci, Davide Carcione, Maria Luisa Biondi, Maria Elisabetta Mancini, Alberto Formenti, Daniele Andreini, Emilio M. Assanelli, Piergiuseppe Agostoni, Marina Camera, Gualtiero I. Colombo, Maurizio Pesce
• Format: Article
• Language: English
• Published: Nature Publishing Group 2021-02-01
• Series: Scientific Reports
• Online Access: https://doi.org/10.1038/s41598-021-83723-x

Abstract Patients requiring diagnostic testing for coronavirus disease 2019 (COVID-19) are routinely assessed by reverse-transcription quantitative polymerase chain reaction (RT-qPCR) amplification of Sars-CoV-2 virus RNA extracted from oro/nasopharyngeal swabs. Despite the good specificity of the assays certified for SARS-CoV-2 molecular detection, and a theoretical sensitivity of few viral gene copies per reaction, a relatively high rate of false negatives continues to be reported. This is an important challenge in the management of patients on hospital admission and for correct monitoring of the infectivity after the acute phase. In the present report, we show that the use of digital PCR, a high sensitivity method to detect low amplicon numbers, allowed us to correctly detecting infection in swab material in a significant number of false negatives. We show that the implementation of digital PCR methods in the diagnostic assessment of COVID-19 could resolve, at least in part, this timely issue.