Optimized protocol for a quantitative SARS-CoV-2 duplex RT-qPCR assay with internal human sample sufficiency control

J Virol Methods. 2021 Aug:294:114174. doi: 10.1016/j.jviromet.2021.114174. Epub 2021 May 10.

Abstract

There is growing evidence that measurement of SARS-CoV-2 viral copy number can inform clinical and public health management of SARS-CoV-2 carriers and COVID-19 patients. Here we show that quantification of SARS-CoV-2 is feasible in a clinical setting, using a duplex RT-qPCR assay which targets both the E gene (Charité assay) and a human RNA transcript, RNase P (CDC assay) as an internal sample sufficiency control. Samples in which RNase P is not amplified indicate that sample degradation has occurred, PCR inhibitors are present, RNA extraction has failed or swabbing technique was insufficient. This important internal control reveals that 2.4 % of nasopharyngeal swabs (15/618 samples) are inadequate for SARS-CoV-2 testing which, if not identified, could result in false negative results. We show that our assay is linear across at least 7 logs and is highly reproducible, enabling the conversion of Cq values to viral copy numbers using a standard curve. Furthermore, the SARS-CoV-2 copy number was independent of the RNase P copy number indicating that the per-swab viral copy number is not dependent on sampling- further allowing comparisons between samples. The ability to quantify SARS-CoV-2 viral copy number will provide an important opportunity for viral burden-guided public health and clinical decision making.

Keywords: COVID-19; RNase P; RT-qPCR; SARS-CoV-2; Viral burden.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19 / diagnosis
  • COVID-19 / virology
  • COVID-19 Nucleic Acid Testing / methods*
  • COVID-19 Nucleic Acid Testing / standards*
  • Gene Dosage
  • Genes, Essential
  • Humans
  • Limit of Detection
  • RNA, Viral / genetics*
  • RNA, Viral / isolation & purification
  • Reference Standards
  • Ribonuclease P / genetics
  • SARS-CoV-2 / genetics*
  • Specimen Handling / methods
  • Specimen Handling / standards*
  • Viral Load

Substances

  • RNA, Viral
  • RPP40 protein, human
  • Ribonuclease P