Assessment of SARS-CoV-2 infectivity of upper respiratory specimens from COVID-19 patients by virus isolation using VeroE6/TMPRSS2 cells

BMJ Open Respir Res. 2021 Feb;8(1):e000830. doi: 10.1136/bmjresp-2020-000830.

Abstract

Background: An outbreak of novel coronavirus (SARS-CoV-2)-associated respiratory infectious diseases (COVID-19) emerged in 2019 and has spread rapidly in humans around the world. The demonstration of in vitro infectiousness of respiratory specimens is an informative surrogate for SARS-CoV-2 transmission from patients with COVID-19; accordingly, viral isolation assays in cell culture are an important aspect of laboratory diagnostics for COVID-19.

Methods: We developed a simple and rapid protocol for isolating SARS-CoV-2 from respiratory specimens using VeroE6/TMPRSS2 cells, a cell line that is highly susceptible to the virus. We also investigated a correlation between isolation of SARS-CoV-2 and viral load detected by real-time RT-PCR (rRT-PCR) using N2 primer/probe set that has been developed for testing of COVID-19 in Japan.

Results: The SARS-CoV-2 isolation protocol did not require blind passage of inoculated cells and yielded the results of viral isolation within 7 days after inoculation. Specimens with cycle threshold (Ct) values of <20.2, determined by rRT-PCR, were predicted to be isolation-positive. On the other hand, 6.9% of specimens with Ct values >35 were virus isolation-positive, indicating that low viral loads (high Ct values) in upper respiratory specimens do not always indicate no risk of containing transmissible virus.

Conclusion: In combination with rRT-PCR, the SARS-CoV-2 isolation protocol provides a means for assessing the potential risk of transmissible virus in upper respiratory specimens.

Keywords: COVID-19; viral infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COVID-19 / transmission*
  • COVID-19 Nucleic Acid Testing
  • Cell Line
  • Chlorocebus aethiops
  • Cytopathogenic Effect, Viral
  • Humans
  • Nasal Cavity / virology
  • Nasopharynx / virology
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / pathogenicity*
  • Saliva / virology
  • Serine Endopeptidases / genetics
  • Specimen Handling
  • Vero Cells

Substances

  • Serine Endopeptidases
  • TMPRSS2 protein, human