Quantitative Detection and Viral Load Analysis of SARS-CoV-2 in Infected Patients

Clin Infect Dis. 2020 Jul 28;71(15):793-798. doi: 10.1093/cid/ciaa345.

Abstract

Background: Coronavirus disease 2019 (COVID-19) has become a public health emergency. The widely used reverse transcription-polymerase chain reaction (RT-PCR) method has limitations for clinical diagnosis and treatment.

Methods: A total of 323 samples from 76 COVID-19-confirmed patients were analyzed by droplet digital PCR (ddPCR) and RT-PCR based 2 target genes (ORF1ab and N). Nasal swabs, throat swabs, sputum, blood, and urine were collected. Clinical and imaging data were obtained for clinical staging.

Results: In 95 samples that tested positive by both methods, the cycle threshold (Ct) of RT-PCR was highly correlated with the copy number of ddPCR (ORF1ab gene, R2 = 0.83; N gene, R2 = 0.87). Four (4/161) negative and 41 (41/67) single-gene positive samples tested by RT-PCR were positive according to ddPCR with viral loads ranging from 11.1 to 123.2 copies/test. The viral load of respiratory samples was then compared and the average viral load in sputum (17 429 ± 6920 copies/test) was found to be significantly higher than in throat swabs (2552 ± 1965 copies/test, P < .001) and nasal swabs (651 ± 501 copies/test, P < .001). Furthermore, the viral loads in the early and progressive stages were significantly higher than that in the recovery stage (46 800 ± 17 272 vs 1252 ± 1027, P < .001) analyzed by sputum samples.

Conclusions: Quantitative monitoring of viral load in lower respiratory tract samples helps to evaluate disease progression, especially in cases of low viral load.

Keywords: COVID-19; RT-PCR; SARS-CoV-2; ddPCR; viral load.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Betacoronavirus / genetics*
  • COVID-19
  • Coronavirus Infections / diagnosis*
  • Coronavirus Infections / virology*
  • Diagnostic Tests, Routine / methods
  • False Negative Reactions
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pandemics
  • Pneumonia, Viral / diagnosis*
  • Pneumonia, Viral / virology*
  • Real-Time Polymerase Chain Reaction / methods
  • Respiratory System / virology
  • SARS-CoV-2
  • Serologic Tests / methods
  • Sputum / virology
  • Viral Load / methods