Quantitative and qualitative subgenomic RNA profiles of SARS-CoV-2 in respiratory samples: A comparison between Omicron BA.2 and non-VOC-D614G

Virol Sin. 2024 Apr;39(2):218-227. doi: 10.1016/j.virs.2024.01.010. Epub 2024 Feb 3.

Abstract

The SARS-CoV-2 Omicron variants are notorious for their transmissibility, but little is known about their subgenomic RNA (sgRNA) expression. This study applied RNA-seq to delineate the quantitative and qualitative profiles of canonical sgRNA of 118 respiratory samples collected from patients infected with Omicron BA.2 and compared with 338 patients infected with non-variant of concern (non-VOC)-D614G. A unique characteristic profile depicted by the relative abundance of 9 canonical sgRNAs was reproduced by both BA.2 and non-VOC-D614G regardless of host gender, age and presence of pneumonia. Remarkably, such profile was lost in samples with low viral load, suggesting a potential application of sgRNA pattern to indicate viral activity of individual patient at a specific time point. A characteristic qualitative profile of canonical sgRNAs was also reproduced by both BA.2 and non-VOC-D614G. The presence of a full set of canonical sgRNAs carried a coherent correlation with crude viral load (AUC ​= ​0.91, 95% CI 0.88-0.94), and sgRNA ORF7b was identified to be the best surrogate marker allowing feasible routine application in characterizing the infection status of individual patient. Further potentials in using sgRNA as a target for vaccine and antiviral development are worth pursuing.

Keywords: Coronavirus; Non-VOC-D614G; Omicron BA.2; RNA-seq; SARS-CoV-2; Subgenomic RNA(sgRNA).

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • COVID-19* / diagnosis
  • COVID-19* / virology
  • Child
  • Child, Preschool
  • Female
  • Genome, Viral / genetics
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • RNA, Viral* / genetics
  • SARS-CoV-2* / genetics
  • SARS-CoV-2* / isolation & purification
  • Subgenomic RNA
  • Viral Load*
  • Young Adult

Substances

  • RNA, Viral
  • Subgenomic RNA

Supplementary concepts

  • SARS-CoV-2 variants