SARS-CoV-2 genomic diversity and the implications for qRT-PCR diagnostics and transmission

Genome Res. 2021 Apr;31(4):635-644. doi: 10.1101/gr.268961.120. Epub 2021 Feb 18.


The COVID-19 pandemic has sparked an urgent need to uncover the underlying biology of this devastating disease. Though RNA viruses mutate more rapidly than DNA viruses, there are a relatively small number of single nucleotide polymorphisms (SNPs) that differentiate the main SARS-CoV-2 lineages that have spread throughout the world. In this study, we investigated 129 RNA-seq data sets and 6928 consensus genomes to contrast the intra-host and inter-host diversity of SARS-CoV-2. Our analyses yielded three major observations. First, the mutational profile of SARS-CoV-2 highlights intra-host single nucleotide variant (iSNV) and SNP similarity, albeit with differences in C > U changes. Second, iSNV and SNP patterns in SARS-CoV-2 are more similar to MERS-CoV than SARS-CoV-1. Third, a significant fraction of insertions and deletions contribute to the genetic diversity of SARS-CoV-2. Altogether, our findings provide insight into SARS-CoV-2 genomic diversity, inform the design of detection tests, and highlight the potential of iSNVs for tracking the transmission of SARS-CoV-2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • COVID-19 / diagnosis*
  • COVID-19 / transmission*
  • COVID-19 / virology
  • Genetic Variation*
  • Genome, Viral*
  • Host-Pathogen Interactions
  • Humans
  • Polymorphism, Single Nucleotide
  • Real-Time Polymerase Chain Reaction / methods*
  • SARS-CoV-2 / genetics*