Hidden genomic diversity of SARS-CoV-2: implications for qRT-PCR diagnostics and transmission.

Sapoval, Nicolae; Mahmoud, Medhat; Jochum, Michael; Liu, Yunxi; Elworth, R A Leo; Wang, Qi; Albin, Dreycey; Ogilvie, Huw; Lee, Michael D; Villapol, Sonia; Hernandez, Kyle; Maljkovic Berry, Irina; Foox, Jonathan; Beheshti, Afshin; Ternus, Krista; Aagaard, Kjersti; Posada, David; Mason, Christopher; Sedlazeck, Fritz J; Treangen, Todd J

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 datasets and 6,928 consensus genomes to contrast the intrahost and interhost diversity of SARS-CoV-2. Our analyses yielded three major observations. First, the mutational profile of SARS-CoV-2 highlights 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.