Rapid spread of a SARS-CoV-2 Delta variant with a frameshift deletion in ORF7a

Foster, C. S. P.; Rawlinson, W. D.

Australia is currently experiencing COVID-19 outbreaks from infection with SARS-CoV-2 Delta variants (B.1.617.2, AY.3). Analysis of the index case reveals a sub-consensus level of sequencing reads (~25%) that support a 17-nucleotide deletion in ORF7a (ORF7a{Delta}17del). ORF7a{Delta}17del induces a frameshift mutation in ORF7a, which truncates the peptide and potentially leads to reduced suppression of host restriction factor BST-2/CD317/Tetherin. Despite this, the mutation has rapidly become represented at the consensus level in subsequent cases: approximately 72% of SARS-CoV-2 genomes in the Australian outbreak possess ORF7a{Delta}17del, and 99.7% (1534/1538) of Delta genomes on GISAID with ORF7a{Delta}17del originate from the current Australian outbreak (5 August 2021). The global abundance of this mutation might be underestimated given the difficulty of variant calling software correctly calling insertion/deletions (indels), the common inability of phylogenetics software to take indels into account, and the tendency of GISAID to not release submissions that contain a frameshift mutation (unless specifically requested). Overall, the rapid increase of persistent ORF7a{Delta}17del variants is concerning, and suggests either a chance founder effect with a neutral mutation yet to be purged, or that the ORF7a{Delta}17del mutation provides a direct selective advantage.