Sequence evidence that the D614G clade of SARS-CoV-2 was already circulating in northern Italy in the fall of 2019

ABSTRACT

Elucidating ancestor-descendant relationships of viral lineages is crucial for addressing the question of when and where a virulent viral strain originated. The D614G clade, with an Aspartate-614 to Glycine (D614G) mutation, includes all recent variants of SARS-CoV-2 and tend to be more infectious than the viral strains isolated in Wuhan. The D614G clade is characterized by TTTG at four nucleotide sites (sites 241, 3037, 14408 and 23403 following the reference genome NC_045512), in contrast to CCCA shared among early SARS-CoV-2 genomes sampled in China and those that can be traced to China. It was believed that the TTTG lineage descended from the early viral CCCA lineages. A set of SARS-CoV-2 sequences collected from Sept. 12 to Dec. 18, 2019, in Lombardy, Milan and Turin in Italy provided, for the first time, strong evidence that the D614G/TTTG lineage has already been circulating in Italy in 2019. I discussed extensively the controversies arising from this set of early SARS-CoV-2 sequences.