SARS-CoV-2 variants lacking ORF8 occurred in farmed mink and pangolin.

ABSTRACT

The SARS-CoV-2 Variant of Concern 202012/01 (VOC-202012/01) is rapidly spreading worldwide owing to its substantial transmission advantage. The variant has changes in critical sites of the spike protein with potential biological significance. Moreover, VOC-202012/01 has a mutation that inactivates the ORF8 protein, whose absence can change the clinical features of the infection. Why VOC-202012/01 is more transmissible remains unclear, but spike mutations and ORF8 inactivation stand out by their known phenotypic effects. Here I show that variants combining relevant spike mutations and the absence of ORF8 occurred in SARS-CoV-2 and related viruses circulating in other host species. A truncated ORF8 (Q23stop) occurred in a SARS-CoV-2-related virus from a pangolin seized in China in 2017, also with several mutations in critical spike sites. Strikingly, I found that variants without ORF8 (E19stop) and with the N501T spike mutation circulated in farmed mink and humans from Denmark. Although with differences to VOC-202012/01, the identification of these variants highlights the danger of having reservoirs of SARS-CoV-2 and related viruses where more transmissible variants may occur and spill over to humans.