Coupled with our demonstration of SARS-CoV-2 ORF6 more strongly downregulating protein expression and copurifying with more Rae1 and Nup98 than SARS-CoV ORF6, the differences between SARS-CoV ORF6 and SARS-CoV-2 ORF6 could explain at least some of the differences in clinical presentations between SARS and COVID-19. Here, RAE1 is linked to severe acute respiratory syndrome.