The ORF8 is one of the six viral accessory proteins of SARS-CoV-2. Dispensable for viral replication, those accessory proteins interact with the immune response, most of them playing a crucial role in the pathogenesis of human coronaviruses. ORF8 is unique among other beta-coronavirus, as the sequence identity between SARS-CoV and SARS-CoV-2 is low (~ 26 %) , probably to best adapt to human hosts 2 . During the last 2-years, studies focused on SARS-CoV-2 showed an increasing trend implicating ORF8 in many aspects of human immune evasion and other enigmatic functions . Recently, SARS-CoV-2 ORF8 has been describe as a virulence factor , as the infection of mice with ORF8-deleted virus and people infected with natural variants lacking ORF8 showed a milder disease, due to the reduction of excesive levels of host pro-inflammatory cytokines. Additionally, ORF8 blood levels correlated with mortality in infected patients .