Considering that both CD169 and ACE2 mediated virus entry resulted in similar levels of SARS-CoV-2 gRNA at 6 h pi but only ACE2-mediated virus entry resulted in productive virus infection, these results implicate a hitherto unappreciated post-entry role for ACE2 in virus life cycle in macrophages. Here, SIGLEC1 is linked to viral infectious disease.