- Magnen, Mélia;
- You, Ran;
- Rao, Arjun A;
- Davis, Ryan T;
- Rodriguez, Lauren;
- Bernard, Olivier;
- Simoneau, Camille R;
- Hysenaj, Lisiena;
- Hu, Kenneth H;
- Maishan, Mazharul;
- Conrad, Catharina;
- Gbenedio, Oghenekevwe M;
- Samad, Bushra;
- Consortium, The Ucsf Comet;
- Love, Christina;
- Woodruff, Prescott G;
- Erle, David J;
- Hendrickson, Carolyn M;
- Calfee, Carolyn S;
- Matthay, Michael A;
- Roose, Jeroen P;
- Sil, Anita;
- Ott, Melanie;
- Langelier, Charles R;
- Krummel, Matthew F;
- Looney, Mark R
In the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, epithelial populations in the distal lung expressing Angiotensin-converting enzyme 2 (ACE2) are infrequent, and therefore, the model of viral expansion and immune cell engagement remains incompletely understood. Using human lungs to investigate early host-viral pathogenesis, we found that SARS-CoV-2 had a rapid and specific tropism for myeloid populations. Human alveolar macrophages (AMs) reliably expressed ACE2 allowing both spike-ACE2-dependent viral entry and infection. In contrast to Influenza A virus, SARS-CoV-2 infection of AMs was productive, amplifying viral titers. While AMs generated new viruses, the interferon responses to SARS-CoV-2 were muted, hiding the viral dissemination from specific antiviral immune responses. The reliable and veiled viral depot in myeloid cells in the very early phases of SARS-CoV-2 infection of human lungs enables viral expansion in the distal lung and potentially licenses subsequent immune pathologies.