RT Journal Article SR Electronic T1 Immediate myeloid depot for SARS-CoV-2 in the human lung JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.04.28.489942 DO 10.1101/2022.04.28.489942 A1 Mélia Magnen A1 Ran You A1 Arjun A. Rao A1 Ryan T. Davis A1 Lauren Rodriguez A1 Camille R. Simoneau A1 Lisiena Hysenaj A1 Kenneth H. Hu A1 The UCSF COMET Consortium A1 Christina Love A1 Prescott G. Woodruff A1 David J. Erle A1 Carolyn M. Hendrickson A1 Carolyn S. Calfee A1 Michael A. Matthay A1 Jeroen P. Roose A1 Anita Sil A1 Melanie Ott A1 Charles R. Langelier A1 Matthew F. Krummel A1 Mark R. Looney YR 2022 UL http://biorxiv.org/content/early/2022/04/29/2022.04.28.489942.abstract AB In the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, considerable focus has been placed on a model of viral entry into host epithelial populations, with a separate focus upon the responding immune system dysfunction that exacerbates or causes disease. We developed a precision-cut lung slice model to investigate very early host-viral pathogenesis and found that SARS-CoV-2 had a rapid and specific tropism for myeloid populations in the human lung. Infection of alveolar macrophages was partially dependent upon their expression of ACE2 and the infections were productive for amplifying virus, both findings which were in contrast with their neutralization of another pandemic virus, Influenza A virus (IAV). Compared to IAV, SARS-CoV-2 was extremely poor at inducing interferon-stimulated genes in infected myeloid cells, providing a window of opportunity for modest titers to amplify within these cells. Endotracheal aspirate samples from humans with COVID-19 confirmed the lung slice findings, revealing a persistent myeloid depot. In the early phase of SARS-CoV-2 infection, myeloid cells may provide a safe harbor for the virus with minimal immune stimulatory cues being generated, resulting in effective viral colonization and quenching of the immune system.Competing Interest StatementThe authors have declared no competing interest.