Low level of tonic interferon signalling is associated with enhanced susceptibility to SARS-CoV-2 variants of concern in human lung organoids.

"flow cytometry data are available at http://flowrepository org/id/fr-fcm-z65r . data availability statement data included in this manuscript have been deposited in figshare at https://doi org/10 6084/m9 figshare 22266313 . data availability statement data included in this manuscript have been deposited in figshare"

"Disclosure statement No potential conflict of interest was reported by the author(s)."

"We would like to thank R. Rosenke and D. Long for assistance with histology and ISH of hLOs, Craig Martens, Kimmo Virtaneva, and Kent Barbian for library preparation and RNA-sequencing, along with Justin Lack and Colton McNinch for helpful bioinformatics discussions. We also thank C. Bushmaker, at Bitterroot Health Hospital; A. Pekosz, Johns Hopkins Bloomberg School of Public Health, and M. Suthar, Emory University School of Medicine for contributing SARS-COV-2 isolates. Vero E6-TMPRSS2-T2A-ACE2 cells were obtained through BEI Resources, NIAID, NIH: Cercopithecus aethiops Kidney Epithelial Cells Expressing Transmembrane Protease, Serine 2 and Human Angiotensin-Converting Enzyme 2 (Vero E6-TMPRSS2-T2A-ACE2), RN-54970. This study was supported by the Intramural Research Program of NIAID, NIH."