Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which may result in acute respiratory distress syndrome (ARDS), multiorgan failure, and death. The alveolar epithelium is a major target of the virus, but representative models to study virus host interactions in more detail are currently lacking. Here, we describe a human 2D air–liquid interface culture system which was characterized by confocal and electron microscopy and single-cell mRNA expression analysis. In this model, alveolar cells, but also basal cells and rare neuroendocrine cells, are grown from 3D self-renewing fetal lung bud tip organoids. These cultures were readily infected by SARS-CoV-2 with mainly surfactant protein C-positive alveolar type II-like cells being targeted. Consequently, significant viral titers were detected and mRNA expression analysis revealed induction of type I/III interferon response program. Treatment of these cultures with a low dose of interferon lambda 1 reduced viral replication. Hence, these cultures represent an experimental model for SARS-CoV-2 infection and can be applied for drug screens.

airway organoids, bronchioalveolar-like, COVID-19, pneumocytes, SARS-CoV-2
dx.doi.org/10.15252/embj.2020105912, hdl.handle.net/1765/133317
EMBO Journal
Department of Virology

Lamers, M.M, van der Vaart, J. (Jelte), Knoops, K. (Kèvin), Riesebosch, S. (Samra), Breugem, T.I. (Tim I), Mykytyn, A.Z. (Anna Z), … Haagmans, B.L. (2021). An organoid-derived bronchioalveolar model for SARS-CoV-2 infection of human alveolar type II-like cells. EMBO Journal. doi:10.15252/embj.2020105912