Human lungs show limited permissiveness for SARS-CoV-2 due to scarce ACE2 levels but virus-induced expansion of inflammatory macrophages

Scarce ACE2 expression limits alveolar SARS-CoV-2 permissiveness and related tissue damage. Instead, non-productive virus uptake by alveolar macrophages leads to a specific pulmonary immune activation. COVID-19 ARDS is most likely caused by immunopathogenesis rather than alveolar viral damage. Spectral microscopy, single-cell/-nucleus RNA sequencing or ACE2 ‘gain-of-function’ experiments were applied on infected human lung explants and adult stem cell-derived human lung organoids to correlate ACE2 and related host factors with SARS-CoV-2 tropism, propagation, virulence and immune activation compared to SARS-CoV, influenza and MERS-CoV. COVID-19 autopsy material was used to validate ex vivo results. >>>Submitter states that raw data are not available due to patient privacy concerns<<<