Visual summary of the HLT model

Ex vivo physiological systems for the study of SARS-CoV-2-host interactions are scarce. We establish a method using primary human lung tissue (HLT) cells for the rapid analysis of cell tropism and identification of therapeutics. Main findings: i) HLT cells preserve main cell subpopulations, including alveolar type-II cells, and expression of SARS-CoV-2 entry factors ACE2, CD147, TMPRSS2 and AXL. ii) HLT cells are readily susceptible to SARS-CoV-2 infection without the need of cell isolation or further cell differentiation. iii) Antiviral testing in HLT cells allows the rapid identification of new drug candidates against SARS-CoV-2 variants, missed by conventional systems. iv) Local inflammation is supported in HLT cells and offers the identification of relevant anti-inflammatory compounds for SARS-CoV-2 infection.