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

"processed sequencing data have been deposited in geo under accession number gse198864."

"analysis code and scripts to generate associated figures are accessible at https://github com/bihealth/hoenzke_et_al_human_lungs_covid_ace2 ."

"Conflict of interest: J-C. Rückert and H. Radbruch report support from DFG RA 2491/1-1, BMBF (Defeat Pandemics). A.E. Hauser reports support from Charité – Universitätsmedizin Berlin and Deutsches Rheuma-Forschungszentrum Berlin, and grants from Deutsche Forschungsgemeinschaft (HA5354/10-1, TRR130,P17 and C01, HA5354/8-1). T. Wolff reports support from Federal Ministry of Education and Research (BMBF) grant 01K12006F. M. Kessler reports grants from BMBF Organo-Strat, Einstein 3R. M. Dohmen reports contracts with Max-Delbrück Center, Berlin; grants from Gender Equality Fund, Berlin Institute of Health. F. Klauschen reports consulting fees, lecture honoraria, travel support and participation on advisory boards with BMS, Novartis, Roche and Lilly, and is a co-founder of AI-BIH/Charité-Spinoff Aignostics GmbH. F. Heppner reports consulting fees, lecture honoraria, payment for expert testimony and leadership roles at Novartis, AstraZeneca and ThinkHealth Hygiene Solutions. V.M. Corman reports the following patents: 20210190797 (Methods and reagents for diagnosis of SARS-CoV-2 infection); 9841834 (Human recombinant monoclonal antibody against SARS-CoV-2 spike glycoprotein); 9909654 (A pharmaceutical combination comprising an anti-viral protonophore and a serine protease inhibitor). D. Niemeyer reports that Technische Universität Berlin, Freie Universität Berlin and Charité – Universitätsmedizin have filed a patent application for siRNAs inhibiting SARS-CoV-2 replication with D. Niemeyer as coauthor. M.A. Müller reports the following patents: 20210190797 (Methods and reagents for diagnosis of SARS-CoV-2 infection); 9841834 (Human recombinant monoclonal antibody against SARS-CoV-2 spike glycoprotein); 9909654 (A pharmaceutical combination comprising an anti-viral protonophore and a serine protease inhibitor); and has participated on an advisory board for ECDC/WHO. S. Ludwig reports consulting fees from Atriva Therapeutics GmbH, Biontec SE; and has patent PCT/EP2021/063485 pending. M. Witzenrath reports grants from Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Deutsche Gesellschaft für Pneumologie, European Respiratory Society, Marie Curie Foundation, Else Kröner Fresenius Stiftung, Capnetz Stiftung, International Max Planck Research School, Quark Pharma, Takeda Pharma, Noxxon, Pantherna, Silence Therapeutics, Vaxxilon, Actelion, Bayer Health Care, Biotest and Boehringer Ingelheim; consulting fees from Noxxon, Pantherna, Silence Therapeutics, Vaxxilon, Aptarion, GlaxoSmithKline, Sinoxa and Biotest; lecture honoraria from AstraZeneca, Berlin Chemie, Chiesi, Novartis, Teva, Actelion, Boehringer Ingelheim, GlaxoSmithKline, Biotest, Bayer Health Care; and has the following patents issued: EPO 12181535.1 (IL-27 for modulation of immune response in acute lung injury), WO/2010/094491 (Means for inhibiting the expression of Ang-2), DE 102020116249.9 (Camostat/Niclosamide cotreatment in SARS-CoV-2 infected human lung cells). All other authors have nothing to disclose."

"Support statement: A.C. Hocke, L-E. Sander and S. Hippenstiel were supported by Berlin University Alliance GC2 Global Health (Corona Virus Pre-Exploration Project). A.C. Hocke, S. Hippenstiel, T. Wolff and C. Drosten were supported by BMBF (RAPID), and A.C. Hocke and S. Hippenstiel by BMBF (alvBarriere-COVID-19). K. Hoenzke, L. Brunotte, S. Ludwig, S. Hippenstiel, C. Drosten, C. Goffinet, T. Wolff and A.C. Hocke were funded by BMBF (NUM-COVID 19, Organo-Strat 01KX2021). K. Hoenzke, N. Suttorp, L-E. Sander, M. Witzenrath, S. Hippenstiel, A.D. Gruber, C. Drosten, T. Wolff and A.C. Hocke were supported by DFG (SFB-TR 84). A.C. Hocke was supported by BIH and Charité-Zeiss MultiDim. A.C. Hocke and S. Hippenstiel were supported by Charite 3R. K. Hoenzke, A.C. Hocke, M. Kessler, A.D. Gruber and S. Hippenstiel were supported by Einstein Foundation EC3R. K. Hoenzke and C. Drosten were supported by BMBF (Camo-COVID-19). M. Witzenrath, N. Suttorp and S. Hippenstiel were supported by BMBF (PROVID). C. Goffinet and A.C. Hocke were funded by BIH. M. Witzenrath and N. Suttorp were supported by BIH and BMBF (SYMPATH, CAPSyS, NAPKON). B. Obermayer and D. Beule were funded through the BIH Clinical Single Cell Bioinformatics Pipeline. Computation was performed on the HPC for Research cluster of the Berlin Institute of Health. L. Brunotte was supported by the BMBF (CoIMMUNE), the DFG (KFO 342) and the IZKF of the Medical Faculty of the WWU. A.E. Hauser, R. Mothes and A. Pascual-Reguant were supported by funding from the DFG, HA5354/10-1, SPP1937 (HA5354/8-2) and TRR130 P17. H. Radbruch was supported by DFG (RA 2491/1-1). Funding information for this article has been deposited with the Crossref Funder Registry."