ArticleThe European respiratory journal2022
Human lungs show limited permissiveness for SARS-CoV-2 due to scarce ACE2 levels but virus-induced expansion of inflammatory macrophages.
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Article in The European respiratory journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers, 1 of them a synthesis that pooled it.
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37citing papers in PubMed, 1 pooled it
5.9field-weighted citation impact, top 3% of its field
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Low reporting quality limits the contribution of human organ models to COVID-19 research: a systematic review.EBioMedicine · 2026Pooled it
- The cell with many faces: lung macrophage plasticity and function in response to environmental and pathogenic insults.Physiological reviews · 2026Review
- Efferocytosis of apoptotic bodies drives SARS-CoV-2 infection and macrophage inflammation.Nature communications · 2026Article
- Differential effects of SARS-CoV-2-targeted infection of ATII, club cells, and macrophages on lung immunopathology and antiviral responses.Mucosal immunology · 2026Article
- SARS-CoV-2 infection induces pro-fibrotic and pro-thrombotic foam cell formation.Nature microbiology · 2025Article
- A survey of SARS-CoV-2 tropism.Infectious diseases & immunity · 2025Review
- Diagnostic electron microscopy in human infectious diseases - Methods and applications.Journal of microscopy · 2025Review
- Kidney Stone Disease: Epigenetic Dysregulation in Homocystinuria and Mitochondrial Sulfur Trans-Sulfuration Ablation Driven by COVID-19 Pathophysiology.Biomolecules · 2025Review
- Toll-like receptor 7 (TLR7)-mediated antiviral response protects mice from lethal SARS-CoV-2 infection.Journal of virology · 2025Article
- Cryopreservation of human lung tissue for 3D ex vivo analysis.Respiratory research · 2025Review
- A Modular Mathematical Model of the Immune Response for Investigating the Pathogenesis of Infectious Diseases.Viruses · 2025Article
- Aging shapes infection profiles of influenza A virus and SARS-CoV-2 in human precision-cut lung slices.Respiratory research · 2025Article
- A Novel In Vitro Primary Human Alveolar Model (AlveolAir™) for H1N1 and SARS-CoV-2 Infection and Antiviral Screening.Microorganisms · 2025Article
- Host cell lectins ASGR1 and DC-SIGN jointly with TMEM106B confer ACE2 independence and imdevimab resistance to SARS-CoV-2 pseudovirus with spike mutation E484D.Journal of virology · 2025Article
- Assessment of upper respiratory and gut bacterial microbiomes during COVID-19 infection in adults: potential aerodigestive transmission.Scientific reports · 2025Article
- Alveolar Macrophages in Viral Respiratory Infections: Sentinels and Saboteurs of Lung Defense.International journal of molecular sciences · 2025Review
- Microenvironmental acidification by pneumococcal sugar consumption fosters barrier disruption and immune suppression in the human alveolus.The European respiratory journal · 2024Article
- SARS-CoV2 infection in whole lung primarily targets macrophages that display subset-specific responses.Cellular and molecular life sciences : CMLS · 2024Article
- Immediate myeloid depot for SARS-CoV-2 in the human lung.Science advances · 2024Article
- SARS-CoV-2 tropism to intestinal but not gastric epithelial cells is defined by limited ACE2 expression.Stem cell reports · 2024Article
Corrections and comments
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Authors and funding
54 authors at 8 institutions in 1 country.
Katja HönzkeDepartment of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Benedikt ObermayerBerlin Institute of Health at Charité - Universitätsmedizin Berlin, Core Unit Bioinformatics, Berlin, Germany.ORCID https://orcid.org/0000-0002-9116-630X
Christin MacheUnit 17 "Influenza and other Respiratory Viruses", Robert Koch Institut, Berlin, Germany.
Diana FatykhovaDepartment of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Mirjana KesslerDepartment of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Simon DökelDepartment of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
Emanuel WylerBerlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) and IRI Life Sciences, Institute for Biology, Humboldt Universität zu Berlin, Berlin, Germany.
Morris BaumgardtDepartment of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.ORCID https://orcid.org/0000-0003-2077-3716
Anna LöwaDepartment of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Karen HoffmannDepartment of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.ORCID https://orcid.org/0000-0002-1528-6617
Patrick GraffDepartment of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Jessica SchulzeUnit 17 "Influenza and other Respiratory Viruses", Robert Koch Institut, Berlin, Germany.
Maren MiethDepartment of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Katharina HellwigDepartment of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Zeynep DemirDepartment of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.ORCID https://orcid.org/0000-0001-5329-5517
Barbara BiereUnit 17 "Influenza and other Respiratory Viruses", Robert Koch Institut, Berlin, Germany.
Linda BrunotteInstitute of Virology, Westfaelische Wilhelms Universität, Münster, Germany.
Angeles Mecate-ZambranoInstitute of Virology, Westfaelische Wilhelms Universität, Münster, Germany.
Judith BusheDepartment of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
Melanie DohmenDepartment of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Christian HinzeMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Sefer ElezkurtajDepartment of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Mario TönniesHELIOS Clinic Emil von Behring, Department of Pneumology and Department of Thoracic Surgery, Chest Hospital Heckeshorn, Berlin, Germany.
Torsten T BauerHELIOS Clinic Emil von Behring, Department of Pneumology and Department of Thoracic Surgery, Chest Hospital Heckeshorn, Berlin, Germany.ORCID https://orcid.org/0000-0003-1275-7361
Stephan EggelingDepartment of Thoracic Surgery, Vivantes Clinics Neukölln, Berlin, Germany.
Hong-Linh TranDepartment of Thoracic Surgery, Vivantes Clinics Neukölln, Berlin, Germany.
Paul SchneiderDepartment for Thoracic Surgery, DRK Clinics, Berlin, Germany.
Jens NeudeckerDepartment of General, Visceral, Vascular and Thoracic Surgery, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Jens C RückertDepartment of General, Visceral, Vascular and Thoracic Surgery, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Kai M Schmidt-OttMax Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Jonas BuschClinic for Urology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Frederick KlauschenDepartment of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
David HorstDepartment of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.ORCID https://orcid.org/0000-0003-4755-5743
Helena RadbruchInstitute for Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Josefine RadkeInstitute for Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Frank HeppnerInstitute for Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.ORCID https://orcid.org/0000-0001-9816-8917
Victor M CormanInstitute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.ORCID https://orcid.org/0000-0002-3605-0136
Daniela NiemeyerInstitute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Marcel A MüllerInstitute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Christine GoffinetInstitute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Ronja MothesDepartment of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Anna Pascual-ReguantDepartment of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID https://orcid.org/0000-0002-5042-3699
Anja Erika HauserDepartment of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Dieter BeuleBerlin Institute of Health at Charité - Universitätsmedizin Berlin, Core Unit Bioinformatics, Berlin, Germany.
Markus LandthalerBerlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) and IRI Life Sciences, Institute for Biology, Humboldt Universität zu Berlin, Berlin, Germany.
Stephan LudwigInstitute of Virology, Westfaelische Wilhelms Universität, Münster, Germany.
Norbert SuttorpDepartment of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Martin WitzenrathDepartment of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Achim D GruberDepartment of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
Christian DrostenInstitute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Leif-Erik SanderDepartment of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Thorsten WolffUnit 17 "Influenza and other Respiratory Viruses", Robert Koch Institut, Berlin, Germany.
Stefan HippenstielDepartment of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Andreas C HockeDepartment of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany andreas.hocke@charite.de.
Humboldt-Universität zu Berlin · DEMax Delbrück Center · DERobert Koch Institute · DEFreie Universität Berlin · DEUniversity of Münster · DEBerlin Institute of Health at Charité - Universitätsmedizin Berlin · DEHelios Klinikum Emil von Behring · DEVivantes Klinikum · DE
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilises the angiotensin-converting enzyme 2 (ACE2) transmembrane peptidase as cellular entry receptor. However, whether SARS-CoV-2 in the alveolar compartment is strictly ACE2-dependent and to what extent virus-induced tissue damage and/or direct immune activation determines early pathogenesis is still elusive.
methodsSpectral microscopy, single-cell/-nucleus RNA sequencing or ACE2 "gain-of-function" experiments were applied to 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 Middle East respiratory syndrome coronavirus (MERS-CoV). Coronavirus disease 2019 (COVID-19) autopsy material was used to validate
resultsWe provide evidence that alveolar ACE2 expression must be considered scarce, thereby limiting SARS-CoV-2 propagation and virus-induced tissue damage in the human alveolus. Instead,
conclusionsCollectively, our findings indicate that severe lung injury in COVID-19 probably results from a macrophage-triggered immune activation rather than direct viral damage of the alveolar compartment.
Indexed as
COVID-19Influenza, HumanAdultAngiotensin-Converting Enzyme 2HumansLungMacrophages, AlveolarPeptidyl-Dipeptidase ASARS-CoV-2Viral TropismACE2 protein, humanAngiotensin-Converting Enzyme 2Peptidyl-Dipeptidase A
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