Suppressive myeloid cells are a hallmark of severe COVID-19
Suppressive myeloid cells are a hallmark of severe COVID-19
Abstract ‘Severe Acute Respiratory Syndrome - Coronavirus-2’ (SARS-CoV-2) infection causes Coronavirus Disease 2019 (COVID-19), a mild to moderate respiratory tract infection in the majority of patients. A subset of patients, however, progresses to severe disease and respiratory failure with acute respiratory distress syndrome (ARDS). Severe COVID-19 has been associated with increased neutrophil counts and dysregulated immune responses. The mechanisms of protective immunity in mild forms and the pathogenesis of dysregulated inflammation in severe courses of COVID-19 remain largely unclear. Here, we combined two single-cell RNA-sequencing technologies and single-cell proteomics in whole blood and peripheral blood mononuclear cells (PBMC) to determine changes in immune cell composition and activation in two independent dual-center patient cohorts (n=46+n=54 COVID-19 samples), each with mild and severe cases of COVID-19. We observed a specific increase of HLA-DRhiCD11chi inflammatory monocytes that displayed a strong interferon (IFN)-stimulated gene signature in patients with mild COVID-19, which was absent in severe disease. Instead, we found evidence of emergency myelopoiesis, marked by the occurrence of immunosuppressive pre-neutrophils and immature neutrophils and populations of dysfunctional and suppressive mature neutrophils, as well as suppressive HLA-DRto monocytes in severe COVID-19. Our study provides detailed insights into systemic immune response to SARS-CoV-2 infection and it reveals profound alterations in the peripheral myeloid cell compartment associated with severe courses of COVID-19.
Conrad Claudia、Grasshoff Martin、Kr?mer Benjamin、Brumhard Sophia、Saglam Adem、Thibeault Charlotte、Pfeiffer Moritz、Hippenstiel Stefan、Hocke Andreas、Machleidt Felix、de Jarcy Laure Bousquillon、Stegemann Miriam、Kaiser Kim Melanie、Paclik Daniela、Schlickeiser Stephan、Volk Hans-Dieter、Vinh Michael To、Aschenbrenner Anna C、Krammer Tobias、Kapellos Theodore S.、Mei Henrik E.、Becker Matthias、Geffers Robert、Witzenrath Martin、Sawitzki Birgit、Schulz Axel R.、Kurth Florian、Uhrig Alexander、Schulte-Schrepping Jonas、Reusch Nico、Sander Leif Erik、Drews Anna、De Domenico Elena、Wendisch Daniel、Suttorp Norbert、Beckstette Michael、Deutsche COVID-19 OMICS Initiative (DeCOI)、M¨1ller-Redetzky Holger、Heim Katrin-Moira、Saliba Antoine-Emmanuel、Xu Cheng-Jian、Bonaguro Lorenzo、Dietrich Oliver、Herbert Miriam、Horne Arik、J¨1rgens Linda、Gl?senkamp Christoph R.、Ulas Thomas、Ba?ler Kevin、Schultze Joachim L.、Pecht Tal、Meisel Christian、Goffinet Christine、Raabe Jan、Rieke Gereon、Kunkel D¨|sir¨|e、H?ndler Kristian、Nattermann Jacob、von Kalle Christof、Drosten Christian、Li Yang、Vafadarnejad Ehsan、Zhang Bowen
Department of Infectious Diseases and Respiratory Medicine, Charit¨| Universit?tsmedizin BerlinCentre for Individualised Infection Medicine (CiiM) & TWINCORE, joint ventures between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH)Department of Internal Medicine I, University Hospital BonnDepartment of Infectious Diseases and Respiratory Medicine, Charit¨| Universit?tsmedizin BerlinPRECISE Platform for Single Cell Genomics and Epigenomics, German Center for Neurodegenerative DiseasesDepartment of Infectious Diseases and Respiratory Medicine, Charit¨| Universit?tsmedizin BerlinDepartment of Infectious Diseases and Respiratory Medicine, Charit¨| Universit?tsmedizin BerlinDepartment of Infectious Diseases and Respiratory Medicine, Charit¨| Universit?tsmedizin Berlin||German Center for Lung Research (DZL)Department of Infectious Diseases and Respiratory Medicine, Charit¨| Universit?tsmedizin Berlin||German Center for Lung Research (DZL)Department of Infectious Diseases and Respiratory Medicine, Charit¨| Universit?tsmedizin BerlinDepartment of Infectious Diseases and Respiratory Medicine, Charit¨| Universit?tsmedizin BerlinDepartment of Infectious Diseases and Respiratory Medicine, Charit¨| Universit?tsmedizin BerlinDepartment of Internal Medicine I, University Hospital BonnInstitute of Medical Immunology, Charit¨|, Universit?tsmedizin BerlinInstitute of Medical Immunology, Charit¨|, Universit?tsmedizin Berlin, Berlin, Germany & BIH Center for Regenerative Therapies, Charit¨| and Berlin Institute of Health, Charit¨|, Universit?tsmedizin BerlinInstitute of Medical Immunology, Charit¨|, Universit?tsmedizin Berlin||Institute of Medical Immunology, Charit¨|, Universit?tsmedizin Berlin, Berlin, Germany & BIH Center for Regenerative Therapies, Charit¨| and Berlin Institute of Health, Charit¨|, Universit?tsmedizin Berlin||Institute of Medical Immunology, Charit¨|, Universit?tsmedizin Berlin Labor Berlin-Charit¨| Vivantes, Department of ImmunologyDepartment of Internal Medicine I, University Hospital BonnLife & Medical Sciences (LIMES) Institute, University of Bonn, Germany and Radboud UMCHelmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz-Center for Infection Research (HZI)Life & Medical Sciences (LIMES) Institute, University of BonnMass Cytometry Lab, DRFZ Berlin, a Leibniz InstitutePRECISE Platform for Single Cell Genomics and Epigenomics, German Center for Neurodegenerative DiseasesGenome Analytics, Helmholtz-Center for Infection Research (HZI)Department of Infectious Diseases and Respiratory Medicine, Charit¨| Universit?tsmedizin Berlin||German Center for Lung Research (DZL)Institute of Medical Immunology, Charit¨|, Universit?tsmedizin BerlinMass Cytometry Lab, DRFZ Berlin, a Leibniz InstituteDepartment of Infectious Diseases and Respiratory Medicine, Charit¨| Universit?tsmedizin Berlin||Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine & I. Department of Medicine, University Medical Center Hamburg-EppendorfDepartment of Infectious Diseases and Respiratory Medicine, Charit¨| Universit?tsmedizin BerlinLife & Medical Sciences (LIMES) Institute, University of BonnLife & Medical Sciences (LIMES) Institute, University of BonnDepartment of Infectious Diseases and Respiratory Medicine, Charit¨| Universit?tsmedizin Berlin||German Center for Lung Research (DZL)PRECISE Platform for Single Cell Genomics and Epigenomics, German Center for Neurodegenerative DiseasesPRECISE Platform for Single Cell Genomics and Epigenomics, German Center for Neurodegenerative DiseasesDepartment of Infectious Diseases and Respiratory Medicine, Charit¨| Universit?tsmedizin BerlinDepartment of Infectious Diseases and Respiratory Medicine, Charit¨| Universit?tsmedizin Berlin||German Center for Lung Research (DZL)Centre for Individualised Infection Medicine (CiiM) & TWINCORE, joint ventures between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH)Department of Infectious Diseases and Respiratory Medicine, Charit¨| Universit?tsmedizin BerlinDepartment of Infectious Diseases and Respiratory Medicine, Charit¨| Universit?tsmedizin BerlinHelmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz-Center for Infection Research (HZI)Centre for Individualised Infection Medicine (CiiM) & TWINCORE, joint ventures between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH)||Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical CenterLife & Medical Sciences (LIMES) Institute, University of BonnHelmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz-Center for Infection Research (HZI)Life & Medical Sciences (LIMES) Institute, University of BonnLife & Medical Sciences (LIMES) Institute, University of BonnDepartment of Infectious Diseases and Respiratory Medicine, Charit¨| Universit?tsmedizin BerlinDepartment of Infectious Diseases and Respiratory Medicine, Charit¨| Universit?tsmedizin BerlinPRECISE Platform for Single Cell Genomics and Epigenomics, German Center for Neurodegenerative DiseasesLife & Medical Sciences (LIMES) Institute, University of BonnLife & Medical Sciences (LIMES) Institute, University of Bonn||PRECISE Platform for Single Cell Genomics and Epigenomics, German Center for Neurodegenerative DiseasesLife & Medical Sciences (LIMES) Institute, University of BonnInstitute of Virology, Charit¨| Universit?tsmedizin BerlinInstitute of Virology, Charit¨| Universit?tsmedizin Berlin||Berlin Institute of HealthDepartment of Internal Medicine I, University Hospital BonnDepartment of Internal Medicine I, University Hospital BonnFlow & Mass Cytometry Core Facility, Charit¨| Universit?tsmedizin Berlin and Berlin Institute of Health (BIH)PRECISE Platform for Single Cell Genomics and Epigenomics, German Center for Neurodegenerative DiseasesDepartment of Internal Medicine I, University Hospital Bonn||German Center for Infection Research (DZIF)Clinical Study Center (CSC), Berlin Institute of Health (BIH), and Charite Universit?tsmedizin BerlinInstitute of Virology, Charit¨| Universit?tsmedizin Berlin||German Center for Infection Research (DZIF)Centre for Individualised Infection Medicine (CiiM) & TWINCORE, joint ventures between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH)Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz-Center for Infection Research (HZI)Centre for Individualised Infection Medicine (CiiM) & TWINCORE, joint ventures between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH)
医学研究方法基础医学
COVID-19SARS-CoV-2monocytesimmunosuppressive neutrophilsneutrophilsimmunosuppressive neutrophilsscRNA-seqmass cytometryCyTOF
Conrad Claudia,Grasshoff Martin,Kr?mer Benjamin,Brumhard Sophia,Saglam Adem,Thibeault Charlotte,Pfeiffer Moritz,Hippenstiel Stefan,Hocke Andreas,Machleidt Felix,de Jarcy Laure Bousquillon,Stegemann Miriam,Kaiser Kim Melanie,Paclik Daniela,Schlickeiser Stephan,Volk Hans-Dieter,Vinh Michael To,Aschenbrenner Anna C,Krammer Tobias,Kapellos Theodore S.,Mei Henrik E.,Becker Matthias,Geffers Robert,Witzenrath Martin,Sawitzki Birgit,Schulz Axel R.,Kurth Florian,Uhrig Alexander,Schulte-Schrepping Jonas,Reusch Nico,Sander Leif Erik,Drews Anna,De Domenico Elena,Wendisch Daniel,Suttorp Norbert,Beckstette Michael,Deutsche COVID-19 OMICS Initiative (DeCOI),M¨1ller-Redetzky Holger,Heim Katrin-Moira,Saliba Antoine-Emmanuel,Xu Cheng-Jian,Bonaguro Lorenzo,Dietrich Oliver,Herbert Miriam,Horne Arik,J¨1rgens Linda,Gl?senkamp Christoph R.,Ulas Thomas,Ba?ler Kevin,Schultze Joachim L.,Pecht Tal,Meisel Christian,Goffinet Christine,Raabe Jan,Rieke Gereon,Kunkel D¨|sir¨|e,H?ndler Kristian,Nattermann Jacob,von Kalle Christof,Drosten Christian,Li Yang,Vafadarnejad Ehsan,Zhang Bowen.Suppressive myeloid cells are a hallmark of severe COVID-19[EB/OL].(2025-03-28)[2025-06-07].https://www.medrxiv.org/content/10.1101/2020.06.03.20119818.点此复制
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