Protective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection
Protective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection
Abstract The immune system of most SARS-CoV-2 infected individuals limits viral spread to the upper airways without pulmonary involvement. This prevents the development of pneumonic COVID-19. However, the protective immunological responses causative of successful viral containment in the upper airways remain unclear. Here, we combine longitudinal single-cell RNA sequencing, proteomic profiling, multidimensional flow cytometry, RNA-Seq of FACS-sorted leukocyte subsets and multiplex plasma interferon profiling to uncover temporally resolved protective immune signatures in non-pneumonic and ambulatory SARS-CoV-2 infected patients. We compare host responses in a high-risk patient population infected with SARS-CoV-2 but without pulmonary involvement to patients with COVID-19 pneumonia. Our data reveal a distinct immunological signature of successful viral containment, characterized by an early prominent interferon stimulated gene (ISG) upregulation across immune cell subsets. In addition, reduced cytotoxic potential of Natural Killer (NK) and T cells, as well as a monocyte phenotype with immune-modulatory potential are hallmarks of protective immunity. Temporal resolution across disease trajectories highlights ISG upregulation as particularly prominent early in the disease and confirms increased expression also in comparison to healthy controls. We validate this distinct temporal ISG signature by in-depth RNA-seq of FACS-sorted leukocyte subsets in a large prospective ambulatory SARS-CoV-2 infected cohort confirming early and robust ISG upregulation particularly in monocytes and T cells. In conclusion, our data demonstrate a protective ISG phenotype in patients with successful containment of SARS-CoV-2 infection without progression to COVID-19. This early protective interferon response might be exploited as a therapeutic approach and for disease course prediction.
Gold Christoph、Kirchner Marieluise、Wange Lucas E.、Pekayvaz Kami、Brambs Sophia、Janjic Aleksandar、Popp Oliver、Polewka Vivien、Hellmuth Johannes C、De¨￠k Flora、Linder Andreas、Enard Wolfgang、Kroidl Inge、Hubner Norbert、H?lscher Michael、Massberg Steffen、Nicolai Leo、Tomas Lukas、Eser Tabea、Geldmacher Christof、Zimmer Ralf、Joppich Markus、Kuhl Niklas、Keppler Oliver T.、Saar Kathrin、Mertins Philipp、Schulz Christian、von Bergwelt-Baildon Michael、Scherer Clemens、Kaiser Rainer、Muenchhoff Maximilian、Leunig Alexander、Stark Konstantin
Medizinische Klinik und Poliklinik I University Hospital Ludwig-Maximilian University MunichMax Delbr¨1ck Center for Molecular Medicine (MDC) and Berlin Institute of Health (BIH)Anthropology and Human Genomics, Faculty of Biology, Ludwig-Maximilians University MunichMedizinische Klinik und Poliklinik I University Hospital Ludwig-Maximilian University Munich||DZHK (German Centre for Cardiovascular Research), partner site Munich Heart AllianceMedizinische Klinik und Poliklinik I University Hospital Ludwig-Maximilian University MunichAnthropology and Human Genomics, Faculty of Biology, Ludwig-Maximilians University MunichMax Delbr¨1ck Center for Molecular Medicine (MDC) and Berlin Institute of Health (BIH)Medizinische Klinik und Poliklinik I University Hospital Ludwig-Maximilian University MunichCOVID-19 Registry of the LMU Munich (CORKUM), University Hospital||Medizinische Klinik und Poliklinik III, University Hospital Ludwig-Maximilian University MunichGerman Center for Infection Research (DZIF)||Division of Infectious Diseases and Tropical Medicine, University Hospital Ludwig-Maximilian University MunichGene Center and Department of Biochemistry, University Hospital Ludwig-Maximilian University Munich||Medizinische Klinik und Poliklinik II, University Hospital Ludwig-Maximilian University MunichAnthropology and Human Genomics, Faculty of Biology, Ludwig-Maximilians University MunichGerman Center for Infection Research (DZIF)||Division of Infectious Diseases and Tropical Medicine, University Hospital Ludwig-Maximilian University MunichMax Delbr¨1ck Center for Molecular Medicine (MDC) and Berlin Institute of Health (BIH)German Center for Infection Research (DZIF)||Division of Infectious Diseases and Tropical Medicine, University Hospital Ludwig-Maximilian University MunichMedizinische Klinik und Poliklinik I University Hospital Ludwig-Maximilian University Munich||DZHK (German Centre for Cardiovascular Research), partner site Munich Heart AllianceMedizinische Klinik und Poliklinik I University Hospital Ludwig-Maximilian University Munich||DZHK (German Centre for Cardiovascular Research), partner site Munich Heart AllianceMedizinische Klinik und Poliklinik I University Hospital Ludwig-Maximilian University Munich||DZHK (German Centre for Cardiovascular Research), partner site Munich Heart AllianceGerman Center for Infection Research (DZIF)||Division of Infectious Diseases and Tropical Medicine, University Hospital Ludwig-Maximilian University MunichGerman Center for Infection Research (DZIF)||Division of Infectious Diseases and Tropical Medicine, University Hospital Ludwig-Maximilian University MunichDepartment of Informatics, University Hospital Ludwig-Maximilian University MunichDepartment of Informatics, University Hospital Ludwig-Maximilian University MunichGene Center and Department of Biochemistry, University Hospital Ludwig-Maximilian University Munich||Medizinische Klinik und Poliklinik II, University Hospital Ludwig-Maximilian University MunichMax von Pettenkofer Institute & GeneCenter, Virology, Faculty of Medicine||German Center for Infection Research (DZIF)||COVID-19 Registry of the LMU Munich (CORKUM), University HospitalMax Delbr¨1ck Center for Molecular Medicine (MDC) and Berlin Institute of Health (BIH)Max Delbr¨1ck Center for Molecular Medicine (MDC) and Berlin Institute of Health (BIH)Medizinische Klinik und Poliklinik I University Hospital Ludwig-Maximilian University Munich||DZHK (German Centre for Cardiovascular Research), partner site Munich Heart AllianceCOVID-19 Registry of the LMU Munich (CORKUM), University Hospital||Medizinische Klinik und Poliklinik III, University Hospital Ludwig-Maximilian University MunichMedizinische Klinik und Poliklinik I University Hospital Ludwig-Maximilian University Munich||DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance||COVID-19 Registry of the LMU Munich (CORKUM), University HospitalMedizinische Klinik und Poliklinik I University Hospital Ludwig-Maximilian University Munich||DZHK (German Centre for Cardiovascular Research), partner site Munich Heart AllianceMax von Pettenkofer Institute & GeneCenter, Virology, Faculty of Medicine||German Center for Infection Research (DZIF)||COVID-19 Registry of the LMU Munich (CORKUM), University HospitalMedizinische Klinik und Poliklinik I University Hospital Ludwig-Maximilian University Munich||DZHK (German Centre for Cardiovascular Research), partner site Munich Heart AllianceMedizinische Klinik und Poliklinik I University Hospital Ludwig-Maximilian University Munich||DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance
医药卫生理论医学研究方法基础医学
Gold Christoph,Kirchner Marieluise,Wange Lucas E.,Pekayvaz Kami,Brambs Sophia,Janjic Aleksandar,Popp Oliver,Polewka Vivien,Hellmuth Johannes C,De¨￠k Flora,Linder Andreas,Enard Wolfgang,Kroidl Inge,Hubner Norbert,H?lscher Michael,Massberg Steffen,Nicolai Leo,Tomas Lukas,Eser Tabea,Geldmacher Christof,Zimmer Ralf,Joppich Markus,Kuhl Niklas,Keppler Oliver T.,Saar Kathrin,Mertins Philipp,Schulz Christian,von Bergwelt-Baildon Michael,Scherer Clemens,Kaiser Rainer,Muenchhoff Maximilian,Leunig Alexander,Stark Konstantin.Protective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection[EB/OL].(2025-03-28)[2025-04-26].https://www.biorxiv.org/content/10.1101/2021.02.03.429351.点此复制
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