Immunological characterization and comparison of children with COVID-19 from their adult counterparts at single-cell resolution
The immunological characteristics that could protect children with coronavirus disease 2019 (COVID-19) from severe or fatal illnesses have not been fully understood yet. Here, we performed single-cell RNA sequencing (scRNA-seq) analysis on peripheral blood samples of 15 children (8 with COVID-19) an...
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Published in | Frontiers in immunology Vol. 15; p. 1358725 |
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01.08.2024
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Abstract | The immunological characteristics that could protect children with coronavirus disease 2019 (COVID-19) from severe or fatal illnesses have not been fully understood yet.
Here, we performed single-cell RNA sequencing (scRNA-seq) analysis on peripheral blood samples of 15 children (8 with COVID-19) and compared them to 18 adults (13 with COVID-19).
The child-adult integrated single cell data indicated that children with the disease presented a restrained response to type I interferon in most of the major immune cell types, along with suppression of upstream interferon regulatory factor and toll-like receptor expression in monocytes, which was confirmed by
interferon stimulation assays. Unlike adult patients, children with COVID-19 showed lower frequencies of activated proinflammatory CD14+ monocytes, possibly explaining the rareness of cytokine storm in them. Notably, natural killer (NK) cells in pediatric patients displayed potent cytotoxicity with a rich expression of cytotoxic molecules and upregulated cytotoxic pathways, whereas the cellular senescence, along with the Notch signaling pathway, was significantly downregulated in NK cells, all suggesting more robust cytotoxicity in NK cells of children than adult patients that was further confirmed by CD107a degranulation assays. Lastly, a modest adaptive immune response was evident with more naïve T cells but less activated and proliferated T cells while less naïve B cells but more activated B cells in children over adult patients.
Conclusively, this preliminary study revealed distinct cell frequency and activation status of major immune cell types, particularly more robust NK cell cytotoxicity in PBMC that might help protect children from severe COVID-19. |
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AbstractList | The immunological characteristics that could protect children with coronavirus disease 2019 (COVID-19) from severe or fatal illnesses have not been fully understood yet.IntroductionThe immunological characteristics that could protect children with coronavirus disease 2019 (COVID-19) from severe or fatal illnesses have not been fully understood yet.Here, we performed single-cell RNA sequencing (scRNA-seq) analysis on peripheral blood samples of 15 children (8 with COVID-19) and compared them to 18 adults (13 with COVID-19).MethodsHere, we performed single-cell RNA sequencing (scRNA-seq) analysis on peripheral blood samples of 15 children (8 with COVID-19) and compared them to 18 adults (13 with COVID-19).The child-adult integrated single cell data indicated that children with the disease presented a restrained response to type I interferon in most of the major immune cell types, along with suppression of upstream interferon regulatory factor and toll-like receptor expression in monocytes, which was confirmed by in vitro interferon stimulation assays. Unlike adult patients, children with COVID-19 showed lower frequencies of activated proinflammatory CD14+ monocytes, possibly explaining the rareness of cytokine storm in them. Notably, natural killer (NK) cells in pediatric patients displayed potent cytotoxicity with a rich expression of cytotoxic molecules and upregulated cytotoxic pathways, whereas the cellular senescence, along with the Notch signaling pathway, was significantly downregulated in NK cells, all suggesting more robust cytotoxicity in NK cells of children than adult patients that was further confirmed by CD107a degranulation assays. Lastly, a modest adaptive immune response was evident with more naïve T cells but less activated and proliferated T cells while less naïve B cells but more activated B cells in children over adult patients.ResultsThe child-adult integrated single cell data indicated that children with the disease presented a restrained response to type I interferon in most of the major immune cell types, along with suppression of upstream interferon regulatory factor and toll-like receptor expression in monocytes, which was confirmed by in vitro interferon stimulation assays. Unlike adult patients, children with COVID-19 showed lower frequencies of activated proinflammatory CD14+ monocytes, possibly explaining the rareness of cytokine storm in them. Notably, natural killer (NK) cells in pediatric patients displayed potent cytotoxicity with a rich expression of cytotoxic molecules and upregulated cytotoxic pathways, whereas the cellular senescence, along with the Notch signaling pathway, was significantly downregulated in NK cells, all suggesting more robust cytotoxicity in NK cells of children than adult patients that was further confirmed by CD107a degranulation assays. Lastly, a modest adaptive immune response was evident with more naïve T cells but less activated and proliferated T cells while less naïve B cells but more activated B cells in children over adult patients.Conclusively, this preliminary study revealed distinct cell frequency and activation status of major immune cell types, particularly more robust NK cell cytotoxicity in PBMC that might help protect children from severe COVID-19.ConclusionConclusively, this preliminary study revealed distinct cell frequency and activation status of major immune cell types, particularly more robust NK cell cytotoxicity in PBMC that might help protect children from severe COVID-19. IntroductionThe immunological characteristics that could protect children with coronavirus disease 2019 (COVID-19) from severe or fatal illnesses have not been fully understood yet.MethodsHere, we performed single-cell RNA sequencing (scRNA-seq) analysis on peripheral blood samples of 15 children (8 with COVID-19) and compared them to 18 adults (13 with COVID-19).ResultsThe child-adult integrated single cell data indicated that children with the disease presented a restrained response to type I interferon in most of the major immune cell types, along with suppression of upstream interferon regulatory factor and toll-like receptor expression in monocytes, which was confirmed by in vitro interferon stimulation assays. Unlike adult patients, children with COVID-19 showed lower frequencies of activated proinflammatory CD14+ monocytes, possibly explaining the rareness of cytokine storm in them. Notably, natural killer (NK) cells in pediatric patients displayed potent cytotoxicity with a rich expression of cytotoxic molecules and upregulated cytotoxic pathways, whereas the cellular senescence, along with the Notch signaling pathway, was significantly downregulated in NK cells, all suggesting more robust cytotoxicity in NK cells of children than adult patients that was further confirmed by CD107a degranulation assays. Lastly, a modest adaptive immune response was evident with more naïve T cells but less activated and proliferated T cells while less naïve B cells but more activated B cells in children over adult patients.ConclusionConclusively, this preliminary study revealed distinct cell frequency and activation status of major immune cell types, particularly more robust NK cell cytotoxicity in PBMC that might help protect children from severe COVID-19. The immunological characteristics that could protect children with coronavirus disease 2019 (COVID-19) from severe or fatal illnesses have not been fully understood yet. Here, we performed single-cell RNA sequencing (scRNA-seq) analysis on peripheral blood samples of 15 children (8 with COVID-19) and compared them to 18 adults (13 with COVID-19). The child-adult integrated single cell data indicated that children with the disease presented a restrained response to type I interferon in most of the major immune cell types, along with suppression of upstream interferon regulatory factor and toll-like receptor expression in monocytes, which was confirmed by interferon stimulation assays. Unlike adult patients, children with COVID-19 showed lower frequencies of activated proinflammatory CD14+ monocytes, possibly explaining the rareness of cytokine storm in them. Notably, natural killer (NK) cells in pediatric patients displayed potent cytotoxicity with a rich expression of cytotoxic molecules and upregulated cytotoxic pathways, whereas the cellular senescence, along with the Notch signaling pathway, was significantly downregulated in NK cells, all suggesting more robust cytotoxicity in NK cells of children than adult patients that was further confirmed by CD107a degranulation assays. Lastly, a modest adaptive immune response was evident with more naïve T cells but less activated and proliferated T cells while less naïve B cells but more activated B cells in children over adult patients. Conclusively, this preliminary study revealed distinct cell frequency and activation status of major immune cell types, particularly more robust NK cell cytotoxicity in PBMC that might help protect children from severe COVID-19. |
Author | Zhai, Xiaowen Xu, Jin Hu, Shiwen Zeng, Mei Lu, Lijuan Chang, Hailing Xu, Menghua Li, Zifeng Jia, Ran Qian, Maoxiang Liu, Pengcheng |
AuthorAffiliation | 1 Department of Clinical Laboratory, Children’s Hospital of Fudan University, National Children’s Medical Center , Shanghai , China 2 Department of Hematology and Oncology, Children’s Hospital of Fudan University, National Children’s Medical Center , Shanghai , China 3 Department of Infectious Diseases, Children’s Hospital of Fudan University, National Children’s Medical Center , Shanghai , China 4 Institute of Pediatrics and Department of Hematology and Oncology, Children’s Hospital of Fudan University, National Children’s Medical Center, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University , Shanghai , China 5 Shanghai Institute of Infectious Disease and Biosecurity, Fudan University , Shanghai , China |
AuthorAffiliation_xml | – name: 3 Department of Infectious Diseases, Children’s Hospital of Fudan University, National Children’s Medical Center , Shanghai , China – name: 2 Department of Hematology and Oncology, Children’s Hospital of Fudan University, National Children’s Medical Center , Shanghai , China – name: 4 Institute of Pediatrics and Department of Hematology and Oncology, Children’s Hospital of Fudan University, National Children’s Medical Center, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University , Shanghai , China – name: 1 Department of Clinical Laboratory, Children’s Hospital of Fudan University, National Children’s Medical Center , Shanghai , China – name: 5 Shanghai Institute of Infectious Disease and Biosecurity, Fudan University , Shanghai , China |
Author_xml | – sequence: 1 givenname: Ran surname: Jia fullname: Jia, Ran – sequence: 2 givenname: Zifeng surname: Li fullname: Li, Zifeng – sequence: 3 givenname: Shiwen surname: Hu fullname: Hu, Shiwen – sequence: 4 givenname: Hailing surname: Chang fullname: Chang, Hailing – sequence: 5 givenname: Mei surname: Zeng fullname: Zeng, Mei – sequence: 6 givenname: Pengcheng surname: Liu fullname: Liu, Pengcheng – sequence: 7 givenname: Lijuan surname: Lu fullname: Lu, Lijuan – sequence: 8 givenname: Menghua surname: Xu fullname: Xu, Menghua – sequence: 9 givenname: Xiaowen surname: Zhai fullname: Zhai, Xiaowen – sequence: 10 givenname: Maoxiang surname: Qian fullname: Qian, Maoxiang – sequence: 11 givenname: Jin surname: Xu fullname: Xu, Jin |
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Keywords | COVID-19 single-cell RNA sequencing innate immunity children NK cell |
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SubjectTerms | Adaptive Immunity Adolescent Adult Cellular Senescence - immunology Child Child, Preschool children COVID-19 COVID-19 - immunology Cytotoxicity, Immunologic Female Humans Immunology innate immunity Interferon Type I - immunology Killer Cells, Natural - immunology Male Middle Aged Monocytes - immunology Monocytes - metabolism NK cell SARS-CoV-2 - immunology Single-Cell Analysis single-cell RNA sequencing Young Adult |
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Title | Immunological characterization and comparison of children with COVID-19 from their adult counterparts at single-cell resolution |
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