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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Viral Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1358725

Immunological characterization and comparison of children with COVID-19 from their adult counterparts at single-cell resolution

Provisionally accepted
  • 1 Department of Clinical Laboratory, Children's Hospital of Fudan University, Shanghai, China
  • 2 Department of Hematology and Oncology, Children’s Hospital, Fudan University, Shanghai, Shanghai Municipality, China
  • 3 Department of Infectious Diseases, Shenzhen Children's Hospital, Shenzhen, China
  • 4 Department of Infectious Disease, Children's Hospital, Fudan University, Shanghai, Shanghai Municipality, China
  • 5 Institute of Pediatrics, Children’s Hospital of Fudan University, Shanghai, Shanghai Municipality, China
  • 6 State Key Laboratory of Medical Epigenetics and Molecular Metabolism, Institute of Biomedical Sciences, Fudan University, Shanghai, Shanghai, China
  • 7 International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, China
  • 8 Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China

The final, formatted version of the article will be published soon.

    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 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.

    Keywords: COVID-19, Children, single-cell RNA sequencing, innate immunity, NK cell

    Received: 20 Dec 2023; Accepted: 17 Jul 2024.

    Copyright: © 2024 Jia, Hu, Li, Chang, Zeng, Liu, Lu, Xu, Zhai, Qian and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Xiaowen Zhai, Department of Hematology and Oncology, Children’s Hospital, Fudan University, Shanghai, 201102, Shanghai Municipality, China
    Maoxiang Qian, Institute of Pediatrics, Children’s Hospital of Fudan University, Shanghai, Shanghai Municipality, China
    Jin Xu, Department of Clinical Laboratory, Children's Hospital of Fudan University, Shanghai, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.