Robust innate responses to SARS-CoV-2 in children resolve faster than in adults without compromising adaptive immunity.

Maria Vono, Angela Huttner, Sylvain Lemeille, Paola Martinez-Murillo, Benjamin Meyer, Stephanie Baggio, Shilpee Sharma, Anais Thiriard, Arnaud Marchant, Gert-Jan Godeke, Chantal Reusken, Catia Alvarez, Francisco Perez-Rodriguez, Isabella Eckerle, Laurent Kaiser, Natasha Loevy, Christiane S Eberhardt, Geraldine Blanchard-Rohner, Claire-Anne Siegrist, Arnaud M Didierlaurent
Author Information
  1. Maria Vono: Center of Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
  2. Angela Huttner: Center of Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland; University of Geneva Medical School, Geneva, Switzerland; Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland; Center for Clinical Research, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
  3. Sylvain Lemeille: Center of Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
  4. Paola Martinez-Murillo: Center of Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
  5. Benjamin Meyer: Center of Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
  6. Stephanie Baggio: Division of Prison Health, Geneva University Hospitals, Geneva, Switzerland; Office of Corrections, Department of Justice and Home Affairs of the Canton of Zurich, Zurich, Switzerland.
  7. Shilpee Sharma: Institute for Medical Immunology, Universit�� libre de Bruxelles, Charleroi, Belgium.
  8. Anais Thiriard: Institute for Medical Immunology, Universit�� libre de Bruxelles, Charleroi, Belgium.
  9. Arnaud Marchant: Institute for Medical Immunology, Universit�� libre de Bruxelles, Charleroi, Belgium.
  10. Gert-Jan Godeke: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
  11. Chantal Reusken: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
  12. Catia Alvarez: Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, 1205 Geneva, Switzerland.
  13. Francisco Perez-Rodriguez: University of Geneva Medical School, Geneva, Switzerland; Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland.
  14. Isabella Eckerle: Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland; Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, 1205 Geneva, Switzerland; Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland; Geneva Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland.
  15. Laurent Kaiser: Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland; Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, 1205 Geneva, Switzerland; Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland; Geneva Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland.
  16. Natasha Loevy: Pediatric Platform for Clinical Research, Department of Woman, Child and Adolescent Medicine, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
  17. Christiane S Eberhardt: Center of Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
  18. Geraldine Blanchard-Rohner: Center of Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Unit of Immunology and Vaccinology, Division of General Pediatrics, Department of Pediatrics, Gynecology and Obstetrics, Geneva University Hospitals, University of Geneva, Geneva, Switzerland.
  19. Claire-Anne Siegrist: Center of Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland; University of Geneva Medical School, Geneva, Switzerland.
  20. Arnaud M Didierlaurent: Center of Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Geneva Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland. Electronic address: arnaud.didierlaurent@unige.ch.

Abstract

SARS-CoV-2 infection in children is less severe than it is in adults. We perform a longitudinal analysis of the early innate responses in children and adults with mild infection within household clusters. Children display fewer symptoms than adults do, despite similar initial viral load, and mount a robust anti-viral immune signature typical of the SARS-CoV-2 infection and characterized by early interferon gene responses; increases in cytokines, such as CXCL10 and GM-CSF; and changes in blood cell numbers. When compared with adults, the antiviral response resolves faster (within a week of symptoms), monocytes and dendritic cells are more transiently activated, and genes associated with B cell activation appear earlier in children. Nonetheless, these differences do not have major effects on the quality of SARS-CoV-2-specific antibody responses. Our findings reveal that better early control of inflammation as observed in children may be key for rapidly controlling infection and limiting the disease course.

Keywords

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MeSH Term

Adaptive Immunity
Adolescent
Adult
Antibodies, Viral
B-Lymphocytes
COVID-19
Chemokine CXCL10
Child
Child, Preschool
Cytokines
Granulocyte-Macrophage Colony-Stimulating Factor
Humans
Immunity, Innate
Infant
Inflammation
Interferons
Longitudinal Studies
Middle Aged
Monocytes
SARS-CoV-2
Sequence Analysis, RNA
Transcriptome
Viral Load
Young Adult

Chemicals

Antibodies, Viral
CSF2 protein, human
CXCL10 protein, human
Chemokine CXCL10
Cytokines
Granulocyte-Macrophage Colony-Stimulating Factor
Interferons

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