IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-57655-3.html
   My bibliography  Save this article

Age-associated differences in mucosal and systemic host responses to SARS-CoV-2 infection

Author

Listed:
  • Jillian H. Hurst

    (Duke University School of Medicine
    Duke University School of Medicine)

  • Aditya A. Mohan

    (Duke University School of Medicine)

  • Trisha Dalapati

    (Duke University School of Medicine)

  • Ian A. George

    (Duke University School of Medicine)

  • Jhoanna N. Aquino

    (Duke University School of Medicine)

  • Debra J. Lugo

    (Duke University School of Medicine)

  • Trevor S. Pfeiffer

    (Duke University School of Medicine)

  • Javier Rodriguez

    (Duke University School of Medicine)

  • Alexandre T. Rotta

    (Duke University School of Medicine)

  • Nicholas A. Turner

    (Duke University School of Medicine)

  • Thomas W. Burke

    (Duke University School of Medicine
    Duke University School of Medicine)

  • Micah T. McClain

    (Duke University School of Medicine
    Duke University School of Medicine
    Durham Veterans Affairs Medical Center)

  • Ricardo Henao

    (Duke University
    Duke University School of Medicine)

  • C. Todd DeMarco

    (Duke University School of Medicine)

  • Raul Louzao

    (Duke University School of Medicine)

  • Thomas N. Denny

    (Duke University School of Medicine)

  • Kyle M. Walsh

    (Duke University School of Medicine
    Duke University School of Medicine)

  • Zhaohui Xu

    (St. Jude Children’s Research Hospital)

  • Asuncion Mejias

    (St. Jude Children’s Research Hospital)

  • Octavio Ramilo

    (St. Jude Children’s Research Hospital)

  • Christopher W. Woods

    (Duke University School of Medicine
    Duke University School of Medicine
    Durham Veterans Affairs Medical Center
    Duke University School of Medicine)

  • Matthew S. Kelly

    (Duke University School of Medicine)

Abstract

Age is among the strongest risk factors for severe outcomes from SARS-CoV-2 infection. Here we describe upper respiratory tract (URT) and peripheral blood transcriptomes of 202 participants (age range of 1 week to 83 years), including 137 non-hospitalized individuals with mild SARS-CoV-2 infection and 65 healthy individuals. Among healthy children and adolescents, younger age is associated with higher URT expression of innate and adaptive immune pathways. SARS-CoV-2 infection induces broad upregulation of URT innate and adaptive immune responses among children and adolescents. Peripheral blood responses among SARS-CoV-2-infected children and adolescents are dominated by interferon pathways, while upregulation of myeloid activation, inflammatory, and coagulation pathways is observed only in adults. Among SARS-CoV-2-infected individuals, fever is associated with blunted URT immune responses and more pronounced systemic immune activation. These findings demonstrate that immune responses to SARS-CoV-2 differ across the lifespan, from distinct signatures in childhood and adolescence to age-associated alterations in adults.

Suggested Citation

  • Jillian H. Hurst & Aditya A. Mohan & Trisha Dalapati & Ian A. George & Jhoanna N. Aquino & Debra J. Lugo & Trevor S. Pfeiffer & Javier Rodriguez & Alexandre T. Rotta & Nicholas A. Turner & Thomas W. B, 2025. "Age-associated differences in mucosal and systemic host responses to SARS-CoV-2 infection," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57655-3
    DOI: 10.1038/s41467-025-57655-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-57655-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-57655-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57655-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.