The risk of severe outcomes following respiratory tract infections is significantly increased in individuals over 60 years, especially in those with chronic medical conditions, i.e., hypertension, diabetes, cardiovascular disease, dementia, chronic respiratory disease, and cancer. Down Syndrome (DS), the most prevalent intellectual disability, is caused by trisomy-21 in ~1:750 live births worldwide. Over the past few decades, a substantial body of evidence has accumulated, pointing at the occurrence of alterations, impairments, and subsequently dysfunction of the various components of the immune system in individuals with DS. This associates with increased vulnerability to respiratory tract infections in this population, such as the influenza virus, respiratory syncytial virus, SARS-CoV-2 (COVID-19), and bacterial pneumonias. To emphasize this link, here we comprehensively review the immunobiology of DS and its contribution to higher susceptibility to severe illness and mortality from respiratory tract infections.

Original languageEnglish
Article number621440
JournalFrontiers in Immunology
StatePublished - 25 Jun 2021

Bibliographical note

Publisher Copyright:
© Copyright © 2021 Illouz, Biragyn, Iulita, Flores-Aguilar, Dierssen, De Toma, Antonarakis, Yu, Herault, Potier, Botté, Roper, Sredni, London, Mobley, Strydom and Okun.


This research was supported in part by the Clore Israel Foundation and the Intramural Research Program of the National Institute on Aging. We thank Yael Laure for the thorough editing of this manuscript.

FundersFunder number
Clore Israel Foundation
National Institute on AgingZIAAG000444


    • COVID-19
    • Down syndrome
    • hospitalization
    • immune dysregulation
    • interferon
    • respiratory tract infections


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