Abstract
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.
Highlights
Reviewed by: Bernard Khor, Benaroya Research Institute, United States Michael E
Here we comprehensively review the immunobiology of Down Syndrome (DS) and its contribution to higher susceptibility to severe illness and mortality from respiratory tract infections
A retrospective study that was conducted in New York and included 7246 patients hospitalized with COVID-19, 12 of them with DS, found that these patients exhibit a more severe disease than controls, an increased incidence of sepsis and need of mechanical ventilation [58]
Summary
DS is the most common genetic disorder causing a variable degree of intellectual disability (ID). It was first clinically described in 1866 by Langdon Down [27]. Chr contains approximately 233 protein-coding genes (GRCh38.p13, Genecode database), 423 non-protein-coding genes, and numerous other functional genomic elements [29] that may be of importance for the phenotypic variability of DS. In this respect, DS is considered a disorder of altered gene expression [29]. The consequences of gene dosage imbalance, including in immune related genes (Figure 2), is widespread and include immune dysregulation [22]
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