Down Syndrome and COVID-19: A Perfect Storm?

Abstract

People with Down syndrome show signs of chronic immune dysregulation, including a higher prevalence of autoimmune disorders, increased rates of hospitalization during respiratory viral infections, and higher mortality rates from pneumonia and sepsis. At the molecular and cellular levels, they show markers of chronic autoinflammation, including interferon hyperactivity, elevated levels of many inflammatory cytokines and chemokines, and changes in diverse immune cell types reminiscent of inflammatory conditions observed in the general population. However, the impact of this immune dysregulation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and CoV disease of 2019 (COVID-19) remains unknown. This Perspective outlines why individuals with Down syndrome should be considered an at-risk population for severe COVID-19. Specifically, the immune dysregulation caused by trisomy 21 may result in an exacerbated cytokine release syndrome relative to that observed in the euploid population, thus justifying additional monitoring and specialized care for this vulnerable population.

COVID-19 and Children With Down Syndrome: is There Any Real Reason to Worry? Case Report

“…In a recent study, it was reported that 30.4% of children admitted for hospitalisation were obese [18] and that obesity is prevalent in DS [19] This currently presents a challenge in distinguishing the role of comorbidities in the development of COVID-19 in DS. Research studies suggest that children with trisomy 21 could be genetically vulnerable to severe infections by the SARS-CoV-2 virus [1].…”

“…Research studies have showed that T cell lineages of adults with DS show clear signs of differentiation and hyperactivation even in the absence of any obvious infections, a phenomenon which may be attributed to chronic IFN hyperactivity [4]. These data indicate that the IFN response, which is crucial for escalating antiviral responses besides driving and amplifying the cytokine storm, is vigorous in people with DS [1].…”

“…Down syndrome (DS) is associated with several immune dysregulations [1]. Consequently, the risk of recurrent and severe infections, autoimmune diseases, and in ammatory conditions are commonly reported [2][3][4][5].…”

“…Among the major immune regulators encoded on chromosome 21 are 4 interferon (IFN) receptors which serve as a receptor subunit for cytokines IL-10, IL-22, and IL-26 [6]. Moreover, immune and non-immune cell types in DS are hypersensitive to IFN stimulation [1]. Research studies have showed that T cell lineages of adults with DS show clear signs of differentiation and hyperactivation even in the absence of any obvious infections, a phenomenon which may be attributed to chronic IFN hyperactivity [4].…”

“…It is unclear how individuals with DS respond to this infection. In a recent review, Espinosa provided scienti c evidence for considering individuals with trisomy 21 as being at a relatively high risk of developing more severe symptoms and increased rates of hospitalisation, intensive care admission, secondary bacterial infections, and mortality from SARS-CoV-2 infection [1]. In addition to immune dysregulation, it is well known that a majority of children with DS are also affected by various types of congenital anomalies that may increase the risk of developing severe symptoms.…”