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Why People With Down Syndrome May Be At Risk for Severe COVID-19


A strong interferon response may lead to harmful cytokine storms.

People with Down syndrome may be more susceptible to developing some of the most serious consequence of COVID-19, including the so-called cytokine storms that can lead to acute respiratory distress syndrome, cardiac damage, and multiorgan failure,  according to a monograph published in Cell Reports Medicine, a new journal published by publisher that publishes Cell.

In his conclusion, Joaquin M. Espinosa, Ph.D., the author of the monograph, acknowledges the current lack of clinical and epidemiologic data showing that COVID-19 poses a special risk for people with Down syndrome. But Espinosa reviews evidence that Down syndrome is associated with immune system dysregulation and argues that people with the condition should be considered at high risk for developing severe COVID-19 symptoms.

“I hope this analysis of the literature prompts physicians around the world to pay special attention to individuals with DS [Down syndrome] and adopt measures to counteract the effects of cytokine release syndrome and other potential risk factors in the population,” Espinosa wrote.

Espinosa is executive director of Linda Crnic Institute for Down Syndrome at the University of Colorado Anschutz Medical Campus in Aurora, Colorado. His “competing interest” statement says he is co-inventor of a strategy for quelling cytokine storms in COVID-19 patients. Cytokine storm is the more informal term for cytokine release syndrome, which is also sometimes called hypercytokinemia.

Espinosa notes that people with Down syndrome are disproportionately affected by a variety of autoimmune diseases, including celiac disease, type 1 diabetes, and several autoimmune skin diseases. He also cites evidence that people with the condition have higher rates of hospitalization related to illness from viral lung diseases, such as respiratory syncytial virus and H1N1 influenza A.

Cytokine storms occur when the immune system goes into overdrive, producing an excess of cytokines, the immune system’s signaling molecules. Cytokines in such abundance spill out of the immune system and damage tissue. According to Espinosa, people with Down syndrome have immune responses that feature a strong interferon response, which can dysregulate the immune response and generate cytokine storms. The amped-up interferon response may help fend off an initial infection with SARS-CoV-2, but  if the infection gains a foothold, it may also make the cascade into a cytokine storm more likely.  Down syndrome is also called trisomy 21 because people with the condition have a third copies of chromosome 21, not the usual two. Espinosa says that several genes on that chromosome encode interferon receptors and that may explain the heightened interferon response.

A greater risk for secondary bacterial infections is another reason that COVID-19 may be more dangerous for people with Down syndrome, according to Espinosa. He  notes that children with Down syndrome have a higher rate of pneumonia than children who don’t have the syndrome and that bacterial pneumonia is a leading cause of death among adults with Down syndrome. One of feature of the immune response of people with Down syndrome is an overproduction of interleukin-10, a cytokine with anti-inflammatory properties that help modulate the immune response. But Espinosa references evidence interleukin-10 in abundance may stifle the arm of the immune response that works against bacterial infections.

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