Covid 19 is 10 times more deadly for people with Down syndrome

When Covid 19 was born last winter, Catherine Ross Very scared. His 36-year-old sister who Amanda Ross He has Down Syndrome, which makes him vulnerable to respiratory viruses. Amanda Ross has been hospitalized several times for pneumonia. He needed a ventilator in 2017 and was close to death. In April, he underwent artificial respiration again. Amanda lives in a group care home in Summers, New York, and was diagnosed with Covid on March 31. The doctor told his relatives that, given his background, they should prepare for the worst. “We were shocked,” says Catherine Ross. She says her sister and others with Down Syndrome, also known as Trisomy 21, have a hard time dealing with the Corona virus.

Among people at higher risk of death from Covid 19, such as people with diabetes, people with Down syndrome are also notable: According to a large British study published in October, if these people become infected, compared to the general population , They are 5 times more likely to be hospitalized and 10 times more likely to die. Other studies confirm this high risk.

Researchers speculate that background immune abnormalities, combined with additional copies of important genes in people with Down syndrome (which have three copies of chromosome 21 instead of two), make them more vulnerable to severe Covid 19. Julia Hippiesley-Cox“This is a vulnerable population that may need to implement conservation policies,” said epidemiologist, Oxford University School of Medicine and lead author of the British study.

On December 2, the British Joint Vaccination and Immunization Committee recommended that people with Down syndrome be given priority for rapid vaccination. But the Centers for Disease Control and Prevention (in the United States) has not yet listed Down Syndrome as a condition that increases the risk of severe Covid.

Hepisley-Cox and colleagues analyzed databases of 26.8 million people in the UK. The results of their study were published in the Annals of Internal Medicine. The tremendous risk they realized was present even after correction for a number of contributing factors, including obesity, heart disease, diabetes, and living in a caregiver’s home.

Another pre-published article, which includes the findings of a major international study, found that people with Down syndrome who are hospitalized for Covid 19 and are 40 years of age or older have the highest risk, with a mortality rate of 51%. . The death rate of Covid 19 is 7% in people with Down syndrome under the age of 40. That Holmes “By the age of 40, things are really getting worse … their mortality rate is equal to that of people over the age of 80 in the general population,” said a biostatist at the Rollins School of Public Health at Amory University.

Experts say the common anatomy of people with trisomy 21, including the large tongue, small jaws, and large tonsils and adenoids, along with weak throat muscle tone, may help explain the higher rates of respiratory infections in these people. But genetics may also make people with Down syndrome vulnerable to the causative virus, SARS-CoV-2. They have three copies of a gene on chromosome 21 called TMPRSS2. This gene encodes an enzyme that the virus steals to enter human cells. The TMPRSS2 enzyme breaks down the spike protein on the surface of the virus, initiating steps that allow the virus to attack the host cell.

Based on an analysis conducted in June Mara DirsenThe biopsy of TMPRSS2 in the cells of people with Down syndrome is 1.6 times higher than in the cells of people who do not have the condition. “People with Down syndrome may be susceptible to infection due to the tripling of TMPRSS2,” says Dearsen.

Experts say immune system abnormalities may pose an additional risk. In people with Down syndrome, T cells do not grow well and the levels of circulating B cells in their body are low. They also have low levels of a key protein that prevents immune cells from invading the body’s own tissues. In contrast, the levels of signaling proteins that induce inflammation are high, causing chronic inflammation even in the absence of infection. Wakin Spinoza“The cells of people with Down syndrome are constantly fighting an infection that doesn’t really exist,” says geneticist at the Linda Crick Institute at the University of Colorado. “It indicates an evoked immune system that may lead people with trisomy 21 to a highly inflammatory condition that is characterized by severe and fatal cases of Covid,” he says.

Spinoza’s group in 2016 showed that the response of interferon, which is the first line of defense against viruses, is continuously activated in patients with Down syndrome. He says there are four genes for important interferon receptors on chromosome 21 that could lead to too many receptors and, therefore, interferon activity.

In August, a group of researchers led Jean Laurent Casanova Rockefeller University supported this hypothesis with an article. Their paper showed that some white blood cells in patients with Down syndrome show extra interferon receptors on their surface. A strong interferon response may be helpful early in the course of Covid 19 infection, but the increased interferon activity seen in people with Down syndrome is not necessarily protective.

Louise Mall Chronic underlying stimulation can prevent interferon receptors from responding to further stimulation, says the Icon School of Medicine in Montserrat. He co-authored another study in New York City hospitals that found that patients with Down syndrome were, on average, 10 years younger than their age-matched controls and were significantly more likely to develop severe cases of Covid.

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Andre Oum“Over-activity of interferon could help boost immunosuppression in people with Covid 19,” says Down Syndrome neuroscientist at King’s University London, who co-authored the paper. A safety storm is a reaction that causes the death of Covid 19 within a week or more of symptoms. Um says the picture is complex and not fully understood, but what is clear is that immune differences in people with Down syndrome are likely to have an adverse effect on fighting Covid 19 infection and its consequences.

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Public health experts in some countries agree. A few days after the article was published in the Annals of Internal Medicine, Britain listed people with Down syndrome as “clinically very vulnerable” who should be protected against the virus. Since then, the International Association for Trisomy 21 Research has issued a statement calling for people with Down syndrome, especially those 40 years of age and older, to be vaccinated.

But in the United States, a panel advising the Centers for Disease Control and Prevention on vaccine prioritization has not yet defined the vulnerability groups that may be included in the second wave of vaccination. “There is currently insufficient evidence to suggest that adults with Down syndrome are at higher risk for severe Covid disease,” said a spokesman for the center, despite new studies.

Bo Ans“Because the prognosis for patients with Down Syndrome with Covid 19 can be very poor, they should be given priority for monoclonal antibody therapies that are lacking,” says a University of Washington neurologist who cares for Down Syndrome patients. To be. “A 40-year-old person with Down syndrome who develops Covid 19 is one of those people about whom doctors should consider early antibody treatment,” he said.

Physicians should also consider prescribing a drug called baricitinib because it blocks one of the signaling pathways necessary for the interferon response. In a study published last month in the journal Cell Reports, the Ens group found that the drug prevented severe immune sensitivity in mice with trisomy 21, which can be fatal. This result suggests that baricitinib may help inhibit the out-of-control immune response in patients with Down syndrome with Covid 19. The Food and Drug Administration last month authorized baricitinib in combination with RamedSivir for emergency use in critically ill patients with Quid 19.

Amanda Ross survived the infection. He was able to detach himself from the ventilator after 6 days and was released 6 days later. He has now returned to his home in a group home. “I can not say how happy I am that we still have him,” says Catherine Ross. But he still worries about his sister and others with Down Syndrome, and says the severity of their infection with Covid 19 indicates that they should be vaccinated after front-line staff.

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