Researchers point out why Covid is more severe in people with Down syndrome

Brazilian researchers try to understand why Down syndrome causes more critical conditions of Covid-19. Among the hypotheses, three prevail as the most likely: anatomical formation, immune system and gene expression.

Down syndrome is a result of a genetic change on chromosome 21 that is tripled in people with the condition. According to estimates, it is the most common syndrome, with an average incidence of 1 in 700 births in Brazil. As a way of bringing visibility to the condition, March 21 is marked as International Down Syndrome Day.

“Patients with this syndrome usually have a degree of intellectual disability, which is variable, they can have heart problems and there are also greater propensities for respiratory disorders, for example”, says Márcia Amorim, professor at the Institute of Biology at UFF (Universidade Federal Fluminense). ).

Amorim is one of the authors of an article, published in the journal Neurological Sciences, which points out the importance of prioritizing people with Down syndrome in vaccination against Covid, since the disease tends to have a more critical condition in patients with this genetic condition. .

“Some studies have pointed out that patients with Down syndrome had a greater hospitalization, chance of intubation and deaths [ao terem Covid em comparação com o grupo controle]”, says the teacher.

A study cited in Amorim’s article noted that patients with the condition over the age of 40 are three times more likely to die from Covid-19 than those who do not have the genetic condition.

According to her, a hypothesis that may elucidate the severity for this population is related to a gene expression — TMPRSS2 (type II transmembrane serine protease).

The explanation of why this specific gene could cause more severe cases of Covid has to do with the mechanism that Sars-CoV-2 has to cause an infection. As already investigated, the virus can invade and replicate in human cells through the angiotensin-converting enzyme 2 (ACE2).

In addition to it, the pathogen also needs TMPRSS2, a protein that is encoded by the gene of the same name. The point is that this gene expression that encodes the protein is found on chromosome 21, the one that people with Down syndrome have tripled.

“Because the individual has three copies of the TMPRSS2 gene, because it is located on chromosome 21, and the protein encoded by it is extremely important for the virus to be able to invade the cell, this may be a mechanism that explains the severity of Covid in these patients” , says Amorim.

However, there are two other explanations that can explain this phenomenon.

“In the case of patients with Down syndrome, they usually have cardiac and pulmonary abnormalities, in addition to having changes in the functioning of the immune system. This makes them more vulnerable to Covid-19”, says Danielle Silva, postdoctoral student at microbiology from UFMG (Federal University of Minas Gerais) and author of another article that also addresses the particularities of people with Down syndrome when they are infected by the coronavirus.

Together with other professionals from UFMG, Silva developed this study “to give greater visibility to this group that has some peculiar characteristics and also to draw the attention of the medical community itself. As they have these particularities, the clinical view of them has to be differentiated “.

She explains that, due to the genetic alteration of people with Down, some anatomical formations of the body are different and this can represent a more critical scenario for infections, such as Covid.

An example is problems in the constitution of the lungs or the malformation of the heart valves. “Not all, but most people with Down syndrome have [essas disfunções]”says Silva.

Another point is the immune system, which has changes, causing it not to have the same behavior found in individuals without the condition. The researcher says that this problem can accentuate the cytokine storm – a phenomenon that the immune system produces in excess in the face of an infection and that can lead to negative effects for the patient’s own body.

“In the case of people with Down, the cytokine storm can be exacerbated because of problems in the immune system, causing them to proceed to a more serious condition”, explains Silva.

Although these three explanations observed by Amorim e Silva may already indicate the reasons why Covid is more severe in those who have Down syndrome, it is still not possible to indicate this with certainty.

“The problem is that the number of patients with Down syndrome and Covid is small, so it is difficult to get a large sample”, says Amorim. In the article published by her, for example, there was not really a sample analysis of these people with the condition, but a discussion of why the genetic alteration could influence the severity of Covid in this group.

Even so, she and other researchers are already looking for ways to investigate how these people respond to being infected by Sars-CoV-2.

“We have a sample of patients with Down and we have an idea of ​​doing an initial survey to have reports of those who had Covid, in order to understand how the disease was, if evolution occurred, if they had more severe conditions. It would be an interview to try understand the aspects of the disease in this population”, he says.