Study links death by Covid to cell anomaly that regulates immune response

A study carried out by researchers from the Institute of Biological Sciences and the Faculty of Medicine of UFMG (Federal University of Minas Gerais) showed that dysfunctions of immune system regulatory cells lead to severe inflammation in the lungs and are associated with cases of death from Covid-19. 19.

The results were published last Wednesday (9) in the journal Immunology, recognized as one of the main international journals in this field.

Out of balance, the immune system can experience very deleterious inflammation, the researchers explain. Some mechanisms prevent it from getting out of control. One is the Treg (T regulatory) cell, which the immune system has to keep inflammation at healthy levels.

In those who die from Covid-19, Treg goes into dysfunction. It stops working properly and, instead of maintaining inflammation, causes hyperinflammation, which is associated with death.

“Every infection needs an inflammatory response from the immune system. The organism creates inflammation and kills the virus. If the organism cannot mount an immune response, the infection gets out of control and the patient can die”, explains Helton Santiago, physician and associate professor at the Department of Biochemistry and Immunology at ICB/UFMG. “On the other hand, the inflammatory response has a limit that, if exceeded, can have serious consequences for the patient’s health and lead to death. This is what we believe happens with severe Covid-19”, he points out.

For the study, the researchers collected and analyzed samples of blood and secretions from the lungs of a group of 40 admitted to the CTI (Intensive Care Center) of the Hospital das Clínicas da UFMG, at the peaks of the pandemic in 2020 and 2021.

The patients — all with comorbidities, in a serious condition and undergoing mechanical ventilation — were between 41 and 75 years old. Of the total, 21 did not resist the disease.

The reason why some died and others is not unknown. The clinical and immunological parameters and the level of comorbidity of the patients were similar. Differences were concentrated in age.

Despite this, what is striking is that on the first day of admission to the ICU, patients had the same level of production of interleukin 10 (IL-10) —a cytokine produced by regulatory cells—, which is responsible for balancing the activity of other cells. involved in the process; on the seventh day, IL-10 disappeared in those who died.

“Those who survived managed to sustain this production and even slightly increase the level of presence in the lungs”, points out Santiago.

On the other hand, the regulatory cells of the patients who died began to produce another interleukin, IL-17, which is pro-inflammatory.

Despite not knowing the mechanism that leads to the dysfunction of regulatory cells, the researchers have some hypotheses that are related to the functioning of the immune system. One of them is the absence of interleukin, IL-2, which regulates the activities of white blood cells, responsible for immunity. Another is excess IL-6, which induces Treg to misread the microenvironment and become pro-inflammatory.

Scientists believe that this dynamic is not unique to Covid-19. “We are studying other infectious diseases that course with an inflammatory process and we have observed that this cell is dysfunctional. This mechanism can help us to understand other diseases that course with an inflammatory profile, when inflammation gets out of control”, he says.

The data can be used to create new prognostic tests and understand, by the time the patient is admitted to the ICU, if there are signs that the cells will go into dysfunction.

Another advance is the opening for the development of new therapies. “Today, there are medications being developed to stimulate these cells. Knowing that their dysfunction contributes in an important way to the fatal evolution of Covid-19, we can start working on therapies to return their function and avoid a fatal evolution”, he concludes.

The doctor points out that this is the first work that shows that patients who die have clear and profound dysfunction of these cells.

In addition to Helton da Costa Santiago, authors of the study are Marcela Helena Gonçalves-Pereira, Luciana Santiago, Cecilia Gomez Ravetti, Paula Frizera Vassallo, Marcus Vinícius Melo de Andrade, Mariana Sousa Vieira, Fernanda de Fátima Souza de Oliveira, Natália Virtude Carobin, Guangzhao Li, Adriano de Paula Sabinoculo and Vandack Nobre. The team is multidisciplinary, formed by researchers in the areas of medicine, physiotherapy, biomedicine, pharmacy, biology and statistics.

Funding was provided by the Higher Education Secretariat of the Ministry of Education and the National Institute of Science and Technology in Vaccines.