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Covid-19 can lead to immune system exhaustion even in young people with a mild condition, says study

Infection with the coronavirus can cause severe changes in the immune system even in young and healthy people, with mild or moderate cases of Covid-19. Preliminary data are from a study carried out at the São Paulo State University (Unesp). In the work, Brazilian and Portuguese researchers evaluated the defense cells of unvaccinated individuals between 30 and 180 days after infection.

“The immune cells of patients infected with the virus were in exhaustion, something similar to what happens with the cells of people with grade 2 or 3 obesity, with chronic diseases such as diabetes, or in the elderly. But it is something completely unexpected for young people without health problems”, says Fábio Santos de Lira, professor at the Faculty of Science and Technology (FCT-Unesp), Presidente Prudente campus.

The data, which were presented at a congress promoted by the International Society of Immunology and Exercise in the United States, are part of the Fit Covid project, supported by the São Paulo Research Foundation (FAPESP).

The objective of the group, which involves researchers from institutions in São Paulo and the University of Coimbra, in Portugal, is to investigate the effects of Covid-19 on the immune, vascular and autonomic nervous systems (a branch of the central nervous system that controls breathing, blood circulation and other vital functions) of people under 40 years of age who had mild and moderate cases of COVID-19. The proposal is to monitor the impact of the disease on volunteers up to two years after infection.

“Our project seeks to know the effects of Covid-19 on the young and healthy population, which was totally neglected at the beginning of the pandemic. These individuals went to the hospital, were diagnosed, but, as they had mild or moderate symptoms, they were not assisted. So, they returned home and did the isolation without any follow-up. However, our studies are showing that even these people, when infected, may have suffered severe damage to the analyzed systems”, says Lira.

The researcher explains that the main sign of changes observed in the immune system of these individuals was extreme fatigue. The group compared the immune system of 20 infected people with that of 20 uninfected and observed a series of changes in those who had Covid-19, including impaired lung function, lower level of physical activity and – unlike patients who had severe disease – lower concentration of pro-inflammatory molecules known as cytokines, which are produced to warn the immune system about the need to send more defense cells to the site of infection.

“This is self-regulation of the immune system. Perhaps, due to the low amount of cytokines, these individuals did not have the severe form of the disease. It was a mechanism that managed to counterbalance the effects of the virus. This is because there was a decrease in interleukin-6 [importante mediador da resposta inflamatória conhecida como tempestade de citocina]”, it says.

“In addition, there was an increase in interleukin-10 and the soluble TNF-alpha receptor [citocinas anti-inflamatórias]. There was also an increase in prostaglandin, which is an inflammatory molecule, and a change in the lipid profile – these individuals had a high fraction of triglycerides and more leptin [hormônio envolvido na regulação do apetite]”, he explains.

Sample collection took place in May 2021, when this population had not yet been vaccinated. In addition to the data measured right after infection, the researchers collected blood samples from these patients after the complete vaccination schedule (when all had already been vaccinated) and will collect them one year after vaccination.

Exhaustion

The researcher explains that, because they are young and clinically healthy, it was expected that these people would have minor changes in the immune system.

“But what we saw when evaluating the energy metabolism of immune cells is that it is completely altered. The virus manages to reprogram the immune cells and take them to a fully inflammatory status. It is, therefore, a very aggressive virus, even for young, healthy people who have proven to have no clinical problems”, highlighted Lira.

Another finding of the study was the partially protective role of physical activity against the harmful effects of SARS-CoV-2 on the immune system. By analyzing defense cells, including monocytes and T lymphocytes, the researchers observed that infected individuals had a reduced anti-inflammatory profile of regulatory T cells. The PD1 protein – which has the function of preventing T cells from attacking other cells in the body – was increased in both CD4 and CD8 T lymphocytes.

“Interestingly, the level of physical activity in these patients partially protected against changes in the immune system. The higher the level of physical activity, the greater the protection against changes in [célula T] CD8, but not on CD4”, says the researcher.

The researchers also analyzed muscle condition, measuring hand pressure strength and performing tests such as sit and stand, six-minute walk and quadriceps strength.

“Among the muscle strength parameters, we only found a difference in the six-minute test. The Covid group covered a shorter distance than the control group. But when we looked at the respiratory part – respiratory function, both absolute and relative, and forced volume – everything was statistically impaired in the infected group. All values ​​were minor. So this confirms that they had compromised lung function and also compromised exercise tolerance,” he says.

The energy metabolism of immune cells was also evaluated, which showed a predominance of glycolytic metabolism [geração de energia por meio da quebra de glicose] in the body’s energy production. “The predominance of glycolytic metabolism means that there is a pro-inflammatory character. Therefore, the cell is exhausted, as it is producing a lot of cytokine at rest, and when stimulated, it does not respond. This whole picture demonstrates a huge deficiency in the immune system, ”he says.

Changes in the nervous system

In addition to monitoring the immune system of young individuals who had Covid-19 before being vaccinated, Fit Covid is analyzing the damage to the autonomic nervous system – which works involuntarily for heartbeats to occur, for example. The data show that, five months after being cured of the disease, the damage to the autonomic nervous system was restored, returning to normality.

The results of this arm of the research were presented in two scientific articles published in the journal Environmental Research and Public Health in February from 2022 and in January this year.

It is worth remembering that the autonomic nervous system is divided into two parts: the sympathetic and parasympathetic systems.

The sympathetic system is responsible for changes in the body in alert situations, preparing the body to face or flee a threat. Therefore, it involves greater expenditure of energy. It is up to this branch to increase heart rate and blood pressure, release adrenaline, contract and relax muscles, dilate the bronchi, dilate the pupils, increase perspiration. The parasympathetic nervous system, on the other hand, normalizes the functioning of internal organs after the alert situation.

In this part of the study, analysis of heart rate up to 180 days after the subjects were infected showed increased sympathetic activity during rest.

“It is expected that at rest, parasympathetic activity is higher than sympathetic activity, as the sympathetic nervous system is related to physical activity. If a person suddenly needs to run for some reason, it is the sympathetic nervous system that controls the body’s responses, such as increased heart rate, to this stress. Therefore, especially in young and healthy adults, parasympathetic activity at rest would be higher than sympathetic activity”, explains Ana Paula Coelho Figueira Freire, professor at the Universidade do Oeste Paulista (Unoeste) and first author of the articles.

Freire points out that the imbalance in the autonomic nervous system found in young, healthy people infected with SARS-CoV-2 may be related to higher inflammatory levels.

“Some factors that may be associated with this imbalance in the autonomic nervous system and its recovery five months later is the control of the inflammatory storm over time. It is the immune system recovering and reducing inflammatory levels, which can impact the autonomic nervous system, that is, the resolution of inflammation over time”, says Freire.

“The heart rate variability demonstrated that the higher levels of the sympathetic system may be related to a possible cardiovascular comorbidity and even sudden death”, he says.

Freire emphasizes that, even with the recovery of the autonomic nervous system after five months, the finding gives a greater perspective for researchers and health professionals to understand the course of the disease.

“Even young adult individuals are not exempt from presenting impairments caused by Covid-19. Even with the autonomic nervous system having recovered within a period of five months, it is important for us to deepen our understanding of how the disease behaves, especially in this young population”, says Freire.

In addition to monitoring these patients two years after they were infected, Fit Covid has a second phase of studies that aims to evaluate immune cells from Olympic athletes who were not infected by the coronavirus before they were vaccinated.

“Our goal is to isolate the immune cells of these Olympic athletes – which are known to be very efficient – ​​and, in the laboratory, observe how they react to the blood serum of these young, healthy individuals. We want to know if these cells manage to mitigate the pro-inflammatory effects of the serum of the infected individual before the vaccine and after the vaccine”, says Lira.

Source: CNN Brasil

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