COVID-19 and Immune System in Youth

Tempo de Leitura: 5 minutos

Although COVID-19 manifests primarily as a respiratory disease, many studies have shown that this is a systemic infection involving multiple systems and affecting individuals of all ages. Thus, preliminary data from a study done at the São Paulo State University (Unesp) suggest that SARS-CoV-2 infection may compromise the immune system of healthy young people with mild or moderate COVID-19.

Better explained, results from these surveys show that even in young adults, shortly after mild or moderate COVID-19, autonomic modulation was shown to be impaired. That said, data show that these disruptions in autonomic regulation by a viral pathogen are associated with a Cytokine storm immune response , which results in oxidative stress leading to cell damage.

Given this, COVID-19 cases among young adults are a cause for concern around the world, as this population may account for 70% of those infected globally. In addition, for a long time this audience was overlooked, as the researcher Fábio Santos de Lira, a professor at the Faculty of Science and Technology (FCT-Unesp), quotes, “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, had the diagnosis, but because they had mild or moderate symptoms, they were not assisted. So they went back home and did the isolation without any follow-up […]”. This neglect is possibly due to the fact that young adults are at the lowest risk of serious negative outcomes.

COVID-19, Nervous System and Immune System

Today, it is well established in the literature that the autonomic nervous system (ANS) plays an important role in the homeostasis of the organism, influencing systemic bodily functions. Thus, the dysfunctions found in the ANS can result in harmful effects of physiological processes associated with respiratory, vascular, immunological, hematological and renal processes.

It is noteworthy that the autonomic nervous system is divided into two parts: the sympathetic system (SNS) and the parasympathetic system (PNS). The system sympathetic is responsible for changes in the body in alert situations, preparing the body to face or flee from a threat, thus involving a greater expenditure of energy. Therefore, this part of the nervous system is tasked with increasing heart rate and blood pressure, releasing adrenaline, contracting and relaxing muscles, dilating the bronchi, dilating the pupils, increasing sweating. On the other hand, the nervous system parasympathetic normalizes the functioning of internal organs after the alert situation.

Given this, study findings show that even in mild and moderate infection, young adults with COVID-19 had higher sympathetic activity and a decrease in parasympathetic activity.. This imbalance in the autonomic nervous system may be a result of higher inflammatory levels and markers of oxidative stress during COVID-19 infection.

Therefore, it is believed that oxidative stress and the subsequent release of inflammatory cytokines that accompany SARS-CoV-2 infection could explain the changes in ANS. On the other hand, factors involving behavioral changes during and after infection, such as changes in physical activity, nutritional status, and consumption of food and fluids, may also explain ANS changes.

In addition, autonomic imbalance may persist after acute SARS-CoV-2 infection, which may be related to a persistent systemic inflammatory condition observed in the post-viral phase. This imbalance is commonly accompanied by several other post-COVID-19 conditions, including postural orthostatic tachycardia syndrome, dysautonomia, fatigue, cerebral hypoperfusion syndrome, and impaired endothelial function, all of which are associated with this condition regardless of hospitalization.

COVID-19, Autonomic Function and BMI

It is worth mentioning that in addition to acute SARS-CoV-2 infection, other factors can directly affect autonomic function, including obesity. Research results show that overweight or obese patients in the post-COVID-19 group had significantly lower parasympathetic activity compared to eutrophic individuals in the control group. This is a possible result of chronic low-grade inflammation, characteristic of obesity, in combination with the cytokine storm response of COVID-19 infection, a profile that can promote and even worsen autonomic dysregulation in these patients.

In addition, the literature shows that obesity is associated with a poor prognosis for SARS-CoV-2 infection, hospitalization in intensive care, and disease progression. With every 1-unit increase in body mass index (BMI), there is a 12% increase in the risk of severe COVID-19.

COVID-19 and Physical Activity

Physical activity levels may directly influence autonomic modulation, as well as may be associated with reduced risk and severity of COVID-19 symptoms.. At the same time it is related to improvements in immunity and cardiorespiratory fitness, as well as can help prevent and treat obesity, cardiovascular disease, diabetes, liver disease, cancer and other chronic diseases, indirectly reducing the threat of COVID-19.

In fact, in physically active participants cardiac autonomic modulation levels were better when compared to those of their inactive peers, even in participants who had COVID-19. This can be explained by the fact that regular physical exercise can promote functional and structural changes in the central and peripheral mechanisms of the cardiovascular system to ensure adequate blood perfusion and cardiac response according to metabolic demands.

In addition, physical activity helps in the modulation of the ANS. For peripheral stress induced by skeletal muscle contraction or mechanical stress in the organs sends afferent signals to the central nervous system, thus inducing the release of catecholamines (epinephrine and norepinephrine) to alter the function of the ANS to meet the metabolic demands of exercise. The release of epinephrine and norepinephrine increases SNS activity, consequently promoting PNS activity during exercise recovery.

Physical Activity and Immune Response

Physical activity is important in modulating immune responses. Their increased levels are associated with better cytokine responses, thereby reducing the severity of COVID-19 disease. It also helps modulate the release of anti-inflammatory factors, which may aid in the immune response to SARS-CoV-2 infection by increasing antioxidant capacity and increasing stimulation of the T-Helper 2 cell pathway.

For example, physical activity increases the level of oxidative stress in skeletal muscle as a product of metabolic processes. Thus, we have a feedback mechanism that increases antioxidant levels – as a defense against the presence of reactive nitrogen species and reactive oxygen species, which are also in inadequate immune stimulation.

Still, when analyzing defense cells, including monocytes and T lymphocytes, researchers observed that individuals infected with SARS-CoV-2 had a reduced anti-inflammatory profile of regulatory T cells. While the PD1 protein — which has the function of preventing T cells from attacking other cells in the body — was augmented in both TCD4 and TCD8 lymphocytes. Thus, results show that the higher the level of physical activity, the greater the protection against changes in the CD8 T cell, but not in the CD4.

Improved Autonomic Function

To recap, mild to moderate SARS-CoV-2 infection promotes changes in the ANS of young adults and may persist after the acute phase of the disease. Thus, when observed the effects of mild or moderate COVID-19 on the ANS in young adults, before and at least six weeks after complete immunization against SARS-CoV-2, it resulted in the improvement of autonomic function after approximately five months of follow-up. This change is characterized by significant reductions in the indices of the NHS and significant increases in the PNS indices.

Clinical practice

As the data presented show that COVID-19 can compromise the immune system of young people with mild symptoms, physical activity can be used as a protective factor for it. Therefore, the World Health Organization recommends that adults participate in 150 minutes of moderate physical activity per week or 75 minutes of vigorous physical activity to observe the physiological benefits that can protect against COVID-19 outcomes and reduce the risk of many diseases.

Bibliographic references

Suggested reading:
What is the role of food in COVID-19?

Watch the video on Science Play Karina Al Assal:
Microbiota post-covid

Autonomic function
: Freire APCF, Lira FS, Morano AEvA, Pereira T, Coelho-E-Silva M-J, Caseiro A, Christofaro DGD, Marchioto Júnior O, Dorneles GP, Minuzzi LG, Pinho RA, Silva BSdA. Role of Body Mass and Physical Activity in Autonomic Function Modulation on Post-COVID-19 Condition: An Observational Subanalysis of Fit-COVID Study. International Journal of Environmental Research and Public Health. 2022; 19(4):2457.

Physical activity
: Freire APCF, Amin S, Lira FS, Morano AEvA, Pereira T, Coelho-E-Silva M-J, Caseiro A, Christofaro DGD, Dos Santos VR, Júnior OM, Pinho RA, Silva BSdA. Autonomic Function Recovery and Physical Activity Levels in Post-COVID-19 Young Adults after Immunization: An Observational Follow-Up Case-Control Study. International Journal of Environmental Research and Public Health. 2023; 20(3):2251.

FAPESP Article

: Maria Fernanda Ziegler. COVID-19 can lead immune system to exhaustion even in young people with mild or moderate condition. FAPESP AGENCY. Published March 20, 2023. Accessed March 20, 2023.

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