THE Covid long , also called post-Covid syndrome, encompasses a set of symptoms that remain active in some patients after the acute phase of SARS-CoV-2 infection. A new study, conducted at the Institute of Biomedical Sciences at the University of São Paulo (USP), presents new pieces to the puzzle of prolonged symptoms of the disease.
Researchers analyzed the autoantibodies (antibodies that “attack” the body’s own antigens) from 80 patients who had Covid-19, as well as those from 78 seronegative or asymptomatic individuals.
“Although autoantibodies are best known for being present in autoimmune diseases, recent studies have shown their role in regulating both the sick and the healthy organism”, explains Otávio Cabral Marques, USP researcher and study coordinator. The work was supported by the State of São Paulo Research Foundation (FAPESP) and the results were published in the journal Frontiers in Immunology.
Autoantibodies are a first line of defense against infections, in addition to contributing to the balance – called homeostasis – of the immune system, explains Marques. In some autoimmune disorders, for example, they may be present before the first symptoms, serving as biomarkers and helping with diagnosis and treatment.
In the study now published, data from seronegative or asymptomatic volunteers were compared with those from patients who developed the so-called chronic fatigue syndrome, which can include symptoms such as extreme tiredness, sleep, memory and concentration problems. Also known as myalgic encephalomyelitis, chronic fatigue syndrome has been observed since the beginning of the pandemic in 10% to 20% of patients who recover from Covid-19.
In volunteers with this condition, the scientists observed a low prevalence of autoantibodies directed at vessel and immunoregulatory receptors, in addition to others involved in the autonomic nervous system, which controls the functioning of organs.
“Autoantibodies are necessary for the regulation of various body functions. They cannot be too high or too low. In the case of this study, the low concentrations suggest failures in the functioning of vessel and immunoregulatory receptors due to a possible functional loss of autoantibodies”, explains Igor Salerno Filgueiras, who performed the bioinformatics analysis of the study during his master’s degree at USP.
Detection and treatment
Using computational tools, the scientists found a correlation between the low amount of some autoantibodies with the presence and severity of chronic fatigue, allowing a stratification of patients.
Molecules with low levels targeted the so-called G-protein coupled receptors (GPCRs), a family of proteins of great importance in cell signaling and, therefore, in vital physiological systems for human beings.
Among the targets of autoantibodies with low levels in patients with post-Covid syndrome were ADRB2, ADRA2A and STAB1. They proved especially useful in classifying patients on the prognosis of the post-Covid condition, predicting when the patient had or did not have chronic fatigue.
ADRB2 is related to cardiac function, while ADRA2A acts in the nervous system, activating receptors in blood vessels, heart and kidneys, among other functions.
STAB1, in turn, has the function of a “garbage bin”, eliminating cell debris and other remnants of tissue damage, an important role in tissue balance and in the resolution of inflammation.
The low rate of autoantibodies that targeted ADRB2 further indicated the severity of symptoms in patients with chronic fatigue syndrome. With fewer autoantibodies, other molecules of the organism itself may be in excess, impairing the proper functioning of the organism.
“These and other autoantibodies may serve as indicators of chronic fatigue syndrome in the future. In addition, there are some drugs that act as inhibitors of these molecules and could be tested in the future as a form of treatment. However, the current indication for treating this syndrome is the practice of physical exercises”, points out Marques.
Age and Covid-19
In another study, published on the medRxiv platform in preprint format (still without peer review), the group coordinated by Marques showed the relationship between autoantibodies and age in cases of Covid-19. However, in this case, the relationship was inverse: the more severe the condition, the greater the age and levels of these molecules.
The analyzes were carried out on samples of 159 individuals with different stages of the disease (71 mild, 61 moderate and 27 severe cases), in addition to 73 healthy individuals. 58 molecules associated with autoimmune diseases were selected.
The researchers concluded that the natural production of autoantibodies increases with age, but is exacerbated with SARS-CoV-2 infection, especially in severe cases. In the study, the levels of these molecules served to stratify patients by age group, between more and less than 50 years of age.
“Our analyzes showed that the most important autoantibodies for stratifying the most severe cases target cardiolipin, claudin and platelet glycoprotein, which together play important roles in the functioning of the organism”, says Dennyson Leandro Mathias da Fonseca, first author of the article and PhD fellow at USP.
The results offer new explanations for the fact that older patients generally have worse responses than young people to Covid-19, reinforcing the role of autoantibodies in the severity of the disease.
In a previously published work, the researchers also observed the relationship between the increase in autoantibodies and the severity of Covid-19.
Source: CNN Brasil
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