Study at the ICBUSP provides information on the diagnosis and treatment of the socalled Chronic Fatigue Syndrome, which affects between 10% and 20% of patients who have recovered from the coronavirus infection (Photo: Freepik)
January 18, 2023
André Julião | Agency FAPESP Study carried out at the Institute of Biomedical Sciences of the University of São Paulo (ICBUSP) and disclosed in the journal Frontiers in Immunology highlights the socalled postCOVID syndrome a term that encompasses the set of symptoms that remain active in some patients after the acute phase of SARSCoV2 infection.
In the work, the researchers analyzed the autoantibodies (antibodies that “attack” the body’s own antigens) of 80 patients who had contracted COVID19, as well as those of 78 seronegative or asymptomatic people.
“Although autoantibodies are best known for being present in autoimmune diseases, recent studies have shown their role in regulation of both the diseased and healthy organism,” he explains. Otavio Cabral Marquesa researcher at ICBUSP and coordinator of the study that included support by FAPESP.
As Marques explains, autoantibodies are a first line of defense against infection and also contribute to the homeostasis (balance) of the immune system. For example, in some autoimmune diseases, they can be present before symptoms appear, serve as biomarkers, and aid in diagnosis and treatment.
The study, now published, compared data from seronegative or asymptomatic volunteers with that of patients who developed what is known as chronic fatigue syndrome, which can include symptoms such as extreme fatigue, problems sleeping, memory and concentration. Chronic Fatigue Syndrome, also known as myalgic encephalomyelitis, has been observed in 10% to 20% of patients recovering from COVID19 since the start of the pandemic.
In volunteers with the condition, the scientists observed a low prevalence of autoantibodies directed against vascular and immunoregulatory receptors, in addition to others involved in the autonomic nervous system that controls organ function.
“Autoantibodies are necessary for the regulation of various bodily functions. They must be neither too high nor too low. In this study, the low concentrations indicate dysfunction of vascular and immunoregulatory receptors due to a possible loss of function of autoantibodies,” explains Igor Salerno Filgueiras, who conducted the bioinformatic analyzes of the study during his master’s degree at ICBUSP.
detection and treatment
Using computer tools, the scientists found a correlation between the low levels of some autoantibodies and the presence and severity of chronic fatigue, allowing for stratification of the patients.
Molecules at low concentrations targeted the socalled G proteincoupled receptors (GPCRs), a family of proteins that are important for cell signaling and therefore vital physiological systems for humans.
Targets of low level autoantibodies in patients with postCOVID syndrome included ADRB2, ADRA2A and STAB1. They proved particularly useful in classifying patients by postCOVID prognosis, predicting when the patient had chronic fatigue and when not.
ADRB2 is related to heart function, while ADRA2A acts in the nervous system, activating receptors in blood vessels, heart and kidneys, among others.
STAB1, in turn, has the function of a “garbage can” that removes cellular debris and other remnants of tissue damage, an important role in tissue balance and resolution of inflammation.
The low level of autoantibodies targeting 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, affecting the proper functioning of the organism.
“These and other autoantibodies could serve as indicators for chronic fatigue syndrome in the future. In addition, there are some drugs that act as inhibitors of these molecules that could be tested as a form of treatment in the future. However, the current indication for the treatment of this syndrome is the practice of physical exercise,” confirms Marques.
Age and COVID19
In another study released on the medRxiv platform in preprint format (not yet peerreviewed), the group coordinated by Marques showed the association between autoantibodies and age in COVID19. In this case, however, the relationship was reversed: the more severe the condition, the greater the age and concentration of these molecules.
The analyzes were performed on samples from 159 people with different stages of the disease (71 mild, 61 moderate and 27 severe cases) and 73 healthy people. 58 molecules associated with autoimmune diseases were selected.
The researchers concluded that the natural production of autoantibodies increases with age, but is amplified in SARSCoV2 infection, especially in severe cases. In the study, levels of these molecules were used to stratify patients by age group between over and under 50 years.
“Our analyzes showed that the most important autoantibodies for stratifying the most severe cases target cardiolipin, claudin and platelet glycoprotein, which together serve important functions for the functioning of the organism,” he says. Dennyson Leandro Mathias da FonsecaFirst author of the article and scholars Doctorate at the ICBUSP.
The results offer new explanations for the fact that older patients are generally less responsive to COVID19 than young people, reinforcing the role of autoantibodies in disease severity.
In a previously published paper, the researchers also observed the association between increases in autoantibodies and the severity of COVID19 (read more at: agency.fapesp.br/36829/).
school closings
There is also a third study recently published by the Marques Group that analyzed data from COVID19 testing on students and education professionals from the public education network in Sergipe State between November 2020 and January 2021.
The results, disclosed in the journal Heliyon show that the return to school brought with it a large number of asymptomatic cases, both among students and among teachers and other educational workers. 2,259 people (1,139 students and 1,120 professionals) were tested in schools in 28 municipalities across the country.
“The work is part of a task force that began in March 2020 to test different groups of essential workers and was supported by the State Department of Labor and the state government. In total, more than 180,000 tests were performed,” says Lysandro Borges, physician and professor at the Federal University of Sergipe (UFS), who is doing a postdoctoral internship at the ICBUSP and shares first authorship of the article.
In addition to students and educators, Quilombola communities, members of the prison system, security guards, firefighters and blood samples from blood transfusion centers have been tested, which will result in further work.
The material was collected 30 days after schools reopened, before the start of vaccination against COVID19. The majority of students (421) and professionals (446) tested had active SARSCoV2 infection, while 515 students (45%) and 415 (37%) employees did not test positive for antigens or antibodies.
However, only 16% of the participants had symptoms, albeit mild. Headaches, sore throats, and coughs were the most common, even among the reinfected.
“The results show, despite being in one state, that many infections were asymptomatic while schools were open. The study shows how important coordinated public health work is to ensure a safe school environment without increasing the social inequalities that already exist in the country,” says Marques.
Globally, Brazil is one of the countries where schools have been closed the longest due to the pandemic. The result was a delay in education, particularly for poor students, in addition to social, psychological, and economic losses to them, their families, and educators.
The study Dysregulated autoantibodies targeting vaso and immunoregulatory receptors in postCOVID syndrome correlates with symptom severity can be read at: www.frontiersin.org/articles/10.3389/fimmu.2022.981532/full.
The preprint SARSCoV2 infection induces autoantibody production in severe COVID19 patients in an agedependent manner is available at: www.medrxiv.org/content/10.1101/2022.12.04.22282902v1.
And the article CrossSectional Analysis of Students and School Workers reveals high number of asymptomatic SARSCoV2 infections during school opening in Brazilian cities: www.cell.com/heliyon/fulltext/S24058440(22)026561.
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