Severity of post-Covid syndrome may be related to antibodies present in autoimmune diseases

A study conducted at the Institute of Biomedical Sciences at the University of São Paulo (ICB-USP) and published in the journal Frontiers in Immunology sheds light on the so-called post-Covid syndrome — a term that encompasses the set of symptoms that remain active in some patients after the phase acute onset of SARS-CoV-2 infection.

In the work, the researchers analyzed the autoantibodies (antibodies that “attack” the body’s own antigens) of 80 patients who had Covid-19, as well as those of 78 seronegative or asymptomatic individuals.

“Although autoantibodies are better 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, researcher at ICB-USP and coordinator of the study, which had the support of Fapesp.

As Marques explains, autoantibodies are a first line of defense against infections, in addition to contributing to homeostasis (balance) of the immune system. 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, 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 carried out the study’s bioinformatics analysis during his master’s degree at ICB-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 a “garbage bin” function, 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 in the future serve as indicators of chronic fatigue syndrome. Furthermore, 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”, attests 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 to stratify the most severe cases target cardiolipin, claudin and platelet glycoprotein, which together play important roles in the body’s functioning”, says Dennyson Leandro Mathias da Fonseca, first author of the article and doctoral fellow at ICB-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 (read more here).

school closures

There is also a third study recently published by the Marques group in which data from Covid-19 tests were analyzed in students and education professionals from the public education network in the state of Sergipe, between November 2020 and January 2021.

The results, published in the magazine Heliyon, show that the return to school brought a large number of asymptomatic cases, both in students, teachers and other education workers. 2,259 individuals (1,139 students and 1,120 professionals) were tested in schools in 28 municipalities in the state.

“The work is part of a task force that started in March 2020 to test different groups of essential workers and which had the support of the Public Ministry of Labor and the state government. In total, there were more than 180 thousand tests carried out”, says Lysandro Borges, physician and professor at the Federal University of Sergipe (UFS) who is carrying out a postdoctoral internship at ICB-USP and shares the first authorship of the article.

In addition to students and education professionals, quilombola communities, members of the prison system, security forces, firefighters and blood samples from blood centers were tested, which will result in other works.

The material was collected 30 days after the reopening of schools, before the start of vaccination against Covid-19. The majority of students (421) and professionals (446) tested had active SARS-CoV-2 infection, while 515 students (45%) and 415 (37%) employees did not test positive for antigens or antibodies.

However, only 16% of participants had symptoms, even so, mild. Headache, sore throat and cough were the most common, including among those reinfected.

“The results, although located in one state, indicate that many infections were asymptomatic during the opening of schools. The study shows how important a coordinated public health work is to guarantee a safe school environment, without increasing the social inequalities that already exist in the country. country,” says Marques.

Worldwide, Brazil was one of the countries that remained with schools closed the longest because of the pandemic. The effect was a delay in education, especially for poor students, in addition to social, mental and economic losses for them, their families and education professionals.

The study Dysregulated autoantibodies targeting vaso- and immunoregulatory receptors in Post COVID Syndrome correlate with symptom severity can be read here.

The preprint SARS-CoV-2 infection induces the production of autoantibodies in severe COVID-19 patients in an age-dependent manner is available here.

And the article Cross-sectional analysis of students and school workers reveals a high number of asymptomatic SARS-CoV-2 infections during school reopening in Brazilian cities can be accessed here.