Neurological problems are among the most frequent complications of covid-19 outside the pulmonary system and affect more than 30% of patients. Memory loss, lack of concentration and attention, slow thinking, drowsiness, excessive fatigue, anxiety, depression, language difficulties and other cognitive and brain damage can be effects of the disease.
The conclusions are from a study coordinated by the State University of Campinas (Unicamp) and the University of São Paulo (USP) and recently published in the prestigious journal Proceedings of the National Academy of Sciences (PNAS). The symptoms are usually associated mainly with severe conditions, but they also affect those who had moderate or mild cases of the disease, the publication points out.
“Covid-19 is capable of modifying the brain and its cortical structure with or without the presence of the virus in the brain. The disease is capable of doing that”, says Daniel Martins-de-Souza, professor of biochemistry at Unicamp and one of the researchers.
In cases where the coronavirus reaches the brain, it mainly infects astrocytes — the most abundant brain cells responsible for sustaining and nourishing neurons. Neurons that feed on infected astrocytes end up having their functioning impaired or dying. Astrocytes are the main site of infection and possibly replication of the virus in the brain.
“Not everyone with neurological symptoms had the virus in the brain. Sometimes, the symptom comes from the systemic inflammation caused by the disease”, explains Martins-de-Souza. “Cases in which the virus reaches the brain can potentially be more serious, but we cannot say this with certainty”, observes the biologist, doctor and post-doctoral fellow in biochemistry from Unicamp and with postdoctoral experiences at the Max Planck Institute in Psychiatry in Germany and the University of Cambridge in the United Kingdom.
The researchers will continue to follow up on the study patients, which may bring more answers in the future, for example, to see if the neurological effects will be transient or lasting. The research also found evidence of a correlation between Covid-19 and neurodegeneration, but the data is preliminary. As the investigation continues, the researchers also want to determine whether the virus causes similar changes in other organs, which could shorten treatment pathways.
Study used diversified methodology
The group of 89 researchers from Unicamp and USP used magnetic resonance imaging to compare the brain structure of 81 healthy people with that of 81 who had probably been infected with the original strain of the Sars-Cov-2 coronavirus and were recovering from mild or moderate conditions. of covid-19 about two months ago. “To a greater or lesser degree, all those infected had significant brain changes”, comments Martins-de-Souza.
In some cases, scans have revealed atrophy in the front part of the brain, an area critical to reasoning and attention and associated with anxiety and depression. “The tests showed more symptoms of depression and anxiety in these patients and we were able to verify that it wasn’t just about the fact that we were in a pandemic.”
Part of those who had the disease also underwent tests of cognitive functions and performed worse than those who were not infected. The study also analyzed the brain structure of 26 patients who died of Covid-19 and found severe damage in five of them. Only in the deceased was it possible to identify or not the presence of the virus in that organ.
For Pâmela Billig Mello Carpe, a neuroscientist in the neurobiology of learning and memory who was not involved in the study, an important point of the work was to use different research methods. Therefore, the associate professor at the Federal University of Pampa (Unipampa) says that “the set of results allowed us to reach a more precise conclusion and, without a doubt, contributed to world science to expand the understanding of the pathophysiology of the disease”.
Brazilian pioneering
The Unicamp and USP research was mainly financed by the São Paulo Research Foundation (FAPESP) and lasted about a year and a half. Work began when it was still thought that covid-19 was just a respiratory disease. The patients analyzed were infected with the coronavirus between March and July 2020 and, on average, had had the disease for two months.
“What sparked this particular interest in us was the fact that the patients had a loss of smell, a mechanism mediated by the brain. This made us think that it could have some brain implications”, says Martins-de-Souza Martins-de-Souza.
Before being published in PNAS, the results of the research were published, in October 2020, as a preprint, a kind of preview of the study still without peer review, before being submitted for publication in a scientific journal. However, the research was only officially published last week. Martins-de-Souza highlights the fact that the study is 100% Brazilian and brings unprecedented findings.
“Actually, scientific journals did not trust the data so much at that time. After other studies in the area were published, we managed to publish it, but we were the first group in the world to disclose what we published. The preprint has already had 70 quotes and has the good part of showing who put their foot on the ground first”, he says.
“Seeing colleagues publishing their work in this journal, which is widely recognized on the international scene, makes us Brazilian researchers very proud,” says Matheus de Castro Fonseca, Research Associate at the Tianqiao and Chrissy Chen Neuroscience Research Building at the California Institute of Technology (Caltech) .
Research is essential to develop treatment
The research has not identified ways to prevent or mitigate brain damage from Covid-19, other than trying not to catch the disease. However, the area has motivated researchers to find new ways.
“Now that we have a large number of post-infection patients to be analyzed, several studies around the world have shown chronic damage to cognition, working memory and even control of fine movements, such as tremors”, points out Matheus de Castro Fonseca, Master in Cell Biology and Doctor in Physiology and Pharmacology from the Federal University of Minas Gerais (UFMG).
He and Pâmela Billig Mello Carpe note what rehabilitation strategies can be used. “Cognitive functions in general can be trained, as our nervous system has an important function, the so-called neuroplasticity, which allows it to change according to the stimuli it receives”, explains the doctor in physiological sciences from the Federal University of Rio Grande. do Sul (UFRGS).
“For the development of specific treatments, it is essential to know the mechanisms involved in the generation of sequelae, so encouraging research is essential”, adds the professor.