Task force to combat Covid-19 results in two works published on the medRxiv platform and signed by 65 and 74 authors, respectively
Two studies coordinated by Unicamp researchers, published on the medRxiv platform, provide new and important information about Covid-19 – and represent a fruitful example of cooperation between dozens of scientists from universities and research institutes. The first work, signed by 65 authors and published on September 28, shows that the Sars-Cov-2 virus is capable of infecting and killing lymphocytes, compromising the patient's immune system. The second research, which has 74 collaborators, published on October 13, proves that the new coronavirus can also infect astrocytes (brain tissue cells), leading, even to individuals with the mild form of Covid-19, the risk of damage of functions such as memory, attention, consciousness and language.
Both studies have already had an impact on the area of combating the pandemic. Therefore, what is worth highlighting now is the success of this model of scientific collaboration, in the opinion of Professor Marcelo Mori, who coordinated the study with lymphocytes together with Professor Alessandro Farias, his colleague at the Institute of Biology (IB) at Unicamp. “It is a model already adopted by many groups in Brazil and around the world – such as the Cepids [Research, Innovation and Diffusion Centers] financed by Fapesp and the INCTs [National Institutes of Science and Technology] from CNPq. It is a form of interaction that was enhanced by the Covid-19 pandemic.”
Mori also highlights the way in which researchers dealt with the disease, setting up a task force that from the beginning was very interdisciplinary and very focused on goals. “Everyone came together in an altruistic and supportive way, with the sole purpose of helping society face the new coronavirus. Another aspect that enhanced the model was the organization, given the tendency that, due to the desire to find solutions individually, scientists ended up dispersing these initiatives. The task force brought researchers together to discuss and disseminate ideas, evaluating what each had to offer and how to contribute. The groups were subdivided into different fronts, but with a common objective. It was a great example of cooperation.”
According to Marcelo Mori, the work involving lymphocytes has already started with partnerships and taking advantage of each person's expertise, such as that of Alessandro dos Santos Farias, head of the Department of Genetics, Evolution, Microbiology and Immunology at IB-Unicamp. “Professor Farias has been working with lymphocytes for a long time and was one of those who headed the task force, including coordinating the diagnostic front. He was interested in understanding how the Sars-Cov-2 virus affected these cells, as it was already known that there was a decrease in the number of lymphocytes in Covid-19 patients.”
As head of the Department of Biochemistry and Tissue Biology at Unicamp, Mori, in turn, sought the collaboration of the group of professor Robson Carvalho, from Unesp, to identify, computationally, the interaction of the virus spike protein with a molecule on the surface of the lymphocytes. “The tests showed that the interaction really happens. It was important to understand how the virus impacts the immune system, as it is this immune response that determines whether the individual will progress to the severe form of the disease or not. And we observed that the mechanism used by Sars-Cov-2 to infect very important cells in orchestrating this response is similar, although not exactly the same, to that of HIV. We think that elucidating this mechanism can help understand how the immune dysfunction that occurs during Covid-19 occurs.”
The Unicamp professor notes that to make the study viable, the help of computational scientists was necessary, such as professor Munir Skaf, from the Institute of Chemistry, who models molecular interactions, as well as virologists, immunologists and other specialists from different areas, all organized into groups. “We had weekly meetings to discuss the results, which we shared with groups on WhatsApp. Alessandro Farias and I coordinated the initiatives so that each one acted in a timely manner, in order to build a story. We knew the important points to be studied and this ended up moving the research much faster.”
Marcelo Mori participated in the most recent study published on the platform medRxiv, coordinated by professor Daniel Martins-de-Souza, also from IB-Unicamp. There, Mori points out, structural changes in the brain associated with neuropsychiatric symptoms, such as anxiety and cognitive problems, were identified in individuals infected with Sars-Cov-2 but who did not develop severe respiratory symptoms. “We observed these neuropsychiatric symptoms in between 20% and 50% of those infected, which is quite significant; and this in the period of 20 to 120 days after detection of the virus, that is, the symptoms last for a while, which is a worrying aspect.”
In an attempt to associate the neuropsychiatric and structural changes in the brain with the infection mechanism of the new coronavirus, it was found that it was able to reach the central nervous system and that it was present in patients mainly in cells called astrocytes – very important in the care of the neuron and for the nervous system to function. “When these astrocytes are infected, they end up altering their metabolic profile and the pattern of secretion of molecules that leads to the death of neurons in greater quantities. The study is important to determine, or at least propose, the mechanism of nervous system dysfunction observed in some infected individuals”, says Mori.
Scary facet
Daniel Martins-de-Souza, who led this research with astrocytes, was the one who created the Neuroproteomics Laboratory at IB-Unicamp, the first in Latin America, where the biochemical pathways of the central nervous system associated with schizophrenia are studied. “The more we know about Sars-Cov-2, the more tools we will have to combat it, even though the results of our research seem scary: 'Wow, another facet of this virus, can it also reach the brain?' Yes. But in the medium and long term, the results may indicate more assertive treatments in relation to where the virus is in the body: if the person has neurological symptoms, is there any point in treating the lung disease? Apparently, a medicine for Covid-19 does not exist, so we will have to treat symptoms and cure the disease wherever it takes hold.”
Obviously, Martins did not work alone. The investigations were conducted by several groups from Unicamp and USP, all financed by Fapesp, and also collaborated with researchers from the National Biosciences Laboratory (LNBio), the D'Or Institute for Research and Education (Indor) and the Federal University of Rio de Janeiro. January (UFRJ). “This model of cooperation ends up being accentuated when there is an emergency for answers – what we did at Unicamp was to bring together several researchers from three Cepids, expanding and enhancing the work, because we have to respond quickly. We will hardly be able to compete with countries like the United States or Europe, in terms of the quality of science, by carrying out research alone in the laboratory.”
Daniel Martins states that another important point to highlight in the collaborative model is operationalization, which requires organization and a person who can move through all groups to integrate them. "There are 74 authors, who are located not only in different departments at Unicamp, but also in other universities and institutes. The operationalization of the research is based on friendly and sincere dialogue between researchers and the commitment to fulfill tasks, showing that everyone is working for the sake of science, for the best we can do to resolve these important issues.”
Open laboratory
Professor Marcelo Mori cites fundamental partners in the two studies published in medRxiv, such as pathologists Alessandro Fabro and Thiago Cunha, from the Faculty of Medicine of Ribeirão Preto (FMRP-USP), and Paulo Saldiva, from USP in São Paulo; at Unicamp, Clarissa Yasuda, from the Faculty of Medical Sciences (FCM) and the Institute for Research on Neurosciences and Neurotechnology (Brainn), and José Luiz Proença Módena, from IB, who literally opened his Emerging Virus Studies Laboratory (Leve) to all research groups, including those outside Unicamp. Leve is the only space at the University with biosafety level 3 (NB3), necessary to work with highly pathogenic organisms, such as the Sars-Cov-2 virus.
Mori also praises the students' great desire to help, also motivated by the importance of the findings. “More than publishing an article as first author, they were driven by the simple fact of contributing, which was very important. Also at the hospital, while a neurologist focused on his part, many people collected samples from patients, perhaps far from what was happening in the laboratory, but knowing that they were contributing to the understanding of something important – and they did their work quite efficiently. We didn't have any major problems with data transfer or collaboration between people, quite the opposite.
Marcelo Mori considers that this model of scientific cooperation is necessary for Brazilian institutions, so that the country can compete by proposing methods and actions on an equal basis with groups from other countries, as in the case of these two articles recently deposited on the platform medRxiv. “In the case of Covid-19 it was easier because the objective was very well defined and people were willing to collaborate, voluntarily. But one question must remain for the post-pandemic: how to motivate people to work in groups and in such a supportive way, when faced with problems that are not so urgent or emerging, but for the benefit of society?”
Read more:
SARS-CoV-2 Uses CD4 to Infect T Helper Lymphocytes
SARS-CoV-2 infects brain astrocytes of COVID-19 patients and impairs neuronal viability
SARS-CoV-2 uses a strategy similar to HIV to infect defense cells
Study proves that new coronavirus affects the brain and details its effects on nerve cells
"Pandemic has made the way of working essentially collaborative”
