Federal University of Pará (UFPA), Evandro Chagas Institute (IEC) and other institutions are carrying out studies to identify effective therapy to fight the new coronavirus. The first results, although initial, are encouraging for scientists
On December 31st, 2019, the World Health Organization (WHO) was alerted to several cases of pneumonia in Wuhan City, of China. It was a new type of coronavirus that had not been identified in humans before. Since then, scientists around the world have started a race – against time and against the SARS-CoV-2 virus, which causes Covid-19. Some of these scientists are in the Amazon, a region of the planet with natural wealth that is also rich in knowledge production. In this part of the world, as soon as Covid-19 appeared, the doctoral professor in genetics and molecular biology André Khayat was already starting, with other researchers from the Federal University of Pará (UFPA), an investigation into a therapy potentially capable of destroying the virus in cells infected with cancer.
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Called “target therapy”, it uses a methodology already tested in oncology, including medicines approved by the Health Surveillance Agency (Anvisa), for the treatment of rare diseases. Due to the pandemic situation, the group decided to contribute to worldwide studies and apply its knowledge in cancer also against Covid-19. “Given the worldwide need, we thought: how about if we use this same targeted therapy approach to silence and block the action of the coronavirus gene in the cell?” the investigators stated.
The explanation is that where the targeted therapy was applied, the virus was silenced and prevented from multiplying as it occurs in the untreated cell group. “Currently, there are hundreds of SARS-CoV-2 variants being sequenced worldwide, and for all of them, the drug would be potentially effective. We chose to target a specific part of the virus, a gene that remains in it despite mutations, that is, it is present in all variants. Therefore, the treatment can be effective even for the Delta variant”, reinforces researcher André Khayat.
The experiments were carried out on human cells and developed in partnership with the Evandro Chagas Institute (IEC), another renowned research institution in the Amazon. These cells were infected by the coronavirus and only one group of them received the treatment with the interfering RNA. One day after infection, the treated group showed a decrease in viral load, while the other continued with a progressive increase. “The reduction in viral load from one group to another was around 99%”, confirmed the researcher.
Despite being optimistic about the good results, the researchers state that it is important to keep our “foot on the ground” - which in this research means a long road to conclusive results, which depend on the next tests to be resumed in the next semester, this time in animals, in partnership with the University of São Paulo (USP). If, in this next step, the effects observed in the cell are repeated in animals, the group will be able to claim tests in humans. “It is important to remember that what happens in an in vitro cell (in the laboratory) is not always repeated in subsequent experiments. So, we still don't have a remedy. What we have as protection is the vaccine”, emphasize the professors.
Throughout the process, Professor Khayat faced the disease and had even stronger motivations for efforts to unravel the mysteries of the virus , which became recognized as a worldwide problem in March 2020, when the WHO declared Covid-19 as pandemic, which until this week has infected over 186 million people worldwide. Of these, more than 4 million died. In Brazil, the third country with the most cases and the second with the most deaths, there are already more than 500 thousand Brazilians killed by the disease.
One of them was Professor Khayat's brother. “My family and I suffer a lot from this disease. I was hospitalized for days, at risk of death , and when I finally recovered, I lost a brother”, said the researcher.
The experience of facing the disease drove him to dive even further into research. “After this tragic experience, I felt more impelled to go deeper into research. In addition to being more willing to study, this experience makes me hope that everything works out and other families don't go through what mine and so many others went through. I tell people to have faith in God and believe in science. We scientists are dedicating ourselves and joining forces to find a way out of this pandemic”, concludes André Khayat.
The discovery of the “new” coronavirus makes it clear that little is known about it. In addition to chasing vaccines, the scientific community felt the need to seek for new strategies that allow a better understanding of the action of the virus and its impact on different populations around the world. . Therefore, one of the ongoing researches in Pará investigates the variations present in the viral genome and in all expressed human genes (EXOMA), including the populations that inhabit the Amazon region – especially those in the State of Pará.
Funded by the Amazon Foundation for Research Support (Fapespa) and in partnership with the Vale Technological Institute (ITV), the research carried out by UFPA seeks to identify genetic markers that may be associated both with the worsening of the disease, as well as with its protection or evolution in the Covid-19 infection. Since the beginning of the studies, still in 2020, the project has sequenced the virus genome of more than a thousand from Pará and has identified at least 20 different types of variants or strains of the coronavirus. The samples were collected from patients at the João de Barros Barreto University Hospital, from UFPA servers and from the Central Laboratory of Pará (Lacen), Belém Municipal Health Department (Sesma) and the Neurogenesis Institute, collaborators in the research.
"Currently, we have observed the worsening of the Covid-19 clinical picture not only in the elderly, but also in young people without apparent comorbidities" - Ândrea Ribeiro, researcher.
The professor and researcher Ândrea Ribeiro, project coordinator of "Genomics Surveillance Covid-19" at UFPA, says the different types of viruses circulating in the population may be responsible in part for medical conditions such disparate. “However, genetic variants present in the human genome can also originate and aggravate these differences in the evolution of the clinical picture”, he assesses.
The result of this research may be the key to identifying the change in the profile of the disease, which, at the beginning, indicated the elderly population as the greatest “risk group”. Today, Professor Ândrea highlights something that caught the eye in the second wave of the pandemic: the worsening of Covid-19 in a high number of young people. “Currently, we have observed the worsening of the Covid-19 clinical picture not only in the elderly, but also in young people without apparent comorbidities”, she says.
She says the research should identify genetic factors that influence this group of people, apparently healthy, to rapidly progress to death after becoming infected. “Patients infected with the virus can have the most diverse reactions, ranging from the total absence of clinical symptoms to severe respiratory syndrome, which often leads to death, even when infected with the same strain. The cause is still unknown, but we are looking for this answer ”, says the scientist.
UFPA's initiatives take place on different fronts, including initiatives to support current treatment procedures and adaptation of equipment for inclusion. The university campus is also one of the points given to the City of Belém to carry out the vaccination of the population. "Since the beginning of the pandemic, we have mobilized a collective effort in actions to combat the new coronavirus and support the population. Even in a scenario with many adversities for universities and for national science, our researchers made available to society all the scientific knowledge accumulated to collaborate in the diagnosis, prevention and treatment of the disease. Our community is proud of all the work that has been developed to save lives, as a result of UFPA's commitment to the Amazon and Brazil", says Emmanuel Tourinho, dean of UFPA.
In March this year, 52.2% of admissions to Intensive Care Units (ICUs) in Brazil were for people aged up to 40 years. And the total number of patients who required mechanical ventilation reached 58.1%. Priscila Viana, coordinating nurse of the ICUs of the Hospital Beneficente Portuguesa, in Belém, saw this change in the profile of patients with severe cases in the forefront. “At the beginning of the pandemic, the initial risk group was elderly and adults with comorbidities, but the scenario was changing and hospitalization rates soared among young people and without comorbidities”, says the health professional.
The nurse reiterated that, today, everyone should consider themselves a risk group. “Covid-19 is a new disease with numerous mutations and a devastating effect. Therefore, everyone is a risk group, including those who are vaccinated, should remain cautious, until the competent authorities assess future changes in this scenario. I cannot understand the resistance of the community to protect itself through basic measures. If everyone had the opportunity to get to know up close the reality of those who work on the front lines in the ICUs and all the devastating effects of the disease, the reality would undoubtedly be different”, she says.
Eiko Migiyama, from Pará lived this picture of being a young patient, but with seriousness. First, she faced the loss of her grandfather, 76-year-old Katsuhiko Migiyama, who despite his advanced age was an active person: he took walks, went to the gym regularly and still worked in the family's business. On April 6th of last year, he was hospitalized, was released from the ICU after 15 days, but returned and died on May 2nd.
Four days earlier, on April 28th, Eiko fell ill with Covid-19, and even though she was a 21-year-old girl with no apparent comorbidities, she had a very serious condition. “Due to complications, I was hospitalized for a week, needed oxygen, had bronchitis, pneumonia and anemia. During this period of hospitalization I even used disposable diapers because I didn't have the strength to stand up”, says Eiko, who later still needed the help of a wheelchair and caregiver during her recovery.
Eiko still has post-covid issues today. “It's been a couple of months since I took a battery of tests and I still have sequelae in the thyroid, gallbladder, heart and lung. I went back to exercising to improve cardio-pulmonary activity and I'm still being followed up”, she says, who now allows herself to have more hope. “I have not received any more news of deaths, neither from my acquaintances nor from my friends, and this makes me very hopeful, especially regarding vaccination. Thank God my grandparents and my parents are already vaccinated, and I can't wait to be vaccinated and for us to get out of this”, she says.
Brazil is among the 32 countries in the world that are part of the “Scourge” project, a global survey in Covid-19, funded by the European Union, with 91 study centers. This is an international agreement to investigate risky genetic biomarkers for Covid-19 infection. In Brazil, of the three collaborating centers of the consortium, the UFPA's Oncology Research Center is the only one in the Amazon. The other two are from Rio Grande do Norte, a state in the northeast of Brazil, and Brasília, the country's capital .
The project brought together 150,000 genetic samples from patients around the world, 3,000 of them from Brazil and around 500 from Pará, to carry out the sequencing of the human genome and discover which genetic characteristics can make men more susceptible to severe cases of the disease. "Our question is: why do we have individuals who, when infected, have severe forms of Covid -19, which represent a group of 5% and why do we have individuals who do not manifest severe forms of the disease, which are the majority?", asks the research coordinator, Professor Dr. Ney Santos, also from the NPO.
He says that among the benefits of such research seeking to understand virus host singularities are improved in the forms of prevention, in which an individual to know who has the gene "friend of the virus" redouble their care, and to amend the lists of priorities for vaccine, or even in the post-infection, in which the doctor can adapt the service to the needs of the patient who already has a predisposition to worsening or death.
"Knowledge is cyclical and accumulates, it will never be thrown away. That's why it's important to invest in science" - Sidney Santos, Director of the NPO.
The director of the NPO, Sidney Santos, says that the answers to so many current questions would already be answered if the scientific community had acted with the same force as today, in previous studies on other diseases, such as the H1N1 pandemic, “because the information collected previously, it would have made the research on Covid-19 move at a speed dozens of times faster”, he assesses.
However, Sidney ponders that the benefits of the knowledge produced so far do not end when a cure for the disease is found. “Knowledge is cyclical and accumulates, it will never be thrown away. That's why it's important to invest in science. This is the highest profit: we will not stand still, we produce information that will be used in other situations, besides the Covid-19, "says the scientist optimistically.
Until now, it is known that the best protection against Covid-19 is the care with detachment, hand hygiene and masks. It was in this last item that a project was developed by the UFPA Team Enactus, to assist women in a situation of socioeconomic vulnerability, reinventing itself in the pandemic. “Costuraê” started producing and donating protective masks for vulnerable communities in the Amazon, an attitude that opened the door to yet another solution: masks adapted for deaf people.
In the manufacturing process, a technology was used based on the reuse of PET bottles, a choice that enabled the selection of the initiative in the notice "Ford Fund Covid-19 College Challenge", as it provides oral transparency that enables oral reading of deaf people and a more effective communication.
“We started producing the masks in April of last year, when we were selected in an international public notice that aimed to provide a financial incentive for innovative ideas with the objective of minimizing the impacts of Covid-19, and then we started to produce and donate. Costuraê focuses on cutting and sewing, and women were without income, so we combined the useful with the pleasant”, says Beatriz Araújo, a member of the project.
The technology gained international recognition and in 2020 1,121 masks were produced. This year, 444 were all donated to various organizations, such as the Astério de Campos School, Felipe Smaldone Institute, Regional Pastoral for the Deaf and the Association of Parents and Friends of the Disabled (APAE), among others.
Another UFPA project reinvented the ambu, manual resuscitation equipment. The idea was to develop the automated “ambu” to serve poor regions of Pará. It is a low-cost emergency auxiliary equipment to be used in ICUs, in the ventilation of patients with intermediate severity.
The tool is being produced to facilitate use in more distant locations and even without electricity. “This ambu is not dependent on electricity, therefore, it can be used in regions of the Amazon where there is still no access to energy”, explains Lucas Henrique, a Biomedical Engineering academic and member of the project. "The equipment only needs electricity for the compressor that supplies the compressed air tanks, but it does not stop working when there is a power outage, which is common in the interior".
Lucas Henrique emphasizes that the idea is to expand the use of the equipment to the interior of the North and Northeast. “It could be a support in the public health system, reducing causes of death due to the lack of respirators”, he explains. The group has already manufactured two prototypes and is in the process of improving the equipment to make it more compact.
“It is important to remember that the automatic resuscitator does not replace the respirator, and is not indicated for severe cases or in the ICU, but it helps in the oxygenation of patients in mild forms of the disease”, he pondered. The project is linked to the Graduate Program in Mechanical Engineering (PPGEM), Mechanical Engineering Course (FEM) and Biomedical Engineering Course (FEB) at UFPA.
• The Federal University of Pará (UFPA), the largest public university in the North of Brazil, is an international reference in Covid-19 research. Within the institution that develops research in the Amazon region for over 60 years, researchers from the Oncology Research Center (NPO) and the Human and Medical Genetics Laboratory (LGHM) are dedicated to finding solutions for a SARS-CoV-2 pandemic.
• The Institute Evandro Chagas (IEC), located in Ananindeua, metropolitan region of Belem, is a reference in cell culture techniques, with laboratories established in the 60s. The human cells used in the experiment that seeks a cure for Covid 19 are from the laboratory of Cytogenomics and Environmental Mutagenesis.