One of the studies will evaluate the effectiveness of drugs that inhibit bradykinin against pulmonary inflammation in critical patients. The other will analyze the transmission dynamics of the novel coronavirus in a small town in Amazonia (image: bradykinin / Wikimedia Commons)
Published on 03/25/2021
By Karina Toledo | Agência FAPESP – On March 31 FAPESP announced the first two grants approved under the call for research proposals entitled “Fast track supplements for projects against COVID-19 (Coronavirus Disease 2019)”, issued on March 21. The Scientific Directorate took only four days to analyze the proposals submitted.
One of the projects will study the effectiveness of two drugs to combat pulmonary inflammation in critical patients. The other will analyze the transmission dynamics of the novel coronavirus in a malaria-endemic town in the Amazon.
“FAPESP issued the call to stimulate researchers who already have funding to redirect their projects’ human and financial resources to focus on ways of contributing to the fight against the COVID-19 pandemic. The proposals are analyzed as they are submitted, based on an assessment of the magnitude of the redirected resources compared with those requested, and the quality and impact of their potential scientific contribution,” said Carlos Henrique de Brito Cruz, FAPESP’s Scientific Director.
At the University of Campinas (UNICAMP), two professors in the Department of Clinical Medicine, Licio Velloso and Maria Luiza Moretti, will lead a clinical trial with 180 patients treated for pulmonary edema confirmed by CT scan at the university’s teaching hospital, Hospital de Clínicas. The aim is to test the effectiveness of two drugs that have already been licensed for human use in treating the rapidly progressing acute inflammation that has caused the death of most patients infected by the novel coronavirus (SARS-CoV-2).
The two drugs chosen for the study inhibit the action of bradykinin, a peptide with potent pro-inflammatory action and part of the innate immune response, in which physical, chemical and cellular defenses are activated against an invading pathogen.
“The immune system releases bradykinin to trigger an inflammatory response designed to eliminate the invader, but enzymes that degrade the peptide rapidly go into action to avoid excessive inflammation that could damage lung tissue,” said Velloso, principal investigator for the Obesity and Comorbidities Research Center (OCRC), a Research, Innovation and Dissemination Center (RIDC) funded by FAPESP and hosted by UNICAMP.
The main problem in the case of COVID-19 is that when the virus infects lung cells it binds to angiotensin-converting enzyme 2, or ACE-2, precisely one of the main bradykinin-degrading enzymes.
“Our hypothesis is that the coronavirus blocks the activity of ACE-2 by binding to it, so that bradykinin accumulates in the lungs. This would explain why some patients develop pulmonary edema [a buildup of fluid in the alveoli that prevents gas exchange] so quickly that they die not long after admission to hospital. When the degree of edema is very high, even sophisticated ventilators can’t maintain respiration,” Velloso said.
The group expects the treatment to mitigate inflammation in the lungs, helping to reduce mortality, which is currently around 20% for critical patients, and shortening the time they spend in intensive care units.
Dissemination in Amazonia
In the second project just approved, the scientists will study the transmission dynamics of the novel coronavirus in Mâncio Lima, a small town in Acre, Brazil’s westernmost state, not far from the border with Peru. The principal investigator is Marcelo Urbano Ferreira, a professor in the University of São Paulo’s Biomedical Science Institute (ICB-USP) who for many years has carried out fieldwork in the region with the aim of combating malaria.
“Mâncio Lima has 18,000 inhabitants and is the Brazilian municipality with the highest incidence of malaria,” Ferreira said. “We’ve conducted household surveys of a sample of the population every six months. We call on 2,000 homes, apply questionnaires, and collect blood samples for a range of studies.”
The studies are part of the Thematic Project “Scientific basis for elimination of residual malaria in the Brazilian Amazon”.
The latest collection of blood samples took place in September-October 2019, before the novel coronavirus arrived in Brazil. The next was scheduled for this April but has had to be postponed owing to the social isolation measures taken to combat COVID-19.
“We’ve decided that in May-June we’ll collect samples only from patients suspected to have COVID-19 by a local health service so that we can keep track of the acute cases. The next household survey will hopefully take place in September-October of this year, when we aim to assess the rate of seroconversion in this population, estimating how many people who didn’t have antibodies against SARS-CoV-2 and now do,” Ferreira said.
The analysis, he added, will enable the researchers to predict the number of people in the region who are still susceptible to the novel coronavirus and may be infected if there is a second wave of the epidemic.
The next batch of surveys, planned for April-May and September-October 2021, will enable them to find out whether the antibodies are still in the organisms of the participants who tested positive in the previous analysis.
“No one yet knows if the immunity induced by infection is permanent or disappears after a period, as it does in the case of influenza,” Ferreira said.
The group used the answers to the questionnaires from previous surveys to map networks of social interaction among the town’s inhabitants. According to Ferreira, this information will enable them to estimate the transmission dynamics of SARS-CoV-2, working out who transmitted the virus to whom and in what circumstances.
“We assume that many SARS-CoV-2 infections aren’t noticed and that asymptomatic bearers may continue spreading the pathogen in their everyday social interactions,” he said.
The call will remain open until June 22, 2020, for short-term research projects as supplements to ongoing grants for Thematic Projects, Young Investigators, Research, Innovation and Dissemination Centers (RIDCs), and Engineering Research Centers (ERCs).
Projects must redirect part of their research efforts to contribute significantly to the understanding and surmounting of the risk represented by SARS-CoV-2 and/or possible ways of managing or preventing it.
FAPESP will invest up to BRL 10 million in the projects approved under this call, which must last 24 months. Per project funding is capped at BRL 100,000 per year. Over and above this limit, researchers can apply for a postdoctoral scholarship, which lasts 24 months.
The full call for proposals is available (in Portuguese) at www.fapesp.br/14082.
Source: https://agencia.fapesp.br/32956
