Researchers join forces to combat coronavirus

Researchers at the University of Campinas are organizing professionals, supplies and equipment to test for COVID-19, understand how the virus works, identify existing drugs that are effective against the disease, and use 3D printing to produce parts for ventilators and personal protective equipment.

By André Julião  |  Agência FAPESP – Researchers and staff at the University of Campinas (UNICAMP) in the state of São Paulo, Brazil, have joined forces to assemble equipment, supplies and volunteers so that more testing can be done as part of the effort to combat COVID-19. They are also studying novel detection methods, researching the action of the virus in the organism, and looking for drugs that may be effective to treat the disease.

Another aim of the group is to assure maintenance of the medical devices needed, as well as 3D printing of parts and personal protective equipment (PPE) for doctors, nurses and other healthcare workers at the front line of the COVID-19 pandemic response.

The resources come from ongoing research projects funded by FAPESP and the National Council for Scientific and Technological Development (CNPq), a Brazilian government agency, as well as from UNICAMP itself. Companies, philanthropists and the Labor Law Prosecution Service (MPT) have made donations.

José Luiz Proença Módena, a professor in UNICAMP’s Biology Institute (IB) and head of its Laboratory for Research on Emerging Viruses (LEVE), is charged with increasing the diagnostic testing capacity of the Clinical Pathology Laboratory (LPC) at the university hospital (Hospital de Clínicas).

The head of LPC is Magnun Nueldo Nunes dos Santos, a professor in UNICAMP’s Medical School (FCM). At the start of April the laboratory was certified by Adolfo Lutz Institute (IAL) in São Paulo as a WHO-accredited testing facility, so that tests performed there do not have to be double-checked by IAL as the reference laboratory for the state of São Paulo.

Módena replicated the first viral RNA samples for use as positive controls in diagnostic testing. The samples were supplied by Edison Luiz Durigon, a professor at the University of São Paulo’s Biomedical Sciences Institute (ICB-USP) and leader of the group of researchers who isolated and cultured the coronaviruses obtained from the first two infected patients in Brazil. His group also assists the production of reagents and other consumables for diagnostic tests and viral assays (read more at: agencia.fapesp.br/32908/).

“With this material we were able to standardize and implement diagnostic testing at UNICAMP’s hospital,” Módena said. “It’s now being ramped up so that testing can be done on a large scale for the Campinas region. The supply of reagents and other inputs will enable us to test a large number of patients.” 

Módena is principal investigator for the project “Pathogenesis and neurovirulence of emerging viruses in Brazil”, which is funded by FAPESP. 

Testing

Large-scale testing requires massive amounts of laboratory supplies, equipment such as thermal cyclers for real-time PCR and centrifuges, and trained personnel to operate all these types of apparatus. Obtaining the viral samples was not all the researchers had to worry about: they also had to find more of these machines and people qualified to run the tests.

Alessandro dos Santos Farias, a professor in IB-UNICAMP, is one of a group of researchers who have set up a network to find equipment and train teams of professionals at the university hospital as well as volunteers to operate it.

“Other countries have suffered from a lack of trained personnel to do the testing,” Farias said. “However, our research routines require reactions of this kind all the time, and the machines are available in many labs. We issued a call to the community and got equipment and volunteers.” 

Farias is principal investigator for a Regular Research Grant project and a Multiuser Equipment Program project, both funded by FAPESP.

The LPC’s own staff are being trained first, and four real-time PCR machines will be used to identify the viral genes. Each machine can analyze 96 samples concurrently. At least four other machines will serve as backups. To scale up testing there are other PCR machines available, as well as some 400 volunteers, most of whom have experience in molecular biology. They include university faculty, staff and graduate students.

“Over 80% of the volunteers have experience in molecular biology, showing the importance of public funding not just to acquire laboratory equipment but also to train the skilled personnel to run it. Thanks to all these resources we’re now able to respond to society’s urgent needs,” said Marcelo Mori, a professor in IB-UNICAMP and principal investigator for a Thematic Project supported by FAPESP.

In addition to trying to understand why older people are more susceptible to COVID-19, Mori acts as liaison for UNICAMP’s hospital, Bioscience Institute and Presidency with the initiative’s funders, including its Fund to Support Education, Research and Outreach (FAEPEX), as well as companies and individuals who wish to make donations for the procurement of supplies and equipment.

Understanding the virus

Diagnostic testing is only one of the task force’s activities. Módena’s laboratory, the sole BSL-3 facility in the region (the highest level of biosafety is BSL-4), will characterize the virus found in patients who test positive for SARS-CoV-2 in Campinas.

“The aim is to understand how the virus is circulating here, how this differs from its circulation in São Paulo City, and how it may affect the patient’s clinical condition,” Módena said.

His laboratory is partnering for this purpose with the Brazil-UK Center for Arbovirus Discovery, Diagnosis, Genomics and Epidemiology (CADDE), which is supported by FAPESP and coordinated by Ester Sabino, a professor in the University of São Paulo’s Medical School (FM-USP) and head of the university’s Institute of Tropical Medicine (IMT-USP). 

Sabino led the team that sequenced the genome of SARS-CoV-2 sampled from the first patient diagnosed with COVID-19 in Brazil (read more at: agencia.fapesp.br/32656). 

William Marciel de Souza is also on the team that is characterizing the virus. Souza is a postdoctoral fellow at the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP) with a scholarship from FAPESP, linked to a Thematic Project for which the principal investigator is Luiz Tadeu Moraes Figueiredo, a professor in FMRP-USP.

Another important initiative, which will be supported by Módena’s laboratory, will be viral load monitoring of critical patients treated in UNICAMP’s hospital. This information is essential to knowing when to discharge patients and make beds available.

The samples obtained will also be analyzed in search of cytokines and other inflammatory mediators produced by the organism to combat COVID-19. “The aim is to understand how not just comorbidities but also other factors distinguish the response of a patient who progresses to a critical condition from another in the same age group who gets better, for example,” Módena said.

Medications

Módena also collaborates with groups that are screening medications already available on the market for potential use to treat COVID-19, such as a group at the National Energy and Materials Research Center (CNPEM) in Campinas that is currently testing the action of five drugs on one of the enzymes that play a key role in the virus’s life cycle (read more at: agencia.fapesp.br/32909). 

Another group is pursuing the same goal at the Center for Innovation in Biodiversity and Drug Discovery (CIBFar), one of the Research, Innovation and Dissemination Centers (RIDCs) funded by FAPESP. CIBFar’s principal investigator is Glaucius Oliva, a professor in the University of São Paulo’s São Carlos Physics Institute (IFSC-USP).

UNICAMP’s Center for Medicinal Chemistry (CQMED), also supported by FAPESP, will supply other molecules for testing by Módena’s team.

“We all want to find drugs that have proved safe for use in humans to treat other diseases and could be effective against COVID-19,” he said.

3D printing of PPE

The task force is also engaged in repairing mechanical ventilators and other hospital equipment, fabricating replacement parts, and producing PPE for health workers.

UNICAMP’s Center for Biomedical Engineering (CEB), led by Leonardo Abdala Elias, a professor in the School of Electrical and Computer Engineering (FEEC), is to provide support, maintenance and rehabilitation services for ventilators, multiparametric monitors, infusion pumps and defibrillators.

The university’s Biofabrication Laboratory (Biofabris), led by Rubens Maciel Filho, has received donations from MPT for the acquisition of polymers to produce face shields by 3D printing. Face shields are PPE items that protect the entire face, providing a second layer of protection, and can be disinfected and reused. The laboratory’s printer can also produce replacement parts for hospital equipment.

“Besides repairing broken-down equipment, this technology enables us to replace parts that are often imported, and hence costly, as well as taking too long to get here. We use 3D printing to make parts quickly and accurately, and we ourselves do the necessary fittings,” said Maciel, who is also principal investigator for the Center for Innovation in New Energies (CINE), one of the Engineering Research Centers (ERCs) set up by FAPESP with partners who include Shell.

Biofabris can also produce molds for surgical masks to be supplied by companies certified for this purpose by ANVISA, Brazil’s public health surveillance authority.