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COVID-19 Updates, News, Science & Research

Brown Research Seed Fund fuels ongoing research on COVID-19

University faculty lead projects to build blood biorepository, investigate viral genome, study human hormones

By
Science and Research Editor
Wednesday, June 10, 2020

The University distributed $350,000 in research funds through the COVID-19 Seed Awards this April to faculty carrying out experiments on the virus and its societal impact. The 15 diverse projects, selected from about 50 applicants, range from the sciences and medicine, to engineering, public health and data analysis, according to Vice President for Research and Professor of Mathematics Jill Pipher and the University website.

As faculty wished to pursue innovative projects to understand and combat COVID-19, the University used its operating budget to establish the fund and “make it possible to do this aspirational work at the most critical time,” Pipher wrote in an email to The Herald. The research chosen for the fund appeared to have a “potential significant, rapid impact on human health” or “would create products of immediate need for the health care system.” 

A cohort of studies are tackling the molecular aspects of the pandemic. These projects include the establishment of a blood sample biorepository, research of the virus through its genome and investigations on hormonal impacts on the virus.

Building a blood biorepository

Blood lies at the heart of numerous translational and biomedical research studies — those related to COVID-19 and not — but accessing clinically-relevant patient samples, especially during a pandemic, has proven challenging. 

A newly-built blood biorepository housed at the Lifespan Clinical Research Center is preserving human blood samples at freezing temperatures to help facilitate COVID-19 investigations, said the project’s principal investigator, Senior Associate Dean for the Program in Biology and Professor of Medical Science Edward Hawrot. He hopes the samples will be readily accessible — and thus, used quickly. 

“‘The goal of this biobank is to go bankrupt,’” Hawrot said, quoting co-principal investigator Bharat Ramratnam, associate professor of medicine, chief science officer of Lifespan, and medical director of the Lifespan Clinical Research Center.

The samples are drawn from patients visiting the Rhode Island and Miriam Hospitals’ emergency rooms. These patients have been informed about the risks and benefits that come with participating in this program and have consented to donate their blood to research studies. They typically do not know whether or not they have COVID-19 at the time the blood samples are obtained, but they will have exhibited symptoms, Hawrot said.

To date, at least 100 people have donated their blood to the biorepository, according to the Advance Clinical Translational Research website. The volume collected from each participant will be shared among many researchers in smaller quantities. 

Researchers interested in using these samples are able to apply through the Advance-CTR website, which opened May 29. They can also obtain pertinent demographic or medical data about the patients whose samples they receive if it is necessary for their research, but this process is “highly regulated” to protect any personal information, Hawrot said. Researchers’ detailed requests must go through an institutional review board.

Investigators from Rhode Island hospitals, Brown and the University of Rhode Island have expressed interest in using the samples, Hawrot added. 

Professor of Medical Science and of Pathology and Laboratory Medicine Wafik El-Deiry’s lab, which also received a COVID-19 Seed award, hopes to use these blood serum samples to compare spike and cytokine protein levels in healthy people, those with varying levels of COVID-19 severity and those with COVID-19 and cancer, El-Deiry said.

The biorepository team is also in discussions with the University of Nebraska Medical Center about making these blood samples available at the United States’s other clinical and translational research centers through a virtual COVID-19 biobank, Hawrot said. This way, researchers who may have a shortage of samples in their area could request more from other CTRs. 

The University team also includes co-PIs Professor of Emergency Medicine, Medicine and Engineering Gregory Jay and Associate Professor of Emergency Medicine Francesca Beaudoin.

Funding from the group’s COVID-19 Seed award is being allocated toward supplies and compensating additional personnel who have been collecting and processing the blood samples.

Gathering information from the genome

The virus responsible for COVID-19, SARS-CoV-2, uses RNA as its genetic material and passes these molecules from cell to cell upon infection. Another group of University researchers aims to use their expertise in infectious disease and engineering to assess the virus on a molecular level through its genome and ultimately help address the pandemic on personal and public health levels.

Identifying variations in the virus’s genome across locations and in people over time could illuminate more about the origins and development of the virus, which “could be relevant for the current wave of the pandemic or (a) future wave of the pandemic,” said Professor of Medicine Rami Kantor, a principal investigator of this COVID-19 Seed-funded project. 

Kantor’s lab has previously collaborated with the other principal investigator of the project: Anubhav Tripathi, professor of engineering and medical sciences (courtesy). Kantor and Tripathi have worked on similar studies considering the RNA genome of HIV in efforts to address the development of drug resistance to the virus. 

The project’s other researchers include Vlad Novitsky, MD, PhD; Akarsh Manne, MS and Mark Howison ‘06, MS from Kantor’s lab and Lindsay Schneider GS, Kiara Lee GS and Dulguunnaran Naranbat GS from Tripathi’s lab. 

But to carry out their new experiments, the researchers must first sequence the viral genome. 

This process often requires polymerase chain reaction, which replicates a small quantity of starting RNA — a technique which is costly and time-consuming.

To accommodate the high quantity of virus samples expected for this study, Tripathi and members of his lab are developing devices and technological methods that are “faster, cheaper, easier and (of) greater use,” he said.

Once the researchers sequence the RNA of viruses from infected patients in Rhode Island, they plan to examine these sequences in the context of other sequences from the region and around the world to learn how mutations in the genomes compare, Kantor said. 

They plan to compare viral genomes based on COVID-19 severity and other health conditions in the patients that the virus infected. The team could also investigate reinfection from the virus, Kantor said.

The experiments “could help us track the infection, track its origin, track different waves of it and hopefully help prevent people from getting infected currently or in the future,” he said.

Following a hunch about hormones

COVID-19 seems to affect male and female patients differently: Infected males on the whole tend to have more serious symptoms and outcomes than females, said Assistant Professor of Molecular Microbiology and Immunology Lalit Beura, the principal investigator leading a study in his lab on the possible link between hormone levels and COVID-19 pathogenesis, the progression of the disease.  

Before the pandemic, Beura’s lab was already studying how other diseases disproportionately affect men and women. They turned their attention to coronaviruses once the pandemic was underway. 

“Having this funding opportunity from Brown definitely opens up possibilities … to start a new area of research,” Beura said.

This discrepancy may be due to differences in hormone levels. While estrogen and progesterone hormones are more common in females, testosterone is generally abundant in males. The researchers are using mouse models and a coronavirus that infects mice — related to but different from the COVID-19 virus — to determine whether there is a relationship between hormone levels and illness severity, Beura said. By manipulating testosterone levels in mice, they can watch how COVID-19 manifests in response and how this change impacts immune cell activity, which spurs the disease when excessive. Another possibility is investigating the potentially protective attributes of estrogen, Beura added.

Once the researchers develop an evidence-based idea of the hormones’ either helpful or harmful influence on the disease, this knowledge will have “direct applicability to how we treat this disease (and) how we design our policies to avoid having such disparate outcomes,” Beura said. This research could then lead to clinical applications in the long run whereby drugs related to hormone molecules could help regulate COVID-19 in patients.

Sharing sentiments with the other researchers, Beura said the University funding helped make this unprecedented research possible.

Although the COVID-19 Seed fund has already been exhausted, Pipher wrote that the fund’s intention was to propel COVID-19 research efforts quickly in their early stages. 

For example, the award helped the blood biorepository get off the ground, Hawrot said. “That’s the advantage of these awards. …  You build trust and cooperative spirit.”

For researchers still seeking funding for COVID-19-related work, the University has sustained its commitment to connect faculty with funding from external organizations, Pipher wrote.

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