Summer 2020
Just as we were getting ready to wrap up our spring issue, the University of Pittsburgh, and much of the United States, began operating on modified status in response to the pandemic. We paused the magazine’s production to assess the new landscape. It quickly became apparent that Pitt people—healers, discoverers, inventors, activists—were not sitting still; they were not waiting for someone else to come along and find solutions to get us out of these difficult circumstances.
Every day, our magazine team learns of new ways that Pitt people are applying their talents and inspiration to take on COVID-19. We designed this special section to give you a glimpse of those stories. There will be more to share. —The Editors
Pilot Grants For COVID-19 Research
This spring, the University of Pittsburgh Clinical and Translational Science Institute (CTSI) launched the COVID-19 Pilot Grant Program. The grants to 17 projects, addressing different aspects of the pandemic, totaled $900,000.
Funding for the projects was provided by the CTSI, the Office of the Provost, the Office of the Senior Vice Chancellor for Research and the DSF Charitable Foundation, which contributed $350,000.
Steven Reis, director of the CTSI, associate vice chancellor for clinical research, health sciences, and Distinguished Service Professor of Medicine, says that the grant program was created with the intent to support research initiatives that will make immediate progress toward reducing the harm to individuals, groups and society from COVID-19.
“We need to look at all options to deal with the COVID-19 pandemic,” Reis says. The CTSI received applications for 157 projects, and 46 universities were represented on the project teams. Investigators from 14 Pitt schools appeared on the list of applicants.
Nick Beldecos, DSF Charitable Foundation executive director, says that he’s confident that the Pitt experts involved in the grant program will help “produce significant and timely advances” in the fight against COVID-19.
The proposals were put through an accelerated and extensive peer-review process.
A team led by W. Paul Duprex, the Jonas Salk Professor for Vaccine Research and director of the Center for Vaccine Research, received $100,000 for its study on the novel coronavirus SARS-CoV-2 and efforts to create and evaluate vaccines. Anita McElroy, assistant professor of pediatrics, and Alan Wells, professor of pathology and bioengineering, are coprimary investigators on the grant with Duprex.
“These grants represent the best of research—creative minds working in collaboration with partners to innovate for benefit to society,” said Rob Rutenbar, senior vice chancellor for research. “It’s an honor to help support such vital investigation.”
Recipients of $50,000 Awards (Programs and project leaders):
Biomarkers for Predicting Viral Pneumonia Severity
John Alcorn (Pitt Med)
Cellular Mechanisms of SARS-CoV-2 Infection
Sally Wenzel and Xiuxia Zhou (Pitt Public Health)
Coronavirus and Lung Microbiome Interactions
Georgios Kitsios (Pitt Med)
COVID-19 Neurologic Manifestations
Sherry Hsiang-Yi Chou (Pitt Med)
COVID-Insight Triage and Monitoring Tool
David Salcido (Pitt Med)
Determinants of COVID-19 Clinical Outcomes
Christian Fernandez, Ernesto Marques, Donald Burke and Philip Empey (Pitt Public Health and Pharmacy)
Generation of Transgenic hACE2 Knock-in Mice
Andrea Gambotto, Louis Falo, Mark Shlomchik and William Klimstra (Pitt Med)
Impact of Maternal COVID-19 Infection on Newborns
Anne-Marie Rick and Judith Martin (Pitt Med)
Lung-Targeting SARS-CoV-2 Therapeutic
Raymond Frizzell (Pitt Med)
Modeling Strategies for the COVID-19 Pandemic
Mark Roberts (Pitt Public Health)
Pediatric Epidemiology SARS-CoV-2 Antibody Response
Sarah Wheeler, Glenn Rapsinski and Megan Culler Freeman (Pitt Med)
SARS-CoV-2 Cellular Imaging System
Zandrea Ambrose (Pitt Med)
SARS-CoV-2 Immune Escape Variants in Treatment
Jana Jacobs (Pitt Med)
SARS-CoV-2 Prevention Spray
Lisa Rohan and Sravan Kumar Patel (Pitt Pharmacy)
Therapeutic Nanobodies for SARS-CoV-2
Yi Shi (Pitt Med)
Therapy for COVID-19 Induced Acute Respiratory Distress Syndrome
Pitt Moves Quickly,
Develops Two COVID-19 Vaccine Candidates
In February, Pitt joined the global effort to develop a vaccine for the novel coronavirus (SARS-CoV-2) when its Center for Vaccine Research received a sample of the virus from the U.S. Centers for Disease Control and Prevention.
The center’s Regional Biocontainment Laboratory is one of a few labs across the country equipped to handle highly pathogenic infectious agents like SARS-CoV-2 (for severe acute respiratory syndrome coronavirus).
W. Paul Duprex, director of the center who holds the Jonas Salk Chair for Vaccine Research, and his colleagues quickly started culturing the virus and producing stocks to be used to assess the efficacy of small molecule inhibitors, antibodies and vaccine candidates. They are developing a COVID-19 vaccine based on the measles vaccine, as well as animal models for testing.
A second Pitt team, led by Louis Falo and Andrea Gambotto, was the first to publish on another COVID-19 vaccine candidate. On April 2, almost 65 years to the day that Jonas Salk told the world that his group had successfully tested a polio vaccine, Falo and Gambotto announced that they had developed a potential vaccine against SARS-CoV-2. Their paper appeared in EBioMedicine (an open-access journal published by The Lancet). Falo is chair of dermatology, and Gambotto is associate professor of surgery.
Duprex spoke of Pitt’s expertise and obligation to help find an intervention at a recent University Senate Council meeting: “At Pitt, we have a long history of studying viral and bacterial diseases—and addressing emerging and reemerging infections. We no longer have to deal with the poliovirus because a vaccine was developed here.” Pitt’s COVID-19 vaccine candidates are two of at least 100 being tested worldwide.
Duprex answered questions about his group’s vaccine in a UPMC interview excerpted below.
Approach
Duprex: “We take portions from the SARS coronavirus—little pieces of genetic sequence that makes SARS coronavirus—and pop those into the measles vaccine. And whenever we inject that candidate vaccine into a person or an animal, as we do in trials, they should make antibodies against measles, because that’s what the measles vaccine does. But they should also make antibodies against SARS coronavirus. And that means that if that person, that vaccinee, met the virus in the real wide world, they would have the antibodies that remember what the SARS coronavirus looks like, and they would be ready and primed for action. That’s the basis of vaccination.”
Timeline
Duprex: “We are working to establish the animal model of disease and select the optimal vaccine candidate to take through the process. [Assuming that goes well,] manufacturing will be taking place in Europe, of that vaccine candidate, to make clinical material that will be produced and ready to be tested in a phase I trial in Europe, hopefully this summer.”
Falo (left) and Gambotto described their work at the virtual press conference (sitting 6 feet from each other, of course) in April.
Approach
Falo and Gambotto call their experimental vaccine PittCoVacc, short for Pittsburgh coronavirus vaccine. Their candidate follows an established approach to building vaccines—employing lab-made pieces of viral protein to build immunity. It’s the same way some flu shots work.
Gambotto had worked on earlier coronavirus outbreaks—SARS-CoV in 2003 and MERS-CoV (Middle East respiratory syndrome coronavirus) in 2014. They taught his team that a “spike” protein (or “S” protein) is important for inducing immunity against the virus.
“We knew exactly where to fight the new virus,” Gambotto said. “That’s why it’s important to fund vaccine research. You never know where the next pandemic will come from.”
Unusual Delivery
A fingertip-sized patch of 400 tiny needles, called a microneedle array, delivers that spike protein into the skin, where the immune reaction is often strongest. After the patch gets applied like a Band-Aid, the needles—which are made of sugar and the spike protein—simply dissolve into the skin.
“It feels like Velcro,” Falo said.
When tested in mice, PittCoVacc generated a surge of antibodies against SARS-CoV-2 within two weeks of a microneedle prick. Those animals haven’t been tracked for an extended period of time, but the researchers point out that the mice that got their experimental MERS-CoV vaccine produced a sufficient level of antibodies to neutralize the virus for at least a year, and so far the antibody levels of the SARS-CoV-2 vaccinated animals seem to be following the same trend.
Microneedles build on the original scratch method used to deliver the smallpox vaccine to the skin, says Falo. For years, his lab has been focusing on using the tiny patches for inducing an immunological response to combat skin cancer.
Falo called the scratch method efficient, reproducible and painless. It also is highly scalable. Once manufactured, the vaccine can sit at room temperature until it’s needed, eliminating the need for refrigeration during transport or storage.
“For most vaccines, you don’t need to address scalability to begin with,” Gambotto said. “But when you try to develop a vaccine quickly against a pandemic, that’s the first requirement.”
Timeline
Falo and Gambotto plan to apply for an investigational new drug approval from the Food and Drug Administration in the next couple of months. The process to begin testing patients takes at least a year, usually longer, according to Falo.
“This particular situation is different from anything we’ve ever seen,” Falo said. “So, we don’t know how long the clinical development process will take. Recently announced revisions to the normal processes suggest we may be able to advance this faster.” —Gavin Jenkins
Dream Teams
Hundreds of Pitt experts in medicine, critical care, immunology, virology, infectious disease, neuroscience, public health and other fields are collaborating to unlock the new coronavirus. Here are a few of the puzzles those dream teams intend to solve:
Drug Screening
Toren Finkel is known for advancing science’s understanding about how aging affects disease. He directs the Aging Institute of UPMC Senior Services and the University of Pittsburgh. Finkel is working with a team that includes the institute’s Bill Chen and Yuan Liu, as well as investigators in Shanghai. They have extensive experience screening drugs and are now evaluating FDA-approved drugs that may limit SARS-CoV-2 entry into cells.
Finkel is a professor of medicine and the G. Nicholas Beckwith III and Dorothy B. Beckwith Professor in Translational Medicine. Liu is an assistant professor of medicine and expert in lung injury who holds several patents. Chen is an associate professor of medicine, director of the Small Molecule Therapeutic Center and codirector of the Acute Lung Injury Center of Excellence.
Tracking the Evolution of the Virus
Vaughn Cooper is an evolutionary biologist tracking how SARS-CoV-2 moves through populations. That work could reveal where a virus from a given individual likely came from for public health or scientific purposes. He’s been studying the evolutionary dynamics of the virus using publicly released genomes, which identify mutations and constraints in the virus that could affect treatment. Cooper is a professor of microbiology and molecular genetics and director of the Center for Evolutionary Biology and Medicine.
Neurocritical
COVID-19 mostly affects the respiratory system, yet some patients seem to have nervous system impairments such as seizures, strokes and encephalopathy. Sherry Hsiang-Yi Chou, associate professor of critical care medicine, neurology and neurosurgery, is leading a multicenter research consortium, endorsed by the Neurocritical Care Society, to study this set of conditions. “There’s no ventilator for the brain,” as Chou pointed out to The New York Times recently.
A Mysterious Blood Disorder
COVID-19 is characterized by a unique disorder, where blood clotting does not happen correctly; this can create severe complications. The mechanisms of the disorder remain unknown. Jansen Seheult and Matthew Neal have established a series of conventional and also novel tests and measurements to understand how the condition unfolds in COVID-19. The team measures samples in conjunction with genomic profiling studies performed by the Immune Transplant and Therapy Center, a partnership between Pitt and UPMC. Seheult is a clinical assistant professor of pathology. Neal (MD ’06, Res ’14, Fel ’15) is also running the anticoagulation domain of the adaptive COVID-19 clinical trial platform directed by Derek Angus. He is an attending trauma and critical care surgeon and the Roberta G. Simmons Assistant Professor of Surgery.
Answers Needed Now
A novel clinical trial platform developed by researchers at Pitt Med and launched at UPMC will address one of the most important questions raised during the COVID-19 pandemic: How should doctors decide which treatments are best for patients when these treatments have not been vetted in long, rigorous clinical trials?
“The solution is to find an optimal tradeoff between doing something now, such as prescribing a drug off-label, or waiting until traditional clinical trials are complete,” says Derek Angus, professor and chair of critical care medicine. Their solution, he says, is a clinical trial model that adapts and learns as it goes. It’s looped into UPMC’s electronic health records and pulls in data from medical centers throughout the world. COVID-19 patients who opt in get the standard of care, as well as two or three experimental therapies.
More COVID-19 Coverage:
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Coping Strategies for Older Adults
In light of the challenges related to the pandemic, geriatric psychiatrist Charles (Chip) Reynolds III suggests a few practical coping strategies to stave off depression. READ MORE >
Married to Uncertainty
Rachel Mennies, spouse of critical care doctor and Pitt alumnus Nicholas Goodmanson (MED ’13, ’16, ’18), writes about the worries and moments of connection she and other partners of physicians are experiencing during the pandemic. READ MORE >