NEXT | Winter 2020

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The Future of Discovery at VCU Health

Winter 2020

Welcome to NEXT Dear Friends, This issue is focused exclusively on COVID-19 research so that we can share with you the latest work being accomplished by the amazing clinicians and researchers on the MCV Campus at VCU Health to stem this pandemic.

From antiviral drugs such as remdesivir, to nanovaccines as a delivery system for the future, to the application of prior research and medicines to reduce excessive inflammation, to developing inhouse testing and mask decontamination, to reimagining care for those experiencing isolation, to combating health disparities highlighted by this crisis, VCU Health investigators are working around the clock to find solutions and save lives.

It is through the generosity of donors like Lorna M. Breen, M.D., was a VCU School you that VCU Health researchers are able of Medicine alumna and emergency to continue their important work, especially department medical director who bravely in the early stages of groundbreaking treated those with COVID-19 in New York City. After contracting the virus and research, before public funding is available. recovering, she died on April 26, 2020.

In FY20, the MCV Campus health science For more information about her legacy, visit www.drlornabreen.org. schools and college received $192.3 million Photo: Chris Leary in new research and sponsored awards, raising the total MCV Campus sponsored research and award amount to $688.5 million.

We dedicate this issue to Lorna M. Breen, M.D., and to all of you who work so tirelessly in the fight against COVID-19. We have gained so much in your heroic effort, dedication and sacrifice. And for those of you who have lost loved ones, we stand with you and honor their memory.

We hope this issue brings you a level of comfort, knowing that the people of VCU Health bravely continue to provide leading-edge care and search for innovative solutions every day. And if you feel so inspired, please join our community and become a part of the next great discovery.

Margaret Ann Bollmeier

Wyatt S. Beazley IV

PRESIDENT, MCV FOUNDATION

BOARD CHAIR, MCV FOUNDATION

WINTER 2020

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The Great Shake Up Clinicians pivot to respond to the crisis and accelerate the pace of diagnosis and treatment.

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Patient Profile: Carter Fox VCU Health’s first COVID-19 patient.

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Remdesivir: Establishing a Standard of Care for COVID-19 Clinical trials give patients early access to a drug that has become a standard treatment.

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Big Things in Small Packages Nanovaccines may be the future of vaccinations, using microneedles that can be applied at home.

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Amid Crisis, Inventing Solutions

Clinicians study inflammation as a common

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Team members show resourcefulness as shortages

denominator in the most serious COVID-19 cases.

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threaten patients and care providers.

About the Cover

health disparities highlighted by COVID-19.

microscope image shows

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causes COVID-19 — emerging

care for those experiencing social isolation.

in the lab. Image captured and colorized at NIAID’s

Healthier Together One community-driven partnership is reimagining

from the surface of cells cultured

Montana. The number “19” was added by NEXT.

Access & Equity Dr. Winn leads Massey and the effort to combat

This transmission electron

Rocky Mountain Laboratories (RML) in Hamilton,

Patient Profile: Kathy White COVID-19 patient and clinical trial participant.

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SARS-CoV-2 — the virus that

Calming the Cytokine Storm of COVID-19

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Follow-Up

Credit: NIAID. License: creativecommons.org/

Stories previously covered in NEXT gain new

licenses/by/2.0/

relevance in their application to COVID-19.

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THE GREAT

CAR T-CELL THERAPY OFFERS HOPE to Cancer Patients When Other Treatments Fail

How COVID-19 upended and refocused research at VCU Health

By Jackie Kruszewski VCU C. Kenneth and Dianne Wright Center for Clinical and Translational Research

It isn’t how anyone expected to spend their spring. But for the hundreds of human health researchers at Virginia Commonwealth University, many of them also practicing doctors, COVID-19 required a drastic reorganization of priorities, processes and protocols.

Petri dishes and slides were frozen. Study plans F. Gerard Moeller, M.D., were amended. Some director of the C. Kenneth research pivoted. And more and Dianne Wright Center for Clinical and Translational than 50 new projects at Research, oversaw a VCU emerged to combat the committee that prioritized new virus on multiple fronts. and facilitated different COVID-19 related projects Research projects that once through review processes. took months to get off the Photo: Allen Jones, VCU University Marketing ground took days, under five for many of them.

“Our researchers and administrators really stepped up to the plate in every way,” said F. Gerard Moeller, M.D., director of the C. Kenneth and Dianne Wright Center for Clinical and Translational Research. “It’s not a scenario that individual researchers can really plan for, but they have really managed it well.”

The pandemic facilitated a nimble, collaborative response to the unprecedented challenges. Going forward, researchers look to build on the unexpected momentum that the virus brought to health and science research.

UNITING AGAINST AN UNKNOWN ENEMY As VCU Health prepared for a potential surge of patients, clinical research teams looked to fill gaps in knowledge about this new virus.

“There weren’t approved treatments when this began in March,” said Dr. Moeller. “But we saw immediate mobilization from our researchers to understand its effects on patients, consider available drugs and contribute to the global search for effective treatments.”

“We wanted to prioritize the studies that were likely to have a large impact,” said Antonio Abbate, M.D., Ph.D., a cardiologist and the lead for the canakinumab trial.

“Not only an impact for our patients, but also an impact for having immediate or early readout that could get a Food and Drug Administration approval and then can help everybody else in the U.S. and possibly worldwide.”

With decades of clinical research experience under their belts, doctors like Arun Sanyal, M.D., a liver specialist, had access to the contacts and infrastructure he needed

to bring the most promising COVID-19 treatments to VCU Health patients.

A day after Virginia Governor Ralph Northam’s March 23 announcement, ordering nonessential workers home, VCU reported that it had partnered with other universities and a pharmaceutical company to test an experimental antiviral drug on volunteer patients with moderate and severe symptoms of COVID-19. Dr. Sanyal had brought clinical trials for remdesivir to VCU. As you’ll read on page 8, the remdesivir trials yielded great promise. Armed with data that VCU helped provide, the FDA issued emergency use authorization in May for remdesivir as a treatment for COVID-19, and the drug is now distributed to hospitals across the U.S. Two more trials, both testing drugs developed for arthritis, soon joined remdesivir as options for COVID-19 patients. (See “Calming the Cytokine Storm of COVID-19” on page 16, regarding the arthritis drug canakinumab.)

By June, there were three more drug treatment trials up and running, giving eligible patients a number of options.

Initiated by researchers from cardiology, liver specialties, pulmonology, surgery and pharmacy, the trials spoke to the breadth and depth of VCU’s research capacity.

“One of the reasons I’m so proud to be at VCU is that we’re at the ready to do all these studies,” says Paula Ferrada, M.D., a trauma surgeon and the principal investigator for one of the studies. “It’s not going to be one thing, one drug or convalescent plasma, or a vaccine that solves this.

It’s myriad of different treatments at different stages of the disease that are going to help, and VCU has been able to bring many of the treatments here.”

Other clinical projects from VCU researchers addressed symptoms and recovery, or tackled prevention and future study of the virus. Michael Donnenberg, M.D., senior associate dean for research and research training at VCU School of Medicine, initiated a trial aimed at preventing the transmission of COVID-19 between household members via a treatment of antibodies.

Somaya Albhaisi, M.D., an assistant professor at the VCU School of Medicine, quickly assembled a biobank of samples from volunteer COVID-19 patients, Somaya Albhaisi, M.D., linked to data about those patients an assistant professor with everything from preexisting at the VCU School of Medicine, assembled conditions to socioeconomic a biobank registry that circumstances. “The registry not will help researchers study COVID-19 for only provides blood samples, but years to come. Photo: also the stories of who they belong Thomas Kojcsich, VCU to,” Dr. Albhaisi said. “It’s an University Marketing

Photo: Allen Jones, University Relations

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institutional resource to allow translational scientists to engage in research studies around COVID-19 in order to answer important questions — now and in the future.”

A collaborative spirit marked all the projects, as researchers and clinicians reached across disciplines to fill new, critical needs. “The virus didn’t have a department,” said Dr. Moeller. “Cross-discipline research collaboration was a necessity, and we’re lucky that we have that infrastructure in place here at VCU.” PRE-COVID STUDIES INNOVATE AND ADAPT In mid-March, when news hit of mandated telework beginning in five days, Caitlin Martin, M.D., MPH, had multiple active projects underway. Dr. Martin works with pregnant women and new mothers who struggle with opioid and alcohol use disorders at the Institute for Drug and Alcohol Studies. “I had just hired our new research assistant,” she said. “We had all our staff and then, boom, the virus hit. There were study participants who were just about to give birth.”

VCU released continuity guidance for the nearly 750 active projects at the time, and researchers evaluated their projects based on the health benefit to the patient. Just as doctors turned to telehealth for primary care and follow-up visits, clinical researchers could amend their protocols to include virtual strategies.

Dr. Martin amended one study that could be done remotely. Some studies, she said, would just make Caitlin Martin, M.D., do with a smaller sample size of MPH, had multiple patient participants. “Overall, the ongoing research projects when effects were pretty blunt in that COVID-19 hit. Photo: everyone came to a screeching halt Thomas Kojcsich, VCU University Marketing on their research,” said John Ryan,

Ph.D., a professor in the Department of Biology in the VCU College of Humanities and Sciences and VCU’s associate vice president for research development.

Over in VCU laboratories, “lab hibernation” meant that some projects were simply on pause. Some health research is easy to put on ice for a while — literally. “If you’re working with DNA or RNA in particular, or a lot of biochemical materials, that kind of work is very amenable to placing in the freezer, then coming back to start again later,” said Dr. Ryan.

By June, plans were in place to safely bring health researchers back into their labs and clinics so that studies on other diseases, none of which took a break during COVID-19, could continue. Many researchers pivoted their research to incorporate the effects of COVID-19 on their patients or grapple with the secondary health impacts of the pandemic.

The mandated remote work environment offered new opportunities for VCU researchers who study access to healthcare. They are learning about the benefits of and challenges to telehealth, which could revolutionize how medicine is practiced. Others are studying the impacts of stress and economic upheaval on substance use disorders and intimate partner violence in a way that could have far-reaching effects on individualized care. Some are analyzing the effect of delayed medical care and rethinking what primary care means.

“This is a bizarre, probably once-in-a-generation experience with many people sheltering in place, delaying medical care, contending with a uniquely stressful situation,” said Dr. Ryan. “And there’s a lot of important health research coming out of that already.”

VCU AND ITS DONORS LAY GROUNDWORK FOR EXPANDED RESEARCH An influx of funds has been essential to VCU researchers’ efforts. The Office of the Vice President for Research and Innovation, with the help of the Wright Center, created a fund for researchers who want to conduct COVID-related

TIMELINE OF COVID-19 AND CLINICAL RESEARCH March 16

March 23

May 1

VCU Medical Center announces first confirmed COVID-19 patient.

Governor Ralph Northam orders nonessential workers home.

The FDA issues emergency use authorization for remdesivir.

March 24 Dr. Arun Sanyal announces two open clinical trials for remdesivir.

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April

May

The COVID-19 Clinical Trials Oversight Committee, chaired by Dr. F. Gerard Moeller, is established to prioritize and facilitate virus trials.

Some trials expand to enroll at VCU Health Community Memorial Hospital in South Hill, Virginia.

research. It awarded nearly $350,000 to 31 timely research projects through the fund.

VCU reported an increase in grant submissions from this time last year, fueled by new money for COVID-19 projects, but also by some researchers finding the time to submit for grants while they were briefly kept from their labs and clinics.

John Ryan, Ph.D., “I think we’ll see an increase a professor in the Department of in federal and other funding, Biology in the VCU particularly related to infectious College of Humanities disease,” said Dr. Ryan. “So and Sciences and VCU’s associate vice that means that going forward, president for research we should see VCU’s research development, managed a fund of enterprise growing.” Nationally, $350,000 that went he added, the public health crisis to 31 VCU researchers is likely to lead to more time doing pilot work on COVID-19. Photo: and funding for clinical and Kevin Morley, VCU translational research.

University Marketing Donors contributed to COVID-19 research as well, providing needed funding including $200,000 raised specifically to support Dr. Berry Fowler’s research on Vitamin C treatment for COVID-19 patients.

“I’m optimistic about the future of this, because when you have this kind of crisis, it really makes you reassess what’s important — what do we value, what do we need,” said Dr. Ryan. “I think we’re going to see that the general public is behind promoting health research.”

EXPANDED ACCESS, STREAMLINED PROCESSES WILL OUTLAST THE VIRUS Internally, the pandemic has also jumpstarted a reassessment of priorities and goals. To coordinate multidisciplinary efforts, VCU established a COVID-19 Clinical Trials Oversight Committee, chaired by Dr. Moeller,

in April. The committee helped prioritize and facilitate the different COVID-19 related projects through review processes that sometimes take months. Dr. Sanyal’s remdesivir trial, for example, was approved in a matter of days.

In June, a former VCU Health patient who survived COVID-19 and partook in a clinical trial joined the committee as a community representative — one of many efforts toward better community engagement that the pandemic has brought.

“Researchers often struggle with study enrollment, as patients harbor understandable fears about experimental procedures,” said Dr. Moeller. “There’s hope that the pandemic may pave the way for new models of engagement and recruitment, as well as awareness from the public about the value of participation.”

In May, clinical trials for some of the experimental treatment drugs expanded to VCU Health Community Memorial Hospital in South Hill, Virginia, giving access to those drugs to rural communities. And VCU Health’s medical language services program expanded this summer to accommodate the need for more interpreters and translators, so that Spanish speakers and others could participate in trials.

By mid-summer over 130 patients were enrolled in COVID-19 clinical trials. In August, of the COVID-19-positive patients hospitalized at VCU Health, 25% were eligible for and voluntarily enrolled in clinical trials for potential treatment drugs. And even more have volunteered their samples and data for lab studies and biobank registries that will help researchers study the novel coronavirus for years to come.

“In many ways, this unprecedented event is going to make research better at VCU,” said Dr. Moeller. “We haven’t just contributed to the body of knowledge about COVID-19, but we’ve learned more about how to make clinical and health-related research work for patients, for researchers and for the institution itself.”

May

June

Two more trials begin with drugs developed for arthritis that target the hyper-inflammation caused by the virus.

Three more treatment trials get up and running at VCU Health.

August 20 Dr. Michael Donnenberg announces antibody prevention trial.

May 18

July

The Office of the Vice President for Research and Innovation announces the final recipients of the COVID-19 Rapid Research Funding Opportunity, bringing the total number of projects to 31.

Dr. Somaya Albhaisi launches VCU Registry of SARS-CoV-2, a biobank of samples and data for future research into COVID-19.

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THE PERSONAL TOUCH

CARTER FOX: VCU Health’s First COVID-19 Patient Recovers

By Alex Henley MCV Foundation

Carol and Carter Fox (left, with their dog Joe), are pictured with Tessa Shuck, physical therapist, and Katie McGinn, speech therapist, who are assisting Carter with his ongoing recovery from COVID-19 at Westminster Canterbury Richmond. Photo: Bob Coles

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“We came home from vacation on a Saturday, and a week later he was on a ventilator,” Carol Fox said.

On March 8, Carol and Carter Fox returned to their home at Westminster Canterbury Richmond, a retirement center, from a trip to Florida. Carter has Parkinson’s disease, so no one initially associated his weakness with COVID-19.

His doctor in Florida sent the couple back to Richmond suggesting they would be safer. This was before recommendations on social distancing and travel restrictions were in place.

“Carter didn’t have any typical symptoms,” Carol said.

“With his Parkinson’s, he had never had a fall. After we got back, he fell on Thursday and he fell again on Saturday.

By Sunday he was so weak I said, ‘We’re going to the hospital.’ We knew for a fact that we were going to MCV. We had to pay for the ambulance but there was no doubt about it — we were going to MCV.” Carter and Carol went to the emergency department at VCU Medical Center on the MCV Campus on Sunday, March 15. Carter was examined to check for injuries from his falls, but his condition deteriorated quickly and his oxygen levels began to drop. An X-ray revealed he had pneumonia. “Within two hours everyone was putting on additional PPE (personal protective equipment). Carter went into the ICU at 9 p.m. that night, and by 4 a.m. Monday morning he was on a ventilator. They told us I had to leave and we had to quarantine,” Carol said.

Carter Fox was the first patient at VCU Medical Center to test positive for COVID-19.

“We just knew everything was being done to take care of him. Carter only had a 10% chance of recovery ...

I was never under any assumption other than he was going to get well.”

Carol and Carter Fox are pictured before the pandemic. Photo courtesy of Fox family

Carol Fox

Carol went into quarantine at Westminster Canterbury, which was already on lockdown, and contacted their three children Faulkner, Baylor and Lucy. Baylor came into town to take care of their dog Joe, but the worst part of it all was the waiting.

“We weren’t able to talk to Carter at all at first,” Carol said. “MCV was trying to figure out how to communicate with families. By the next weekend I had gotten him his cell phone so we could FaceTime with him. His nurses were incredible in making that happen. The nurses also read notes that we faxed over. Carter was sedated and on a ventilator for eight days. We have two grandsons who are jazz musicians, and they sent songs for him to listen to.”

After 11 days at VCU Medical Center and two negative COVID-19 test results, Carter was transported to Westminster Canterbury’s healthcare center to finish his recovery. Though now retired, he showed he still had a lot of grit and fight left in him from his days working his way up to CEO of Chesapeake Corp.

Carol has recounted most of his story as Carter’s memories of his time at the hospital are hazy. “I know that there was never any time when I was wanting or needing something that wasn’t there,” Carter said.

“The doctors and nurses at MCV are very nice people, and you could tell that they were working very hard.

They’re doing 12-hour shifts and are constantly under exposure to this disease. Fortunately, they have the right equipment and resources to figure this out.”

The Foxes were told the full recovery time for Carter could be six months and might be complicated by his Parkinson’s disease. While he’s initially recovered from not eating for two weeks, “He’s always been a good eater,” Carol quipped, other parts of his recovery continue.

“There are a lot of symptoms along with the Parkinson’s that he has to overcome. He’s still dealing with some weakness, and many nights he wakes up confused about where he is, but we take it all in stride and handle it with humor,” Carol said.

Carter and Carol were so grateful for the excellent care he received at VCU Health that they reached out to Peter Buckley, M.D., dean of the VCU School of Medicine and VCU Health System executive vice president for medical affairs, to see what they could do to support the healthcare team in their fight against COVID-19. They made a gift to the VCU Health COVID-19 Nursing Research Support Fund, which will support four nurse-led clinical research studies to determine best practices in the treatment of COVID-19 patients.

Carter and Carol’s daughter Lucy is a social worker and made her parents aware of the extra effort she observed to do everything possible to make Carter comfortable.

“We just knew everything was being done to take care of him,” Carol said. “Carter only had a 10% chance of recovery in every book, but I never knew that. I was never under any assumption other than he was going to get well.”

If you would like to support the VCU Health COVID-19 Response Fund, visit www.support.vcu.edu/covidresponse or contact Carrie Bickford at 804-297-6708 or carrie.bickford@vcuhealth.org to learn more.

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Remdesivir

Establishing a Standard of Care for COVID-19

By Eric Peters MCV Foundation

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Arun Sanyal, M.D., describes the early part of 2020 like seeing, without any defenses in place, an army advance around the globe toward Richmond.

“As we were watching COVID-19 march through China, through Singapore, and then through Europe, we knew it was only a matter of time before it landed on our doorstep,” he said.

“Then the first cases started occurring in the U.S., and I was concerned that we would have a large number of cases without any real evidence-based medicine to tackle the problem.”

Dr. Sanyal, a liver specialist and gastroenterologist at VCU Health, started exploring opportunities to bring possible treatments to VCU Health, and he found that an antiviral drug called remdesivir seemed promising.

It had been used in previous SARS (severe acute respiratory syndrome) outbreaks and to fight Ebola. The research and data was limited because of the relative speed at which Ebola was contained, but there was enough preliminary data to make a clear-cut rationale for remdesivir’s use, to see some signs it might be effective, and to know that it was safe.

A company called Gilead Sciences manufactures remdesivir, and in early spring it was selecting sites for the global trial testing the drug’s efficacy against COVID-19.

Dr. Sanyal had previously conducted many trials related to liver disease for the company, so he gave them a call.

“I told them that, as a major academic health center in Central Virginia, we are care providers to many people,” he said. “While the rest of the country was just throwing whatever came to mind at the patient, hoping something would work — which is sort of like throwing a stone in the dark and hoping you’ll hit something or someone — we needed a more targeted approach. Gilead ended up taking us on as a site.”

CLINICAL TRIALS: A TARGETED APPROACH TO TREATMENT Dr. Sanyal said what he has learned about COVID-19 over these past months is that the disease moves through several phases. In the early stage, the virus grabs the lining of the respiratory passages, holds on there, and then penetrates the respiratory passages, causing a sore throat and a mild respiratory illness. Often, just when the patient appears to be getting better, fever sets in with pneumonia. This is a result of the virus traveling to the lungs from the throat and the body’s immune system reacting to the virus.

Photo: Kaesler Media - stock.adobe.com

“That’s when patients get into real trouble,” Dr. Sanyal said. “If you get a really bad pneumonia and you cannot get oxygen into your system — no oxygen, no life. That’s pretty straightforward. And often we learn that people during this process develop blood clots. Many patients die not because of the pneumonia per se, but because they develop a clotting disorder.”

SARS-CoV-2, the virus that causes COVID-19, plays a major role in the first half of the disease. The body’s response plays a major role in the second half of the disease, although the virus is still there. Remdesivir is supposed to work by blocking the enzyme that is involved in virus multiplication, and this trial examined whether it accomplishes that goal, thus reducing the viral load and eventually causing the virus to disappear. Once the disease-inducing agent is gone, the body’s immunological response should also begin to slow.

Dr. Sanyal and his team participated in two trials that enrolled participants with documented COVID-19 infection who had fever and symptoms warranting hospitalization. Doctors at VCU Health administered remdesivir intravenously in five- or 10-day regimens and followed up 28 days later.

One of the trials was for patients who were in the hospital and could maintain their oxygen levels without supplemental oxygen. The second trial was for people who already were sick enough to require supplemental oxygen.

The trial for the more severe group was open-label, meaning both the researchers and the patients were aware of the treatment being given. While a trial conducted at NIH used a placebo, researchers at VCU Health did not use a placebo.

“Given how sick the people were and the anxiety around this disease — rightfully so — it was considered unethical to do a placebo study at that point in time,” Dr. Sanyal said.

In the trial for the moderate group, two-thirds of participants received the drug therapy for different durations of time while the control group received standard-of-care treatment.

The data gathered at VCU Health was compiled with data from more than 100 sites globally. In all the groups, there was improvement in shortening of the time to recover,

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Viral proteins exit and infect more cells.

SARS-CoV-2 Replication

Viral RNA come together to make more viral proteins.

Host cell takes in SARS-CoV-2 protein via endocytosis.

SARS-CoV-2 uses spike proteins to connect to cell at ACE-2 receptor.

RNA polymerase reads viral RNA and makes more.

SARS-CoV-2 unravels viral RNA inside cell.

HUMAN CELL Remdesivir given through IV enters the cell.

Remdesivir mimics part of RNA, tricking the RNA polymerase into incorporating it into new RNA.

New RNA is defective.

Illustration: Tom Edwards

reducing oxygen requirement and getting out of the hospital. Somewhere between 55% and 65% of people fully recovered within the study’s 28-day timeframe, and between 55% and 60% of the patients were discharged from the hospital during that time.

There was low mortality in all arms of the moderate disease trial. There was a small reduction in mortality among the severe group, but the number of patients was not sufficient to achieve statistical significance. Dr. Sanyal says while not statistically significant, the overall results were still clinically significant. “The mortality rate fell from 11% to 8%,” he said. “If you ask the patient, or if you ask yourself, ‘If you had 100 family members and 11 of them died, and you could reduce that number to seven, would you take it?’ I suspect your answer would be that you’ll take it. The lack of statistical significance indicates that the size of the trial was not large enough to identify this difference in outcomes robustly.”

To make remdesivir available to patients in Central Virginia through this trial, the team at VCU Health worked exceptionally fast. “From the first phone call to actually enrolling our first patient was five days,” Dr. Sanyal said.

“That process would normally take three to six months.

It goes to show how when everybody is aligned with a mission just how fast things can move.”

Those who came together around that mission were from hepatology, infectious disease, critical care-pulmonology and cardiology departments at VCU Health. Dr. Sanyal led the trials with a team of infectious disease doctors

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(Gonzalo M. Bearman, M.D., Michael P. Stevens, M.D., and Michelle E. Doll, M.D.), pulmonary critical care doctors (Marjolein de Wit, M.D., Lisa Brath, M.D., and Curtis N. Sessler, M.D.), researchers in inflammation (Antonio Abbate, M.D., Ph.D., and Benjamin Van Tassell, Pharm.D.) and VCU research and ethics staff.

The team also included pharmacists, nursing specialists and support staff, and there were daily calls in the mornings and in the afternoons to review every case that came in and make sure all patients who might benefit were included. “This all happened at the early stage of COVID where we were still learning how to keep ourselves safe while taking care of patients,” Dr. Sanyal said. “We also were training the nursing staff on the floors how to administer study drugs, do it correctly and safely, and complete all the documentation needed to make sure we were compliant with federal regulations while treating a very sick population.”

This seamlessly integrated approach is something that Dr. Sanyal said makes VCU Health a special place.

“There is an established infrastructure here for doing patient-oriented research,” he said. “We have, through the Wright Center for Clinical and Translational Research, a very well established mechanism to evaluate all of the different research ideas that come through and to be able to evaluate them to see which have the greatest scientific and clinical merit, evaluate their feasibility and safety, and then create prioritization schemes to decide what treatments we want to take on. We have a lot of experience

“From the first phone call to actually enrolling our first patient was five days. That process would normally take three to six months.” and expertise in taking on diseases for which no one has answers, finding the answers, then bringing them back so the rest of the world can use them.”

A FAST-TRACKED TREATMENT The remdesivir studies at VCU Health concluded in May, and the early nationally aggregated results showed enough promise to make it one of the first treatments for COVID-19 to receive an emergency use authorization from the U.S. Food and Drug Administration. This made the drug available to patients across the country, and it became part of the standard of care.

“Here at VCU, what we did was help translate research into an evidence-based drug that is available not just in the U.S., but around the world for patients with COVID,” Dr. Sanyal said. “The ideal approach in fighting COVID is to take a drug like remdesivir that attacks the virus, and to use another drug that helps reduce the immune reaction to the virus. Together, you can get both ends of the disease process.”

Dr. Sanyal also reminds those he speaks with that there is always news coming out about COVID-19. It is such an important health issue at the moment that enormous amounts of research are being conducted. Since the remdesivir study, for example, there has been work on dexamethasone, which is a steroid. Other studies have been completed or are underway involving plasma exchange and compounds to control the immune system.

As all of the additional research is completed and released, remdesivir may not continue to be the standard of care, but Dr. Sanyal highlighted the benefit VCU Health created for its patients and many others by being part of early clinical trials during a pandemic.

“First of all, remdesivir helped our patients clinically,” he said. “And now we have the data to say it helped them get out of the hospital faster. For the rest of the world, this provided the evidence that led to approval of remdesivir.

And now it is part of standard of care throughout the world.

Arun Sanyal, M.D. We actually changed how medicine is practiced around the world by participating in this trial. It was a global trial, it was not just us, be we were part of that global effort to establish a scientifically sound basis for treating COVID.” WHAT’S NEXT? Dr. Sanyal hopes to be involved with upcoming trials that will make remdesivir available to outpatients with COVID-19.

“We are excited by this because what we find in people who have a mild form of the disease is if they get two or three doses of remdesivir, they have no mortality,” he said.

“So if we can replicate that and then catch people early and get remdesivir on board, then we might bring mortality down to something like 0.5%, and that would be awesome.

Then you would be talking about an overall mortality closer to influenza.”

Arun Sanyal, M.D., a liver specialist and gastroenterologist at VCU Health, played an instrumental role in bringing clinical trials for the antiviral drug remdesivir to VCU Health. Since then, the drug has become a standard of care for COVID-19 patients.

Photo: Allen Jones, VCU University Marketing

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BIG THINGS in small packages

By Paul Brockwell Jr. MCV Foundation

Future vaccine delivery could involve small patches of microneedles easily mailed and applied at home. That’s the goal of one VCU School of Pharmacy researcher who is exploring how nanovaccines might be used to deliver a vaccine for the novel coronavirus once one is proven safe and effective.

The global race to develop an effective, safe vaccine for the novel coronavirus shifted much of the focus away from how a vaccine might be delivered once developed. Luckily, one School of Pharmacy researcher has been very interested in how to design a mechanism that is both efficient and effective at a mass scale. His vision? A patch, slightly bigger than a postage stamp, that contains microneedles which would dose vaccine into the lymphoid tissue just below the skin. People could one day receive a patch in the mail, apply it and begin developing functional protection from infection.

The needles would be so tiny that patients would not need to wince or feel the normal pinch of pain associated with a vaccine injection in more traditional delivery.

Guizhi “Julian” Zhu, Ph.D., is an assistant professor in the Department of Pharmaceutics and the Center for Pharmaceutical Engineering and Sciences at the VCU School of Pharmacy. Dr. Zhu also joined VCU Massey Cancer Center as an associate member of the Developmental Therapeutics research program in 2018.

His extensive background in engineering, chemistry and pharmacology led him to focus his research on developing targeted drug delivery systems and nanomedicines for the treatment of various diseases, including multiple types of cancer. But, Dr. Zhu said, those principles and concepts can readily be repackaged to develop technologies for delivering a vaccine for the novel coronavirus.

Dr. Zhu’s research attracted early support from the VCU Health COVID-19 Rapid Research Fund and is supported by his department and the VCU Center for Pharmaceutical Engineering and Sciences. The potential for a new type of delivery model is exciting, given the hundreds of millions of vaccines needed in the U.S. and around the world. And the ability to potentially send a patch to patients at home offers an ideal alternative to large groups of still-vulnerable people waiting in lines or crowds to receive a protective dose against COVID-19.

“This is the kind of impactful research the Rapid Research Fund was designed to support and the kind of inventive thinking that will help us successfully fight the novel coronavirus,” said P. Srirama Rao, Ph.D., VCU’s vice president for research and innovation. “The microneedle patch could potentially change the delivery of other vaccines now typically administered in a medical setting.”

Nanovaccines are a new generation of vaccines using the tiniest nanoparticles as the agents of immunization.

It’s a broad term that focuses on how vaccine agents are delivered to the body, and it’s all about immune modulation, Dr. Zhu said. Molecules in a vaccine carry with them coded instructions, whether in a sequence of DNA or RNA, which can suppress or engage immune responses in the body.

For cancer and infectious diseases, Dr. Zhu said, physicians seek to activate an immune response. But for autoimmune

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Julian Zhu, Ph.D., an assistant professor in the Department of Pharmaceutics and the Center for Pharmaceutical Engineering and Sciences at the VCU School of Pharmacy, is researching how to maximize efficient and effective delivery for a potential vaccine for COVID-19.

It’s research he has expanded from work as an associate member of VCU Massey Cancer Center’s Developmental Therapeutics research program. Photo: Danny Tiet, VCU School of Pharmacy

Nanovaccines are a new generation of vaccines using the tiniest nanoparticles as the agents of immunization. It’s a broad term that focuses on how vaccine agents are delivered to the body.

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diseases, doctors often flip the switch to suppress unregulated inflammation responses. The nanovaccines used to deliver the protective material also sheath the encoded information in dissolvable nanoparticles that are harmless to the body and protect the vaccine load prior to injection into the body.

Dr. Zhu’s research on nanomedicines at Massey Cancer Center has focused on how they could provide more effective treatment when clinically translated to immunotherapy regimens in cancer patients. He recently took part in efforts that developed novel vaccines to treat melanoma, glioma and colorectal cancer. The colorectal cancer vaccine successfully treated tumors when used in combination with immune checkpoint inhibitors, which are drugs that inhibit the function of specific proteins.

In preclinical experiments, the combination demonstrated a complete regression without recurrence in about 60% of cancer cells, as indicated by research findings published in Science Advances.1 “Therapeutic tumor vaccines represent an approach to eliciting antigen-specific antitumor immunity,” Dr. Zhu and his colleagues wrote in Science Advances. They also found that conventional tumor therapeutic vaccines demonstrated limited therapeutic efficacy compared to nanoparticle delivery due in large part to central immune tolerance and suboptimal delivery to lymphoid organs where the body coordinates and modulates its immune response.

Now, Dr. Zhu is hoping to apply advances in the targeted delivery of immunotherapy to the virus at the center of the

COVID-19 Nanovaccine Patch

COVID-19 Nanovaccine Patch 1 Nanovaccine patch

applied to skin.

2 121 microneedles

coated with COVID-19 nanovaccine painlessly pierce skin.

3 Microneedle coatings

dissolve, releasing vaccine nanoparticles.

4 Vaccine travels into

5 Lymphatic vessels transport

lymphoid tissue.

vaccine to the body.

.7 cm: actual size

Illustration: Tom Edwards

worst public health crisis since the 1918 flu pandemic.

The basic goal of his research is to be able to synthesize a nanovaccine that can be delivered to lymphoid tissue under the skin, where there are a lot of immune cells. That method means the body will have a better chance to activate the immune system in response to potential exposure.

“It’s such a devastating disease, and we really need vaccines and drugs right now,” Dr. Zhu said. “Many researchers are focusing on how we can repurpose existing treatments to help with COVID-19. Our expertise is working in the drug delivery field to optimize delivery of vaccines or medication to protect or treat patients when one becomes available that is safe and effective. We can isolate small particles and also synthesize them from scratch. They are easy to synthesize, but in quality control the efficacy is very often reduced. What we’re trying to do is use engineering expertise to create better ways to deliver the desired immune response.”

The idea of patch delivery might sound similar to solutions for products like nicotine patches that help people trying to quit smoking, but Dr. Zhu’s design works very differently. To really deliver the vaccine, he needed to go beyond mere chemical adsorption at the skin’s surface.

For that need, he designed a patch that employs more than 100 polymer microneedles to deliver vaccine content into the subcutaneous lymphoid tissue. There, protective nanoparticles would dissolve and release the synthetic fragments of virus material that are often a key ingredient of an effective vaccine.

Dr. Zhu has focused on preclinical studies and is working with partners on the MCV Campus to test patches to ensure consistency in how much vaccine would be delivered when embedded in the protective nanoparticles. After entering the body, the nanoparticles would dissolve and release fragments created to trigger the body’s recognition of the virus and the development of antibodies to recognize and target the threat. Once a vaccine is ready, Dr. Zhu hopes to be prepared for clinical testing of the delivery method.

“As far as a COVID vaccine using a nanovaccine patch, we have multiple lines of progress,” Dr. Zhu said. “We can fabricate the patch and need to further study the efficacy.

Our next job is to select best formulations and to evaluate the patch to test variations in temperature and time that it may be exposed to if mailed.”

If you would like to be a part of advancing the next breakthrough in research related to COVID-19, please visit www.MCVFoundation.org. Go directly to the Give Now button and select the “VCU Health COVID-19 Response Fund” from the dropdown menu.

1. Qianqian Ni, Fuwu Zhang, Yijing Liu, Zhantong Wang, Guocan Yu, Brian Liang, Gang Niu, Ting Su, Guizhi Zhu, Guangming Lu, Longjiang Zhang and Xiaoyuan Chen. “A bi-adjuvant nanovaccine that potentiates immunogenicity of neoantigen for combination immunotherapy of colorectal cancer,” Science Advances, 18 Mar 2020: Vol. 6, no. 12, PMID: 32206706

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Calming the Cytokine Storm of COVID-19

By Alex Henley MCV Foundation

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When scientists look at the subset of COVID-19 patients who become seriously ill and require hospital support, they are finding a common denominator — an overactive inflammatory response called cytokine release syndrome, or a cytokine storm.

Inflammation is a normal part of the body’s response to infection or injury. “It’s how the body starts to heal,” explained Benjamin Van Tassell, Pharm.D., vice chair for clinical research and professor in the VCU School of Pharmacy's Department of Pharmacotherapy & Outcomes Science. “For example, when you sprain your ankle, it’s sometimes a day or two afterwards when the swelling and pain really start. That second wave of injury — swelling, redness and heat — are all signs that inflammation is present. Inflammation brings in proteins to repair tissue in the event of an injury and white blood cells to clear out pathogens if there is an infection. Within a few days the inflammatory response runs its course, shuts itself off and everything should go back to normal.”

However, a problem occurs when certain diseases trigger an extreme inflammatory response and the body doesn’t shut this cycle off appropriately.

The inflammation can become a bigger problem than the original infection because it starts damaging healthy tissue.

“The lungs are quite susceptible to this type of damage,” Dr. Van Tassell said. “The novel coronavirus seems to be particularly good at pushing people into that aggressive immune response that causes acute respiratory distress syndrome, more quickly than other types of infections, and that may be responsible for the majority of deaths that have occurred.”

Antonio Abbate, M.D., Ph.D., the James C. Roberts Esquire Professor of Cardiology in the VCU School of Medicine explained, “Early on, the COVID-19 data coming from China and Europe showed that patients who had an exaggerated inflammatory response were

doing worse. These patients had elevated levels of cytokines in their blood. This reminded clinicians and investigators of the cytokine release syndrome seen relatively rarely as a viral complication, mostly in children, and also after certain types of cancer treatments. These exaggerated levels of cytokines can be mitigated by using cytokine blockers, so that suggested a way to treat this.”

THE CYTOKINE STORM “There are cells in our body that are primed to respond to infection or injury, and they contain a protein structure called the inflammasome. When those cells sense a stressor, like a virus, the inflammasome starts mass-producing inflammatory proteins called cytokines. Cytokines are the messenger proteins that activate other cells and processes to start the immune response. They are most active in the damaged tissue, but they can get in the bloodstream and spark a system-wide response,” Dr. Van Tassell said.

Cytokines can signal the body to perform a wide variety of functions to fight infection, which include raising temperature, increasing heart rate, formulating blood clots, and mass-producing white blood cells or other types of cells and moving them to the area of infection of injury.

These are all important processes to fight infection, but if they aren’t modulated correctly by the immune system, they can start damaging the body by killing healthy cells as well. In vulnerable cases, a very high fever unchecked can cause neurological damage, a high heart rate that can’t be controlled can cause myocardial injury, too many blood clots or an

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“Cytokines are chemical mediators of inflammation. Once the inflammation gets started, it can feed on itself. Damaged tissue creates the need for more inflammation and the process can really snowball in that way.”

Benjamin Van Tassell, Pharm.D., vice chair for clinical research and professor VCU School of Pharmacy

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excessive number of white blood cells flooding an area can lead to organ damage or failure.

This is a cytokine storm — when an infection causes an excessive number of cytokines to be produced, which then starts an exaggerated and damaging inflammatory response throughout the body.

“Cytokines are chemical mediators of inflammation.

Once the inflammation gets started, it can feed on itself.

Damaged tissue creates the need for more inflammation and the process can really snowball in that way,” Dr. Van Tassell said.

A cytokine storm affects the lungs when an excessive amount of white blood cells and fluids flood the area and damage tiny sacs called alveoli that make up the alveolarcapillary barrier. This barrier manages the exchange of gases in the lung by preventing air bubbles from entering the blood stream and fluid from accumulating in the lung.

When the alveoli are damaged, the lung can’t clear fluid and the patient struggles to breath. As oxygen levels fall, patients may not only need supplemental oxygen through a mask, but also a ventilator to support their breathing.

THE CANAKINUMAB TRIAL Prior to COVID-19, clinicians researched a variety of inflammatory conditions to find ways to turn down the body’s excessive immune response. One area of promise has been looking at ways to block cytokines and stop the inflammatory chain reaction early in the process.

Interleukin-1ß is a cytokine that activates very early in the inflammatory process. “Interleukin-1ß, cloned by Charles Dinarello, M.D., more than 35 years ago, is known as the fever molecule. It is a master regulator of the acute and chronic inflammatory response inducing the synthesis and release of thousands of secondary mediators of the inflammatory and coagulation cascade,” Dr. Abbate said.

Clinicians have found success in neutralizing interleukin-1ß with a drug called canakinumab that has already been approved to treat auto-inflammatory conditions, such as juvenile arthritis. Canakinumab contains a monoclonal antibody that has been engineered to recognize and bind to interleukin-1ß, thereby preventing it from attaching to other cell receptors and interrupting its signaling ability.

On April 28, Novartis, the manufacturer of canakinumab, announced plans to begin a multicenter, Phase III clinical trial, called the CAN-COVID trial, to examine the efficacy of using canakinumab as an interleukin-1ß blocker to treat cytokine release syndrome in people with COVID-19 pneumonia.1

The following day, VCU announced it was selected as one of the first sites in the world to begin the CAN-COVID trial at VCU Health, with Dr. Abbate as the principal investigator.

“Dr. Van Tassell and I have a lot of experience working with IL-1ß blockers and have done a number of trials2 looking at how these blockers might affect heart failure and acute myocardial infarction. We are familiar with this drug and have partnered with Novartis before, which made our selection as a test site for this trial a natural fit,” Dr. Abbate said.

For the last 12 years, Drs. Abbate and Van Tassell have worked together studying the effects of inflammation on heart disease. “In heart disease, there are injuries to different parts of the cardiovascular system that trigger an inflammatory response,” Dr. Van Tassell said. “The inflammatory system is designed to put the body on alert, but most of that inflammation may be inappropriate. The larger the inflammatory activation during the heart attack, the worse the outcome is going to be. We’ve spent the last decade figuring out ways to dial down that inflammatory response and promote recovery.

“The inflammatory system is a very complicated process with hundreds of different mediators. One approach is to turn everything off — that’s what steroids do with an across-the-board approach. In heart disease, those attempts have not been successful and may cause more problems than they fix. Our group has been focused on going after certain parts of that inflammatory cascade to be more selective in what we’re turning off. We’ve focused on interleukin-1ß because it sits at the top of the inflammatory cascade. Of all the anti-inflammatory treatments, it seems to be the safest. If you suppress the inflammation too much, you might suppress the immune system and make people more susceptible to infections. IL-1ß blockers have a great track record of hitting the sweet spot — getting the inflammation down without causing immunosuppression.”

Novartis randomized 450 patients worldwide to canakinumab or placebo in the CAN-COVID trial, and VCU Health is the top enrolling site in the world, with 51 patients enrolled and 48 randomized. As this is a randomized, double-blind, placebo-controlled study, no one will know if this drug is successful in helping patients with COVID-19 pneumonia until the trial is complete and the data has been analyzed and shared. Clinicians hope to have preliminary findings near the end of 2020, with an extensive follow-up on patients expected well into 2021.

“Canakinumab was chosen for its established cardiovascular safety profile,” Dr. Abbate said. “We knew that patients at higher risk for developing COVID-19

Dr. Benjamin Van Tassell and Dr. Antonio Abbate have worked together for more than a decade studying ways to mitigate the harmful effects of inflammation. Photo: Cynthia McMullen

complications were going to be patients with cardiovascular risk factors or disease. Canakinumab is the only cytokine inhibitor that has shown reduced risk of adverse cardiovascular events with prior myocardial infarction.3 We saw this as an opportunity to treat COVID-19 patients with a powerful anti-inflammatory drug, while also reducing their cardiovascular risk. The team at VCU Pauley Heart Center has been on the front lines of IL-1ß research for the past 12 years. We are well positioned to do this trial because of our experience.”

The VCU Health team also had constant communication with experts in Italy and France to review their early data, including a former fellow from Pauley Heart Center, Dr. Nicole Potere at the University of Chieti and Pescara in Italy. “Those preliminary findings suggested that IL-1ß

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blockers reduced the severity of disease and mortality rate in patients with COVID-19 pneumonia.4 We knew this was the right drug to test,” Dr. Abbate said.

“During the conduct of the CAN-COVID trial, the results of the dexamethasone RECOVERY trial from the United Kingdom became available, showing a benefit of dexamethasone, a broad-spectrum anti-inflammatory drug in patients with severe and critical COVID-19 pneumonia. Prior to this publication, some patients were receiving steroids and some weren’t, at physician discretion. When these data became available, dexamethasone became standard of care and everyone who did not have contraindications received it. The RECOVERY dexamethasone data support the overall hypothesis that uncontrolled inflammation is harmful and provide an initial effective anti-inflammatory therapy to reduce mortality. The CAN-COVID trial will provide evidence of whether targeted IL-1ß blockade is beneficial on top of dexamethasone and/or in patients in whom dexamethasone is not used,” Dr. Abbate said.

If you would like to support COVID-19 research like this at VCU Health, please consider making a donation to the VCU Health COVID-19 Response Fund at www.support.vcu. edu/covidresponse, or contact Carrie Bickford, VCU Health interim director of development, at 804-297-6708 or carrie.bickford@vcuhealth.org.

1. ClinicalTrials.gov Identifier: NCT04362813.

2. PMID: 28845751, PMID: 30586730, PMID: 30244844, PMID: 32122219 and PMID: 29141858.

3. Claudio Ucciferri, Antonio Auricchio, Marta DiNicola, Nicola Potere, Antonio Abbate, Francesco Cipollone, Jacopo Vecchiet and Katia Falasca. Canakinumab in a subgroup of patients with COVID-19. The Lancet Rheumatology, 2020 Aug;2(8):e457-ee458. PMID: 32835251.

4. Peter Horby, Wei Shen Lim, Jonathan R. Emberson, Marion Mafham, Jennifer L. Bell, Louise Linsell, Natalie Staplin, Christopher Brightling, Andrew Ustianowski, Einas Elmahi, Benjamin Prudon, Christopher Green, Timothy Felton, David Chadwick, Kanchan Rege, Christopher Fegan, Lucy C. Chappell, Saul N. Faust, Thomas Jaki, Katie Jeffery, Alan Montgomery, Kathryn Rowan, Edmund Juszczak, J. Kenneth Baillie, Richard Haynes and Martin J. Landray.

Dexamethasone in Hospitalized Patients with Covid-19 - Preliminary Report.

The New England Journal of Medicine, 2020 Jul 17;NEJMoa2021436. PMID: 32678530.

Inflammation Take-Aways While clinicians await the results of the CAN-COVID trial, ongoing research continues to highlight inflammation as an increasingly important factor in understanding one’s health risk for a variety of diseases, including COVID-19.

“We know there’s an association between risk factors and chronic inflammation. Advice I would give to anyone looking to improve their overall health — eating a healthy diet, maintaining a healthy weight, exercising, controlling your blood pressure, staying away from tobacco smoke and vaping and from other substances that can negatively affect the cardiovascular system like cannabis, cocaine and other stimulants, will help control your inflammation and may protect you from a variety of conditions, likely also severe COVID-19 complications,” Dr. Abbate said.

“Inflammation seems to be involved in more disease states than people originally anticipated, and we’re seeing it show

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up in diseases like obesity, cardiovascular disease and cancer. It underscores the importance of understanding how to selectively and safely manage that inflammation when a patient becomes severely ill,” Dr. Van Tassell said.

THE PERSONAL TOUCH

COVID-19 survivor shares her story as a patient and clinical trials participant

By Jackie Kruszewski VCU C. Kenneth and Dianne Wright Center for Clinical and Translational Research It started with a rash.

Henrico resident Kathy White, 61, began feeling sick in March. When she discovered a rash on her arms and legs, she visited her local clinic, fearing an infection. Diagnosed with bronchitis, she was sent home with medication.

But these were the early days of the COVID-19 outbreak in the U.S. The number of cases was going up, and Kathy was coughing. She and her husband drove to Hampton for a test, the results of which would take several days.

While they waited, Kathy’s cough worsened, and her body temperature wouldn’t regulate. “I had on two pair of flannel pajamas, a flannel robe, two pair of footies, two blankets, sitting in front of the heater and I could not warm up,” she said.

“And I just kept coughing.”

One night she woke up to a sensation she said she’d never forget.

“I got up to go to the bathroom, and it was like the change in altitude on a plane. The weight of the air was on my chest, and I couldn’t breathe,” she said. “My vision was cloudy, blurred.”

In the bathroom, Kathy fell and injured her ankle. She tried calling out to her husband, but she couldn’t scream. That’s when she dialed 9-1-1.

The first responder recorded her temperature at 105.

At VCU Medical Center, Kathy was diagnosed with COVID-19. Isolated in her room following safety precautions, her only connection to her large,

close-knit family was through video chats and calls.

“I kept a lot to myself because I wanted to be strong for my family,” Kathy recalled. “I held so much in.

I was telling my family, ‘Everything’s fine, everything’s fine.’ But I was sick.”

The damage to her lungs made talking exhausting. Trying to maintain a positive outlook added to her fatigue. It was hard not to dwell on the plans she’d made for spring.

Kathy credits VCU Health nurses for getting her through the lonely, isolating experience of hospital quarantine. They created a sitcomstyle family with roles and campy scenarios. One nurse brought her product for her hair. While administering a drug, nurses danced to a playlist Kathy had compiled for her husband’s birthday.

“I had four nurses,” Kathy said.

“I don't think I would have pulled through if it weren't for them.”

Kathy enrolled in one of several active clinical trials for COVID-19 patients. Joining a clinical trial, she said, gave her purpose. “I just felt like, that's the least I could do to contribute to cleaning up this mess.”

From the start of the global pandemic, VCU researchers have moved quickly to bring potential treatment drugs to the hospital for clinical trials. Patients treated at VCU Health have had access to treatments only available at a major research institution.

Kathy White is happy to be home after recovering from COVID-19 at VCU Health.

Photo: Allen Jones, VCU University Marketing

“We’re so grateful to patients like Kathy for joining in these trials,” said Antonio Abbate, M.D., Ph.D, professor in the VCU School of Medicine and an associate director at the C. Kenneth and Dianne Wright Center for Clinical and Translational Research.

“The only way to learn more about this disease — and to save lives — is research and trials. The data we can contribute with the help of volunteers like Kathy are invaluable.”

Later, Kathy joined a committee led by the Wright Center to evaluate and prioritize potential COVID-19 treatment drugs for trials. She provides a valuable survivor’s perspective to the committee of physicians and researchers.

“To be able to survive it, you just feel like you’ve got to do something,” Kathy said.

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FACULTY SPOTLIGHT

Access & Equity Combating Health Disparities and COVID-19 through Community Engagement

By Paul Brockwell Jr. MCV Foundation Robert Winn, M.D., began as director of VCU Massey Cancer Center a little more than three months before the global spread of the novel coronavirus. His first few months on the MCV Campus presented major challenges for healthcare that required him and his team to adapt almost on a continual basis as they worked to provide quality cancer care while keeping staff and their patients, who are especially vulnerable, safe from the virus.

“This has been the most interesting start to a new job that I have ever had,” Dr. Winn reflected this summer. “Despite COVID and everything that has been happening, it’s really been heartening to know how well our team has come together to work through each challenge.”

In some ways, he was especially prepared for this unprecedented moment. Dr. Winn, an expert in lung cancer and community-based healthcare, is keenly aware of how disease can impact the lungs. He came to VCU from the University of Illinois at Chicago, where he was director of the University of Illinois Cancer Center and associate vice chancellor of health affairs for community-based practice at the University of Illinois Hospital and Health Science System.

“Even before this crisis, our at-risk populations had health outcomes that were disproportionately worse than those of the general public,” Dr. Winn wrote in The Cancer Letter, a leading publication for cancer research. “This was visible in all areas of medicine, including cancer. Now, these same populations are at an even greater risk for having a potentially poorer outcome from COVID-19 exposure.”

That persistent and pernicious problem has animated Dr. Winn’s leadership and vision for Massey as a community-engaged cancer center. He has been leading several COVID-19 engagement initiatives for African American communities and co-hosts a monthly radio

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show to help ensure vulnerable and underserved populations have access to health information and care.

“I'm proud to say that many members of VCU Health System have stepped up in ways that have been outstanding,” Dr. Winn said. “We've had everyone from the Departments of Infectious Diseases to Family Medicine join to share their expertise directly with community members.”

In March, he convened a weekly Facts and Faith conference call with local Black church leaders that has quickly expanded to clergy across the city. The goal was simple: to reach vulnerable community members through the institutions and organizations that anchor their lives in uncertain times. The conversations promote the best public health information available about the virus and ways to promote healthier, active lifestyles that can reduce the risk of complications due to heart disease and other factors.

“Massey’s commitment to ensuring equal access to healthcare and information is deeply important to me,” Dr. Winn said. “Whether it is working to relieve suffering and death from cancer or helping to address long-standing health disparities that are exacerbated by the pandemic, Massey’s mission is perfectly aligned with my own values and priorities.”

An accomplished physician-scientist, Dr. Winn is a principal investigator on several community-based projects funded by the NIH and National Cancer Institute, including the All of Us Research Program, an NIH precision medicine initiative. He is committed to developing methods to eliminate health disparities, and he has received national and international acclaim for his efforts to empower underserved patient populations, improve healthcare delivery and ensure equal access to cutting-edge medical treatments. At the University of Illinois, he built a community-to-bench integrated health model that brings

together both the discovery and implementation sciences into one health delivery and research system. Community engagement is central to his vision for Massey’s future and how the cancer center can help in the response to COVID-19.

It also depends on creating an environment where healthcare providers are better informed and able to meet the needs of the community because they are directly engaging with residents about their challenges.

“The engagement piece is truly bidirectional,” Dr. Winn explained. “We're giving and we're getting information that allows us to tweak our strategies for providing care and health education that encourages residents to keep their preventive and wellness visits, to be tested at community sites if needed, and to find the treatment they need to stay healthy.”

Along with community partnership, Dr. Winn is keenly focused on the importance of clinical trials at VCU Health. “One thing that became clearer as we’re moving through this COVID period is the importance of clinical research,” Dr. Winn said.

“The big takeaway for our health system, and really people within our communities, is recognizing the importance of clinical trials and why they matter.

If there is a silver lining to everything we’ve seen with COVID, I think it is recognition of how clinical trials really make a difference.”

Dr. Winn hopes to continue expanding enrollment in clinical trials at Massey, and his team has worked diligently with its campus partners to safely resume both research studies and clinical trials that continue to help patients with access to treatments that can often be lifesaving. This fall, Dr. Winn is proudest of Massey’s participation in a special clinical trial studying cancer patients who also contract COVID-19.

Cancer patients are especially vulnerable to COVID-19 and often develop cardiovascular disease after their treatment. Knowing these troubling factors, scientists are eager to research the best approaches for providing care to this patient population.

“Projects like this one are what I’m really proud of,” Dr. Winn said. “We are thankfully in a position to partner with the National Cancer Institute to improve scientific understanding of how this specific subset of cancer patients with COVID may respond better to certain types of cancer therapy. These insights will be critical to understanding how a vaccine may affect their health and will provide us with better information on how to better treat our patients.”

ROBERT A. WINN, M.D. Director of VCU Massey Cancer Center Senior Associate Dean for Cancer Innovation, VCU School of Medicine Professor, Division of Pulmonary Disease and Critical Care Medicine

Robert Winn, M.D., director of VCU Massey Cancer Center, is an accomplished physician-scientist whose expertise is in lung cancer and health disparities. He began at Massey in December 2019 and has quickly engaged with community members to help alleviate disparities in access to information about COVID-19. Photo: Allen Jones, VCU University Marketing

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Healthier Together

By Paul Brockwell Jr. MCV Foundation

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COVID-19 accelerated how one community-driven partnership is reimagining the way care is provided to vulnerable older adults through inclusion, inquiry and innovation.

Social isolation can be dangerous. And in the spring, it was the shared experience of people across the country as states issued stay-at-home orders to mitigate the spread of COVID-19. Here in Richmond, a group of researchers has long been examining how a lack of social connection can present challenges for many older adults that go beyond the inconveniences of being stuck at home. The loss of social activity can be detrimental to their health, not to mention reduce their access to care when they may not have the means to participate in face-to-face or telehealth visits with providers. For low-income older adults, the affect of social isolation has been especially disproportionate.

In Richmond, one program has been partnering with low-income older adults with the goal of understanding how to build a better healthcare delivery model to meet their needs where they live. The spread of COVID-19 only underscored the value and importance of the Richmond Health and Wellness Program (RHWP). Research on loneliness and social isolation’s affects on health outcomes became a national conversation as lockdowns went into effect and researchers saw a sudden uptick in preventable deaths due to disruptions in access to routine and preventive care. While not researching the virus directly, the program’s efforts to address the secondary impacts of the pandemic on health outcomes received support from the VCU Health COVID-19 Rapid Research Fund. RHWP is a community-based learning lab for exploring both health disparities in older adults living in low-income housing and reimagining how care is provided.

Since 2012, the Richmond Health and Wellness Program has brought together care partners across disciplines to address health disparities in vulnerable older adults and disabled older adults living in low-income housing through collaborative care models that enhance the lives of individuals, decrease healthcare costs and educate future practitioners. Based at the VCU School of Nursing, the program is the idea of Pam Parsons, Ph.D., associate professor and associate dean of practice and community engagement at the school, who was recently named a fellow of the American Academy of Nursing. RHWP also received an important distinction as an Age Friendly Health System Practice.

The designation is given by the Institute for Healthcare Improvement, a national organization encouraging improvement in healthcare delivery and outcomes.

Prior to the pandemic, the program operated weekly with either full or half-day sessions at five housing locations. They also recently expanded to the new VCU Health Hub@25th, a freestanding wellness center developed to serve one of the most health disparate populations in the Richmond region. Participants in the program work with students and faculty to develop collaborative wellness plans customized to the health conditions, social needs and resources of each individual.

Social connectedness serves as a pathway to improved health and wellness, and the relationships built over time through the program have led to improved health outcomes.

“Loneliness is such a huge factor, and it’s at the forefront of NIH to ask what factors related to social isolation are presently influencing health outcomes,” Dr. Parsons said.

“We’re teaching the students what that means using evidence-based tools to assess loneliness and making strategies to connect people to services and help set goals to be more socially connected.”

The social connection provided by the program is one of the key elements of its success and what attracted the attention of the AARP Foundation. In January, the foundation awarded a grant to the program to support more formally measuring the influence of social connection on health outcomes. That work became especially relevant in the era of COVID-19; and the project also received a COVID-19 Rapid Research Grant from VCU. “A really big component of what we’re doing is fulfilling this social need,” said Jodi Winship, Ph.D., an assistant professor of occupational therapy at the VCU College of Health Professions. “For my dissertation, I’d interview program participants about their experiences working with a team of students. I thought I’d hear about how they appreciated student help with managing their medicines and things like that, but one of the biggest things I found in my dissertation research was how much they loved simply talking to the students, both hearing students’ stories and sharing their own.”

The Richmond Health and Wellness Program combines the expertise of various healthcare fields to build a coordinated care model for participants. The partnership includes faculty like Jodi Winship, Ph.D., assistant professor of occupational therapy in the College of Health Professions; Elvin Price, Pharm.D., Ph.D., professor at the School of Pharmacy; and Pam Parsons, Ph.D., associate professor at the School of Nursing. Photos: Chris Ijams

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The Richmond Health and Wellness Program was created from an observed need in the community and is the idea of Pam Parsons, Ph.D., associate professor and associate dean of practice and community engagement at the VCU School of Nursing. “When I started at VCU Health as a nurse practitioner, there were many individuals who would come into our practice site who were aging in place with limited resources and nowhere to go when they needed extra help,” Dr. Parsons explained. “That’s when I became passionate about helping to determine strategies to provide extra support. It is really important to help populations who are underserved and have limited social support. It’s what nursing is all about.”

Dr. Winship connected with the program when she was studying social behavior and sciences as a doctoral student in the VCU School of Medicine. Her academic interest evolved into long-term attachment to RHWP through bringing occupational therapy clinical skills to the program. The team has always known the social component is important, but now there is a specific intention on measuring the effects of loneliness and social isolation on health outcomes and educating students on how to recognize and understand the importance of these factors.

A MULTIDISCIPLINARY AND INTERPROFESSIONAL APPROACH The partnerships RHWP has built are a key part of the success, and they start with the community participants.

“We’re not researching the individuals,” Dr. Winship said.

“In every way, this is a process in which they are as equally engaged in and directing as the faculty and students. We've established a community advisory board, and we're really trying to guide our research based on what the community wants and how we can help them and work together.”

Once the community members identify a need, the program has partnered with an array of experts from multiple disciplines ranging from social work and occupational therapy to law and pharmacy.

One such expert is Elvin Price, Pharm.D., Ph.D., Victor A. Yanchick Associate Professor and Director of the Geriatric

Pharmacotherapy Program at the VCU School of Pharmacy.

Dr. Price is also co-director of the Institute for Inclusion, Inquiry and Innovation (iCubed) Health and Wellness in Aging Core with Dr. Parsons. His expertise in pharmacogenetics has helped the older adults who are part of the RHWP. “Our work centers around making the best decisions possible with medications for people based on their needs and genetic profile,” Dr. Price said. “You may also see this called personalized medicine or precision medicine, but it's a way of being able to optimize medication based on an individual's specific needs and how their body reacts and processes available medicines.”

Dr. Price and his students are genotyping participants to evaluate them for the most commonly characterized drug-gene pairs. The goal is to avoid adverse drug reactions and educate participants on how to best manage their prescriptions based on their genotype. His investment in this work is more than just scientific. Part of what inspired him to pursue his dual doctorates, he said, was growing up and seeing friends and family who suffered from chronic diseases and often lacked adequate, regular access to professionals who could help with understanding prescriptions and ensuring they are optimized to treat the individual’s condition.

“We know that a large percentage of our patients in this program have reported having an adverse drug event,” Dr. Price said. “We gauge their knowledge level and then go through the genetic sequencing hoping to potentially characterize the frequencies of how often we might find bad drug-gene pairs out in our older adults living in the community.”

COVID-19 temporarily halted work on this aspect of the program, but Dr. Price and his team resumed processing and isolating the DNA this fall and continue to receive positive feedback from residents who are interested in participating.

Social isolation is a risk factor for many older adults. COVID-19 has underscored the importance of social connection and employing adaptive technology to connect with vulnerable older adults.

“With the arrival of COVID, the issues became even more apparent,” said Jodi Winship, Ph.D., an assistant professor of occupational therapy at the VCU College of Health Professions.

“Now we have more opportunities to address it with this greater awareness on the issue.”

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Sidebar headline about team

The Richmond Health and Wellness Program had to adapt overnight to continue reaching low-income older adults in the community.

Funding from the AARP Foundation and VCU Health’s COVID-19 Rapid Research Fund enabled them to purchase technology for residents that allows them to connect with program leaders.

DISRUPTION AND RAPID ADAPTATION Overnight, all the work that clinicians were doing with the program had to evolve. Most of the RHWP sites quickly restricted visitors and on-site programs to protect older adults, an especially vulnerable population, from the spread of COVID-19. The program had been acquiring devices that would allow greater communication between residents and program participants, but the suspension of in-person programs accelerated the need to deploy and work with technology in a community that often experiences barriers to access.

Thankfully, some of the locations have recently invested in wireless internet connections that enable the program team to pilot the use of tablets and other personal technology devices.

Helping older adults avoid poor medication outcomes drives the work of Elvin Price, Pharm.D., Ph.D., Victor A. Yanchick Associate Professor and Director of the Geriatric Pharmacotherapy Program at the VCU School of Pharmacy. He and his students are genotyping program participants to evaluate for drug-gene pairs that may put them at risk for adverse drug reactions for patients managing chronic conditions.

Dr. Parsons and the team have been refining and understanding technology needs and how people could and would want to use technology if they are in a different living environment, income bracket or older. They hope this research and the adaptation will yield insights that will help improve delivery of care and social engagement to residents, but also equip students for their careers beyond the MCV Campus. Their biggest questions are whether technology can help address some of the gaps they have seen in the healthcare system for older adults and whether technologically mediated social connection proves as important and valuable to improving health behaviors and conditions. “The work we do over the next three years will add evidence to a growing understanding around models of care for older adults when national policymakers are looking at how to frame care for this health disparate population,” Dr. Parsons said.

More than anything, though, the research team has missed being with their community participants. This fall, they worked on reactivation plans to safely get teams back in the communities to resume work while continuing to adopt a hybrid model to programs they are unable to hold in person.

If you would like to contribute to research associated with the VCU School of Nursing’s Richmond Health and Wellness Program, please contact Pamela Lowe, senior director of development for the School of Nursing, at 804-827-0020 or plowe@vcu.edu.

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Amid Crisis, Inventing Solutions

By Eric Peters MCV Foundation

In the early days of the COVID-19 pandemic in the U.S., “uncertain” was a word that became ubiquitous. Today, as the virus continues to spread, times are indeed still uncertain, but in those spring days in March and into April, no one had any idea what to expect.

Two of the main questions at the time had to do with looming shortages of diagnostic testing and personal protective equipment, especially for doctors, nurses and other hospital and healthcare professionals. There simply were no answers about where these critical lifesaving resources would come from as the entire country braced for impact.

It was in this crisis, as pressure to find any hint of an answer weighed more every day, that the brilliance and creativity of VCU Health’s innovators shined brightest.

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1: IN-HOUSE TESTING

Clarity for Patients and Providers On an afternoon in early March, Chris Doern, Ph.D., was called into a meeting with VCU Health System leadership.

“As a microbiologist, I’m not used to sitting in a room with the C-suite,” he said. “So that’s when I knew things were going to be a little different.”

Dr. Doern, who leads the clinical laboratory providing diagnostic microbiology and immunology services at the health system, was called to the meeting as shortages in diagnostic tests, materials and instrumentation were emerging across the country and backorders for these supplies were growing nationwide. At that time, limited COVID-19 testing was available through the public health laboratory, with two- to three-day turnaround times for test results.

What followed that meeting, Dr. Doern said, was unlike anything he’s experienced in his life. Within two weeks, he and his team developed their own COVID-19 diagnostic test, reduced turnaround time to a matter of hours, and increased capacity to hundreds of tests per day.

“The work of Dr. Doern and his team has been extremely important in battling this pandemic,” said Gonzalo Bearman, M.D., an infectious disease expert, professor of medicine and director of the VCU Medical Center Infection Prevention Program. “Fast, reliable COVID-19 testing is critically important for identifying infected patients, maintaining isolation precautions and for starting timely contact tracing.”

THE IN-HOUSE IMPORTANCE In a pandemic, or in the early stages of battling a new disease, testing usually is done in a public health laboratory.

Dr. Doern said the state lab was doing an amazing job this spring, but the hospital simply needed results faster than the two- to three-day turnaround time.

“We have to treat all patients as if they have COVID-19 until we know otherwise,” said Deb Zimmermann, D.N.P., former chief nursing officer, vice president of patient care services and co-director of the COVID-19 task force at VCU Health. “So without a fast, reliable test, we would have been crippled from a resource perspective. Caring for what we call PUIs, or patients under investigation, uses an incredible amount of resources. With faster testing, we’re able to better deploy resources to where they are needed most.”

THE IN-HOUSE PROCESS To bring any diagnostic test into the health system usually takes years. A pathogen is identified, companies develop tests, scientists like Dr. Doern and his team evaluate the effectiveness of the tests from multiple companies, and then decisions are made about what tests to buy and use in the hospital.

“It’s a nice, comfortable timeframe,” Dr. Doern said.

“The process takes two to three years but, in this case, this thing hit in early 2020, and by March we needed an in-house test immediately.”

Dr. Doern and his team first tried to take a relatively normal, yet fast-tracked route by using tests from the CDC. It quickly became clear, however, that while the tests were effective, they just weren’t capable of the high throughput that VCU Health needed.

“We decided we were just going to make our own test,” Dr. Doern said. “There was nothing else available.”

Christopher Doern, Ph.D., director of microbiology at VCU Health, oversees the implementation of new technologies in the VCU Health clinical microbiology laboratory. This spring he and his team created a diagnostic test for COVID-19 that drastically improved the health system’s ability to diagnose the disease and care for the Central Virginia community. This photo was taken in early 2020, prior to the face mask requirements in VCU Health facilities. Photo: Tom Kojcsich, VCU University Marketing

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Some of the team members who were integral in creating and implementing a high-capacity, short-turnaround diagnostic COVID-19 test at VCU Health include (L to R) Roxanne Mercer, director of laboratory operations; Christopher Doern, Ph.D., director of microbiology; Alexandra Bryson, Ph.D., associate director of microbiology; Scott Turner, Ph.D., assistant director of molecular diagnostics; and Andrea FerreiraGonzalez, Ph.D., chair of Molecular Diagnostics Division. Photo courtesy of Dr. Scott Turner

Ordinarily, Dr. Doern’s lab analyzes, buys and administers tests, but a large part of his training — and that of the associate director in his lab Alexandra Bryson, Ph.D. — is in developing new tests. The two had no choice other than to simply look around their lab to see what they had on hand to make their own test for COVID-19.

Drs. Doern and Bryson realized they could use materials from the CDC’s assay and reconfigured them to work on one of the automated instruments they had in the lab for higher capacity testing. They developed a PCR-based test, which means it searches for nucleic acid — RNA or DNA — of certain organisms. The materials they used from the CDC’s assay were primers and probes that detect genes in SARS-CoV-2, the virus that causes COVID-19.

THE IN-HOUSE RESULT On March 23, just two weeks after Dr. Doern’s meeting with health system leadership and one day before The New Yorker published an article titled, “Why Widespread Coronavirus Testing Isn’t Coming Anytime Soon,” VCU Health administered its first independently developed COVID-19 test.

Moving from a capacity of 10 to 30 per day in the first week of testing to 100 per day in the following weeks, Dr. Doern’s team, in collaboration with the VCUHS Molecular Diagnostics Laboratory — directed

by Drs. Andrea Ferreira-Gonzalez and Scott Turner — gradually built capacity to where it stands today, which

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is 500 to 600 tests per day. As of press time, more than 50,000 tests have been administered.

The lab averages 10 hours to provide test results and has a goal to always provide results within 24 hours, which they do more than 99% of the time. “The demand has only increased,” Dr. Doern said.

“But we have guarded vigilantly our ability to produce test results in under 24 hours. That’s not been the case around the country and for many other labs.”

The lab has become so efficient, that in addition to serving VCU Health, it has helped with testing in the region, including assisting Virginia Department of Health with outbreak investigations, serving as the test facility for some of the early nursing home outbreaks, and helping surrounding healthcare systems, especially the Hunter Holmes McGuire VA Medical Center.

Dr. Doern said his lab’s success did not occur in a vacuum, and that countless people around the health system made the testing development and implementation possible.

He gives specific credit to that team of leaders who called him into the meeting in March. “I’ve got a small community of microbiologists from around the country who I communicate with very closely,” he said. “I can say in no uncertain terms that the support and the compassion we’ve experienced here from hospital leadership is not common. In fact, it’s an anomaly.”

Hospital leadership is equally impressed with Drs. Doern and Bryson.

“Chris and his team worked tirelessly to bring in-house testing to the organization with rapid speed,” Dr. Zimmermann said. “Then they worked miracles to get the supply and product so we can test. That has ensured we can continue treating anyone who is in need of our care, and that patients can get the right level of care for their condition.”

A Student’s Impact on the Hidden Front Line Kevin Wills is a student worker in the VCU Health diagnostic microbiology and immunology lab that Drs. Doern and Bryson manage. Having played an important role in diagnostic testing throughout the COVID-19 pandemic, he’s been offered a full-time position in the lab upon graduation this December. Photo: Eric Peters

Kevin Wills beat cancer twice at ages 10 and 11.

His experiences from that time immediately ignited a desire and a pursuit to one day work in healthcare.

This spring and summer, the VCU College of Health Professions student fulfilled that goal and more by contributing to a critically important — yet often overlooked — component of the healthcare system during the deadliest pandemic in more than 100 years.

Kevin is a student worker in the diagnostic microbiology and immunology lab that Drs. Doern and Bryson manage. He’s stayed longer than the usual student workers and has taken on responsibilities beyond the usual student workload, helping log, process and complete diagnostic testing, especially for COVID-19.

In fact, he estimates that this spring and summer, he touched at least half of all COVID-19 tests that came through the VCU Health lab. He also played a big role in validating VCU Health’s in-house test by running numerous blank and positive specimens, ensuring results were consistent and that there were no false positives or false negatives.

“I keep a list of people I’m going to thank for all they’ve done for us during this time, and Kevin stands out,” Dr. Doern said. “That young man has saved us throughout this. You ask him to do something and he’s doing it, and he works weekends. He is one of the heroes of this thing.

Without him, I’m not sure where we would be.”

Kevin’s meaningful contributions are made possible by his time as a student in the Department of Medical Laboratory Sciences at the college, where as a master’s degree student he says he’s been given incredible opportunities to learn practical skills as well as theory, and to explore his interests outside his degree’s concentration.

The department trains scientists to play critical roles on healthcare delivery teams. Its graduates — which make up most of Dr. Doern’s staff — provide data in hematology, microbiology, immunology, medical chemistry transfusion medicine and molecular diagnostics that physicians need for accurate diagnoses and effective disease management.

The education and training have paid off for Kevin as he’s been offered a full-time position in the VCU Health lab after he graduates in December.

He said he’s overjoyed to find a career in lab sciences after setting his mind to it so many years ago.

Kevin made that decision after beating rhabdomyosarcoma and adrenocortical carcinoma.

“Ever since that, I’ve wanted to get into healthcare in some way,” he said. “I didn’t know the lab existed back then, but when I look back on it, I probably wouldn’t have ever been diagnosed correctly if it weren’t for the lab. They were there the entire time and I never knew it.”

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2: DECONTAMINATING MASKS

Ensuring Safety for the Front Line It was early on a Saturday in March when Stephen Kates, M.D., saw a call coming in from his colleague in the Department of Orthopaedic Surgery at VCU Health. On the other end of the line was Gregory Golladay, M.D., who had been serving on a committee discussing solutions for the health system to the nationwide N95 mask and personal protective equipment (PPE) shortage.

At the time, news outlets, including The Washington Post, were reporting that some hospital workers in the U.S. were resorting to using bandanas and sports goggles to protect themselves from COVID-19 infection.1 It is critical during a pandemic to keep healthcare workers safe and healthy, and it is not hard to understand that without physicians, nurses, intake coordinators, sanitation workers and many others, hospitals simply don’t work.

As pressure surrounding these national issues intensified on that Saturday in March, Dr. Golladay thought to call Dr. Kates. The committee had developed some ideas, and VCU Ventures, the university’s startup support office, had developed some drawings to implement a mask decontamination process that would use high-intensity

ultraviolet light. Using devices that emit this type of light is an effective means of sterilizing hospital environments such as patient and operating rooms, so VCU Health already owned several, which Dr. Kates described as looking like R2-D2 from “Star Wars.”

Because this process had never been used before to sterilize masks at high volume, there was no equipment in existence that they could use to hang and transport the masks during decontamination, and that is where Dr. Kates’s unique skillset came into play. It’s a hobby he picked up as a young man in trade school classes — metalworking.

FABRICATING THE RACKS On that Saturday night after he and Dr. Golladay first talked about the mask decontamination idea — and the racks that would make it possible — Dr. Kates went to the hardware store, purchased some steel and worked on a prototype late into the evening. By Sunday morning, the two had inspected and discussed the prototype and assembled a team to come help build more.

The team included Drs. Kates and Golladay; Laura Lahaye, M.D., an associate professor in the Department of Anesthesiology; Blane Kelly, M.D., a resident in the Department of Orthopaedic Surgery; and a team from VCU Ventures that included Justin Kauszler, Kevin Leslie and Ace Caldwell.

Dr. Kates’ metal shop is extensive, so he was able to show everyone on the team how to grind steel and provide everyone with their own grinder. Most of the team ground and passed the steel to Dr. Kates, who worked with Dr. Kelly to square and weld the racks. By the end of the day Sunday, the group had cut and polished enough metal for 20 racks and had completed eight racks, which was enough to start evaluating the decontamination process at the hospital.

An outside company completed the final 12 racks.

Stephen Kates, M.D., the John Cardea Professor and Chair of Orthopaedic Surgery at VCU Health, learned welding in trade school as a child. It has been a hobby ever since, and during the COVID-19 pandemic became a key part of ensuring VCU Health employees and members of the community had access to clean, safe masks. Photo courtesy of Dr. Stephen Kates

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On Monday morning, just two days after their initial phone call, Drs. Kates and Golladay delivered eight racks to VCU Health and began solidifying a mask decontamination plan that could yield 12,000 clean masks per day and help VCU Health continue saving lives.

DECONTAMINATION The process for collecting and decontaminating masks began on each hospital unit. Throughout their shifts, staff members would discard into bins their used masks, all of which were labeled with their names. Sometimes nurses can go through up to 10 masks per shift. After each shift, bins would be taken to a separate building on campus.

Masks soiled with blood, dirt or makeup were discarded, while the rest would be placed on the racks and arranged around the UV light sources in a hexagonal shape. There were enough racks to enable one set of six to be loaded while one set of six could be in the decontamination process and one set could be unloaded. This allowed for up to 12,000 masks per day to be decontaminated, a maximum yield that thankfully was never needed.

Before all these steps were put into place, Dr. Kates’ team worked for two weeks to ensure the process was safe.

Initially, the team thought it would take about seven minutes to sterilize the masks, but after they measured quite a bit with Kevin Leslie from the VCU Ventures team, they decided to expose the masks to light for 12 minutes on each side.

“There was no standard,” Dr. Kates said. “We know it takes about 2 millijoules of UV light to kill a COVID virus strand, so we gave each mask about 1,000 millijoules on each side. We wanted to make sure there was nothing living on the masks when we gave them back to the employees.

We don’t want any bacteria, mold, spores, viruses, nothing.”

The team set the UV light devices to the appropriate setting and used secondary light meters to gauge whether the appropriate amount of light reached the masks. They also completed extensive testing to gauge whether the masks became wet after the process, whether they still blocked particles, whether they were breathable and whether they were damaged structurally.

“Believe it or not, the masks passed testing after 20 uses,” Dr. Kates said. “They passed breathability, fit testing, destructive fit testing and moisture metering. We also absolutely guaranteed they got the right amount of light because every single load had two UV-C light meters measuring the light delivered to each side of each mask.

So, we felt that we had done a good job scientifically with it.”

After a quick response that enabled the process to be evaluated, followed by extensive safety testing, VCU Health announced April 9 that it had begun to

THE DECONTAMINATION PROCESS

1 A VCU Health employee inspects a used mask from the hospital. If the mask is not damaged, it will be decontaminated and used again.

2 A VCU Health employee arranges N95 masks on a rack designed and fabricated by VCU Health staff members. Once full, racks are placed around UV light sources and the masks are decontaminated for future use.

3 N95 masks are arranged around a UV light source in a hexagon shape so they can be decontaminated and reused by VCU Health employees. This is part of a critical process that VCU Health implemented to avoid mask shortages during the COVID-19 pandemic.

Photos courtesy of Dr. Stephen Kates

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”We wanted to make sure there was nothing living on the masks when we gave them back to the employees.”

Gregory Golladay, M.D.

“safely decontaminate N95 masks using equipment and a method developed by VCU Health and VCU Ventures.”

The independently developed method of decontaminating and reusing masks was poised to enable VCU Health to replenish its own supply nearly indefinitely.

Other mask decontamination processes available, which include peroxide vapor and plasma gas, have proven to be effective, but destructive to the masks after just two decontaminations. The fact that masks are still usable after 20 iterations of the UV light process, coupled with the high throughput process at VCU Health, is what has made the project so successful.

The other essential ingredient, Dr. Golladay said, was the people who make up the VCU Health community and team.

“We were fortunate to have help from a lot of can-do people who are bright and were willing to work and willing to provide collective input into a process,” he said. “We’ve never lacked adequate PPE for employees because of the collective institutional response.”

A SAFER HOSPITAL, COMMUNITY AND REGION

By September, VCU Health had decontaminated more than 100,000 N95 masks for its employees. It was a true universitywide effort that included researchers and staff from the VCU Health departments of orthopaedic surgery and infectious diseases, supply chain, high-level disinfection and plant operations departments, VCU Ventures and the VCU da Vinci Center for Innovation.

“This decontamination process gave our healthcare workers assurance that they would have access to these critically important masks while many hospitals across the country were running out of them,” said David Lanning, M.D., interim chief medical officer and co-director of the COVID-19 task force at VCU Health. “It protected our

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Gregory Golladay, M.D., associate professor in the Department of Orthopaedic Surgery at VCU Health, inspects racks that hold N95 masks for decontamination and reuse at the hospital and throughout the Central Virginia community. Photo: Eric Peters

staff and was a huge source of pride in our health system that we were able to implement this.”

Dr. Zimmermann agreed, saying, “We made a promise to our team that we would absolutely ensure they had the appropriate PPE no matter how long this pandemic lasted.

What Dr. Kates’ team did was give us the ability to keep that promise.”

The innovative process also helped the community and the state. Masks have been sterilized for local fire and EMS departments and the VCU School of Dentistry, which is the only dental school in the commonwealth. In addition, Dr. Kates provided UVA Health and other state hospital systems with photos, diagrams, drilling templates and other details explaining the process from start to finish.

Sharing knowledge and skills is what people across VCU Health have done for the many months that this pandemic has been a part of daily life. The actions, ideas and desire to serve among all the teams described above and many others across the health system have protected fellow staff members and the Central Virginia community.

“Both of these teams who worked on the diagnostic test and the decontamination process put patient care first and understood the importance of their role in protecting our employees, while ensuring we could deliver an appropriate level of care to patients,” Dr. Zimmermann said. “I consider them heroes — superheroes.”

1. www.washingtonpost.com/health/2020/03/19/hospital-workers-battlingcoronavirus-turn-bandanas-sports-goggles-homemade-face-shields-amidshortages/

Applying Previous Research to the Current Crisis

By Paul Brockwell Jr., Alex Henley and Eric Peters

Vitamin C When Alpha A. “Berry” Fowler III, M.D., a professor in the Division of Pulmonary Disease and Critical Care Medicine in VCU School of Medicine’s Department of Internal Medicine, first saw COVID-19 causing breathing complications and pneumonia in some patients, he immediately thought of applying his research with Vitamin C. We covered Dr. Fowler’s groundbreaking work using Vitamin C to treat sepsis in the inaugural issue of NEXT in fall 2017. Sepsis is a life-threatening condition that occurs when the body’s immune response to a viral or bacterial infection becomes excessive and actually does more damage than the original infection. The lungs tend to be particularly vulnerable when the immune system goes into overdrive, which can result in acute respiratory distress syndrome, acute lung injury or pneumonia.

“My colleagues and I hypothesized that if we started Vitamin C treatment just as COVID patients were beginning to show a need for oxygen support, we could

calm the lung with Vitamin C as an anti-inflammatory therapy,” Dr. Fowler said.

Those colleagues include Brian Davis, M.D., assistant professor of medicine in the Gastroenterology Division at Hunter Holmes McGuire VA Medical Center; and Markos G. Kashiouris, M.D., MPH, an intensivist and assistant professor in VCU’s Division of Pulmonary Disease and Critical Care Medicine.

Dr. Davis has an open-label clinical trial underway at Hunter Holmes McGuire VA Medical Center using Dr. Fowler's Vitamin C protocol, and has enrolled 20 veterans hospitalized with COVID-19 pneumonia.1 “So far, the Vitamin C protocol has been very well tolerated without significant side effects, and most veterans have an improvement in oxygenation while receiving Vitamin C. Since veterans represent one of the highest-risk groups for complications related to COVID-19, it is critical to develop safe and effective therapies that dampen the damage triggered by this virus,” Dr. Davis said. Final analysis of this study will be submitted to a peer-reviewed journal for publication later this year.

Drs. Davis, Fowler and Kashiouris recently received approval from the FDA to run a two-center safety trial using their Vitamin C protocol to treat 60 study participants with COVID-19 pneumonia. Once this trial, called EVICT-CORONA-ALI, is complete, they hope to launch a much broader clinical trial.

“We’re excited to begin this trial, but none of this would be possible without MCV Foundation board member Harry Thalhimer,” Dr. Fowler said. “I’ve known Harry for years and taken care of many of his family members.

He’s been working behind the scenes to make sure we have funding. We’re not receiving any federal grants at this stage, so this trial will be completely supported by donors who are passionate about this area of research.”

Alpha A. “Berry” Fowler III, M.D., professor in the Division of Pulmonary Disease and Critical Care Medicine in VCU School of Medicine’s Department of Internal Medicine. Photo: Bill Tiernan, The Virginian-Pilot

1. ClinicalTrials.gov Identifier: NCT04357782

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Medicines for All

Frank Gupton, Ph.D., reimagines the drug manufacturing process from his lab at VCU’s Medicines for All Institute.

Photo: Kevin Schindler

The supply chain for prescription drugs in the U.S. and around the world is far more vulnerable than many people would like to think. More than 100 drugs are in short supply in the U.S. and approximately 80% of all medications consumed in the U.S. are produced in India or China.

Our Spring 2020 cover story of NEXT highlighted how Frank Gupton, Ph.D., the Floyd D. Gottwald Jr. Chair in Pharmaceutical Engineering and chair of the Department of Chemical and Life Science Engineering at VCU, is attempting to resolve this issue as CEO of VCU’s Medicines for All Institute.

Dr. Gupton and his team are reinventing the drug manufacturing process by using new materials and methods and switching from batch production to continuous flow manufacturing in order to more efficiently and cost-effectively produce the active pharmaceutical

VCU Health Studies COVID-19 and Smell Loss Also in our Spring 2020 issue of NEXT, we covered the pioneering work of VCU Health researchers to restore a sense of smell in patients experiencing anosmia, or complete loss of the sense, through electrical stimulation.

Patients who experience permanent loss of smell usually have experienced head trauma that severs the connections between neurons in the nose and the brain’s olfactory bulb, but anosmia can also be caused by viral infections, as the world would become keenly aware of in March.

Loss of smell and/or taste was quickly identified as a symptom commonly reported in patients who contract the novel coronavirus. Many health organizations identified loss of smell or taste as significant enough to warrant evaluation for the virus. What scientists did not have a clear picture of at the time was how long this symptom might endure. That’s where VCU Health’s team has been particularly focused.

“Our initial research looked at presentation and saw, among other things, that almost 40% of people presented with loss of smell as their first or only symptom of COVID,” said Evan Reiter, M.D., professor of otolaryngology and medical director of the VCU Health Smell and Taste Disorders Center. “That underscored the need

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to incorporate smell loss as a hallmark symptom of COVID and the importance of raising awareness of that.”

VCU Health’s Smell and Taste Disorders Center, one of few centers of its kind in the U.S., was uniquely positioned to evaluate long-term effects of the virus on sense of smell and taste. Early in the pandemic, Dr. Reiter led a team of researchers to design a patient survey and enroll participants so they could build a better understanding of smell and taste changes associated with coronavirus disease.

The group recently received $25,000 in funding through the MEDARVA Foundation, which will allow them to continue the nationwide longitudinal survey of COVID-19 patients who experienced smell loss as one of their symptoms.

“We wanted to set up a longitudinal database so that we could watch people through the whole process and see what they went through and see how they’re recovering,” Dr. Reiter said. “We’re seeing the vast majority of people who experience losses are recovering within a few weeks — but not all of them. That’s one of the things we’ll continue to watch.”

The research team included Daniel Coelho, M.D., professor in the Department of Otolaryngology — Head and Neck Surgery at VCU School of Medicine; Richard Costanzo, Ph.D., the center’s research director and professor emeritus

ingredients found in critical medications. This allows for the safe and affordable production of these essential medications, making them more accessible to the patients who need them most.

In May, VCU announced a partnership among Phlow Corp., the Medicines for All Institute, Civica Rx and AMPAC Fine Chemicals to establish a supply chain consortium in Richmond, Virginia, that will help reduce U.S. dependency on overseas drug manufacturers.

The U.S. Department of Health and Human Services followed with a $354 million four-year contract to the leader of the consortium, Phlow Corp., to accelerate the initiative.

Phlow Corp. was co-founded by VCU alumnus Eric Edwards, M.D., Ph.D., who serves as CEO, and Dr. Gupton, who serves on the board.

“The COVID-19 pandemic shined a light on the need to address this issue,” Dr. Gupton said. “We are focused on essential drugs required to treat COVID-19 patients. A lot of these drugs are not available due to acute demand and chronic shortages. We are also working on COVID-19 drugs with the Gates Foundation on developing processes for drugs like remdesivir and other antiviral drugs.”

NEXT is published by the MCV Foundation to share the latest breakthroughs occurring at VCU Health and the positive impact these exciting innovations have on our patients.

MANAGING EDITOR:

Alex Henley ASSOCIATE EDITORS:

Eric Peters and Paul Brockwell Jr. GRAPHIC DESIGN:

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Joseph T. DiPiro, Pharm.D. Alpha A. “Berry” Fowler III, M.D. Steven R. Grossman, M.D., Ph.D. F. Gerard Moeller, M.D. Jerome F. Strauss III, M.D., Ph.D. Wanchun Tang, M.D. The Medical College of Virginia Foundation was established in 1949 to inspire and steward philanthropic resources for our MCV Campus Partners at VCU Health.

The MCV Foundation manages more than $600 million in assets to ensure VCU Health remains at the forefront of excellence and innovation in patient care, research and education as one of the top academic health centers on the East Coast. Through 1,700 funds, the MCV Foundation provides scholarships, professorships, research and program funds to support the lifesaving work occurring at VCU Health every day. The MCV Foundation’s campus partners include: VCU College of Health Professions, VCU School of Dentistry, VCU School of Medicine, VCU School of Nursing, VCU School of Pharmacy, VCU Massey Cancer Center and VCU Medical Center.

in the Department of Physiology and Biophysics; and Zachary Kons, a third-year medical student at VCU. Their research will be published in the American Journal of Otolaryngology in November.

If you would like to support any of the research mentioned above, please contact Brian Thomas, MCV Foundation vice president and chief development officer, at brian.thomas@vcuhealth.org or 804-828-0067.

The original articles can be found by clicking on “past issues” at www.mcvfoundation.org/next.

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