The Year of COVID

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OVID-19 was a presence in Miami long before the actual virus showed up. On January 6, 2020, Vincent Torres, emergency management director for UHealth and the Miller School of Medicine, convened a meeting to discuss highly infectious diseases. Chinese health authorities had recently reported an outbreak in Wuhan, putting it front and center on the agenda.

“That was the first meeting here in which the words ‘novel coronavirus’ were spoken,” Torres said.

The discussion was mostly routine. Still, people were worried.

“We monitor everything, but it was evident from the beginning that this virus was a threat, and had the potential, as had earlier viruses, to spread around the world,” Torres said. “It was early, but we had to be prepared.”

There were nine people from four departments at that first meeting, but it wasn’t long before Zoom calls involving more than 100 participants from dozens of health system units were a daily event. An incident command structure — an organizational chart of teams dedicated to COVID-19 response — was developed by Emergency Management. Driven by the public health disasters unfolding in places like Seattle and New York City, the teams worked quickly.

Those early preparations made all the difference. Although students and most employees were sent home; classes, meetings and appointments were moved online; and a majority of elective clinical procedures were cancelled, the medical campus was still abuzz with activity. By the time the first two confirmed COVID-19 inpatients were admitted to UHealth Tower on March 17, 2020, the University of Miami Health System was ready.

“We had to immediately begin operating in crisis mode,” said Stephen D. Nimer, M.D., director of Sylvester Comprehensive Cancer Center, who chaired the Testing Committee. “There was an imperative to make sure we created a safe environment for our patients and our employees. We were dealing with an unfamiliar disease, there were no established testing programs and protocols, and meeting our goals often required collaborating with colleagues we hadn’t worked with before.”

“In the beginning, when there was a shortage of laboratory instruments in the market, we sent out a call for help to our research faculty and investigators. Amazingly, in less than one week, we had a lab built without spending any money,” Dr. Jorda said. “We had molecular scientists join our team, and we were very lucky to have them to help implement and validate different testing platforms.

“My department was also fortunate to have an array of Ph.D.s, pathologists, laboratory managers and administrators who were able to lead implementation and further the growth of our COVID-19 testing capacity with extraordinary turnaround times. This allowed our health system to maintain urgent procedures during the first weeks of the pandemic.”

Even as a high-volume in-house testing capability was being built, the University of Miami was also serving as the first U.S. university site for a revolutionary pilot study of a rapid coronavirus test that examines air droplets from a person’s breath. The testing subject blows into a small plastic tube, which is then placed into a COVID-19 scanner. The results are available in minutes at a fraction of the time and cost of the conventional nasal swab test.

“Your breath is not dry,” said Roy E. Weiss, M.D., Ph.D., chair of the Department of Medicine and the University of Miami’s chief medical officer for COVID-19. “It contains moisture, and that moisture contains droplets. And if you have COVID, the virus will be in those droplets.”

Following the pilot test last December, the device was used to test thousands of UM students this spring when they returned to campus.

Given COVID’s infectiousness, patients would have to receive the best care possible, while being isolated from everyone else.

“We essentially ran two parallel hospitals,” said Kymberlee J. Manni, Ph.D., CEO of University of Miami Hospital and Clinics, who led the planning and implementation of its COVID care strategy. “One was just for COVID-19 patients. They weren’t in separate buildings, but they were on separate floors, with different personnel taking care of them.”

Following the direction of Dr. Parekh as COO, UHealth’s comprehensive approach to managing elective procedures during pandemic surges addressed patients’ needs and safety, as well as the financial stability of the hospital. Tanira B. D. Ferreira, M.D., chief medical officer for University of Miami Hospital and Clinics, explained how it was done.

“We developed a model that allows us to locally predict what the expected census will be for our organization within the next seven to 14 days,” she said. “We can plan for the increased beds we will need for COVID-19 patients, while safely caring for non-COVID-19 patients.”

Similarly, when the COVID patient population was high, anesthesia machines that were going unused due to cancelled elective procedures could perform double duty as ventilators.

The plan caught the attention of one of the most prestigious scientific journals in the U.S., the New England Journal of Medicine, which published an article written by Dr. Ferreira about the UHealth model.

“Having a plan that safely accommodates COVID-19 and non-COVID-19 patients in a single institution during a pandemic surge is no small effort,” she said. “The challenge and our response brought out the best in us.”

Most of the COVID patients entering the hospital came in through the Emergency Department, which quickly adapted its processes to handle the new threat. It was critically important to keep COVID and non-COVID patients separate — particularly cancer patients, who might have suppressed immune systems.

“We initially developed an outdoor triaged section, where we would have a nurse, a tech and registration to see patients when they arrive and determine if they were experiencing COVID symptoms,” said David Lang, D.O., clinical chief and medical director of emergency medicine at UHealth Tower. “We had a duty to keep patients, family and our own staff as safe as we could.”

Eventually, the triage section grew into an outdoor clinic, complete with a large, air-conditioned tent, in which many patients could be tested, treated, and discharged without ever having to enter the main building — essentially, a second emergency department. People who were severely ill were quickly moved to the new COVID ICU facilities on the hospital’s top floors.

But for hospital staff, perhaps the greatest challenge was endurance, as they dealt with some of the sickest patients for months.

“I have been in practice for 26 years, and this was the most exhausting,” Dr. Lang said. “I think the resiliency of everyone in the hospital — medical staff, nursing, registration — has been incredibly impressive. The unsung heroes are the people in Environmental Services. Physicians go in and out of patients’ rooms, but Environmental Services cleans those rooms when patients leave. They deserve maximum credit.”

The protection of staff, clinicians and physicians was a massive and ongoing task. The Equipment and Resources Committee, headed by Shivank Bhatia, M.D., chair of the Department of Interventional Radiology, used the skills of physicians, supply chain professionals and others to help ensure the hospital would provide excellent care throughout the pandemic.

“It was a group effort,” Dr. Bhatia said. “Our committee worked tirelessly to ensure both adequate supplies and quality of care.”

That meant ventilators and other supplies, but especially personal protective equipment. University leadership invested heavily in PPE early on because it allowed teams to protect themselves against COVID, as well as protecting the patients from cross-contamination.

Thankfully, things are different now.

“We have 90 days’ supply on hand,” Murphy said, “and we have negotiated some longer-term deals on allocations, so we are protected.”

Murphy gives credit to all the Supply Chain Services workers behind the scenes who did so much to keep both patients and frontline workers safe.

“They made it happen,” he said. “Unlike what you saw in the news about other places, we didn’t have anyone here walking around in garbage bags and using socks for gloves. There was a concerted effort to do it right, and they should be proud.”

Ensuring the safety of patients and staff also required physical renovations and instructional signage in the health system’s many buildings. In all, UHealth Facilities, Operations and Planning visited more than 200 clinics and patient-care areas, as well as 37 faculty, staff and student buildings. In the process, they conducted more than 50 site assessments to provide recommendations on how to align to COVID guidelines.

“With the assistance of Hospital Operations and leadership, we installed close to 1,000 plexiglass respiratory shields, prepared more than 20 auditorium and classroom areas, and installed nearly 1,500 signs across the UHealth and Miller School system,” said Edward Hengtgen Jr., assistant vice president for planning, design and construction.

Early on, UHealth needed to handle high call volume, as people sought COVID information. On March 11, 2020, when there were still only 20 diagnosed cases in Florida, the Department of Health contacted Richard Weisman, Pharm.D., at the Miller School to ask if the Florida Poison Control Network could take over the Department of Health’s COVID-19 hotline. Overnight, the call volume had gone from 500 to 2,000 calls per day, swamping the Department’s existing capabilities.

Dr. Weisman, who oversees the UM/JMH Poison Control Center, a cooperative venture with Jackson Memorial Hospital, reached out to the state’s other two poison centers in Tampa and Jacksonville. The centers have a long history of operating the state’s emergency hotlines for H1N1, Zika, and the Deepwater Horizon oil spill, so they had the structure in place. The plan was to move calls to the poison centers within 48 hours, and on March 13, 2020, it went live.

“On that first day, we answered 2,800 calls,” Dr. Weisman said. “It was all hands on deck for our staff and rotating residents and medical students, and we could see that we would need more help, and quickly. Working closely with the leadership at the Miller School and Jackson, we formulated a strategy to staff the center.”

Dr. Weisman, who is also associate dean for admissions, knew the first place to turn — The Mitchell Wolfson Sr. Department of Community Service (Wolfson DOCS), a medical student volunteer group. He contacted the Wolfson DOCS Emergency Response Team, and the response was immediate. The number of volunteers eventually grew to 175 — nearly an entire medical school class.

“The hotline is now the official Florida Department of Health Adverse Reaction Hotline for all of the COVID vaccines in the State of Florida,” Dr. Weisman said.

Other students at the Miller School, and across the country, responded to the challenge by setting up charitable organizations to provide PPE, meals, groceries — even child care — for health care workers on the front lines. Social media connected similar efforts at other medical schools. Through this contact, students shared what they were doing, what was working and the challenges they had encountered.

“We learned to work from our offices and even from home, often sharing the space and camera with our loved ones to deliver health care and education,” Dr. Weiss said. “Nine months later, we mobilized again, rolling out the first vaccines to our frontline health care workers and staff, then to our most vulnerable patients.”

“For society in general, this is a game changer,” Dr. Weiss said. “This will enable us — several months from now, depending upon the rate at which we vaccinate people — to be able to resume a life similar to what we knew before the pandemic. When you stop to think about all that has happened in a year, it really is quite remarkable.”

Still, not everything could be planned, and the health system pivoted as the crisis demanded, at one point supporting Miami-Dade Fire Rescue and the U.S. Coast Guard as they evacuated two cruise ships. Caring for patients from skilled nursing facilities posed another challenge. Patients recovered but still tested positive for the virus, so they couldn’t be released to their home facilities.

Even having people work remotely proved problematic. The hospital soon learned its VPN network wasn’t designed to handle the load. Additional resources had to be acquired, quickly, but they also had to be secure; hospital data systems around the country were being attacked by opportunistic hackers.

“This wasn’t just one black swan event, it was a flock,” Torres said. “We had COVID and civil unrest right outside our door, a major brush fire in Naples, cyber threats. Events that are only supposed to happen one time in a century were happening all at once. COVID really tested us, and sometimes broke things, but we all worked together as a team to fix them. We kept it all working.”

Antibody testing has been an ongoing concern. Even now, lab tests cannot tell clinicians if a patient has antibodies that actually neutralize the SARS-CoV-2 virus — a major diagnostic gap for hospitals around the world.

To overcome that, David Andrews, M.D., associate professor in the Department of Pathology and Laboratory Medicine, and Dr. Nimer are leading a clinical trial to study a new instrument that tests for neutralizing antibodies.

“If the FDA approves this device, we’re going to be one of the early adopters,” Dr. Andrews said.

Dr. Andrews and colleagues in the Department of Pathology are also paying close attention to viral variants. Because Miami is an international destination, virtually all variants end up here eventually. The pathology team is using genomic sequencing to track which ones have come in and how deeply they have entered the population.

“We have seen a significant increase in the U.K. variant, which is now in roughly half of the positive tests,” Dr. Andrews said.

Some of these variants are evolving resistance to the body’s immune response, which could drive reinfections in those who have already contracted the virus but have not been vaccinated. The good news is that current vaccines (and there are more on the way) are showing strong protection against all variants.

“Even if they are exposed to one of these variants, people who are vaccinated have at least good partial protection,” Dr. Andrews said, “which means it will keep you out of the hospital.”

As challenging as the COVID-19 pandemic has been, UM did not go it alone. Dr. Parekh, as the chief operating officer, held ongoing conversations with federal and state authorities, and other hospitals and health systems.

“It has been critically important that we work together to share our experiences for the benefit of our patients and community,” he said. “Frequent collaboration and communication with partners was key.”

UM set up a Therapeutics Committee, one of many COVID-focused groups, which brought in experts in infectious diseases, ethics, and critical care medicine. Committee members spoke often with colleagues around the country to learn from their experiences. These conversations likely saved many lives.

“We learned a lot from colleagues in places like New York and Seattle, which had it much worse in the beginning,” Dr. Weiss said. “For example, early intubation, where we place a tube in the patient’s lungs, was not always the right thing to do. As a result, our mortality rates were much better because we learned from what they had already experienced.”

COVID testing has been a critical part of the pandemic response, but it’s a cumbersome process. Instrumentation is expensive and people often wait too long for results.

Sylvia Daunert, Pharm.D., M.S., Ph.D., Lucille P. Markey professor and chair of the Department of Biochemistry and Molecular Biology, and her colleagues saw this problem early and began working on a fast, point-of-care COVID-19 diagnostic that could be easily deployed in emergency rooms, community clinics and doctors’ offices.

Clinicians take a pharyngeal swab or saliva sample, combine it with reagents, and apply it to a test strip. The test can be conducted at room temperature, simplifying the process even further. Much like a pregnancy test, a positive result produces two lines, a negative only one.

The test platform, which is currently being evaluated, is not limited to COVID-19 and can be reconfigured to diagnose a variety of viruses, providing a leg up if and when another pandemic comes along.

“Our platform is easy to tune to different pathogens,” Dr. Daunert said. “We can just develop reagents that are specific to the new virus, and we can do that very quickly.”

Millions have been tested, sometimes frequently, to determine if they have contracted the SARS-CoV-2 virus. But what if we could detect an infection earlier, before noticeable symptoms, simply by tracking biometric data?

That’s the idea behind a study sponsored by the Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA). Researchers at the Miller School and other institutions are studying a wearable device, similar to an Apple watch, that records biometric information to see if it can detect physiological changes prior to developing COVID infections.

Frank Penedo, Ph.D., associate director for Cancer Survivorship and Translational Behavioral Sciences at Sylvester Comprehensive Cancer Center is heading the Miami arm of the study.

“This watch collects a whole set of biometric data, and we hope to capture signs a person may be infected, even before they have a positive PCR test,” Dr. Penedo said.

The watch measures heart rate and heart rate variability, blood pressure, respiration, temperature, skin conductance and other markers. The researchers believe they may be able to capture patterns that provide an early warning for COVID infection.

“This is a really novel approach that may help us identify and isolate individuals about to seroconvert,” Dr. Penedo said. “If we can capture that before the disease becomes active and contagious, we can quarantine people so they don’t pass the virus to others.”

To better understand how these physiological changes can be used to predict disease, the scientists will compare the biometric data to daily COVID tests results. The study is currently recruiting health care workers to test this approach.

“We are very eager to analyze the data,” Dr. Penedo said. “It’s going to take a little bit of time, but I think we’re going to learn a lot about how COVID starts impacting the body’s physiology before it’s obvious a person has contracted the virus.”

Over the course of the pandemic, clinicians and researchers have learned a lot about treating COVID patients, but there’s a lot more to discover.

Camillo Ricordi, M.D., who directs the Diabetes Research Institute and Cell Transplant Center, has been studying the therapeutic effects of mesenchymal stem cells (MSCs) in diabetes and other conditions for decades.

When COVID first hit, he quickly petitioned the Food and Drug Administration to begin a Phase 1/2a clinical trial to test the safety and efficacy of umbilical cord-derived MSCs to treat the lung inflammation associated with severe COVID. Specifically, he wanted to determine if MSCs could mitigate the COVID-induced cytokine storm — an overactive, and sometimes deadly, immune response.

“These cells are immunomodulatory and anti-inflammatory,” Dr. Ricordi said. “They fight the cytokine storm and promote tissue repair and regeneration. We reasoned that if you deliver them to the lungs via a simple peripheral vein infusion, they should help.”

The results from the first small trial, which began in April 2020, were impressive. The researchers infused MSCs into 12 COVID patients with potentially deadly acute respiratory distress syndrome. Of those, 100% of the subjects less than 85 years of age were alive at the one-month follow-up. Overall, only one patient died, and there were no serious adverse effects from the treatment. The survival rate in the control group was less than 42%.

While the primary goal was survival, the study also looked at recovery times and found MSC infusions improved those, as well. Participants in the control group often took a month or longer to leave the hospital, while infused patients often recovered in two weeks.

“In this initial clinical trial, we demonstrated that MSCs are safe, improve patient survival and time to recovery, and block the cytokine storm that characterizes the most severe cases of COVID-19,” Dr. Ricordi said.

Dr. Ricordi’s team is continuing its work in a Phase 2b/3 COVID-19 trial and in other conditions.

“Now that we have shown the safety profile and the anti-inflammatory and immunomodulatory effects, we are moving forward with more robust trials for COVID-19,” Dr. Ricordi said. “In addition to COVID, we see many other possible clinical applications.”

For some, COVID infections come in two phases: the acute, potentially deadly, onset followed by a series of chronic symptoms. One of these is brain fog. Though poorly understood, brain fog describes mental sluggishness that doesn’t go away.

“The term ‘brain fog’ is, in itself, a little foggy,” said neurologist James Galvin, M.D., M.P.H. “There’s no real medical term because there’s no clear understanding of what it actually is. It describes people who previously had no troubles with their thinking, but now everything seems cloudy, unclear or hazy. They just can’t think clearly.”

Brain fog is not unique to COVID. People with diabetes experience it when their glucose levels go unregulated. Patients with lung conditions, like emphysema, may experience fuzzy thinking because their brains are not getting enough oxygen. COVID patients can encounter a similar condition.

“If your lungs aren’t functioning at peak capacity, your brain may suffer from relative lack of oxygen,” Dr. Galvin said.

The immune response may also contribute to brain fog, as can antihistamines and cough medicines, which may contain dextromethorphan, a compound that can cloud thinking, particularly for older people.

While there’s no evidence the virus attacks neurons, there are indications it affects small blood vessels, which might indirectly affect brain cells.

“If you have lots of microvascular changes with a high inflammatory response that’s going on throughout the body, it could also happen in the brain,” Dr. Galvin said. “A likely symptom would be a general lack of sharpness. If the virus has an impact on the inflammatory and microvascular systems, that could be generating these long-term effects.”

On top of everything else, a year of COVID has generated stress, isolation and other conditions that are bad for our brains.

“People are isolated, they’re under more stress,” Dr. Galvin said. “They’re concerned about their disease risk and financial situations; they’re figuring out how they’re going to manage their kids, who are being homeschooled. You have to factor in these psychological aspects.”

People worldwide have been understandably excited about the Pfizer, Moderna and J&J vaccines, but there are more on the way. Given the virus’s potential to evolve resistance, this is excellent news.

Natasa Strbo, M.D., D.Sc., assistant professor in the Department of Microbiology and Immunology, has been working with a North Carolina company called Heat Biologics on one of these next-generation vaccines.

The platform uses a protein called GP96, part of a family of immune-system-signaling molecules. When cells die, GP96 notifies the immune system, the biological equivalent of “cleanup in aisle 5.” Dr. Strbo’s lab is combining GP96 with SARS-CoV-2 antigens to wake up immune cells and generate T cells that will clear out infected cells.

The GP96 vaccine could be used on its own or in combination with the other vaccines to enhance their efficacy.

“Our vaccine will induce antibody responses, as well as T cell responses,” Dr. Strbo said. “Antibodies attack the virus particles that aren’t inside cells. But once the virus is inside, antibodies are no longer effective. T cells get rid of the cells that have been infected by the virus. So, both are important for overall protection against viral infection.”

Dr. Strbo and her collaborators have been busy generating cell lines and testing the vaccine in preclinical models, which have shown it is both safe and effective. The team is now pursuing more sophisticated preclinical studies to pave the way for human trials.

“COVID’s challenges continue, but so does our commitment to our patients and our community,” Dr. Parekh said. “I have great confidence in our world-class researchers, clinicians, staff, and students. Their teamwork has made all the difference in our fight against COVID and fulfilling our mission.”

Maya Bell, Lisette Hilton and Janette Neuwahl Tannen contributed to this story.

UNIVERSITY OF MIAMI MEDICINE

SPRING 2021