“Just putting it on and taking it off is an adventure in itself,” said Harrod, professor in the Department of Anesthesiology and Perioperative Medicine. “You have to be especially careful when taking it off to not touch the outside. There’s a bit of a gymnastics aspect.”

This is Harrod’s third pandemic. During the first SARS outbreak in 2003, Harrod directed experimental model testing of candidate vaccines. Within three weeks of the first cases of H1N1 swine flu appearing in the United States in 2009, “we had the virus in my lab and NIH contracts to work on research,” he said. “I’ve been down this path before and know what it takes to get these things started.”

That is why Harrod received one of 14 pilot grants from the $1.1 million Urgent COVID-19 Clinical Research and Laboratory Research Fund, established by UAB through philanthropic giving and funding from Might’s Precision Medicine Institute. But the PMI is providing more than money, Harrod noted.

“This grant is really built on a team of computationalists who use artificial intelligence approaches to identify drugs that are already FDA-approved and can be repurposed,” he said. “Scientists will probably figure out whole new drugs to treat COVID-19, but that will take years.

This pandemic will probably be gone by then. We said, ‘What can we do now?’”

Harrod provides the biological validation of the drug candidates identified by the team from PMI. Before researchers can figure out how to kill SARS-CoV-2, Harrod and his team had to figure out how to grow it.

“Some viruses are hard to grow in the lab, but we had our practice with the first SARS 17 years ago,” he said. “We used many of the same methods, and lo and behold, they worked well.”

The onset of the COVID-19 pandemic caught Harrod between grants as he was building up to work on influenza. Adrie Steyn, Ph.D., professor in the Department of Microbiology, has a team working on tuberculosis, which also requires biosafety level 3 precautions.

“He said, ‘If you need people, my team is ready to help,’” Harrod said. “There has been a great deal of camaraderie and collaboration at the School of Medicine. Everyone is bringing their level of expertise to bear. That is one ancillary benefit of these tough times.”

In addition to supporting UAB research efforts, Harrod’s lab is serving the Biomedical Advanced Research and Development Authority, which is the federal agency charged with developing countermeasures against COVID-19.

“We’re providing the virology support,” Harrod said. “We grow the viruses, measure them and provide them to the BARDA contractor.”

Harrod has already begun to unleash compounds identified by PMI on viral cultures in the lab.

“We have a three-tier screen that we work through,” moving through a range of cell types, ending with human lung cells, he said.

Steven Rowe, M.D., professor and director of the Cystic Fibrosis Research Center at UAB, is working to develop animal models of COVID-19, something he has pioneered for cystic fibrosis. Rowe’s team is also growing the human lung cells that Harrod tests in his biocontainment lab.

“We have as many as 15 drugs that have been identified, and there are going to be candidates that are worthy of consideration” for human testing, Harrod said. “The beauty is these are all FDA-approved drugs so they could be mobilized really quickly.”

(Courtesy of UAB)

Patients who are potential candidates for the trial include anyone hospitalized with COVID-19 “who is not getting better,” Heath said. Symptoms include shortness of breath, fast respiratory rate and “showing signs they are declining in terms of their ability to oxygenate,” Heath said. “We believe that, the earlier we treat people, the more effective this will be.” She expects to see a benefit within about 72 hours of treatment’s beginning, Heath added.

Convalescent plasma therapy has proved effective during previous outbreaks of severe respiratory infections, including SARS in 2003, H1N1 in 2009 and MERS in 2012. There are indications that the experimental treatment works for COVID-19 as well. In early April, the journal Proceedings of the National Academies of Sciences published a small study from China, in which 10 adults with severe COVID-19 received the therapy. Within three days of their transfusions, the patients’ symptoms had improved rapidly. After a week, virus levels in the patients’ blood were undetectable and lung damage had improved. No severe adverse effects were reported.

The Mayo Clinic trial being conducted at UAB is not a placebo-controlled trial, Heath says.

“Everyone who enrolls gets plasma, and we are using this to treat patients with COVID-19 who are hospitalized on the floor or in ICU,” Heath said. “By contributing the clinical outcomes of all these patients along with other hospitals, we will be able to identify any benefit from this treatment, as well as any potential side effects, more quickly. Hopefully that will help us in the summer and fall, and next winter, be more specific with the way we use this potential treatment.”

Donors needed

The plasma that UAB has used comes from a local blood bank — the hospital has partnered with LifeSouth and the Red Cross.

“We put in requests for the blood samples we need to match to the patient,” Heath said. Just like typical blood transfusions, convalescent plasma must match the recipient’s blood type. The good news is that a single donation should be able to be used to treat two patients, Heath says.

“We have referred about eight to 10 COVID-recovered patients to our local blood banks with help from Audrey Lloyd, a UAB Infectious Disease fellow, and are working on expanding the supply of plasma to treat COVID patients,” Heath said. “But we need more donors.”

Donors must have a confirmed diagnosis of COVID-19 and have been symptom-free for 28 days.

“Most people who are interested in donating plasma will probably be eligible,” Heath said.

Two new studies starting soon — including convalescent plasma as prevention

Heath also is the principal investigator on two new convalescent plasma therapy studies that will open at UAB in the next few weeks. Both are in collaboration with Johns Hopkins University, she says.

“One is treatment of outpatients with COVID-19, and the other is trying to prevent COVID-19 in people who have been exposed,” she said. This “post-exposure prophylaxis” study, Heath said, “means you’ve been exposed to someone with COVID-19 for a long period of time — someone in your house, for example, and you haven’t been wearing a mask and are susceptible to getting COVID. We would treat you with the plasma in the hope this would prevent you from developing the symptoms related to COVID infection.”

The goal, Heath says, is to quickly enroll participants in both those studies. Although the studies will last for 12-16 months, “we will have pre-defined timepoints that allow us to look at the data along the way.”

Although convalescent plasma is a new idea to most people, “we have a long history of treating people with intravenous antibodies,” Heath said. “People in immunocompromised states often receive what is called IV IG — intravenous immunoglobulin. They are getting antibodies from other people to keep their immune systems strong. That has a long and safe history. This time, we’re just saying your immunoglobulin has to come from someone who has recovered from COVID-19, and that protection may be transferrable.”

Research leads the way

While Heath and McCarty treat patients in the hospital, Heath and a research collaborator are working in the lab to better understand the mechanisms involved. Randall Davis, M.D., professor in the UAB Division of Hematology and Oncology, is studying the quality of the donor’s antibody response as a factor in treatment success.

“The science that goes on behind the scenes in these types of clinical trials is very important,” Heath said. “That provides the building blocks we need as we are trying to understand how to make a vaccine or new therapies. As we learn more about these treatments, we can try to duplicate the best antibody response either through a vaccine or through COVID-specific monoclonal antibody development.”

“We want to do this work not only for our patients but also for the benefit of many more people,” Heath said. “We will be able to understand the benefits and risks and find answers much faster to improve the lives of those affected by COVID-19.”

(Courtesy of UAB)

“I have been getting a lot of questions from friends and family because of COVID-19,” Elliott said. “Many of them don’t realize that a vaccine is not the same thing as a cure or treatment. I also have gotten a lot of questions about how the immune system works to protect you from diseases like COVID-19 and how to protect those more at risk.” Elliott’s classmate, Nour Moughnyeh, said “I’ve also been asked quite a bit about the structure of COVID-19 and if I can compare it to the flu so they can get a better understanding of the situation.”

The immune system is an elaborate network of molecules, cells and tissues that work together to defend the body against invading pathogens and disease.  Immunologists — including the renowned investigators at UAB — study this system. Students in the Undergraduate Immunology Program are required to spend a minimum of six credit hours in UAB’s labs, where they can select from positions with more than 100 UAB faculty who are pursuing cutting-edge research in immunology. Many students go far beyond that minimum requirement. Junior McKinley Williams has already “worked in multiple labs at UAB,” she said — first in pediatric infectious diseases research and now in the lab of Michael Seifert, M.D., a pediatric nephrologist in the UAB Department of Pediatrics and at Children’s of Alabama. “The project I am currently working on is a study of immunological rejection and other factors contributing to transplant failure in over 150 renal transplant patients,” she said.

On the front lines

“Immunology is — obviously given the circumstances — a very up-and-coming field and it is very exciting to be on the front lines of understanding such a complex science,” Williams said.

What is obvious now was not so clear a few months ago, when Louis Justement, Ph.D., co-director of the UIP and professor in the Department of Microbiology, and UAB colleagues wrote a paper in the journal Frontiers in Immunology calling for a revolution in the way immunology is taught. “Knowledge in the field of immunology is expanding rapidly, bolstering the need for increased time in the curriculum to facilitate the ability of educators to convey information so that it can be effectively understood and applied,” wrote Justement and his co-authors, Heather Bruns, Ph.D., and Jill Deaver. “We propose that it is time for a renaissance in immunology education at the undergraduate level to better prepare individuals who will subsequently pursue careers in medicine, related health professions, and biomedical research.”

The article was written before the novel coronavirus that causes COVID–19 emerged in China. But its recommendation resonates loudly in the midst of the ongoing pandemic. Today, the vast majority of potential immunologists really only encounter the field in any depth in professional or graduate school, Justement said. This is a far cry from the situation in neuroscience, which has taken off as an undergraduate major during the past several decades. That is one crucial reason why the pipeline of future immunologists — the experts who will design a new generation of vaccines, diagnostic tests and treatments for future pandemics — is relatively meager, Justement said.

“Studying the immune system is hard, and it can take some time before things start to click,” Elliott said. “We have amazing faculty who truly want us to thrive in our learning.”

A next generation for the next pandemic

“We hope to make a difference in creating the next generation of immunologists in health care and research for the next pandemic,” said Bruns, an associate professor in Microbiology. “We’re almost certainly going to be dealing with a pandemic again in our lifetimes. We’ve had three major coronavirus outbreaks in the past 20 years — SARS, MERS and now COVID–19.”

Immunology is a highly interdisciplinary field — a combination of cellular and molecular biology, genetics, biochemistry, physiology and anatomy — that touches every other major organ system and plays a major role in health and disease, Bruns said. In addition to tackling problems such as pandemic viral outbreaks, immunologists are also making ever greater contributions to the fights against cancer, allergies and asthma and efforts to expand organ transplantation to more patients.

Yet according to data that Bruns, Justement and Deaver gathered from the National Center for Educational Statistics, there were only 10 immunology-related majors offered in the United States in 2017–18 — most of them a combination of microbiology and immunology. By comparison, there were 210 undergraduate programs in neuroscience. (UAB’s Undergraduate Neuroscience Program, now a decade old, enrolls roughly 80 students per year, while the UIP brings in 20-25, Justement said.)

“We always say, ‘It’s tough to compete against those cool pictures of the brain,’” Bruns said. “A lymph node doesn’t look like much in comparison.”

Sharing what they know

But the COVID–19 pandemic has changed that. “We think it’s exciting to be an immunology major at any time, but certainly now,” Justement said. As the scale of the crisis in Wuhan, China emerged in January, Rodney King, Ph.D., an assistant professor in Microbiology, began to incorporate regular updates to his junior-level class on adaptive immunity. Bruns, who has joined King in teaching the class as it transitions to remote teaching, has started sending emails to her students that link the latest research papers and news articles to subjects they have covered in class. Justement, who teaches the freshman course on Current Topics in Immunology, is planning to add a focus on the therapeutic potential of using serum from convalescent patients to help those newly infected with COVID–19.

“We’re currently doing a journal analysis on immune responses to COVID-19 and potential vaccines,” Moughnyeh said. It has been fascinating to read about responses to the SARS and MERS pandemics and how “similar patterns are happening in this current pandemic,” she said.

When the students returned from an extended spring break to resume their formerly in-person classes online, Bruns said she was struck with how many had been able to use their training to help educate friends and family members.

“I have been getting lots of questions,” said J. Brandon Taylor Harris. “They’re often asking if the media is exaggerating claims being made about the virus’s ability to spread quickly or harm victims. They’re worried that the news is lying to them about the severity of the virus and that such widespread quarantine is overkill.” Friends and family also have questions about why older people are more vulnerable than other groups or ask for help in interpreting the results of studies and academic papers, he said.

“The current pandemic has strongly reinforced my decision to pursue a degree in immunology and shows how important this career is,” Harris said. He plans to earn a doctorate in immunology and become a researcher. “I’m leaning towards focusing on mucosal immunology and studying how being vaccinated against parasitic worms could prevent inflammatory diseases like irritable bowel syndrome, multiple sclerosis, asthma and autoimmunity,” Harris said. Moughnyeh, who plans to apply to optometry school, has been particularly intrigued by the effects of autoimmune diseases on the eyes. “I noticed most times the eye is affected in some way as a result of these diseases,” she said. “I got really passionate about wanting to advocate for eye care and really emphasize to people just how much about your overall health can be revealed through the health of your eyes.”

“We want people to realize that scientists are heroes — and immunologists are really important scientists,” Bruns said.

(Courtesy of UAB)