The scramble to combat the coronavirus has produced an avalanche of research focused on developing a vaccine, deploying infection-blocking therapies, and using drugs to mitigate the worst symptoms of the disease.
Now a rapidly formed group of diverse specialists at the University of Colorado School of Medicine is playing a longer game, looking also to develop tools to understand why the infection affects people differently and use that information to sharpen patient care.
The working group, informally dubbed the COVID-19 research consortium, had its first meeting March 16. It includes basic research scientists, clinicians, information technology specialists and environmental health and safety experts. The group is working with Vice Chancellor for Research Dr. Thomas Flaig to build a biorepository of clinical samples (nasal swabs and blood, for example) taken from patients who test positive for COVID-19 at UCHealth University of Colorado Hospital on the Anschutz Medical Campus, Children’s Hospital Colorado, the Rocky Mountain Regional VA Medical Center and potentially Denver Health.
The idea is that analysis of these samples will give researchers a window into the still mysterious disease that is caused by a virus, SARS-CoV-2, that our immune systems have never seen, said Dr. David Schwartz, chairman of the Department of Medicine and professor of Medicine and Immunology at CU. Schwartz initiated the consortium with Dr. Rosemary Rochford, professor in the school’s Department of Immunology & Microbiology. Many investigators and trainees are involved in the project, Schwartz added.
Fighting in the dark
SARS-CoV-2 is very similar to other coronaviruses, including MERS-CoV and SARS-CoV, which cause Middle East respiratory syndrome and severe acute respiratory syndrome, respectively, Schwartz said. In some ways not yet understood, however, SARS-CoV-2 carries biologic weaponry that the other viruses lack.
“It challenges our immune systems in unique ways,” Schwartz said.
In addition, the immune response among people who contract COVID-19 varies in unpredictable ways. For example, in some infected patients, the immune system mounts a massive inflammatory attack that exacerbates the pneumonia that the disease causes. Some people who are exposed to the disease bounce back very quickly, while others get very sick – even those who are not otherwise obviously vulnerable because of age and/or other diseases that weaken their defenses.
Dialing up the data
Enter the biorepository and its potential cache of valuable biologic and genetic data.
“It will allow us to ask questions about why certain people are affected and why the disease is so different in one person than another,” Schwartz said. For example, researchers might consider to what extent, if any, an individual’s age, medications or diseases like diabetes, hypertension or various types of lung problems influence the body’s inflammatory response to the SARS-CoV-2 infection and how immune cells attack it, he explained.
Answers to those questions, in turn, would help clinicians decide the level of risk for individual patients and make more informed medical decisions about the care they require: who can be safely sent home to isolate and care for themselves; who should be hospitalized at least briefly; and who needs intensive care. Such an approach could help to ease the strain on already scarce resources, most importantly ventilators, while potentially saving lives.
“We want to understand who is at risk for severe disease,” Rochford said. “If you can identify those people when they come in, you can intervene early on.”
Setting the research table
The consortium is primarily focused on disease prediction, but the group is also coordinating with researchers interested in finding new treatments and developing vaccines, Schwartz said. In fact, deeper knowledge of the microbiology of SARS-CoV-2, and its effects on the immune system work hand-in-hand with clinical discoveries, Rochford added.
For example, she said, understanding the immunologic response of people who ward off the most serious effects of COVID-19 aids vaccine research, while identifying the triggers for a dangerous inflammatory response – proteins like cytokines, for example – helps to direct investigation of ways to mitigate the disease.
The information from the biorepository, which could be analyzed by consortium members from a variety of perspectives, will help to “set the table” for focused research studies, Rochford noted.
“You have to know what you are working with before you start developing interventions,” she said. “Who is the enemy? How are we seeing that enemy and what is it doing to us? What are the biomarkers you can screen for? We have to start there.”
Rochford also emphasized the importance of cooperation between basic science researchers and clinicians in finding the answers to these questions. “Working together is the way we tackle this thing,” she said. “We’ve been talking for years about ‘Team Science.’ This is it. We can be more creative when we bring all minds to the table to address the problem.”
The consortium is still working out operational details for the biorepository and developing a protocol for collecting and administering samples. That will be coordinated through Flaig’s office, Schwartz said. And while the idea for the biorepository was initiated through the consortium, an advisory group will be established so that any scientist on the campus can put forth a proposal and if approved have access to these samples.
The overall goal of the protocol is to ensure safety while building a deep biorepository of data, Schwartz explained.
“We are trying to minimize exposure of staff to the coronavirus and to patients that are COVID-19 positive and at the same time maximize use of the specimens so that the largest number of investigators can use them,” he said.
That means not only taking appropriate steps to protect health care workers from virus transmission in the clinical setting but also ensuring safety in the lab, where researchers will be working with this dangerous pathogen.
Search for safe treatments
The blizzard of research into COVID-19 treatments continues to grab plenty of headlines as SARS-CoV-2 claims victims at an accelerating pace. They include investigations into vaccines, most notably a National Institutes of Health study of using messenger RNA to spur cells to express a virus protein that revs up the body’s immune response to SARS-CoV-2.
Other experiments have focused on using existing drugs developed for other purposes. The Centers for Disease Control and Prevention has detailed information on these drugs. Another useful review of current (at least for the moment) COVID-19 pharmacology is here.
In addition, a clinical trial now recruiting patients looks at the rheumatoid arthritis drug sarilumab, which blocks the IL-6 protein that may drive the massive inflammatory response that ravages the lungs of some COVID-19 patients. University of Colorado Hospital is involved with the study of sarilumab, as well as two studies of remdesivir – a drug that was previously tested against the Ebola virus in humans and against MERS-CoV and SARS-CoV in animals – to treat patients with moderate and severe cases of COVID-19. Dr. Thomas Campbell, professor of Medicine-Infectious Diseases at CU, said he hoped the sarilumab trial could start late in the week of March 23, while the remdesivir trials might begin in a week or two.
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But despite the obvious hunger for a cure or at least a highly effective treatment for the disease, Schwartz cautioned that responsible research requires both time and dispassionate analysis driven by data, not by hope or anecdotal evidence. In addition, the belief that it is worth trying anything in the hopes of finding success is misguided.
For example, while he sees promise in the anti-IL-6 trial, Schwartz added, “We don’t know whether it will work or not, and that’s why the research must be done. The lay public needs to know these drugs are powerful and might cause more problems than they solve,” he said.
Keeping our distance
In addition, Schwartz urged people to adhere to the basic tenets of public health that medical experts and responsible government leaders have been urging for many weeks: physical distancing, also known as social distancing; regular handwashing; minimizing contact with infected individuals; and using personal protective equipment when it’s necessary to be around someone who is infected.
“These are measures that we know will prevent passing the virus from one person to the next,” he said. He emphasized that the rapid spread of COVID-19 dictates that social distancing can no longer be casually observed, but rather “needs to be strictly enforced.” In Colorado, that is at the heart of the stay-at-home orders issued for Denver on March 24 and followed by a statewide edict by Governor Jared Polis that began March 26.
“We need to stay at home and limit our exposure to people outside of our families. This will be tough for all of us but it’s the only thing that will slow the spread of the virus. Only go to stores for essentials,” Schwartz said.
It’s up to all of us to take those preventive steps. At the same time, the research consortium is intent on bringing its combined experience and expertise to the broad fight against COVID-19, Schwartz concluded.
“This has been an incredibly cooperative group of individuals who are dedicated to reducing the risk of COVID-19 infections across our population and understanding how to best treat patients who develop this infection,” he said.