Posted on: April 22, 2020
As the number of COVID-19 cases continues to climb across the country and throughout South Carolina, there is a growing public thirst for information about treatment options. A Google search leads to the arduous task of discerning fact from fiction. When social media amplifies misinformation, understanding the realities of COVID-19 becomes complicated for patients, loved ones, and health care providers.
Infectious diseases (ID) experts are at the forefront of the COVID-19 crisis. The University of South Carolina College of Pharmacy is fortunate to claim two of these front line heroes as our own. UofSC's Clinical Associate Professor Julie Ann Justo, Pharm.D., M.S., and alumnus and Associate Professor Brandon Bookstaver, '04 Pharm. D., are ID pharmacists. They complement their teaching of pharmacy students in the College of Pharmacy with clinical practice at Prisma Health Richland.
Their worlds have changed significantly in the past few months. In addition to providing care for patients who have contracted COVID-19, they continue to work with patients affected by other diseases. Beyond direct patient care, both Justo and Bookstaver develop and continually revise inpatient and outpatient treatment guidance for this novel infection. They regularly field questions about COVID-19 from physicians, nurses, and other medical staff and now carry COVID-19 pagers.
Lack of an Evidence-based Therapeutic Regimen
Justo and Bookstaver continue to invest many hours in reviewing and assessing COVID-19 literature, however, both have noted unique challenges in the published evidence for this novel coronavirus. The volume of information received daily, combined with increasing pressure to release data as quickly as possible, has negatively impacted the valuable peer-review process for COVID-19 literature.
The urgency and speed of this emerging data have been overwhelming. I think it's important to admit that ...
Julie Ann Justo, Pharm.D. Clinical Associate Professor
"The urgency and speed of this emerging data have been overwhelming. I think it's important to admit that," said Justo. "All of us are struggling one way or another to maintain a high bar for literature review. We've started to see a lot more publications and journal articles that are coming out at the stage we call 'pre-print.' This means someone literally wrote a manuscript and posted it online, not necessarily waiting for the point where the piece has gone through peer review, critical analysis, and editing from experts in the field."
"This has caused much confusion, and many feel this has somewhat decreased the overall quality of literature that is currently being made available online," Justo explains. Justo says that her job is to optimize the benefit-to-risk ratio for a particular therapy for each patient and assess if the available evidence for the specific therapy meets her high bar for quality care. "Doing that helps me sift through the noise - some of which is good and some of it not so good. It is gut-wrenching to have a patient, a physician, or nurse turn to you and ask, 'What else can I do?' and feel like you don't have a sufficient answer. I understand our tendency for bias – we all want answers, but first, we must do no harm."
Clinical Trials
Both Justo and Bookstaver say that whenever possible, patients are enrolled in clinical trials. Both are quick to point out that the clinical trial process represents collaborative work from multiple health professionals. Both Bookstaver and Justo share enthusiasm for working with clinical trials. They also acknowledge the related challenges.
Bookstaver explains, "With the trials going on, you can imagine it is a little bit overwhelming for a relatively small research division at Prisma Health Midlands. You have folks that are working to the extreme, and sometimes things get stretched." The responsibility of quickly assessing and prioritizing which of the available trials holds the most promise is a significant one, along with meeting trial enrollment goals.
Data from clinical trials is critical, says Justo. "When we don't have an answer for whether agents will work, the best venue and format to deploy the therapies is in the context of a trial. We have been liaising with the clinical trials department within Prisma Health as well as with research collaborators at the University of South Carolina, many of which have been in the College of Pharmacy and the School of Medicine. The clinical trial process is a big piece of it."
Justo shares her excitement about Prisma Health Richland's participation in the Gilead Sciences' clinical trials, which is treating patients with its antiviral medicine, remdesivir. Remdesivir is one of the first medicines thought to have a potential impact on SARS-CoV-2, the novel coronavirus that causes COVID-19 infection. Justo explains the drug was one of the investigational antivirals studied as a possible treatment for Ebola but was ultimately shown to be ineffective against that particular virus. In vitro data suggest it may be successful against SARS-CoV-2.
Bookstaver shares information about another angle being explored by the ID specialists and their partners, involving the introduction of convalescent plasma to the therapeutic regimen of COVID-19 patients who are not effectively fighting the virus. Convalescent plasma contains antibodies from patients who have recovered from COVID -19.
If a convalescent plasma is developed locally, it is probably going to be first used locally ...
Brandon Bookstaver, Pharm.D. Clinical Associate Professor
"We are not alone in trying to do this, but it is important that we are engaged with this and have been for weeks." Bookstaver explains that the local development of convalescent plasma therapy would decrease dependence on sourcing from other parts of the country. "Further, if a convalescent plasma is developed locally, it is probably going to be first used locally. I think that's logical."
Inside the Storm
Cytokine storm, a condition representing an overreaction of the body's immune system, has received media attention in part for the dramatic and rapid way it can negatively affect the status of a patient with COVID-19. While cytokines naturally play an essential part of the human body's immune response, cytokines may, without warning, get out of control, creating an immune response that can damage organs like the lungs and kidneys. They also can cause death. Justo shares that there are some laboratory markers and other non-specific clinical symptoms that physicians and other health care professionals can look for to assess when a patient may be entering cytokine storm. Cytokine storms are not specific to COVID-19.
Are there therapies for preventing or stopping cytokine storm? Justo shares information about tocilizumab, one of the first agents being studied for its potential to blunt cytokine storm in an individual patient. Tocilizumab is a monoclonal antibody with indications for rheumatoid arthritis and giant cell arteritis. Tocilizumab is also used to treat severe and life-threatening cytokine release syndrome (CRS) caused by an overactive immune response to certain types of blood cell cancer treatments. Justo says the downside of the drug is its short supply, high price point, and potential side effects like weakening of the immune system against other possible infections. She adds that approximately half of the experimental agents they are currently working with are classified as immunotherapies, or agents used to blunt cytokine storms and other exaggerated reactions of the immune system.
New Opportunities
Bookstaver and Justo are leading the development of a COVID-19 specific state-wide treatment registry to measure treatment outcomes in South Carolina. The registry will also serve as a robust database for clinicians, regulatory agencies, and researchers. "We have secured partnership letters from several large medical centers and health systems in the state, DHEC and three major pharmacy and infectious diseases organizations in South Carolina," Bookstaver said. "We are excited to move this forward."
At a national level, the U.S. Department of Health and Human Services (HHS) recently published guidance on April 8, under the Public Readiness and Emergency Preparedness (PREP) Act, authorizing licensed pharmacists to order and administer FDA- approved COVID-19 tests, including serology tests, for the duration of the COVID-19 pandemic. Bookstaver shares that there will be opportunities for local pharmacists to be involved in the rollout, potentially as evaluators or trainers.
A joint statement was recently released by the American College of Clinical Pharmacy (ACCP), Society of Infectious Diseases Pharmacists (SIDP), Infectious Diseases Society of America (IDSA), Society of Healthcare Epidemiology of America (SHEA) and the Pediatric Pharmacy Association (PPA) applauding HHS's recognition of the significant responsibilities pharmacists have during this epidemic and the high value of their strategic considerations. Bookstaver was one of the contributors to the guidance document.
In addition to a shared commitment to their joint roles as faculty and clinicians, Bookstaver and Justo are highly involved in national pharmacy organizations. Bookstaver serves on the ACCP Board of Regents while Justo serves on the SIDP Board of Directors as its communications director. In response to COVID-19, Justo helped produce and release educational videos from SIDP's member pharmacists who are dealing with experimental agents related to COVID-19. This SIDP COVID-19 Resources page also includes other helpful resources, such as a COVID-19 podcast episode featuring Justo.