PHILADELPHIA—New data suggest statins as a potentially helpful class of drugs to fight COVID-19, and pointing to that study, two researchers in the Perelman School of Medicine at the University of Pennsylvania propose a framework for a systematic approach to drug repurposing for the novel coronavirus. Their commentary published today in Cell Metabolism.
“I prescribe statins to patients with high cholesterol very often—these medications are safe, affordable and widely available. To be able to use a drug with this long history of safety, that is relatively cheap and that is already in production around the world, compared to the time and cost it takes to develop entirely new drugs, would be a major step forward in treating this virus,” said Daniel Rader, MD, chair of Genetics and associate director of Penn’s Institute for Translational Medicine and Therapeutics.
Earlier this month, Xiao-Jing Zhang and colleagues reported the first large observational study of statin use among 13,981 patients hospitalized with COVID-19 in Hubei Province, China in Cell Metabolism, and they found the risk for 28-day all-cause mortality was 5.2 percent in the statin group and 9.4 percent in the non-statin group.
Rader and co-author David Fajgenbaum, MD, MBA, MSc, an assistant professor of Translational Medicine & Human Genetics and director of the Center for Cytokine Storm Treatment & Laboratory (CSTL), an assistant professor of Translational Medicine & Human Genetics and director of the Center for Cytokine Storm Treatment & Laboratory (CSTL), suggest there are several possible ways in which statins could be helpful in COVID-19 patients. In COVID-19, the host’s immune system must mount an effective response to control the virus but avoid responding too aggressively and inducing a ‘cytokine storm,’ which poses the greatest risk of death. This has led to great interest in medicines that could potentially limit immune hyperactivation, of which statins are one. Another potential mechanism of action of statins in COVID-19 could be through inhibiting SARS-CoV-2 entry into cells by binding the main protease. It is also possible that these results were due to some confounding factor and that statins are not effective in COVID-19.
Nevertheless, this observational study by Zhang establishes statins as a class of medication that merits additional observational (replication), mechanistic, proof-of-concept, and randomized studies to better understand its potential to help fight COVID-19, Rader and Fajgenbaum wrote.
“Everyone wants effective treatments for COVID-19 as soon as possible, but we have to be disciplined about evaluating the data,” Fajgenbaum said. “COVID-19 is an incredibly complex disease. This is an interesting result, but it is not the final answer on whether statins are effective treatments for COVID-19. These results warrant further research through well-designed randomized-control trials — that is our best bet to save lives.”
Fajgenbaum began the COVID Registry of Off-label & New Agents (CORONA) project in March 2020 to collect data on all treatments that have been used against COVID-19 in a central, high-quality database. His team analyzes the studies so that physicians currently treating COVID-19 patients know what treatments are being used worldwide and so that promising drugs can be appropriately prioritized for well-designed randomized controlled trials.
“Dexamethasone recently illustrated why we need to be doing randomized controlled trials,” Fajgenbaum said. “It has been around for years and costs less than a dollar a day, but many organizations strongly recommended against its use at the beginning of this pandemic because of its potentially negative effects during the SARS-1 epidemic. In our database we were really surprised early on because we kept seeing corticosteroids like dexamethasone being given over and over, despite the international recommendations. Then a randomized control trial in the United Kingdom showed it to be really effective in the most severely ill COVID-19 patients. Unfortunately, there are also experiences where drugs look really promising initially and then fail to show an effect in RCTs.”
RCTs, as randomized controlled trials are known, are able to help ensure that patients on a given drug are compared against patients with similar disease severity who are not given the drug. Observational studies, like Zhang’s statin paper, provide insights into potentially effective treatments and how to best design RCTs, but the RCTs must be done to determine effectiveness.
Adding further complexity, research to date suggests that COVID-19 will likely need different drugs depending on the patient’s severity of illness and timing within the disease course. Rader and Fajgenbaum say randomized controlled trials are needed to provide evidence-based results, so that clinicians and researchers can save the most lives and be better prepared for future epidemics.
Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $8.6 billion enterprise.
The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $494 million awarded in the 2019 fiscal year.
The University of Pennsylvania Health System’s patient care facilities include: the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center—which are recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report—Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.
Penn Medicine is powered by a talented and dedicated workforce of more than 43,900 people. The organization also has alliances with top community health systems across both Southeastern Pennsylvania and Southern New Jersey, creating more options for patients no matter where they live.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2019, Penn Medicine provided more than $583 million to benefit our community.