Status Report: Drugs Under Study for the Treatment of COVID-19
by Stephen Berger, MD
As of April 10, 2020, thirty-one individual drugs had been suggested for the treatment of COVID-19. And as of that date, none was proven to be effective. The most contentious issue in all of this is the word “proven.”
Over 330 agents are used in the field of Infectious Disease, sold under more than 29,300 trade names worldwide. Drugs used against bacteria, parasites, and fungi take advantage of the biological nature of these organisms and disrupt their ability to grow and multiply, or utilize oxygen, sugars, proteins and other nutrients. Viruses, however, do none of these things – instead invading our cells and converting them into “factories” which produce yet more viruses. Thus, most drugs used against viral disease interfere with various stages of cell invasion or the interaction of viral DNA/RNA with the host cell.
Inevitably, a wide variety of existing antiviral drugs have been proposed for the treatment of COVID-19. These agents are already used for the treatment of Influenza, Hepatitis C, HIV/AIDS, and other infections. Initial results suggest that many of these, which are commonly administered in clinical practice (Oseltamivir, Paramivir, Zanamivir, Ganciclovir, Acyclovir), lack activity against SARS-CoV-2, the agent of COVID-19. Others which have been mentioned include Favipiravir, Galidesivir, Interferon alpha, Interferon beta, Lepdipasvir, Lopinavir, Remdesivir, Ribavirin, Ritonavir, Sofusbuvir, Telbivudine, Tenofovir, and Velpatasvir. Remdisivir and Lopinavir (used in the treatment of Ebola and HIV/AIDS, respectively) have attracted much interest in recent days.
As in many infectious diseases, the signs, symptoms, and complications of COVID-19 are largely determined by the reaction of the patient’s immune system. In a very real sense, a patient with severe and fatal infection will have been killed by his own “over-reaction” to the disease. One key factor in this process is a substance called Angiotensin Converting Enzyme (ACE) inhibitor. ACE is widely distributed in the heart, kidneys, lungs, and testes, and dampens a second process (the Renin-Angiotensin system) which is associated with disruption of blood vessels, triggering of clotting factors, and other elements of inflammation. Ultimately, these local processes lead to massive release of cytokines, chemicals which normally mobilize local anti-infective elements (leucocytes, et al) to contain and destroy invading pathogens.
A key element in COVID-19 infection involves binding of the virus to ACE in the human cell, leading to disruption of these processes.
Thus, the treatment of COVID-19 has increasingly focused on drugs which either block viral attachment or modulate the vascular and immune responses which cause the actual “disease.” Anecdotal reports and small case series have suggested that Chloroquine and Hydroxychloroquine, drugs used in the treatment of malaria and certain inflammatory diseases, are effective in controlling these processes. Colchicine, Ivermectin, Metronidazole, Statin drugs, Sarilumab, Teicoplanin, and Tocilizumab may act through similar mechanisms. Not surprisingly, many publications have also examined the use of traditional Chinese medicines and serum obtained from patients who had recovered from COVID-19.
A key in all of this is how best to facilitate development and release of drugs for COVID-19. The standard processes of committee approval, animal testing, studies in healthy humans, ethical review, licensing, patent issues… are extremely time consuming. Since many of the drugs currently under consideration are already licensed for use in other diseases, both scientists and decision makers will call for an expedited “short-track” approach.
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Stephen A. Berger, MD, is affiliated with the Tel Aviv Medical Center, where he has served as Director of both Geographic Medicine and of Clinical Microbiology. He also holds an appointment as Emeritus Associate Professor of Medicine at the University of Tel-Aviv School of Medicine. Dr. Berger co-founded GIDEON Informatics, developers of the GIDEON (Global Infectious Diseases and Epidemiology Network) web app and the GIDEON series of ebooks. [Full bio.]