The United States has surpassed China and Italy with the highest number of novel coronavirus (COVID-19) cases. As of March 30th, the US has an estimated 149,000 confirmed cases and 2,600 deaths spanning all 50 states and the District of Columbia. The rapid surge in positive cases is a testament to how contagious the virus is and the nationwide expansion of coronavirus testing.
Medical experts, including Dr. Anthony Fauci, Director of National Institute of Allergy and Infectious Disease, anticipate the virus could become a seasonal occurrence and the most effective way to prevent future pandemics would be a vaccine, like the seasonal flu shot. However, coronavirus vaccines will require at least 12 to 18 months of clinical study before they are approved for use.
Meanwhile, clinical trials are underway worldwide to evaluate various treatments for coronavirus infected patients to identify those that are safe and effective. Drugs under consideration include some that are available now because they are FDA approved to treat other diseases. Therefore, the possibility of repurposing these drugs to treat COVID-19 has been a primary focus for researchers.
Avigan (favipiravir) has demonstrated promise in shortening the duration of fever and cough in patients infected with COVID-19; also known as SARS-CoV-2. More importantly, as hospital admissions increase in the US, favipiravir has been shown to reduce the need for a ventilator in a clinical trial of 200 patients in the Chinese cities of Wuhan and Shenzhen. The shortage of ventilators, required to keep people alive and breathing in severe respiratory illnesses, is a major concern in the United States.
Perhaps the most extensively discussed COVID-19 treatment candidate is hydroxychloroquine, which was approved by the FDA today as an emergency treatment for COVID-19 along with other FDA approved conditions for this drug, i.e. lupus, rheumatoid arthritis, and malaria. By now most people have heard about the French study of hydroxychloroquine in combination with azithromycin, an antibiotic commonly known as “Z-PAK”. The results of this study are promising; however, this positive news has led to unintended consequences. Pharmacists are seeing a massive increase in hydroxychloroquine prescriptions as physicians are prescribing it off-label for themselves and family members.
In efforts to contain this potential shortage, pharmacy benefit managers such as Express Scripts and CVS Health have implemented quantity limits and fill restrictions while state pharmacy boards have issued emergency restrictions on how the drugs can be dispensed. Walgreens now has a 14-day limit for new prescriptions and a 30-day supply limit for refills of hydroxychloroquine. Furthermore, medical authorities issued a warning about self-treatment after a tragic case of poisoning where an Arizona couple in their sixties were hospitalized after ingesting a form of chloroquine sold to clean fish tanks.
Remdesivir, a drug administered only intravenously, as opposed to oral drugs chloroquine and Avigan, remains a top candidate to become one of the first antiviral drugs to gain FDA approval in the United States. Remdesivir, which was originally being developed by Gilead to treat Ebola, incorporates itself into viral RNA and prevents the virus from replicating. It has shown in laboratory studies to be more effective against coronavirus than Avigan and chloroquine. With more clinical data showing safety and efficacy, it is feasible to see it gain FDA approval. Analysts from Seeking Alpha previously reported intravenous remdesivir would only be used for severe cases of COVID-19 infection. However, after positive reports of the effectiveness of Avigan, a related antiviral drug, they now also view remdesivir as a treatment for more moderate cases. Unfortunately, the most recent development with remdesivir is that its manufacturer, Gilead Sciences, is so backed up with compassionate use requests that it is now limiting its availability to clinical trial use.
Recent weeks brought two noteworthy updates about the HIV drug Kaletra (lopinavir/ritonavir) which has been studied around the world for COVID-10 treatment. AbbVie, the manufacturer of Kaletra altruistically suspended their global patent rights to help the global community with the supply of this drug. Unfortunately, the other noteworthy update was one of disappointment. In an article in the New England Journal of Medicine, researchers reported that Kaletra failed to show a benefit in reducing mortality rates and time to clinical improvement in a clinical trial of 199 people in China. To put this result in context, it is important to note that patients were very sick and had been symptomatic for two weeks before they started the treatment. However, the authors express their opinion that Kaletra was not particularly potent against COVID-19. Kaletra has been noted to be effective in other worldwide reports and continues to be studied for treatment of COVID-19.
Specialty drugs, Kevzara and Actemra, continue to be evaluated in the role they may play in dealing with the repercussions of lung inflammation caused by the coronavirus. If fewer patients progress from needing supplemental oxygen therapy to being intubated with a ventilator, scarce resources may be better used. Researchers are postulating that the aggressive immune response to COVID-19 that leads to lung inflammation and pneumonia is caused by what is known as a cytokine storm. Another drug that has promise in modulating cytokine storm and severe pulmonary complications of COVID-19 infection is leronlimab. Two critically ill patients in New York City were taken off ventilators and out of intensive care after they received leronlimab, an experimental drug being developed for HIV and breast cancer.
Serology testing, also known as antibody testing, allows researchers to evaluate how many people have been previously exposed to the virus and able to fight it off without being symptomatic. When a person is exposed to a disease-causing agent like SARS-CoV-2, their immune system produces antibodies to fight off infection. Antibody tests require only a small blood sample, are relatively inexpensive, and can produce results in about 15 minutes. It is possible antibody testing can be used to determine who can go back to work and who needs to stay home for a 14-day quarantine before returning to work.
New York, which has the highest number of confirmed cases and casualties in the country, is conducting a trial to test how effective convalescent plasma from people who have recovered from COVID-19 can be as a treatment. This method has previously been proven to be effective during the Spanish Flu epidemic of 1918, the SARS outbreak of 2003 and the Ebola epidemic of 2013. The infusion of convalescent plasma introduces antibodies that can illicit an effective immune response and shorten the duration and severity of infection.
As the effects of COVID-19 continue to create more devastation globally, the race to find a treatment and vaccine are of the utmost importance. Ongoing clinical trials and increased testing have helped to more accurately identify the magnitude of the virus’ traumatic effects and possibly identify safe and effective ways to treat those who are infected. Until then, precautionary measures remain the best way to avoid contracting the virus.
With a larger number of infected patients worldwide comes a greater set of data which scientists are able to leverage to gain a better understanding of how the virus is spread, the progression of symptoms, and most importantly which medications may be effective to reduce the severity of symptoms and shorten the time for an infected person to recover and test negative for the virus.