The most common symptoms of COVID-19 are fever, dry cough, and general fatigue, however, some individuals are also asymptomatic. Severe symptoms of COVID-19 include shortness of breath, persistent chest pain, and high fever. Patients with severe symptoms may be hospitalized and require oxygen to support their respiration. Due to the high number of cases of COVID-19 worldwide, human clinical trials have urgently been testing potential treatments for this infectious disease. One such treatment is the drug remdesivir (brand name Veklury), which has been authorized or approved as a temporary COVID-19 treatment in approximately 50 countries around the globe. So, how does remdesivir work?
How does remdesivir work?
Nucleic acids are a category of macromolecules that include single-stranded RNA and double-stranded DNA. RNA and DNA are made up of repeating nucleotides – the building blocks of nucleic acids. RNA acts as a messenger by converting DNA-stored information into proteins, which perform cellular functions in the body. Other responsibilities of RNA include coding, decoding, and regulating genes found in DNA. Coronaviruses, including SARS-CoV-2 which causes COVID-19, contain RNA as their sole genetic material.
Remdesivir is an anti-viral drug, meaning it works by interfering with viral replication. The viral replication process for the genetic material of SARS-CoV-2 requires an enzyme called RNA-dependent RNA polymerase (RdRp). Remdesivir converts to a nucleoside analog called NTP in the body, which takes the place of the naturally existing nucleotide – ATP – in the new RNA strand. This means, remdesivir works to impair the viral polymerase’s ability to produce new viral RNA strands, thereby blocking the virus’ ability to reproduce in an infected person’s body.
Remdesivir is typically administered intravenously to patients. The U.S. food and drug agency (FDA) outlined its use must be within a hospital setting or a healthcare setting that can provide comparable care to that of a hospital to allow for close monitoring.
Remdesivir clinical trials
Prior to the current novel coronavirus pandemic that is affecting numerous countries across the globe, most studies testing the efficacy of remdesivir on coronavirus strains such as Middle East respiratory syndrome (MERS) coronavirus and the severe acute respiratory syndrome (SARS) virus, used cell and animal models. There was a lack of substantial research with human participants until COVID-19 emerged. Due to a lack of treatment options for severe symptoms requiring hospitalization, human clinical trials have quickly been initiated in order for countries to examine the safety, efficacy, and quality of potential drug treatments for their citizens who have developed severe symptoms of COVID-19.
One such clinical trial was recently published in the New England Journal of Medicine. It was a double-blind, randomized, placebo-controlled trial – the gold standard – of administering remdesivir intravenously for 10 days into 532 adults who presented with symptoms of lower respiratory tract infection while being hospitalized for COVID-19. Faster recoveries – defined as being discharged or no longer needing supplemental oxygen and medical care – and greater odds of improving one’s condition were experienced in patients who received remdesivir compared to the placebo group.
According to the national institutes of health (NIH), it could not be concluded that the reduced all-cause mortality rate in the remdesivir group compared to the placebo group was not due to chance. These results are similar to other studies’ findings that indicate there may be a benefit to administering remdesivir in hospitalized patients, however, the benefits may be limited and remdesivir may not be sufficient as the sole treatment, especially in severe cases.
In contrast, a trial published by the World Health Organization concluded that remdesivir did not definitively reduce mortality in hospitalized patients, initiation of ventilation or the duration of hospitalization. The study involved 405 hospitals in 30 countries testing four anti-viral drugs on hospitalized COVID-19 patients, with 2750 patients allocated to being administered remdesivir for 10 days.
Are there risks?
As with most drugs, patients who receive remdesivir as a treatment may experience side effects. The food and drug agency outlined possible symptoms including fever, increased liver enzymes indicating liver injury, as well as blood pressure and heart rate changes.
Who can access remdesivir?
Many countries are authorizing or approving the use of remdesivir to treat hospitalized COVID-19 patients. Health Canada has issued emergency use authorization of remdesivir with the requirement that Gilead Science Canada – the drug manufacturing company – maintains the drug’s safety, quality, and efficacy as found in the government’s initial review of the drug. The drug can only be used on COVID-19 patients aged 12 or older who weigh a minimum of 40kg and have been hospitalized presenting severe symptoms of COVID-19 including pneumonia. Recently, the food and drug agency approved remdesivir for use in hospitalized COVID-19 patients who meet the same age and weight requirements that Health Canada outlined as seen above, marking remdesivir as the first approved drug for COVID-19 treatment in the USA. The approval of remdesivir as a COVID-19 treatment is based on the results of three randomized, controlled clinical trials using a sample of hospitalized COVID-19 patients experiencing mild to severe symptoms, one of which is the New England Journal of Medicine clinical trial described above, according to the NIH.
References:
Amirian, E. S., & Levy, J. K. (2020). Current knowledge about the antivirals remdesivir (GS-5734) and GS-441524 as therapeutic options for coronaviruses. One Health, 100128.
Beigel, J. H., Tomashek, K. M., Dodd, L. E., Mehta, A. K., Zingman, B. S., Kalil, A. C., … & Finberg, R. W. (2020). Remdesivir for the treatment of Covid-19—final report. The New England Journal of Medicine. doi: 10.1056/NEJMoa2007764
Gilead. (2020). About veklury. Retrieved from https://www.gilead.com/purpose/advancing-global-health/covid-19/about-veklury
Government of Canada. (2020). Remdesivir authorized with conditions for the treatment of patients in Canada with severe COVID-19 symptoms. Retrieved from https://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2020/73621a-eng.php
National Institutes of Health. (2020). Final report confirms remdesivir benefits for COVID-19. Retrieved from https://www.nih.gov/news-events/nih-research-matters/final-report-confirms-remdesivir-benefits-covid-19
U.S. Food and Drug Administration. (2020). FDA approves first treatment for COVID-19. Retrieved from https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-covid-19
Wang, Y., Zhang, D., Du, G., Du, R., Zhao, J., Jin, Y., … & Hu, Y. (2020). Remdesivir in adults with severe COVID-19: A randomised, double-blind, placebo-controlled, multicentre trial. The Lancet, 395(10236), 1569-1578. doi:10.1016/S0140-6736(20)31022-9
World Health Organization. (2020). Coronavirus disease (COVID-19). Retrieved from https://www.who.int/emergencies/diseases/novel-coronavirus-2019/question-and-answers-hub/q-a-detail/coronavirus-disease-covid-19
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