As remdesivir leads COVID-19 treatments, medications that are typically used to treat other conditions are being tested to see if any are effective against the virus.
Gilead Science’s antiviral drug remdesivir has become the first and only Food & Drug Administration (FDA)-approved drug in the U.S. for treating the coronavirus. The company received the green light from the FDA on October 22, 2020.
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Remdesivir was one of the treatments U.S. President Donald J. Trump received during his recovery with COVID-19. It is given by intravenous (IV) infusion in the hospital and has been shown to reduce disease progression among severely ill patients and those requiring oxygen.1
It was previously shown effective at treating Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and Ebola in cell and animal testing.2,3
The drug is sold under the brand name Veklury and was granted emergency use authorization by the FDA in May as COVID-19 recovery efforts ramped up.
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Remdesivir’s approval follows newly published results from Gilead’s Phase 3 ACTT-1 trial demonstrating speedier recovery times for adults with mild-moderate or severe coronavirus cases treated with the drug.4
As remdesivir leads the pack of COVID-19 treatments, medications that are typically used to treat other conditions are being tested to see if any are effective against the virus.
Dexamethasone, a corticosteroid commonly used to treat conditions such as autoimmune conditions and allergic reactions, is undergoing testing in the UK as a possible COVID-19 treatment.5
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The Randomised Evaluation of Covid-19 Therapy (RECOVERY) trial is also researching several other medications, including azithromycin (a commonly used antibiotic), tocilizumab (an anti-inflammatory treatment given by injection), convalescent plasma (collected from donors who have recovered from COVID-19 and contains antibodies against the virus) and REGN-COV2 (Regeneron’s combination of monoclonal antibodies directed against coronavirus).5
The FDA issued an Emergency Investigational New Drug (eIND) application for the use of convalescent plasma to treat people infected with COVID-19 in March 2020. Convalescent plasma is the liquid part of blood that is collected from patients who recovered from an infection, which may carry antibodies.
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A Mayo Clinic study tested over 35,000 patients hospitalized with COVID-19 who were treated with convalescent plasma. After 1 week, the death rate was lower for a group who received convalescent plasma within 3 days of diagnosis compared to a group who received it after 4 or more days. Death rates were also found to be lower in patients who received convalescent plasma with higher antibody levels compared to plasma with lower antibody levels.6
The paper has not yet been peer reviewed, and there was no control group. Therefore, it is unclear if the difference found in death rates is due to the treatment or other factors.
A review of 8 convalescent plasma studies with a total of 32 participants found inconsistencies.7 The studies used different dosing and timing approaches for drug delivery. Additionally, some studies reported a benefit with treatment while others did not.
Genentech’s antiviral medication Tamiflu, commonly used to treat influenza, is being examined in combination with other medications for coronavirus treatment by several clinical trials.8
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A hospital in Wuhan, China, reported poor results with the drug in a study of 138 hospitalized patients, 124 of whom received Tamiflu along with other medications.9 Trial results showed 85 of 124 patients were still hospitalized at the end of testing, and 6 had died.
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The antibiotic azithromycin or Z-Pak (Zithromax, Pfizer), commonly used to treat bacterial infections, has been shown to have in vitro activity against viruses like influenza A and Zika in testing.10,11 However, the drug did not work in a clinical trial against the coronavirus responsible for MERS.12
When tested in combination with hydroxychloroquine for COVID-19, azithromycin cleared the virus in 93 percent of patients within 8 days.13 However, there was no control group. So, it is unclear whether patients would have recovered without the medications.
There are concerns about potentially serious side effects when using azithromycin and hydroxychloroquine together, particularly in patients with cardiovascular disease.14 The National Institutes of Health (NIH) currently recommends caution when using the drug combination.15
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Tocilizumab and other IL-6 inhibitors
Tocilizumab (Actermra, Genentech) is an IL-6 inhibitor approved for inflammatory diseases such as rheumatoid arthritis. It works by blocking a protein involved in immune responses called interleukin-6 (IL-6) which normally alerts cells to activate the immune system.
An overactive immune system can become a potentially fatal problem if inflammation gets out of control.
Some COVID-19 infected patients become at risk of an overactive immune system as their bodies ramp up an infection-fighting response. Therefore, blocking IL-6 helps patients by calming the immune system.
A multicenter trial from France reported that individuals who received tocilizumab were less likely to require ventilation or die.16 In the trial, 129 patients were randomized, 65 to standard of care with tocilizumab and 64 to standard of care alone. The proportion of patients who reached the primary outcome was significantly lower in the tocilizumab arm of the trial. Study results will be submitted for publication in a peer-reviewed journal.
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1. Grein J, Ohmagari N, Shin D, et al. Compassionate Use of Remdesivir for Patients with Severe Covid-19. N Engl J Med. 2020;382:2327-2336.
2. Sheahan TP, Sims AC, Graham RL, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med. 2017;9(396):eaal3653.
3. Warren TK, Jordan R, Lo MK, et al. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys Nature. 2016 Mar;531(7594):381-385.
4. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of Covid-19 — Final Report. N Engl J Med. 2020 doi: 10.1056/NEJMoa2007764.
5. The RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19—preliminary report. N Engl J Med. 2020 doi: 10.1056/NEJMoa2021436.
6. Joyner MJ, Senefeld JW, Klassen SA, et al. Effect of Convalescent Plasma on Mortality among Hospitalized Patients with COVID-19: Initial Three-Month Experience. MedRxiv. 2020.08.12.20169359 doi: 10.1101/2020.08.12.20169359.
7. Valk SJ, Piechotta V, Chai KL, et al. Convalescent plasma or hyperimmune immunoglobulin for people with COVID‐19: a rapid review. Cochrane Database Sys Rev. 2020. May 14;5(5):CD013600.
8. ClinicalTrials.gov. 20 Studies found for: Oseltamivir | COVID. NIH. Available at https://clinicaltrials.gov/ct2/results?cond=COVID&term=Oseltamivir&cntry=&state=&city=&dist=. Accessed20/23/20.
9. Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China. JAMA. 2020;323(11):1061–1069.
10. Tran DH, Sugamata R, Hirose T, et al. Azithromycin, a 15-membered macrolide antibiotic, inhibits influenza A(H1N1)pdm09 virus infection by interfering with virus internalization process. J Antibiot (Tokyo). 2019 Oct;72(10):759-768.
11. Bosseboeuf E, Aubry M, Nhan T, et al. Azithromycin Inhibits the Replication of Zika Virus. J Antivir Antiretrovir. 2018;10(1):6-11.
12. Arabi YM, Deeb AM, Al-Hameed F, et al. Macrolides in critically ill patients with Middle East Respiratory Syndrome. Int J Infect Dis. 2019 Apr;81:184-190.
13. Gautret P, Lagier JC, Parola P, et al. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: an observational study. Méditerranée Infection. Available at https://www.mediterranee-infection.com/wp-content/uploads/2020/03/COVID-IHU-2-1.pdf. Accessed 10/23/20.
14. American Heart Association. Caution recommended on COVID-19 treatment with hydroxychloroquine and azithromycin for patients with cardiovascular disease. Available at https://newsroom.heart.org/news/caution-recommended-on-covid-19-treatment-with-hydroxychloroquine-and-azithromycin-for-patients-with-cardiovascular-disease-6797342. Accessed 10/23/20.
15. National Institutes of Health. Chloroquine or Hydroxychloroquine With or Without Azithromycin. Available at https://www.covid19treatmentguidelines.nih.gov/antiviral-therapy/chloroquine-or-hydroxychloroquine-with-or-without-azithromycin/. Accessed 10/23/20.
16. Assistance Hospitaux Publique de Paris. Tocilizumab improves significantly clinical outcomes of patients with moderate or severe COVID-19 pneumonia. Press release. Available at https://www.aphp.fr/contenu/tocilizumab-improves-significantly-clinical-outcomes-patients-moderate-or-severe-covid-19. Accessed 10/23/20.