In December 2019, the first cases of a mysterious pneumonia-like illness appeared in Wuhan City, Hubei Province, in China. Since then, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection has spread worldwide, affecting 185 countries and territories and sickening more than 2.4 million people. Scientists worldwide are racing to develop an effective therapeutic regimen for coronavirus disease (COVID-19), the disease caused by SARS-CoV-2.
Novel Coronavirus SARS-CoV-2 Colorized scanning electron micrograph of an apoptotic cell (blue) infected with SARS-COV-2 virus particles (red), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID
Previous studies have shown the potential of remdesivir in treating people with COVID-19. A new study shows that the drug can prevent the progression of SARS-CoV-2 infection to severe pneumonia.
A team of scientists at the National Institute of Allergy and Infectious Diseases, which is part of the U.S. National Institutes of Health, has tested the efficacy of remdesivir, a nucleotide analog prodrug with a broad antiviral activity, as a COVID-19 treatment.
Effective therapeutics for COVID-19 are much needed to reduce the fatality risk of the viral infection, which is harmful to older adults, those with underlying medical conditions, and those who are immunocompromised.
The Food and Drug Administration (FDA) needs to approve newly developed drugs for the disease, following rigorous trials and quality assurance. In the case of COVID-19, where effective treatment is needed immediately, repurposing already-approved drugs is more feasible and faster.
Effective in animals
Currently, many studies are investigating the therapeutic effects of remdesivir on the coronavirus infection, hoping to find a treatment to help patients. In animal models, remdisivir has previously shown efficacy against the severe acute respiratory syndrome coronavirus (SARS-CoV), which caused an outbreak in 2002, and the Middle East respiratory syndrome coronavirus (MERS-CoV), which caused the MERS outbreak in Saudi Arabia in 2012.
In this study, made public on BioRxiv, an online archive of pre-print studies, remdesivir has shown promise with a significant clinical improvement, reducing pulmonary infiltrates and a decrease in lung disease. It prevents the progression of lung infection to severe pneumonia, which may lead to acute respiratory distress syndrome, which is the common cause of death among COVID-19 patients.
The team exposed rhesus macaques or laboratory monkeys to SARS-CoV-2. In the study, infected monkeys developed mild to moderate respiratory disease with pulmonary infiltrates as seen in radiographs, and a shedding pattern like those observed in patients with COVID-19.
Reduced lung tissue damage
To determine the effect of the drug on SARS-CoV-2, the team grouped 12 monkeys into two groups, exposing them with the virus. Remdesivir was given 12 hours after inoculation with SARS-CoV-2 and continued once daily through six days. One group was given with a loading dose of 10 mg/kg remdesivir, followed by a daily dose of 5 mg/kg. On the other hand, the control group was given an equal dose of a vehicle solution.
The scientists observed the animals twice daily for clinical signs of the disease. A standardized scoring sheet was used to determine the effect of the drug. The person scoring is not aware of which animals received the drug.
The results of the study show those treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on X-ray results. Further, the virus titers in the bronchoalveolar lavages were reduced as early as 12 hours after the first dosage. The viral loads of SARS-CoV-2 in the remdesivir-treated animal's lungs were lower, and there was a distinct reduction in damage to the lung tissue.
"Therapeutic remdesivir treatment initiated early during infection has a clear clinical benefit in SARS-CoV-2-infected rhesus macaques. These data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to severe pneumonia," the researchers concluded.
Remdesivir is a drug developed by Gilead Sciences Inc., which is used to treat viral infections. Now, human drug trials are on the way, and if proven effective, the drug may help reduce mortality among patients with COVID-19.
The study investigators note that the data supports using remdesivir as an early treatment for COVID-19 to achieve its maximum treatment effect. Also, it may help prevent respiratory complications, and potentially improve the disease outcomes.
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
- Williamson, B., Feldmann, F., Schwarz, B., Meade-Whote, K., Porter, D., Schulz, J, et al. (2020). Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. https://www.biorxiv.org/content/10.1101/2020.04.15.043166v1