Study supports COVID-19 clinical testing underway across U.S.
A team of scientists at Rocky Mountain Laboratory (RML) in Hamilton, a part of the National Institutes for Allergy and Infectious Disease (NIAID), led by Dr. Emmie de Witt, an expert in the field of designing animal models to simulate human diseases, has released a promising study in which early treatment with the experimental antiviral drug remdesivir significantly reduced clinical disease and damage to the lungs of rhesus macaques infected with SARS-CoV-2, the coronavirus that causes COVID-19.
Remdesivir is an investigational broad-spectrum antiviral treatment. It was previously tested in humans with Ebola virus disease and has shown promise in animal models for treating Middle East respiratory syndrome (MERS)and severe acute respiratory syndrome (SARS), which are caused by other coronaviruses.
The study was designed to follow dosing and treatment procedures used for hospitalized COVID-19 patients being administered remdesivir in a large, multi-center, clinical trial led by NIAID.
The scientists posted the study on the preprint server bioRxiv. The findings are not yet peer-reviewed and should not be considered clinical advice but are being shared to assist the public health response to COVID-19. A study detailing the development of the rhesus macaque model of mild-to-moderate human disease, conducted by the same team of NIAID scientists, was posted to bioRxiv on March 21.
The current study of remdesivir, a drug developed by Gilead Sciences Inc. and NIAID-supported investigators, involved two groups of six rhesus macaques. One group of monkeys received remdesivir and the other animals served as an untreated comparison group. Scientists infected both groups with SARS-CoV-2. Twelve hours later the treatment group received a dose of remdesivir intravenously, and then received a daily intravenous booster dose thereafter for the next six days. The scientists timed the initial treatment to occur shortly before the virus reached its highest level in the animals’ lungs.
Twelve hours after the initial treatment, the scientists examined all animals and found the six treated animals in significantly better health than the untreated group, a trend that continued during the seven-day study. They report that one of the six treated animals showed mild breathing difficulty, whereas all six of the untreated animals showed rapid and difficult breathing. The amount of virus found in the lungs was significantly lower in the treatment group compared to the untreated group, and SARS-CoV-2 caused less damage to the lungs in treated animals than in untreated animals.
The investigators note that the data supports initiating remdesivir treatment in COVID-19 patients as early as possible to achieve maximum treatment effect. The authors, from RML, also note that while remdesivir helped prevent pneumonia, it did not reduce virus shedding by the animals. “This finding is of great significance for patient management, where a clinical improvement should not be interpreted as a lack of infectiousness,” they write.
“This is a very, very encouraging study,” said RML Administrative Director Marshall Bloom, “especially for those studying the effects of remdesivir in humans with COVID-19.”
The clinical trials in which NIAID is participating with Gilead Sciences is the first clinical trial in the United States to evaluate an experimental treatment for COVID-19. The study is a multi-center trial that will be conducted in up to approximately 100 sites globally. It was begun at the University of Nebraska Medical Center in Omaha. Andre Kalil, MD, professor of internal medicine at UNMC and an infectious diseases physician at Nebraska Medicine, is leading the trial at UNMC. The first trial participant was an American who was repatriated after being quarantined on the Diamond Princess cruise ship that docked in Yokohama, Japan and volunteered. Subsequently thirteen people repatriated by the U.S. State Department from the Diamond Princess cruise ship were transported to the National Quarantine Unit, located within the Training, Simulation and Quarantine Center on the UNMC/Nebraska Medicine campus in Omaha on February 17, 2020. The passengers were in a close setting where there had been significant spread of COVID-19 and were sent to the unit for continued isolation and possibly further care. The CDC has since reported that 11 people in the UNMC unit have confirmed SARS-CoV-2 infection.
Bloom said that initial results from the clinical trials may be coming out in the next 3 to 4 weeks.
“The speed with which the research enterprise has been able to address this horrible pandemic has been truly remarkable,” said Bloom. He said all of the previous work done by NIAID and others is proving to have been very good groundwork and a lot of the methods being employed in the COVID-19 outbreak have been tested with things like the Ebola outbreak in West Africa.
“That kind of work involves an incredible amount of cooperation between research scientists, clinical investigators, and regulatory agencies and, of course, the patients that volunteer to be part of these studies,” said Bloom.
Clinical trials of remdesivir are also ongoing in China. NIAID developed the current study taking those designs into account, and in accordance with consultations convened by the World Health Organization (WHO) on the development of a therapeutic trial for patients with COVID-19.
NIAID Director and U.S. Coronavirus Task Force member Anthony S. Fauci, M.D. was quoted on the CDC website, saying “We urgently need a safe and effective treatment for COVID-19. Although remdesivir has been administered to some patients with COVID-19, we do not have solid data to indicate it can improve clinical outcomes.” He said a randomized, placebo-controlled trial is “the gold standard” for determining if an experimental treatment can benefit patients.
Dr. Bloom concluded his remarks about the anti-viral drug stating that it is understandable that the world is focused on the COVID-19 pandemic and that other projects were being placed in “hibernation” to concentrate on the new disease, “but we need to remember that the other deadly diseases raging around the world didn’t go into hibernation,” he said. He said the Ebola outbreak in the Democratic Republic of Congo has started up again, people are still getting Lymes Disease and HIV and need to be diagnosed and treated for those. Bloom said we need to get through this pandemic as quickly as we can so that we can get back to working on some of the other diseases as well.
The other thing worth mentioning, he said, is that the work that Dr. de Witt and others are doing would not be possible without the exceptional efforts of information technology, safety, operations and security staffs. They are providing the logistics and support needed for the scientific studies.