Cambridge study suggests remdesivir could be an effective antiviral against Covid-19 for some patients
There is new evidence that the drug remdesivir is a highly effective antiviral against the Covid-19 virus, thanks to a study involving University of Cambridge scientists.
It comes after a Covid-19 patient with a rare immune disorder dramatically improved after being given the drug and became virus-free.
Originally developed to treat hepatitis C and later tested against Ebole, the drug has been the subject of large clinical trials that have proved inconclusive.
In early October, the World Health Organization (WHO) reported that the drug did not significantly reduce mortality rates.
But Cambridge researchers, working with scientists at Barts Health NHS Trust, argue the situation is more complicated.
Dr James Thaventhiran from the MRC Toxicology Unit at the University of Cambridge, said: “There have been different studies supporting or questioning remdesivir’s effectiveness, but some of those conducted during the first wave of infection may not be optimal for assessing its antiviral properties.
“Mortality is due to a combination of factors, likely including unchecked viral replication and, importantly, the response of the immune system.
“A clinical trial that looks only at remdesivir’s impact on mortality will have difficulty distinguishing between these two factors. This limits our ability to ask the simple question: how good is remdesivir as an antiviral?”
The researchers examined the case of a 31-year-old man with XLA, a rare genetic condition affecting the body's ability to produce antibodies to fight infection.
Having suffered with fever, cough, nausea and vomiting, he tested positive for SARS-CoV-2 - the virus that causes Covid-19 - after 19 days and was admitted to hospital on day 30, where he was given oxygen due to breathing difficulties.
His case was unusual in that the fever and inflammation of the lungs persisted for longer than 30 days, but without causing severe breathing problems or spreading to other organs.
This may, the researchers suggest, be due to his inability to produce antibodies. Although antibodies fight infection, an over-reaction from them can also cause damage to the body and lead to severe disease.
After initial treatment with hydroxychloroquine and azithromycin had little effect, the treatments were stopped on day 34 and a 10-day course of remdesivir began.
Within 36 hours, the patient’s fever and shortness of breath had improved and his nausea and vomiting had stopped. He was able to come off the supplemental oxygen and levels of C-reactive protein (CRP), which is produced by the liver in response to inflammation, were seen to decline.
Doctors also witnessed an increase in immune cells known as lymphocytes, while chest scans showed his lung inflammation was clearing.
He was discharged on day 43 but a week later his fever, shortness of breath and nausea returned and he was readmitted to hospital on day 54 and given supplemental oxygen.
Having tested positive for SARS-CoV-2 again, he was found to have lung inflammation, his CRP levels had increased and his lymphocyte count had fallen.
A further 10-day course of remsdesivir was begun on day 61 and his symptoms improved rapidly once more, with CRP and lymphocyte counts normalising. The change was swifter this time and he no longer tested positive by day 64.
He was given additional treatment with convalescent plasma on days 69 and 70, discharged three days later and is no longer symptomatic.
The patient’s struggle to clear the infection without the antiviral medication is very likely due to his lack of antibodies.
But there are other immune cells that help us fight infection, including CD8+ T cells and the patient was able to produce these in response to the virus’ spike protein.
These are thought to have contributed to him clearing the virus during the second course of remdesivir
Dr Nicholas Matheson, from the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) at the University of Cambridge, added: “Our patient’s unusual condition gave us a rare insight into the effectiveness of remdesivir as a treatment for coronavirus infection. The dramatic response to the drug – on repeated challenge – suggests that it can be a highly effective treatment, at least for some patients.”
The team believes remdesivir is likely to be most beneficial when administered early in infection, before the virus triggers a potentially deadly immune response.
Dr Matthew Buckland, of the Department of Clinical Immunology, Barts Health, London, said: “The fact that our patient was unable to fight off the disease without treatment suggests that antibodies contribute to the control of SARS-CoV-2. But this lack of antibodies may also have prevented his COVID-19 from becoming life-threatening, because he had no antibodies to trigger a damaging immune response.
“All of this suggests that treatments will need to be tailored for individual patients, depending on their underlying condition – for example, whether it is the virus that is causing the symptoms, or the immune response.
“The extended viral monitoring in our study was clinically necessary because in April 2020 we didn’t know if this drug would be effective. Adopting this approach more widely could further clarify how best to use remdesivir for clinical benefit.”
The research was supported by the Medical Research Council, the NIHR Bioresource, NHS Blood and Transplant, Wellcome and the European Union’s Horizon 2020 programme.