The drug remdesivir is probably a very effective antiviral drug EARS-CoV-2, according to a new study by a team of British scientists. Subscribe Nature communication, the researchers describe giving the drug to a patient with COVID-19 and a rare immune disorder, and the observation of a dramatic improvement in its symptoms and the disappearance of the virus.
The response to the COVID-19 pandemic is hampered by the lack of effective antiviral drugs against SARS-CoV-2, the coronavirus that causes the disease. Scientists have pinned hope on the drug remdesivir, which was originally developed to treat hepatitis C and subsequently tested against Ebola. However, the results of major clinical trials were unconvincing and in early October, the World Health Organization (WHO) announced that the drug would not significantly reduce mortality rates. However, the question is more complicated, and a clinical team has now used a different approach to determine the effects of the drug on COVID-19 in a patient who is closely monitored.
Dr James Thaventhiran of the MRC Toxicology Unit at the University of Cambridge said: “Various studies have been done that support or question the efficacy of brake desivir, but some of the studies done during the first wave of infection may not be optimal. to assess its antiviral properties.
“Mortality rate is the result of a combination of factors, which probably includes uncontrolled viral replication, and, more importantly, the response of the immune system. A clinical trial that only looks at the impact of brake desivir on mortality will be difficult to distinguish between these two factors. This limits our ability to ask the simple question: how good is remdesivir as an antiviral drug? ‘
To answer this question, a team led by scientists from the University of Cambridge and Barts Health investigated the case of a 31-year-old man with XLA, a rare genetic condition that affects the body’s ability to produce antibodies. and thus fights infection.
The patient’s illness started with fever, cough, nausea and vomiting, and on day 19 he tested positive for SARS-CoV-2. His symptoms continued and on day 30 he was admitted to the hospital, where he received supplemental oxygen due to breathing problems.
Unusually, his fever and inflammation of the lungs continued for more than 30 days, but without causing severe breathing problems or spreading to other organs. According to the researchers, this may be due to his inability to produce antibodies. Although antibodies fight infection, they can also cause damage to the body and even lead to serious illnesses.
Initially, the patient was treated with hydroxychloroquine and azithromycin, which had little effect, and the treatments were discontinued on day 34. The patient then began a course of ten days with brakesivir. Within 36 hours, his fever and shortness of breath improved and his nausea and vomiting stopped. Due to the increasing oxygen saturation, he was able to remove supplemental oxygen.
This dramatic clinical response was accompanied by a progressive decrease in levels of C-reactive protein (CRP), a substance produced by the liver in response to inflammation. At the same time, doctors saw an increase in the number of immune cells, known as lymphocytes, and breast examinations showed that he was clearing up pneumonia. The patient was discharged on day 43.
One week after discharge, the patient’s fever, shortness of breath, and nausea returned. He was admitted to hospital again on day 54 and received extra oxygen. He again tested positive for SARS-CoV-2, and he found pneumonia, and his CRP levels increased and his lymphocyte decreased.
At day 61, the patient began treatment with a further ten days of brakes. Again, his symptoms improved rapidly, his fever dropped and he took off supplemental oxygen. His CRP and lymphocyte count normalized. After additional treatment with recovery plasma on days 69 and 70 he was discharged three days later and is no longer symptomatic.
The team found that the patient’s virus levels gradually decreased during his first treatment, which corresponds to the improvement of his symptoms. Its virus levels rose again, as did its symptoms when the first course of treatment was discontinued, but the effect of the second course of remdesivir was even faster and more complete. By day 64, he no longer tested positive for the coronavirus.
The ability for the patient to remove his infection without antiviral medication is likely due to his lack of antibodies, the researchers say. However, there are other immune cells that contribute to the fight against infections, including those known as CD8 + T cells. The team noted that the patient was able to produce CD8 + T cells that respond to the ‘peak protein’ on the surface of the virus – peak proteins give the virus its characteristic crown profile (hence the name coronavirus). Although insufficient to resolve the infection spontaneously, it probably contributed to the clearance of virus during the second course of inhibitor virus.
Dr Nicholas Matheson of the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) at the University of Cambridge added: ‘Our patient’s unusual condition has given us a rare insight into the effectiveness of brake desivir as a treatment for coronavirus infection. The dramatic response to the drug – to repeated challenge – suggests that it may be a very effective treatment, at least for some patients. ‘
The team further suspects that inhibitor virus will probably be most beneficial if administered early in the infection, before the virus can elicit a catastrophic immune response. They say that the course of their patient’s illness also highlights the important – but often contradictory – roles that antibodies play in protecting us from infection.
“The fact that our patient could not fight the disease without treatment suggests that antibodies contribute to the control of SARS-CoV-2,” said Dr. Matthew Buckland of the Department of Clinical Immunology, Barts Health, London, explains. ‘But this lack of antibodies may also have prevented his COVID-19 from becoming life-threatening, as he had no antibodies that elicited a damaging immune response.
‘All of this suggests that treatments need to be tailored to individual patients, depending on their underlying condition – for example, whether it’s the virus that is causing the symptoms, or the immune response. The extensive viral monitoring in our study was clinically necessary because in April 2020 we did not know if this drug would be effective. By applying this approach more broadly, it may be clearer how to make the best use of brake derivatives for clinical benefit. ”
Reference: “Successful Treatment of COVID-19 with brake desivir in the absence of humoral immunity, a case report” by Buckland, MS et al., December 14, 2020, Nature communication.
DOI: 10.1038 / s41467-020-19761-2
The research was supported by the Medical Research Council, the NIHR Bioresource, NHS Blood and Transplant, Wellcome, and the European Union’s Horizon 2020 program.