The drug remdesivir, long touted as a potential Covid-19 treatment, has been used to successfully cure a patient who suffered a rare reaction to the disease.
A 31-year-old man infected with the coronavirus experienced unusual symptoms due to a genetic disorder called XLA, which prevented him from making antibodies to fight infection.
The patient was twice admitted to hospital with confirmed Covid-19, with moderate but persistent symptoms. His condition was stable but did not improve on its own.
On both occasions, treatment with remdesivir rapidly led to improvement in his condition and allowed him to be discharged.
The researchers say the patient’s inability to make antibodies offered a unique insight into the functioning of the drug in Covid-19 patients.
Writing in Nature Communications they say remdesevir likely has antiviral properties and could be highly effective for some patients.
Remdesivir was initially developed to treat hepatitis C and then repurposed as a potential Ebola treatment, Due to the similarity in the structures of these viruses to SARS-CoV-2, the virus which causes Covid-19, experts hoped it may be able to help fight the current pandemic
Remdesivir was initially developed to treat hepatitis C and then repurposed as a potential Ebola treatment.
Due to the similarity in the structures of these viruses to SARS-CoV-2, the virus which causes Covid-19, experts hoped it may be able to help fight the current pandemic.
There is no consensus as to whether it is effective however, with clinical trials showing mixed results.
The NHS has approved it for use on Covid-19 patients in the hope it can help, but are already being forced to ration the drug, which costs £2,400 per course ($3,120).
But in November, the World Health Organization (WHO), said doctors should not treat coronavirus patients with remdesivir ‘regardless of how ill they are’.
Officials at the time said there is ‘no evidence’ it boosts people’s chances of surviving the disease or stops them falling ill enough to need mechanical ventilation’.
They also warned there is the ‘possibility of important harm’ when using the experimental Ebola drug – as it can cause kidney and liver damage in some patients.
However, 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?’
An antiviral is a chemical which actively destroys the virus.
The individual case of the 31-year-old patient provided the perfect opportunity for researchers to assess the antiviral properties of the drug.
His genetic condition prevented him from making enough antibodies to fight off the disease and therefore when the course of his disease plateaued, neither improving or worsening over time, the virus and its host were stuck in a form of grim homeostasis.
However, his inability to manufacture antibodies may well have saved his life because in severe cases of Covid-19, where patients are admitted to ICU and intubated for example, the virus levels are often low.
At this point in disease, the patient’s immune system has started to malfunction and sent into overdrive.
The goal of this is to destroy the virus, but once it gets out of hand, the immune response attacks the body itself, causing inflammation.
In Covid-19 patients this is known as the ‘cytokine storm’ and can be fatal. The absence of such an immune response in the patient from Cambridge means this never happened.
As a result, the disease manifested itself as prolonged, moderate symptoms that, when untreated, did not improve or significantly worsen.
He initially suffered with fever, cough, nausea and vomiting and tested positive for the coronavirus on day 19 of symptoms.
The symptoms persisted and on day 30 he was admitted to hospital, where he was given supplemental oxygen due to breathing difficulties.
Unusually, his fever and inflammation of the lungs persisted for longer than 30 days, but without causing severe breathing problems or spreading to other organs.
The researchers say this may have been due to his inability to produce antibodies.
He was initially treated with hydroxychloroquine and azithromycin — two drugs which early in the pandemic had been suggested as potential treatments — which were ineffective.
Hydroxychloroquine is the anti-malaria drug which Donald Trump championed but has now been widely disregarded as a treatment. Azithromycin a commonly used antibiotic, is still being tested as part of the world-leading RECOVERY trial.
This treatment was halted on day 34 and he them was given a course of remdesevir. The upturn in his condition was rapid, and after just 36 hours the fever had improved, as too had the shortness of breath.
His nausea and vomiting also stopped and he was soon taken off supplemental oxygen.
Further observations revealed inflammation was declining, his immune system was recovering and the damage in the lungs was clearing.
On day 43 of his illness, he was discharged from hospital but a week later his symptoms returned and he tested positive and was readmitted to hospital on day 54.
The improvement seen previously had been wiped out and he was then given a ten-day course of remdesivir.
His condition again improved and he was discharged less than two weeks after starting his second bout of remdesivir treatment.
Researchers found that as his condition improved over both periods of treatment, the levels of virus in his system declined.
This, the researchers believe, is evidence that his XLA prevented him from fighting the virus himself as he does not produce antibodies.
Dr Nicholas Matheson from 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.’