Coronavirus drug with mixed results 'highly effective' in man with rare immune disease

An experimental coronavirus drug that has produced mixed results in previous research was found to be “highly effective” in a man with a rare immune disease.

The antiviral Ebola drug remdesivir was shown to accelerate the recovery of some critically-ill coronavirus patients in a University College London study, however, the World Health Organization later announced the treatment had “little to no effect” on survival.

Feeling the drug could have potential, scientists from the University of Cambridge analysed an unnamed 31-year-old man who required hospital care after the coronavirus triggered lung inflammation.

The man has X-linked agammaglobulinemia (XLA), which reduces a patient’s ability to produce immune-fighting antibodies against an infection. Around one in 200,000 babies is diagnosed with the condition.

After several unsuccessful treatments, he was given a 10-day course of remdesivir.

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While this improved his condition enough to be discharged, the man was readmitted with coronavirus complications 11 days later.

A further 10-day remdesivir course resulted in him testing negative for the infection, with eased symptoms and no further coronavirus-related ill health.

“Our patient’s unusual condition gave us a rare insight into the effectiveness of remdesivir as a treatment for coronavirus infection,” said study author Dr Nicholas Matheson.

“The dramatic response to the drug, on repeated challenge, suggests it can be a highly effective treatment, at least for some patients.”

At the start of the pandemic, critically-ill patients were offered supportive care like ventilation that helped to keep them alive while their immune system worked to fight off the infection naturally.

Studies have since found steroids can cut the risk of death among seriously-ill coronavirus patients by up to a third, prompting the NHS to start using versions of the low-cost drugs.

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With experts continuing to research other treatment options, the Cambridge scientists wondered if remdesivir may have potential for some patients.

“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,” said co-author Dr James Thaventhiran.

“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?”

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The XLA patient tested positive for the coronavirus 19 days after he developed a fever, cough, nausea and vomiting.

Most people clear the infection within around 10 days, with the virus being mild in four out of five cases.

The XLA patient was admitted to hospital on day 30, where he was given supplemental oxygen for relatively mild breathing difficulties.

The Cambridge scientists believe the initial absence of severe complications may have been down to the man’s reduced ability to produce antibodies. Although the proteins help fight off an infection, they can also trigger dangerous inflammation.

The man was first treated with hydroxychloroquine and azithromycin, two drugs that have also produced mixed results in coronavirus patients.

The treatment duo had little effect and was stopped on day 34.

He was than put on a 10-day course of remdesivir. Within 36 hours, his fever and mild shortness of breath had improved, and his nausea and vomiting ceased.

The man’s oxygen levels had also risen sufficiently for him to be taken off the supplemental gas.

This occurred alongside a fall in C-reactive protein (CRP) levels, a marker of inflammation. He also had an increase in immune cells called lymphocytes, while chest scans showed his lung inflammation was clearing.

The man was subsequently discharged on day 43.

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One week later, however, his fever, shortness of breath and nausea returned.

He was readmitted to hospital on day 54, where he was given supplemental oxygen and tested positive for the coronavirus again. He is thought to have not cleared the initial infection, rather than re-catching the virus.

Tests further revealed the man had lung inflammation, along with increasing CRP levels and falling lymphocyte counts.

On day 61, the patient began a further 10-day course of remdesivir.

Once again, his symptoms improved rapidly, allowing him to be taken off supplemental oxygen.

Following additional treatment with plasma therapy on days 69 and 70, he was discharged 72 hours later, with no further symptoms.

Someone who has overcome the coronavirus may donate samples of their plasma in the hope doctors can harness their antibodies for other critically-ill patients.

While research into plasma treatment is limited, studies have so far suggested it does not speed up a patient’s recovery.

Writing in the journal Nature Communications, the Cambridge scientists describe how the man’s virus levels fell progressively during his first course of remdesivir, corresponding with an improvement in symptoms.

His virus levels increased again, along with his symptoms, when the first course of the treatment ended.

The second course of remdesivir had a more rapid and complete effect.

By day 64, he no longer tested positive for the coronavirus.

While the man’s lack of antibodies likely left him unable to clear the infection without antiviral medication, other immune cells also contribute to clearing pathogens from the body.

These immune cells were likely insufficient to rid the infection on their own, but contributed to him recovering during the second course of remdesivir, according to the scientists.

They suspect remdesivir is most beneficial when administered early in an infection, before the virus can trigger a potentially dangerous immune response.

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“This lack of antibodies may have prevented his COVID-19 [the disease caused by the coronavirus] from becoming life-threatening, because he had no antibodies to trigger a damaging immune response,” said co-author Dr Matthew Buckland.

He concluded: “All of this suggests 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.”

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