Antiviral drug cuts coronavirus deaths by a fifth among 'the sickest patients'

An experimental antibody treatment cuts the risk of death among "the sickest" coronavirus patients, research suggests.

The coronavirus is thought to be mild in four out of five cases, with most people recovering naturally as their immune system releases infection-fighting antibodies.

Injecting antibodies has shown promise as a preventative treatment among people who are at risk of becoming seriously ill. It may also benefit those with mild illness, who do not require hospital care.

When it comes to hospitalised patients, the data has been inconclusive, leading some to worry critically ill individuals may be too far along in their illness for antibody infusions to have an effect.

Scientists from the University of Oxford have now shown administering two antibodies cuts the risk of death by a fifth among seriously ill coronavirus patients.

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These patients would have been unable to fight off the virus due to their immune system not launching a natural antibody response. The treatment had no effect, however, among those who had already produced their own antibodies, but became ill regardless.

The two antibodies – collectively known as REGEN-COV – bind to different regions of the coronavirus's spike protein, which it users to enter cells. This binding then neutralises the infection's ability to invade the body.

The preliminary results have been published on the site medRxiv and do not yet appear in a peer-reviewed journal.

"We now know this antibody combination is not only bad for the virus but it is also good for the sickest patients who have failed to mount a natural immune response of their own," said co-lead investigator Professor Sir Martin Landray.

"That is excellent news. It is the first time any antiviral treatment has been shown to save lives in hospitalised COVID-19 [the disease caused by the coronavirus] patients."

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Critically ill coronavirus patients are commonly treated with the arthritis drug tocilizumab and the steroid dexamethasone, both of which target the individual's immune response rather than their infection itself.

In February 2021, the same Oxford scientists found combining the drugs cuts the risk of death by around a third in patients who require oxygen and have a significant amount of inflammation.

REGEN-COV – developed by Regeneron Pharmaceuticals – could be more "additive" still, with the three treatments working together to boost a patient's outcomes.

As part of the ongoing Recovery trial, which looks for effective COVID drugs, the Oxford scientists analysed more than 9,700 patients who were admitted to hospital with coronavirus complications between 18 September, 2020, and 22 May, 2021.

All the patients received the usual care – tocilizumab and dexamethasone – with some also being infused with the antibodies casirivimab and imdevimab.

Overall, around a third of the patients were sero-negative at the start of the experiment, defined as having not mounted their own immune response against the coronavirus. Half were sero-positive, while a sixth had an unknown immune status.

In the usual care only group, those who were sero-negative were twice as likely to have died within 28 days of being admitted to hospital, compared to their sero-positive counterparts.

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Among the sero-negative patients who received REGEN-COV, deaths were reduced by a fifth, with just under a quarter (24%) dying versus nearly a third (30%) in the usual care only group – a "highly statistically significant" difference.

For every 100 sero-negative patients treated with REGEN-COV, six lives would be saved, concluded the scientists.

The effect was lost among the sero-positive patients, however, with 20% on REGEN-COV dying versus 21% in the usual care only group.

When it comes to people who already produce antibodies, "there's no need to give them more", said Professor Landray.

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Deaths aside, the sero-negative patients treated with REGEN-COV were discharged four days earlier than their counterparts just on usual care.

The sero-negative patients who were not on ventilators were also less likely to require the invasive procedure down the line if they had received REGEN-COV.

"The hope was by giving a combination of antibodies targeting the [corona]virus we would be able to reduce the worst manifestations of COVID-19," said co-lead investigator Professor Sir Peter Horby.

"It is wonderful to learn that even in advanced COVID-19 disease, targeting the virus can reduce mortality in patients who have failed to mount an antibody response of their own."

Infusing antibodies was thought to only have potential in the early stages of a coronavirus patient's illness, "but it's not cost effective or practical to treat patients who might have done just fine anyway", said Professor Landray.

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Although promising, REGEN-COV is not licensed in the UK and has only been given emergency authorisation in the US.

"It will need to be assessed by the MHRA [the UK's Medicines and Healthcare products Regulatory Agency] before it becomes practice," said Professor Landray.

Professor Landray expects REGEN-COV could become available within several weeks.

A critically ill patient may then be tested for the coronavirus upon admission to hospital. If positive, their antibody level could be checked.

Sero-negative individuals are not unusual. It could come about due to a pre-existing medical condition suppressing a patient's immune system. These individuals may also only release antibodies down the line, when it could be too late.

The price and availability of antibody tests is somewhat muddled. Professor Horby has described them as a "limited resource", but Professor Landray argued there was never a "purpose" to roll them out before now.

The unknown cost of REGEN-COV itself is likely the bigger issue.

"These products are quite intensive to manufacture," said Professor Horby. "They may be around £1,000 ($1,407) or £2,000 ($2,815), as a one-off treatment."

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Cost aside, REGEN-COV is expected to be effective as new variants emerge, a concern with the coronavirus vaccines.

"The reason it includes two antibodies is to reduce resistance," said Professor Horby.

A variant may evolve resistance to one antibody, but "you still get full potency", he added. The antibodies themselves are "not additive", with each working equally well with or without the other.

"It's a sort of belt and braces [approach]," said Professor Landray. "If your belt breaks, you still have your braces to hold your trousers up."

Speaking of the results, Fiona Watt – from the Medical Research Council – added: "It means patients being hospitalised with COVID-19 can be divided into two groups based on whether or not they have made antibodies to the virus.

"Patients who have made their own antibodies to the virus do not benefit from the new treatment, which is important information given the cost of drugs."