COVID-19: UN health agency issues conditional advice against using remdesivir

Patients with COVID-19 should not be given the antiviral drug remdesivir “regardless of disease severity”, the UN World Health Organization (WHO) said on Friday.

Nonetheless, describing its recommendation as “conditional”, as opposed to “strong”, WHO stressed that data from a global trial on the efficacy of remdesivir was inconclusive, and that further trials should continue into its use for more vulnerable patients.

“We recommend a conditional recommendation – I want to highlight that - against the use of remdesivir in hospitalised patients with COVID-19 regardless of disease severity,” said Dr Janet Diaz, Head of Clinical Care at WHO, during a virtual press conference in Geneva.

According to data from the WHO-led Solidarity trial which was then examined by a panel of international experts behind the recommendation, “possibly remdesivir can lead to 29 fewer deaths per 1,000 patients or up to 11 more deaths per 1000 patients”, Dr Diaz said. “So you can see that …the confidence interval are relatively large…there was no evidence that there was any important effect on mortality, on the need for mechanical ventilation or the time to clinical improvement.”

But this did “not prove” that the antiviral “had no benefit at all”, Dr Diaz insisted. “There could still be potential small benefit, maybe in a health sub-group which is why the panel also recommended continued trials, continued enrolment into clinical trials.”

The WHO official explained that this might be “severe patients versus critical patients” or whether the antiviral is used “early versus late”.

Dr Bram Rochwerg, who was among the experts advising WHO, noted that there would likely be regional “variations” in the use of remdesivir.

While a minority of people will still choose to use it, the majority would not, based on the available data, he said.

“There may be groups (who might benefit) and the data was a bit more of a close call, so that’s why we felt strongly that trials need to continue using remdesivir and studying remdesivir and looking to see if there are specific groups that might, that might benefit,” he said. “We were very explicit that we do believe that these studies need to continue (and) Solidarity is continuing.”

Although the remdesivir development mirrors similar attempts to use other antivirals against the new coronavirus, Dr Diaz said there was no reason to lose hope in the fight against COVID-19.

“I do think there is a tremendous global effort to investigate treatments. You know, I think a lot of interest was done upfront with the repurposed of drugs, repurposed antivirals, you know we saw that with other repurposed drugs such as hydroxychloroquine, lopinavir, and there was a big push to try to test these and they’ve been tested and unfortunately, we just haven’t, you know, the results haven’t been as promising as we had hoped. But I don’t want to forget that we do have one lifesaving drug and even though it’s a repurposed old, old drug dexamethasone, a corticosteroid, we do know that that does reduce mortality, save lives of patient with severe and critical so there is something.”

Latest data from WHO indicates that eight in 10 people infected with COVID report mild symptoms, Dr Diaz said.

“Since the beginning (of the pandemic)…about 80 per cent of people have, you know, mild disease, a proportion maybe moderate disease and then only a small proportion, a smaller proportion, 20 per cent go on to develop severe or critical disease, and critical disease is a small, small portion, it’s five per cent or less, and that is…and that seems to be kind of consistent I think through the literature so most patients do have, if they have mild disease, self-limiting disease, they get better on their own, their immune system kicks in and they get better.”

Nonetheless, there are reports of more “persistent longer-term symptoms”, Dr Diaz noted. “So even though they don’t get severe disease there can be some persistent symptoms that lasts longer than one would have hoped for.”

1. SOUNDBITE (English) — Dr Janet Diaz, Head of Clinical Care, WHO: “We recommend a conditional recommendation - so I want to highlight that, it’s a conditional recommendation - against the use of remdesivir in hospitalized patients - with COVID-19, regardless of disease severity.” 
2. SOUNDBITE (English) — Dr Janet Diaz, Head of Clinical Care, WHO: “Possibly remdesivir can lead to 29 fewer deaths par 1,000 patients or up to 11 more deaths per 1,000 patients so you can see that this is, the confidence interval is a little bit large.” 
3. SOUNDBITE (English) — Dr Janet Diaz, Head of Clinical Care, WHO: “It was not clear that, there was no evidence, that there was any important effect on mortality, on the need for mechanic ventilation or the time to clinical improvement.” 
4. SOUNDBITE (English) — Dr Janet Diaz, Head of Clinical Care, WHO: “This did not prove that remdesivir does not have a benefit at all and that’s why it is a conditional recommendation, there can still be potential small benefit, maybe in a health sub-group, which is why the panel also recommended continued trials, continued enrolment into clinical trials.” 
5. SOUNDBITE (English) — Dr Janet Diaz, Head of Clinical Care, WHO: “You know, is there a sub-group that may benefit more – such as severe patients versus critical patients. Is there a timing in disease that may benefit more - such as early versus late - and those are all considerations that are in the guidelines.” 
6. SOUNDBITE (English) — Dr Bram Rochwerg, practising ITU clinician and expert adviser for WHO-led Solidarity Trial: “There may be groups and the data was a bit more of a close call, so that’s why we felt strongly that trials need to continue using remdesivir and studying remdesivir and looking to see if there are specific groups that might, that might benefit. And as she said, we were very explicit that we do believe that these studies need to continue, Solidarity is continuing, so.” 
7. SOUNDBITE (English) — Dr Janet Diaz, Head of Clinical Care, WHO: “I do think there is a tremendous global effort to investigate treatments. You know, I think a lot of interest was done upfront with the repurposed of drugs, repurposed antivirals, you know we saw that with other repurposed drugs such as hydroxychloroquine, lopinavir, and there was a big push to try to test these and they’ve been tested and unfortunately, we just haven’t, you know, the results haven’t been as promising as we had hoped. But I don’t want to, I don’t want to forget that we do have one lifesaving drug and even though it’s a repurposed old, old drug dexamethasone, a corticosteroid, we do know that that does reduce mortality, save lives of patient with severe and critical so there is something.” 
8. SOUNDBITE (English) — Dr Janet Diaz, Head of Clinical Care, WHO: “Since the beginning, is that about 80 per cent of people have, you know, mild disease, a proportion maybe moderate disease and then only a small proportion, a smaller proportion, 20 per cent go on to develop severe or critical disease, and critical disease is a small, small portion, it’s five per cent or less, and that is…and that seems to be kind of consistent I think through the literature so most patients do have, if they have mild disease, self-limiting disease, they get better on their own, their immune system kicks in and they get better.” 
9. SOUNDBITE (English) — Dr Janet Diaz, Head of Clinical Care, WHO: “We do know that even patients with mild disease may have persistent longer-term symptoms. And that has been now described; so even though they don’t get severe disease there can be some persistent symptoms that lasts longer than one would have hoped for.”