WHO experts suggest antiviral drug for patients with non-severe covid-19 at highest risk of hospitalization

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The antiviral drug molnupiravir is conditionally recommended for patients with non-severe covid-19 who are at highest risk of hospitalization, says a WHO Guideline Development Group of international experts in The BMJ today.

Patients who are at highest risk of hospitalization typically include those who are unvaccinated, older people, and those with weak immune systems or chronic diseases.

However, the panel says that young and healthy patients, including children, and pregnant and breastfeeding women should not be given the drug due to potential harms.

Molnupiravir is an antiviral medicine that works by stopping coronavirus from growing and spreading. Used as early as possible after infection, it can help prevent more severe symptoms developing.

Today's recommendation is based on new data from six randomized controlled trials involving 4,796 patients. This is the largest dataset on this drug so far.

Moderate certainty evidence from these trials suggests that molnupiravir reduces the risk of hospital admission (43 fewer admissions per 1,000 patients at highest risk) and time to symptom resolution (average 3.4 fewer days), while low certainty evidence suggests a small effect on mortality (6 fewer deaths per 1,000 patients).

The panel describes mitigation strategies needed at the population level, including pharmacovigilance and antiviral resistance monitoring, given concerns about genotoxicity (damage to a cell's genetic information causing mutations), emergence of resistance and new variants.

They make no recommendation for patients with severe or critical illness as there are no trial data on molnupiravir for this population.

And they acknowledge that cost and availability issues associated with molnupiravir may make access to low and middle income countries challenging and exacerbate health inequity.

In the same guideline update, the panel recommends a treatment combining two antibodies (casirivimab and imdevimab) to be used in people who are confirmed not to have the omicron variant, as new evidence demonstrates a lack of effectiveness against the omicron variant.

Today's recommendations are part of a living guideline, developed by the World Health Organization with the methodological support of MAGIC Evidence Ecosystem Foundation, to provide trustworthy guidance on the management of covid-19 and help doctors make better decisions with their patients.

Living guidelines are useful in fast moving research areas like covid-19 because they allow researchers to update previously vetted and peer reviewed evidence summaries as new information becomes available.

Today's guidance adds to previous recommendations for the use of Baricitinib, interleukin-6 receptor blockers and systemic corticosteroids for patients with severe or critical covid-19; for the use of sotrovimab for patients with non-severe covid-19 and against the use of convalescent plasma, ivermectin and hydroxychloroquine in patients with covid-19 regardless of disease severity.

The recommendation for remdesivir is undergoing review due to new trial data. Recommendations for fluvoxamine and nirmatrelvir/ritonavir are currently in preparation.

Source:
Journal reference:

Agarwal, A., et al. (2020) A living WHO guideline on drugs for covid-19. The BMJ. doi.org/10.1136/bmj.m3379.

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