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WHO: New guidance against the use of two antibody therapies against COVID

Two COVID-19 antibody therapies are no longer recommended by the World Health Organization (WHO), on the basis that Omicron and the variant's latest offshoots have likely rendered them obsolete.

New guidance from the World Health Organization (WHO) strongly advises against using the antibody therapies sotrovimab and casirivimab-imdevimab to treat patients with COVID-19.

This guidance, published in the British Medical Journal, replaces previous conditional recommendations for the use of these drugs. It’s based on emerging evidence that they’re not likely to work against current COVID variants such as omicron. 

What’s changed
A key challenge that comes with using monoclonal antibodies to manage SARS-CoV-2 infections is that they only bind to a single region of the spike protein. As the virus evolves, this region of the protein that the antibodies recognize can be altered by mutations. So it’s not entirely surprising that lab studies suggest the emergence of omicron has diminished sotrovimab’s efficacy.

Casirivimab-imdevimab combines two monoclonal antibodies, thereby targeting two different regions of the spike protein, to try to overcome the speed at which SARS-CoV-2 can change. But this combination has proven ineffective in preventing omicron infection in lab experiments, leading the WHO to change its advice.

Even though, for the time being, there are no recommended antibody therapies to treat COVID, there are, however, still other treatment options. 

We know that severe COVID is driven by collateral damage from our own immune system. Some of the most effective COVID treatments are anti-inflammatory medicines, which reduce exaggerated immune responses against the virus. Strong evidence continues to support the use of drugs such as corticosteroids, anti-IL-6, and baricitinib.

Separate from anti-inflammatory drugs, we have two types of therapies that directly target SARS-CoV-2, the virus that causes COVID-19. These are antiviral drugs and antibody treatments.

Antiviral drugs allow the virus to enter our cells but prevent it from replicating, thereby reducing the impact of an infection.

Remdesivir, which was originally developed for hepatitis C, retains efficacy against omicron sub-variants BA.2.12.1, BA.4, and BA.5 in the lab. In the new guidance, the WHO has conditionally recommended remdesivir to treat patients with severe COVID but has advised against its use for patients who are critically unwell, based on results from a series of recent randomised trials.

Other antivirals include molnupiravir, which the WHO continues to conditionally recommend, and nirmatrelvir and ritonavir (a combination known as Paxlovid), which are recommended strongly. These drugs are taken orally, while remdesivir is administered intravenously.

Meanwhile, antibody therapies work by coating a protein on the surface of SARS-CoV-2, called the spike protein, thereby blocking the virus from entering human cells. They can also help eliminate infected cells which have been hijacked by the virus.

Sotrovimab is one such antibody therapy. It’s a monoclonal antibody, which means it only targets a specific region of the virus’s spike protein. In clinical trials conducted before the omicron variant emerged, sotrovimab reduced the risk of disease progression.

This led to its emergency authorisation by the US Food and Drug Administration and the UK’s Medicines and Healthcare products Regulatory Agency in 2021.