The WHO Has Advised Against the Use of Two Antibody Therapies Against COVID – Here’s What That Means

So 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 recognise 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.

Evidence Will Evolve Alongside the Virus
Regulatory agencies and the WHO keep a close eye on the way existing treatments respond to emerging variants, and issue prescribing recommendations accordingly.

For drugs such as remdesivir that have a modest impact in certain groups of patients, the WHO issues conditional recommendations. Drugs that continue to work consistently receive strong recommendations, but these are also subject to review as the virus evolves.

While it might seem alarming that the WHO has changed its mind on these two antibody treatments, it’s actually a sign that the scientific process is working as it should.

This is now the 12th iteration of the WHO living guideline, and the advice on the provision of COVID treatments is likely to continue to be updated as the pandemic plays out.

Who Will Be Most Affected?
In the fight against infection, we are not all equal. Vaccination has significantly reduced the risk of severe COVID for the vast majority of the population. However, some people are born with deficient immune systems or receive treatments that weaken their immune responses later in life, for example after receiving an organ transplant or chemotherapy. Certain infections or chronic diseases can further damage the immune system, which also naturally weakens with age.

One of the most common forms of immune deficiency is an inability to produce enough antibodies following vaccination or infection. So antibody therapies, which seek to supplement or replace those antibodies artificially, stand to benefit many people who are immunocompromised in particular.

While guaranteeing monoclonal antibodies remain effective against a rapidly changing virus is an enormous challenge, this isn’t necessarily the end of this type of treatment for COVID. Next-generation monoclonal antibodies that better neutralise omicron subvariants may well be identified, although these too are unlikely to remain effective for long.

For the immunocompromised, but also for the wider public, there is an ongoing need for continued research into, and access to, effective COVID treatments – antivirals, antibodies and otherwise.

Unfortunately, when dealing with RNA viruses, mutations can rapidly bring down our defences. To prolong efficacy, combination treatments will be an important way forward compared with single-agent therapies.

Zania Stamataki is Associate Professor in Viral Immunology, University of Birmingham. Adrian Shields is Associate Professor in Clinical Immunology, University of Birmingham, University of Birmingham. This article is published courtesy of The Conversation.