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Does Monoclonal Antibody Work Against the BA.2 Variant?

May 17, 2022

Written by Rebecca Breed

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This brief report found that certain monoclonal antibodies: imdevimab-casirivimab (also known as REGEN-COV), tixagevimab-cilgavimab (also known as EVUSHELD), and sotrovimab precursor had lower neutralizing ability against the omicron BA.2 variant of COVID-19 than against earlier variants.

Why does this matter?
We are still seeing many COVID+ patients in the ED and may be asked as providers for our recommendations for monoclonal antibody treatment. Some EDs are also offering monoclonal antibody treatment as well. It is important to know which monoclonal antibody treatments your hospital is offering and to be able to speak about their potential efficacy to patients. Let’s be honest, you’re also probably getting questions about this from family and friends with COVID-19 too. 

Don’t get MAB about it
Unfortunately, the circulating variants of COVID-19 are ever changing. As of February 2022, omicron variants had been divided into four sublineages (BA.1, BA.1.1, BA.2, and BA.3). Initially, circulating variants largely belonged to BA.1 lineage, but there are increasing numbers of BA.2 cases circulating as well. The BA.2 variant has 16 amino acid substitutions in the receptor-binding domain of the spike protein compared to the initial strain of the COVID-19 virus. This is important when discussing efficacy of monoclonal antibody treatment, as the spike protein is the primary target of these therapies.

The BA.2 and BA.1 variants share 12 of the 16 substitutions, but this difference of four substitutions in the receptor binding domain seems to be enough to alter the efficacy of monoclonal antibodies to neutralize the virus. As discussed above, there were some antibodies and combinations of antibodies that showed lower neutralizing ability against the BA.2 variant than the original COVID strain, using live-virus focused reduction neutralization testing (FRNT). There were also some antibodies (such as imdevimab) which showed neutralizing activity against BA.2 that was better than previously seen with BA.1.

While this is interesting in the laboratory setting, it might not be as relevant to us in the ED since routine COVID testing does not tell us which variant a patient has, and this was not a clinical efficacy study design. If there are available data on which strain is most prevalent in your area, this article could provide guidance on which antibody therapy to recommend. It also did not consider potential side effects, such as allergic reaction, or indications for monoclonal antibody therapy, so keep these in mind when having the discussion on benefits of treatment.

Source
Efficacy of Antiviral Agents against the SARS-CoV-2 Omicron Subvariant BA.2. N Engl J Med. 2022 Apr 14;386(15):1475-1477. doi: 10.1056/NEJMc2201933. Epub 2022 Mar 9.

What are your thoughts?