Thursday, March 4, 2021

JULIAN WILLETT'S COLUMN

Identifying SARS-CoV-2 Virions Resistant to Monoclonal Antibody Treatment

Review of a paper that studied identification of resistant viral strains.

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While prevention of infection is the most important thing one can do to protect against COVID-19 related complications, sometimes individuals “doing everything right” can still develop the infection. Individuals with more severe disease require more aggressive treatments like monoclonal antibodies. A group of researchers wanted to answer what it would take for this treatment to lose its effectiveness¹.

Monoclonal antibodies were first used in humans in the 1980s². They have gradually become more prevalent with Regeneron, producing and selling this treatment for those with severe COVID-19¹.

Monoclonal antibodies work like our own antibodies to “tag” targets to be attacked by our immune systems. This treatment works for COVID-19 by targeting the virus in the blood and marking it for destruction¹. While potentially life-saving for COVID-19, it comes with risks ranging from flu-like symptoms to an anaphylactic reaction³.

This is why the decision to start such a treatment must be made by a physician working with a patient or a patient’s family to determine if the benefits of the treatment outweigh the risk.

Most current antibody treatments target an aspect of the virus that helps it enter cells, the ACE-2 receptor binding domain¹. The authors created a model that studied how different mutations impacted this viral protein’s function and sensitivity to antibody treatments².

Using this analysis, the authors identified mutations that would prevent the antibodies from appropriately targetting this viral protein¹. While most mutations only prevented targetting by one of the two antibodies in these treatments, mutations that blocked both were identified, the key finding of this paper¹.

This paper’s conclusions are not alarming and do not suggest the current pandemic will immediately get worse. This paper demonstrated that current treatments may need to be revised or have deficiencies addressed where viral evolution to go in a particular direction¹. We already know that the virus evolves. This paper addresses one point that requires surveillance so we can respond appropriately.

Remarks:

The title of source 2 portrayed monoclonal antibodies as “magic bullets”². If not otherwise clear, this treatment has limitations just as other clinical treatments discussed in this article.

References:

  1. https://science.sciencemag.org/content/371/6531/850/tab-pdf
  2. https://link.springer.com/article/10.1023/A:1015860525341
  3. https://pubmed.ncbi.nlm.nih.gov/23835249/

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JULIAN WILLETT, MD

Medika Columnist

M.D. trained in the US, now researching SARS-CoV-2 and COVID-19 in Canada for his Ph.D. After earning my Ph.D., I will be pursuing an Anatomic Pathology residency embracing my path towards being a physician-scientist. My academic interests are directed towards topics that provide the greatest net benefit for the greatest number of people. I love complicated, messy, and poorly understood topics.

I enjoy writing in my spare time, along with 3D printing and staying connected with my family. I have been a longstanding proponent for global health with projects ranging from supporting Doctors without Borders (MSF) to Syrian refugees (Syrian American Medical Society).

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