Thread by @DrMattMcCarthy

COVID question doctors are wrestling with: Should patients with profoundly impaired immune systems receive monoclonal antibody therapies after contracting #coronavirus? 1/

These patients are often prioritized for antibody treatments (made by Regeneron and Eli Lilly). And this makes sense: Their immune systems are weak, and antibodies can potentially help fight infections. But there's an issue. 2/

A new hypothesis argues that patients with weak immune systems could serve as an incubator for viral mutations, leading to new strains like B.1.1. 7 that might be more transmissible. 3/

Immunocompromised patients may hold onto the virus for months and monoclonal antibodies could, in theory, enhance viral mutations through selective pressure. 4/
biorxiv.org/content/10.110…

We worry about these "escape mutations," which cluster in areas targeted by monoclonal antibody therapies, such as the spike protein receptor-binding domain. Changes in spike protein make us anxious because it's the target for all of our vaccines. 5/
sciencedirect.com/science/articl…

Here's an example of the thing we worry about: a patient with a weak immune system who was treated with Regeneron's cocktail several months after the initial COVID diagnosis. The virus continued to mutate throughout the illness, which lasted 5 months. 6/ nejm.org/doi/full/10.10…

Immunocompromised patients are a heterogenous group and we're just beginning to understand how the virus evades antibodies and T cells.  Most of these patients effectively clear the virus. But some don't. And the results can be devastating. 7/

Takeaway: Patients with immune impairment are often targeted for antibody therapies because they're at risk for complications from the virus. That will change if, in fact, these treatments actually accelerate viral evolution and select for mutations that enhance transmissibility.