Thread by @soychicka

Has anyone thought of profiling COVID19 patients to evaluate which IL1-RA alleles are present in those with +/- severe disease presentation, and running a study in those polymorphic or homozygous for IL1-RA allele 2?

I don't see anything at NIH...

covid19treatmentguidelines.nih.gov/immune-based-t…

If you're still reading and don't know what IL1-RA is, it is a molecule that turns off the immune response by blocking the IL-1 receptor, which otherwise causes mast cells to hang out and secrete histamine, nerve growth factor (pain nerves) and other cytokines -

And mast cells that don't get sent away from the site of inflammation after the stimulus is gone can stimulate the production of bradykinins, which have been implicated in explaining many of the symptoms of COVID - like COVID toes, pulmonary edema, etc.

So, on top of the DABK buildup from ACE2, in people with insufficient IL1-RA activity, you'll have mast cells hanging out & upping the gain on the feedback loop.

IIRC, ~8% of the ♀ population is homozygous for allele 2, which -> reduced IL1-RA activity.
pubmed.ncbi.nlm.nih.gov/21349432/

This is one of those things where having more info about the pt - or pt knowing their status in advance of potentially contracting the disease - might be a good motivation for those with the polymorphism to be more cautious.

this is just rough, happy to share more detail, or write it up in a way that is more appropriate for different audiences if anyone would find it useful.

but something someone said today made me realize why all the talk about bradykinin and cytokine storms sounded familiar: it's all about the Mast cell regulation, or lack thereof.

and then I find that this was published last month.

sciencedirect.com/science/articl…