Thanks. It's hard to imagine how LL would block CCL5-CCR5 based immune cell motility but have no effect on CCL4-CCR5 based motility. It just doesn't make sense to say PASC is caused by low intermediate monocyte motility (due to low CCL4), so let's decrease the motility more by blocking CCR5. It's possible there is a floor effect with CCL4-CCR5, though, as noted.

Anyways, I think there is something else, that BP is saying you want those inflammatory non-classical, S1 presenting monocytes adhering to endothelial walls to stay put so as to keep the inflammation from spreading to vessels in the brain and heart, for instance. This idea just doesn't match the low CCL4 causing low intermediate monocyte motility causing persistence and increase of non-classical monocyte reasoning.

Some effects must be stronger than others. Just like another puzzle - for cancer, want LL to block T-Reg motility into cancer and increase T-effector motility into cancer, yet at the same time for auto-immune disease, want LL to block T-effector cell motility to prevent them attacking self and increase T-Reg motility so dampen down autoimmunity. How can one drug do both things?

There must be more to the story than LL effects on immune cell / monocyte motility. Thanks for highlighting some of those possible additional mechanisms.

I wonder if BP is correct about wanting to use both a statin to lower fractalkine and CCR5i to block monocyte motility (no matter that he says low motility is a cause of PASC). or maybe will CCR5i alone lower fractalkine and inhibity damaging non-classical monocyte motility?

Hopefully we get a good trial design for phase 3 of PASC.