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This is such an elegant paper (I love ATS papers!) about pathophysiology of severe Covid; it's the host response we are treating, not the virus...
Areas of inflammation are highly asynchronous geographically with cellular viral location, and poor evidence of viral existence in actual renal tissue despite AKI/histological inflammation.
The hallmark of fatal Covid is extensive pulmonary vasculitis characterised by monocytes (flu is T cells), MRP8+ve monocytes which grossly and destructively bash through endothelium.
That's interesting because I've come across that molecule before in context of it being necessary for constructing microtubules to assist trans-endothelial leukocyte migration. It's also a TLR-4 stimulant.
Certainly explains endothelial damage and steroid benefit tailored more in Covid than other diseases. Doesn't suggest Toci is the be all and end all, and a pathway left to play with. Wonder if colchicine will show willing in Recovery.
Actually a lot more evidence more widely that is the tissue genome and phenotype that determines the local immune response in many septic states and not necessarily innate problems within the immune cells themselves.
Interestingly other findings in paper were unusually high numbers of iron laden macrophages (is this where IL-6 benefit would help?) and splenic damage.
And the pointing out that one of the key things actually higher in covid that other things is GM-CSF (being trialled)
Problem with host responses is very host specific. Even organ specific within host. So how you eke out those signals with steroids ... no wonder we don't get anywhere often.
The other thing particularly convincing about this is this monocytes subset (MRP8), involves this molecule - links microtubule to f-actin filaments which is not only significant for impaired fibrinolysis but genomic/proteome studies find impaired actin clearance = severe Covid
Someone needs to find a way to sort this before the holes in the endothelium appear...
