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Several studies are coming out saying that blood LDH (lactate dehydrogenase) levels early in #COVID19 disease correlates with severe disease progression. This is a clue that #pyroptosis may be a the core of this disease (1/n).……
What is LDH? It is an enzyme found within the cytosol of nearly all cells. Ed Miao's group showed that LDH release is a reliable way to monitor #pyroptosis, a form of cell death that depends on inflammasomes leading to plasma membrane rupture. (2/n)
LDH is not released by apoptosis or even hyperactivation of macrophages. It requires pyroptosis and membrane rupture shown by @jkagan1 's group. (3/n)…
How might #SARSCoV2 induce pyroptosis? A study showed that #SARSCoV1's Orf8 triggers NLRP3 inflammasome activation and pyroptosis in macrophages. Whether #SARSCoV2 Orf8 also activate pyroptosis is unknown. (4/n)
While LDH correlates well with disease severity, this may not be the reason for severe disease. However, pyroptotic (pyro=fire, ptosis=falling) death is very immunogenic, releasing intracellular contents and can lead to blood clotting. (5/n)
Blood clotting is also associated with poor prognosis in #COVID19. (6/n)
There are other reasons why inflammasome inhibitors might be a promising approach - to increase host disease tolerance. Please see a nice thread by @padminipillai explaining this concept. (7/n)

I believe inflammasome inhibitors should be tested for #COVID19 treatment. I've said this before but I believe it is worth repeating here. I hope pharma companies working on developing such inhibitors for other disease indications can help 🙏🏽 (end)…
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