New post: Treating COVID-19 with dornase alfa to cut neutrophil extracellular trapshttps://the-lagrangian.github.io/2020/04/11/treating-covid-19.html …
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Replying to @The_Lagrangian
This is intriguing but I don't *completely* endorse prioritizing this over other clinical trials. My big question is how does this NET mechanism compare in importance to other cellular causes of ARDS and DIC? Does blocking it *completely* prevent these conditions? etc.
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Replying to @s_r_constantin @The_Lagrangian
Normally my heuristic is to ask two questions: first, "COULD this work?" and second, "is there some reason that this is WAY BETTER than everything else out there? is this a "so good it's almost like cheating" situation?"
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Replying to @s_r_constantin @The_Lagrangian
Currently Pulmozyme sounds like a yes on "could it work?" and a no on "does this seem head and shoulders above other approaches?"
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Replying to @s_r_constantin @The_Lagrangian
The only treatment candidate I've seen that's *truly* a no-brainer is convalescent serum. I wish there were more but I'm struggling to find any that seem like they aren't subject to the usual low base rate of drug success in the clinic.
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Replying to @s_r_constantin @The_Lagrangian
why a no brainer? failed RCTs in influenza, some hints antibodies are harmful in some cases of COVID-19, mechanism murky (what fractions of infused antibodies can even make it into lungs/respiratory tract? I’ve seen 1 in 2000 for RSV)...
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Replying to @LucreSnooker @The_Lagrangian
success in SARS and "it just makes sense" mostly, but yeah, those are good points.
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Replying to @s_r_constantin @The_Lagrangian
to me, inhaled or IgA “just makes sense” but injected IgG less so. Favorite studies in SARS? I recall a small “meh” result and a larger “maybe good” result but all single-arm studies etc
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Replying to @LucreSnooker @The_Lagrangian
https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1469-0691.2004.00956.x … (not randomized but big effect & still significant after correcting for comorbidities)
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review study for SARS and influenza finds an OR of mortality of 0.25 compared to placebo or no treatment: https://academic.oup.com/jid/article/211/1/80/799341 …
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Replying to @s_r_constantin @The_Lagrangian
I’m thinking of discussions in https://pubmed.ncbi.nlm.nih.gov/31582359/ and https://www.medrxiv.org/content/10.1101/2020.02.20.20025593v2 …
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Replying to @LucreSnooker @The_Lagrangian
Ah that's interesting, thanks! Seems like an easy way to improve the method is to check in vitro for a donor whose serum neutralizes the virus? If the "active ingredient" isn't a specific antibody but some other circulating immune factors, selecting on antibody could be bad.
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