Covid is a 𝗦𝗲𝗿𝗼𝘁𝗼𝗻𝗶𝗻 𝗦𝘆𝗻𝗱𝗿𝗼𝗺𝗲 and is treatable as such
Rough Draft
Not all tweets are inputted in yet/organized/formatted
tweets may be out of order/double
last edited: 1:50pm
A collection of tweets from
https://twitter.com/farid__jalali
https://twitter.com/__ice9
1st. Zaid et al. directly demonstrated that plasma serotonin is indeed greatly elevated in hospitalized moderate to severe COVID-19. Therefore, this is no longer a theory, but rather an established fact about the disease process.
Notable distinction: Serotonin syndrome is primarily neurological — excessive serotonin signaling in the brain and nerves, usually from a serotonergic drug interaction. In severe COVID-19, *plasma serotonin* from platelets is the source; it just diffuses into nerve tissue too
Zaid et al. directly and thoroughly proved this is the case, so it should be considered a firmly established fact about COVID-19 pathophysiology at this point.
https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.120.317703
2nd. Because the excess plasma serotonin has obvious and serious ramifications for clinical symptoms and management. It is a miserable condition to be in for even hours, much less weeks. People thrashing, hallucinating, clawing at tubes: here’s why:
About 60 percent of severe COVID-19 patients in the ICU exhibit clinical symptoms that look essentially indistinguishable from serotonin syndrome.
Other observations: descriptions similar to video, worse in severe cases (fits 5-HT positive feedback), not just cognitive delirium, highly agitated, poor response to sedatives and neuroleptics, need restraint (matches COVID-19 ICU reports), neuroinvasion still looks rare
Tangential articles: https://karger.com/Article/FullText/505907… Case report: serotonin syndrome induced encephalopathy. https://sciencedirect.com/science/article/abs/pii/0735675794900310… Serotonin syndrome monograph, with notes on platelets and endothelium. https://medrxiv.org/content/10.1101/2020.06.16.20128660v1.full.pdf… COVID-19 metabolome shows elevated serotonin levels.
https://www.karger.com/Article/FullText/505907
The last one makes some… rather speculative claims about MAO-B, but a more parsimonious explanation is just the widespread platelet activation and pulmonary endothelial dysfunction already known to occur. Platelets are serotonin reservoirs. The rest is mostly in mast cells.
Another interesting theme — cyproheptadine as off-label spasmolytic:
https://jnnp.bmj.com/content/jnnp/45/10/923.full.pdf
Might be helpful in making a further case for it.
This fits evidence provided earlier showing elevated plasma serotonin levels in COVID-19. Consistent with observed platelet activation (platelets store most peripheral serotonin) and damage to pulmonary endothelium (clears it from plasma)
Cyproheptadine and famotidine have been noted as effective in the treatment of serotonin syndrome.
Background on the broader context and etiology.
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Further evidence of harms arising specifically from elevated plasma 5-HT in moderate to severe COVID-19:
The disease process is multifactorial, but 5-HT is worth addressing specifically. Zaid results show elevation nearly universal in moderate/severe.
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Mechanism discussion: How moderate to severe COVID-19 causes a large increase in plasma serotonin (5-HT) levels.
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Elevated 5-HT also further exacerbates the effects of viral depletion of CD4+ T lymphocytes.
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Journalists like videos and media, right? Here’s what it looks like. Click this post, scroll up by one for the video.
3rd. https://twitter.com/__ice9/status/13384509857 28020480?s=20
https://twitter.com/__ice9/status/13461530533937 19301?s=20
Imagine if this were your father or uncle or grandfather. Just weeks like that. We can do something about this. It can be blocked.
Quote Tweet
Fourth: Because highly elevated plasma serotonin levels are known to cause the same major immunological effects observed in severe COVID-19. It may or may not be responsible for the entire effect, but it gets the direction right for all of them.
We have a fair number of studies already: Check these out. Cyproheptadine prevents platelets from accumulating in the lungs. 5-HT2A antagonism. Cyproheptadine prevents bleomycin induced pulmonary fibrosis. 5-HT2B antagonism.
Note cyproheptadine also succeeded in animal experiments for preventing pulmonary platelet activation and microthrombosis after e.g. endotoxin exposure or physical trauma.
https://twitter.com/__ice9/status/1345491810756530177
Thread: https://twitter.com/__ice9/status/1345738674793803777
Because treating this issue is simple, inexpensive, accessible, and very low risk. Cyproheptadine is a 5-HT2 antagonist, already standard treatment for serotonin syndrome. Already saving COVID-19 patients.
Summary here, click for full thread: https://twitter.com/__ice9/status/1345500377228201986
5 twitter threads
Fifth: Because medical literature dating back decades already establishes high levels of plasma serotonin promote: — pulmonary embolism — pulmonary vasoconstriction — pulmonary hypertension — right-sided heart failure — fibrosis All in severe COVID-19.
It’s the 5-HT2B receptor activation. It drives tissue fibrosis anywhere enough local damage has occurred.
“Platelet-derived serotonin links vascular disease and tissue fibrosis” 5-HT2B activation by serotonin released from activated platelets promotes tissue fibrosis. Blocking 5-HT2B prevents the effect in vivo. Cyproheptadine blocks 5-HT2B
Cross-referencing here as well: Cyproheptadine helps prevent bleomycin induced pulmonary fibrosis in animal experiments.
Cyproheptadine also succeeded in preventing pulmonary fibrosis in response to bleomycin exposure, a common animal model thereof:
The mechanism is 5-HT2B antagonism (antifibrotic) and 5-HT2A antagonism (antithrombotic/antiplatelet).
Notes on cyproheptadine use and results in severe COVID-19: https://twitter.com/farid__jalali/status/1345548533533790208?s=19… Seems to pair well with famotidine for further effect. Note famotidine has some clinical evidence of efficacy in serotonin syndrome and generally favorable study findings in COVID-19.
Normally this helps repair injuries near activated platelets, even if some scarring occurs, but here the issue has become systemic.
Further favorable practitioner feedback for cyproheptadine in severe COVID-19: https://twitter.com/farid__jalali/status/1345956375935913984?s=19… Note famotidine seems mainly useful as an add-on for further effect if cyproheptadine dosing is limited by side effects (as famotidine has ~none). Mechanism is less direct.
This is literally an account of an independent well respected Intensivist previously at Cornell and part of SCCM on his experience with Cyproheptadine in COVID19. I explained this to him about 6 months ago. RR of 40 and agitation melts away. Vent days cut short drastically.
https://twitter.com/__ice9/status/1293586532054585344
Fifth: Because medical literature dating back decades already establishes high levels of plasma serotonin promote: — pulmonary embolism — pulmonary vasoconstriction — pulmonary hypertension — right-sided heart failure — fibrosis All in severe COVID-19.
It’s the 5-HT2B receptor activation. It drives tissue fibrosis anywhere enough local damage has occurred.
Normally this helps repair injuries near activated platelets, even if some scarring occurs, but here the issue has become systemic.
https://twitter.com/__ice9/status/1346152406221004804?s=20
Sixth: Because hyperactive platelets explain ‘heparin resistance’ in severe COVID-19, when the blood of a patient on anticoagulants still clots in vessels, often in spite of bleeding elsewhere.
https://twitter.com/__ice9/status/1330614811999268869?s=19
AC also increases bleed risk more than antiplatelet drugs.
I mean this is just nightmarish, this ‘heparin resistance’ being observed in the severe cases. It is clearly both a platelet issue and an endothelial issue. In terms of bleed risk, I would much rather see early use of dipyridamole than late use of tPA.
Once more for anyone who didn’t see it yesterday: This happened on heparin. COVID-19 platelet hyperactivation is real.
Coagulopathy in Covid so
! Pt day 21 w/bilat UExt DVTs on 100mg Lovenox BID & worse so
ordered LMWhep level but #nurse can’t even get blood from syringe into lab tube before clotting.
Review: https://journals.lww.com/ccmjournal/_layouts/15/oaks.journals/PageNotFound.aspx
It is due to PLATELET hyperreactivity. Needs anti platelets. No amount of anticoagulation will resolve it. In fact should probably reduce anticoagulation and use antiplatelets. Trust me (I know, so say a hundred other people with ideas). But this is true.
This fits evidence provided earlier showing elevated plasma serotonin levels in COVID-19. Consistent with observed platelet activation (platelets store most peripheral serotonin) and damage to pulmonary endothelium (clears it from plasma)
Downwards arrow Renal blood flow
Shown in AKI in COVID19 Despite NORMAL cardiac function Right pointing backhand index
Study: https://bit.ly/3hyf0kx
Excess plasma Serotonin occurs in COVID19: Right pointing backhand index
Excess plasma Serotonin causes
Downwards arrow renal blood flow:
Medical literature dating back decades already establishes high levels of plasma serotonin promote:
- pulmonary embolism
- pulmonary vasoconstriction
- pulmonary hypertension
- right-sided heart failure
- fibrosis
All in severe COVID-19: https://twitter.com/farid__jalali/status/1345218136149114882?s=20
