Folks - if your covid patient is doing well respiratory wise but suddenly starts to become delirious and agitated and hallucinate -> tachypnea - it is due to SEROTONIN excess and they respond to treatments for it:

Precedex

And far more easily a simple pill called Cyproheptadine
This agitation is the beginning of the end for some that leads to re-intubation and is major source of morbidity and mortality.

Vast majority of the world doesn’t have access to Precedex due to cost. There is an easier way to address this important and life-altering issue.
Just because the micro-thrombi leading to respiratory worsening have been avoided on proper anticoagulation, it does NOT mean that platelets have also reversed their hyper-reactivity due to COVID, and it does not mean pulm endotheliopathy of COVID has been "healed" ....
Those two processes, platelet hyperreactivity of acute COVID and pulm endotheliopathy of acute COVID are STILL ongoing, leading to elevated serotonin release by platelets and reduce reuptake/regulation by (injured) pulm endothelium ...

Serotonin excess will CONTINUE acutely
Leading to ...
(1) myoclonus
(2) CPK elevation
(3) agitation, delirium, hallucination
(4) hyperpnea via CAROTID SINUS action of 5HT

Eventually P-SILI of some sort, tenuous and ineffective respiratory status, and reintubation -> VILI -> worsened pulm endotheliopathy -> mortality
And eventually ...

5HT mediated REDUCED renal blood flow -> AKI (which is erroneously attributed to high CPK)

Once you have renal failure on top of reintubation, with ventilator dyssynchrony due to untreated serotonin excess -> mortality risk
To be avoided are serotonergic medications, with a main culprit not-well-known to many being FENTANYL, which unfortunately is what will be started upon intubation ....

High PEEP to be avoided due to worsening of pulm endotheliopathy of "healthy" alveoli getting overdistended
I will keep repeating these series of Tweets until the world understands ...

To add Haldol, intubate, and add neuromuscular blockers will achieve not much, likely worsens this

Folks need to understand the BIOLOGIC effect of pulm vessels beyond gas exchange: serotonin regulation
And those COVID Toes, appearing like thromboangiitis obliterans, are most likely due to this dysregulated excess extracellular serotonin, per below:

(Image from a publicly shared post)

pubmed.ncbi.nlm.nih.gov/8376917/ ImageImage

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More from @farid__jalali

13 Nov
@TKrackers @AngelaReiersen @WesElyMD @PeterHorby @EricTopol @charlot_summers @iceman_ex SSRIs inhibit SERT.

SERT exists mainly on platelets where 95% of body's total content of serotonin is contained.

Among all vascular beds, SERT exists -ONLY- in the pulmonary endothelium. No other vascular bed.
@TKrackers @AngelaReiersen @WesElyMD @PeterHorby @EricTopol @charlot_summers @iceman_ex We do know that chronic use of SSRI depletes to some extent platelet serotonin content.

As pertinent to this study, the biggest question is, ACUTE HIGH-DOSE of SSRI for 7-14 days leads to which tissue/cell SERT inhibited first, fastest, most potently in COVID19?
@TKrackers @AngelaReiersen @WesElyMD @PeterHorby @EricTopol @charlot_summers @iceman_ex Pulmonary endothelium is a major site of homeostasis and reuptake and regulation of platelet serotonin.

We do know that pulmonary vascular damage (as in COVID19) leads to an IMPAIRED serotonin reuptake via SERT.
Read 9 tweets
11 Nov
Platelet deposition in lung (CD61 staining quantification) in COVID19 > influenza, but equal or less than some bacterial/fungal infections

PATTERN of platelet Antigen deposition in the immune milieu responding to the pathogen, however, is variable.

academic.oup.com/ajcp/advance-a…
My belief is that pericytes of alveolar capillaries, by virtue of ACE2 expression, likely sustain injury due to SARS-CoV-2 and this creates a double-hit scenario ...
where not only platelets are activated (appropriately, to defend), but endothelium is destabilized, further propagating platelet activation to levels no longer protective against the pathogen, but pathologic against the host lung.

ncbi.nlm.nih.gov/pmc/articles/P…
Read 4 tweets
11 Nov
I refrain from recommending a cocktail, but at 200k cases per DAY now of COVID19, I think it may be time to go ahead:

I think folks should consider taking an Aspirin 162 mg daily (the same dose being trialed by RECOVERY I believe) at the onset of symptoms from COVID19.
The medical establishment had 7 months to RCT Aspirin and other anti-platelets and anticoagulants for early symptomatic COVID19, and it didn't. My twitter feed is a testament.

It preferred to spend its time and energy on where the $$$ led it. It's an embarrassment.
I should clarify that I am not alone in recommending this, as it is NOW being trialed by RECOVERY and at Harvard and other large institutions. However, the time is of the essence, and that concept unfortunately never registered with those I pleaded with to listen and trial it.
Read 12 tweets
10 Nov
Yes. Platelets are those cells that in turn activate endothelium. There is a billion of these platelets and megakaryocytes PARKED in the lung microvascular space.

biorxiv.org/content/10.110…
And there is an overabundance of evidence that SARS-CoV-2 significantly activates platelets beyond what is seen typically in ARDS of other etiologies.
There is probably a dysregulated milieu with dysregulated serotonin and other mediators that drive the dysregulated B cell response, leading to afucosylated Ig development that essentially puts the disease in the next gear with autoimmunity that further activates platelets, etc.
Read 7 tweets
9 Nov
Can anyone please explain to me what HYPOXIC PULMONARY VASOCONSTRICTION has to do with ANYTHING in COVID19 patients on a ventilator with plenty of O2 supplied?

Can people please use correct terminology? This is exhausting.

annalsofintensivecare.springeropen.com/articles/10.11…
Alveolar hypocapnia due to alveolar capillary perfusion defects (increased vascular CO2 and decreased pH) leads to localized bronchoconstriction ...

This is the CORRECT PHYSIOLOGIC RESPONSE that is driving physiology in COVID19 lung vasculature ...

watermark.silverchair.com/20190800_0-000…
I'd ask the giants in the field to PLEASE consider advising authors (during peer reviews) to use CORRECT terminology.

HPV is NOT driving physiology in COVID19.
.
.
.
It's dead-space-induced, "alveolar hypocapnic" bronchoconstriction.

@gattinon @ElieAzoulay5 @jlvincen @Dr_Cit
Read 4 tweets
8 Nov
@engc9k It all starts and ends with platelet hyperreactivity. All else in lung and systemically occurs as a downstream effect.

Enough early endotheliopathy and platelet-opathy causes immune complex mediated autoimmunity that activates platelets further, not unlike HIT.
@engc9k Regular HIT at least has a healthy pulmonary endothelium to soak up the released serotonin (recall serotonin release assay) - this disease does NOT even have that healthy lung endothelium to soak up much of serotonin before it reaches systemic circulation -> widespread effects
@engc9k On top of it, due to florid angiogenesis of COVID lung (to help survive the acute disease), you’ll have the widely confirmed florid R to L intrapulm shunts that essentially shunt serotonin to systemic circulation without any exposure to healthy lung capillary endothelium.
Read 4 tweets

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