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ice9 Profile picture
ice9
@__ice9
I do quantitative things. Sometimes I think about society and economics.
13 subscribers
Mar 7, 2021 • 4 tweets • 1 min read
Again, the most useful points for a broad audience:

- get vaccine ASAP; prefer mRNA or Novavax; 2 doses far better than 1

- store RCT-validated early treatments: bromhexine-or-ambroxol + nitazoxanide-or-niclosamide, fluvoxamine, ivermectin

- N100 masks

For a medical audience:

- decide what the word "evidence" means:
a) "clinical results with appropriate sample(s) and endpoints"
b) "what huge lumbering institutions claim ex cathedra with no citations"
c) "what gilead et al. claim"
d) "peer best practices"

- take low-risk bets
Feb 28, 2021 • 5 tweets • 3 min read
The continued failure to trial or use ITPP in critical care is an indictment against the regulatory and productive institutions of our supposedly-advanced (increasingly just shorthand for 'gridlocked') economy.

en.wikipedia.org/wiki/Myo-inosi…

It makes blood transport oxygen better. It costs practically nothing.

Thousands of people already use it for athletic activities.

It has no side effects, is safe at huge doses in animal studies, and has never had a serious adverse event reported in the community ('that's informal' it's post-marketing surveillance..).
Feb 28, 2021 • 5 tweets • 3 min read
Efficacy is nowhere near Novavax or the mRNA options (Pfizer/Moderna).

Much like Sinovac/Sinopharm(/CanSino), the tell for this is the headline numbers focusing solely on severe COVID-19 and ignoring mild/moderate cases. Even for moderate, only 66% effective....

statnews.com/2021/01/29/jj-…

>One hope is that the efficacy of the Johnson & Johnson vaccine could rise if it is given as a two-dose regimen.

Obviously, yes! This is much more promising.
Feb 26, 2021 • 7 tweets • 2 min read
A couple things about which I would like to be clear, from the now-big account (likely smaller over time):

1) do not ever @/DM to ask where I am or act like I owe you something-- pay me a bitcoin if you want that kind of attention, I know that is pocket change to some of you 2) I have a life outside of COVID-19 and a very, very detailed post history that is approximately two clicks away, depending on your choice of platform access method: search feature, "__ice9 <whatever topic>" papers generally do not become 'out of date' and a result is a result
Feb 1, 2021 • 4 tweets • 3 min read
Reminder:

If you test positive for COVID-19 and do not have fluvoxamine on hand, please consider enrolling in this clinical trial.

It's simple, remote, and important. It's a 50% chance to get fluvoxamine.

You can keep using other medications. Delivery is overnight shipping. You can read the protocol summary here for more details on the trial if desired:

clinicaltrials.gov/ct2/show/NCT04…

My prior post about it is here:

Jan 22, 2021 • 5 tweets • 5 min read
NAC apparently has antiviral effects vs. SARS-CoV-2.

chemrxiv.org/articles/prepr…

EC50 ~10μM
163g/mol * 10μM = 1.6mg/L
Plasma, as VoD=0.4L/kg

Hittable at 600mg oral q.i.d.:

pubmed.ncbi.nlm.nih.gov/2029805/

link.springer.com/article/10.100…

Unlike for vWF, Spike inhibition by NAC does not need IV. Note I really do mean 600mg *q.i.d.* (4x/day) if tolerated; short half life. Safe in other studies.

link.springer.com/article/10.100…

Side note: strangely demanding PK study; very rigorous protocol. Hope participants were at least paid well. But they got us a number so I am pleased.
Jan 22, 2021 • 5 tweets • 3 min read
Evidence in vitro for dual entry inhibition:

When TMPRSS is blocked:
- HCQ works
(also implies:)
- nitazoxanide/niclosamide work better

Consistent with RCT efficacy for bromhexine+HCQ in Ansarin et al., which reduced mortality by 100% in moderate hospitalized cases. Cross-referencing to dual entry inhibition thread:

Jan 22, 2021 • 7 tweets • 4 min read
Finally: Calu-3 data for ivermectin.

As suspected, EC50 is much lower vs. Vero.

Still not quite hittable at 200μg/kg, but ~5x lower than Vero figure.

In light of this, results claiming better antiviral effects at 400-600μg/kg are plausible.

Likewise, prophylaxis is plausible. This cements the case for ivermectin as prophylaxis. The missing in vitro data is now present and consistent with observed clinical results.
Jan 22, 2021 • 4 tweets • 2 min read
Or you can take antivirals on day one of symptoms and prevent this with very high probability.

But that requires buying them in advance online yourself, because for some absurd reason practitioner utilization is still very low and monotherapy is common even then. Here are some of the most effective ones in the literature:

Jan 19, 2021 • 6 tweets • 5 min read
GABA administration protects mice from death by mouse hepatitis virus (MHV) infection, another coronavirus often used in animal experiments.

Ivermectin activates GABAAR (GABA is used in e.g. leukocytes, not just CNS).

OTC GABA supplements are safe for brief use and inexpensive. L-glutamine (a GABA precursor) was studied clinically for COVID-19, but the study was poorly designed and results were rather weak. I expect little benefit from glutamine in COVID-19.

ncbi.nlm.nih.gov/pmc/articles/P…

Effect on GABA levels appears limited.

pubmed.ncbi.nlm.nih.gov/17218538/
Jan 6, 2021 • 7 tweets • 3 min read
One request--

If you work in COVID-19 critical care, please consider the following:

We know, with certainty, that plasma *free 5-HT* is highly elevated. Always.

We know, with certainty, that this is *causal* for pulmonary vasoconstriction, thrombosis.

We know the 5-HT2A receptor activates platelets, and the 5-HT2B receptor promotes fibrosis. This is basic physiology.

We know that 5-HT2 antagonists have been proven repeatedly to block these processes in many related contexts: cyproheptadine is one.

Jan 4, 2021 • 7 tweets • 6 min read
@coolnidal @farid__jalali First off:

Because Zaid et al. already 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. @coolnidal @farid__jalali Second:

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.
Jan 4, 2021 • 5 tweets • 2 min read
More autoimmune exacerbation in COVID-19:

Fatal cases have higher levels of autoantibodies to Annexin A2, vs. non-fatal severe cases and non-severe cases.

Inhibiting Annexin A2 promotes thrombosis and pulmonary edema.

Similar to Abs against β2GPI in antiphospholipid syndrome. Interestingly, antibodies to SARS-CoV-2 S2 are also somewhat cross-reactive to Annexin A2.

Not relevant to vaccines using stabilized Spike.

Relevance unclear for natural infection.

May matter during the exaggerated antibody response in severe COVID-19.

Jan 3, 2021 • 6 tweets • 5 min read
Excessive plasma serotonin levels contribute to lymphopenia.

This may partly explain the relative lymphopenia seen in some severe COVID-19 cases and its poor prognostic implications.

H2 antagonists (e.g. famotidine) and cyproheptadine block the effect.

sciencedirect.com/science/articl… More on the effect of excessive plasma serotonin levels in suppressing T cell activity:

tandfonline.com/doi/abs/10.310…

@farid__jalali
Jan 3, 2021 • 4 tweets • 2 min read
@ianbirrell Comprehensive.

Only a few flaws.

The first is the 'missing researcher'-- she left years earlier, irrelevant.

The second is that you missed the EcoHealth Alliance grant, and Daszak explicitly confirmed recombinant CoV testing in humanized mice Nov 2019.

@ianbirrell You need to read this:

Jan 3, 2021 • 5 tweets • 2 min read
What to expect in a COVID-19 case that progresses to the severe phase and ICU admission-- in terms of typical patient experiences.

Note this thread is 14 posts long. The things we are discussing about 5-HT2 antagonists and plasma serotonin, about attempting to halt progression in the early severe stage, are relevant *during* these events.

Rates of PTSD following survival from severe COVID-19 exceed 30%, ditto anxiety and depression.
Jan 2, 2021 • 4 tweets • 5 min read
Cyproheptadine prevents pulmonary platelet trapping in endotoxin shocked or severely beaten dogs.

osti.gov/biblio/5502933…

Further evidence for potential efficacy against development of ARDS via pulmonary microthrombosis-- explicitly discussed.

@farid__jalali ImageImageImageImage @cameronks @pathdoc3 @icedoc61 @Jopo_dr @Acute_Pulmo_Med @ZaidYounes9 @Geurys7 @MARYau_MCU_PH @DrBrandon55 @VectorSting @Crashcart

Interesting earlier result on cyproheptadine and pulmonary platelets.
Dec 30, 2020 • 4 tweets • 3 min read
For anyone interested in the Baric interview on synthetic recombinant SARS-like CoVs earlier, see around 38:00 into this video.

There is also some interesting preliminary discussion starting around 36:30 or so, mostly in English. This provides the video that went missing when a few accounts I had quoted earlier were suspended.

Dec 29, 2020 • 6 tweets • 4 min read
@HenkPoley Yes, am familiar with the issue.

I will see if I can locate my earlier findings on this.

So far I have only located some notes from earlier, but not the actual citation yet.

@HenkPoley This paper indicated that a single exposure to 70% ethanol largely preserved filtration efficacy, comparable to dry heat or UV sanitizing. However, further exposure events gradually worsened filtration efficacy.

medrxiv.org/content/10.110…
Dec 29, 2020 • 15 tweets • 5 min read
To date, anecdotal reports from dual entry inhibition in mild acute COVID-19 remain excellent.

Recovery within 48 hours appears typical, absent significant complications (e.g. secondary infection).

Dual entry inhibition means blocking both:
- TMPRSS2/13/11
- endosomal entry Dual entry inhibition was tested in the Ansarin et al. RCT, adding bromhexine 8mg t.i.d. to a baseline of HCQ 200mg q.d.

Mortality in hospitalized moderate COVID-19 patients fell to zero.

This remains one of the best results of any COVID-19 RCT to date.

Dec 25, 2020 • 10 tweets • 5 min read
Continuing to hear extremely favorable case reports informally for cyproheptadine even in severe COVID-19.

Publications forthcoming, but worth highlighting now given magnitude of improvement-- extubation within days, reversal of renal failure, stark decline in D-dimer, etc. Try it for 48 hours and see. It's just an old allergy medication. Side effects are minor and it is already known to be effective in serotonin syndrome.

It blocks 5-HT2A (platelet activation) and 5-HT2B (cardiac remodeling, pulmonary fibrosis).