Covid19Crusher Profile picture
"I do not believe in the collective wisdom of individual ignorance." Thomas Carlyle
Parler: @PaulSchmehl #ArrestSOMEBODY Profile picture The Real Dr. Steven Horvitz Profile picture Roleigh Martin Profile picture Emmanuel CLEMENCE Profile picture Hasan Ameer Ali Profile picture 7 added to My Authors
13 Jun
The current struggle of Chile against Covid is daunting...

47% of the population is fully vaccinated, another 13% partially.

The government says that full vaccination corresponds to 58% the targeted population.
Nevertheless, critical bed occupation is reaching new pandemic highs.

The nation's capital is back into a strict lockdown.

The nasty P1 virus variant is now dominating the new cases.
However, there is little doubt that vaccination is blunting the fatality rate.
Read 8 tweets
11 Jun
Pr. Raoult's hospital has published the preprint of the cohort study of it 2,111 hospitalized patients.

A few comments...

mediterranee-infection.com/wp-content/upl…
The eye-catchers are definitely in the subgroup analysis:
The simple zinc-no zinc analysis yields no mortality benefit but the Hydoxychloroquine +Azythromicin +/- Zinc does, pointing to a large synergetic benefit.

Confirmation of the role of HCQ as an active Zinc ionophore?

Dr. Zelenko shall be pleased.
Read 5 tweets
5 Jun
The French study associating FIASMA use and much lowered intubation risk in Covid patients is now published.

IPW HR=0.58; 95%CI=[0.46-0.72]; p<0.001
ascpt.onlinelibrary.wiley.com/doi/abs/10.100…
The paper includes a useful list of FIASMAs, with names including:
• Clarityn, Promethazine, Hydroxyzine, Cyproheptadine
• Prozac, Fluvoxamine, Citalopram
• Ambroxol
A reminder of the power of early antihistamines in high-risk patients in this Spanish observational study in Spain (n=84):

• average 85 year-old
• 100% seropositive
• no hospital admission
• no death

Bravo!
sciencedirect.com/science/articl…
Read 4 tweets
3 Jun
Instructive, lowish 3x 12mg, ivermectin Randomized Controlled Trial from Egypt (n=164) in mild/moderate, young hospitalized Covid patients struggles for statistical power:
• Length of hosp. stay 9 vs 11 days p=.08
• Death 3 vs 4, non significant.

onlinelibrary.wiley.com/doi/10.1002/jm…
The comparison with the other Egyptian RCT (Elgazzar, mild arm) provides some important information.

The control groups differ greatly in age, however less people die in the older Elgazzar arm, pointing to more severe cases in Abd-Elsalam.
Unfortunately, that increased, age-controlled, underlying severity in Abd-Elsalam was met with a much lower dosing of ivermectin:

36 mg over 3 days whilst most patients in Elgazzar would have hit the cap of 4x24=96mg over 4 days.

(NB: average weight Egyptian 80kg)
Read 5 tweets
22 May
Sofosbuvir+Ledispavir antivirals perform well against Covid-19 in Egyptian single-blind randomized trial (n=250).

medrxiv.org/content/10.110…
A smaller open-label randomized trial (n=82) had some more mixed results, but suggested activity as well.

mattioli1885journals.com/index.php/acta…
This is not the first time that sofosbuvir is shown active against Covid-19.
Read 4 tweets
21 May
Discussion of under-researched potential role of TMPRSS2 inhibitor Spironolactone against covid-19.
preprints.org/manuscript/202…
The case for Spironolactone trials has been made before:

Read 4 tweets
13 May
The large double blind RCT (n=400) from Bangladesh pitting ivermectin+doxycyline vs placebo in a young population (avg. age 40) is now peer reviewed and published. Took only 7 months...

Faster healing / viral clearance when treated, no death vs 1.5%.

journals.sagepub.com/doi/10.1177/03…
Obviously, a question comes to mind: the same-seize Colombian JAMA ivermectin RCT showed an identical 2 day median faster recovery (10 vs 12), but without statistical difference.

So, why less "separation" or visible drug effect in the outcomes of JAMA?

2 hypotheses:
(1) the Bangladeshi control arm deteriorated 18% of the time, the treated arm only 9% (-9% abs, -50% rel).

Only 3.5% of the Colombian control arm worsened, leaving no headroom for the treated arm to outperform or reach stat. significance: it achieved 2.0% (-1.5% abs, -43% rel).
Read 5 tweets
8 May
🚨🚨🚨Remember the extraordinary, sudden eradication of Covid severity in Mexico City following the distribution of medical kits including ivermectin to all outpatients testing positive since December 2020?

datos.cdmx.gob.mx/dataset/actas-…
Mexico City had promised to publish an observational study of the ivermectin intervention impact.

Here it is and it is a giant one (n=233,849):

osf.io/preprints/soca…
"we found a negative and significant effect of the ivermectin kit on the probability of hospitalization.
Depending on subsampling, the effect ranges from 50% to 76% difference in hospitalization odds between treated and untreated patients, statistically significant in all cases"
Read 5 tweets
28 Apr
Some good results from Famotidine (Pepcid) in tiny (n=20), single-blind, placebo controlled trial of Covid inpatients (6 day discharge vs 9, p=.01).

Not enough to put an end to the data famine on that promising Covid-19 drug.

researchsquare.com/article/rs-462…
Read 4 tweets
25 Apr
When the swamped hospitals in Belém, Brazil, had to deny hospitalizations, 210 patient in respiratory failure (32% severe) got treated home with the cocktail:

Prednisolone + enoxaparin + clarithromycin + axetylcefuroxime

Deaths: 0.9%.

Extraordinary.
medrxiv.org/content/10.110…
A nice video with English subtitles for a bit of context:

HT @HobbesMatraca
More on clarithromycin as the potential macrolide of choice against Covid-19 (1/3):

Read 5 tweets
24 Apr
Another inconclusive, underpowered, aborted outpatients randomized controlled-trial of hydroxychloroquine (n=214 on HCQ, 244 on Kaletra, 227 placebo), with data pointing to efficacy (without statistical significance).

jamanetwork.com/journals/jaman… Image
Do not expect the authors to point out that those hospitalization results are entirely and remarkably consistent with the other 4, all identically underpowered, HCQ outpatient RCTs, homogenously pointing to 30%-ish hospitalization benefit. Image
However, the matter of lack of statistical power is now resolved by the national registry study publish in Iran (n=28,759).

The remarkable match of the HCQ/non-HCQ arms strongly signals quasi-randomization.

And...

⬇️Hospitalization -38%
⬇️Deaths -73%

sciencedirect.com/science/articl…
Read 5 tweets
23 Apr
Pegylated Interferon alpha-2b obtains Emergency Use Authorisation in India in moderate Covid-19 patients.

Phase 3 press release low on detail.

zyduscadila.com/public/pdf/pre…
Strong results from interferon lambda here:

Read 4 tweets
18 Apr
High quality, propensity-score matched, observational study of ivermectin prophylaxis in the Dominican Republic (n=713).

The control arm was made of those who refused the treatment and did not take the right decision as IVM was 74% protective.

medrxiv.org/content/10.110…
The cumulative risk curve shows that IVM becomes nearly fully protective after a week, i.e. on the second dose.

None of the treated participants who became Covid positive deteriorated (0/326 vs 3/387)
Very interestingly, a follow up analysis has shown prophylaxis fatigue as a growing numbers failed to maintain the weekly regimen.

In an important dose-dependency evidence, infections picked up immediately.
Read 4 tweets
17 Apr
Brilliant paper on how some antidepressants (here Amitriptyline in vitro and ex vivo) enzymatically block Sars-Cov-2 cell entry to great effect.

With likely variant robustness as a bonus.

cell.com/cell-reports-m…
A second paper reviewing the same matter with a full FIASMA candidate list.

onlinelibrary.wiley.com/doi/10.1111/jc…
A simple, accessible FIASMA with data already supporting its efficacy:

the cheap, off-patent anti-histamine hydroxyzine (formerly Atarax)

Read 5 tweets
17 Apr
Sigh...

More bad science on hydroxychloroquine now peddled by @nature through another low quality, mortality meta-analysis of randomized trials.

Let's take it apart...

nature.com/articles/s4146…
Let's start with the sad, usual evidence that peer reviewers' standards have collapsed to a lamentable level: they simply do not do their quality-control job anymore and medical journal editors are mediocre enough to let that happen again and again.
The meta-analysis claims to exclude trials where hydroxychloroquine or chloroquine was given in the control arm (the right thing to do).
Read 12 tweets
15 Apr
When immigrant dormitories got infected, Singapore decided to run a large (n=3,037) prophylaxis trial with randomization by floors.

Strong results from all the treatment arms: hydroxychloroquine, ivermectin, povidone-iodine and Zinc+Vit C

Combo optimal?

ijidonline.com/article/S1201-…
A few comments:
• the control arm might be active (16% positive drug effect seen in 6 vitamin C studies so far), optically lowering the efficacy of the other arms
• cluster randomization shows material baseline seropositivity differences: vit C 6.3% HCQ 10 IVM12.4 PVI 14.5
• unclear whether you could be undetected infected at baseline, which could explain the odd infection rate of the IVM arm
• unlike others, IVM was single dose (200 µg/kg with12mg cap), a BIG ask for a 42 day prophylaxis
• >70% adherence only 71% in HCQ arm, lowering efficacy
Read 4 tweets
14 Apr
US Phase 3 double blind, placebo controlled randomized trial of antiparasitic nitazoxanide of of 1,092 patients (379 RT-PCR+ on which the study focused):

• 0.5% progression to severity in NTZ arm vs 3.6%, i.e. -85%
• -84% in high-risk subgroup

prnewswire.com/news-releases/…
Lacunary science by press release does not facilitate assessment but it looks like a clear win for nitazoxanide prima facie.

There is a long tail of positive results associated to nitazoxanide that increases the comfort in the success of the US trial...
Read 8 tweets
11 Apr
Another illustration of the increase of Covid-19 cases likely caused by too many people visiting aerosol-infected vaccine centers over a very short period of time.

Bhutan has vaccinated 60%+ of its population over 2 weeks. Image
Other example of the coincidence: Mongolia.

Stringent precautions at the vaccine centers are critical. Image
And some more: ImageImageImageImage
Read 4 tweets
10 Mar
Oh glorious day!

🇧🇷♥️🍾

Stunning results from antiandrogen

Proxalutamide

in Phase 3 Brazilian trial:
• Multi-centric, randomized, double-blind, placebo-controlled
• n=590, 294 treated with Proxalutamide
• 300mg/day for 14 days
• hospitalized patients, average age 53
• 97% requiring oxygen, 67% high flux or invasive
After 14 days (all p<.0001):

• 3.7% death vs 47.6% placebo
• Hospital days 5 vs 14
• Intubation 4.4% vs 52.7%
• Off oxygen 92.5% vs 33.3%
• Still hospitalized 32.8% vs 89.1%
• Time to clinical improvement 3 days vs 19
• Serious adverse events: 0
Read 6 tweets
9 Mar
Your 84 elderly residents (average age 85) are likely infected with Coivid-19.

25 are already symptomatic.

What do you do?

Treat early with antihistamines and azithromycin.

0 loss of life.

0 hospitalization.

NOBODY NEEDS TO DIE.

sciencedirect.com/science/articl…!
There is already some positive data on antihistamines in Covid-19, here with hydroxyzine.

Another antihistamine, chlorpheniramine has even shown some antiviral action in vivo:

cureus.com/articles/37812…
Read 4 tweets
9 Mar
Instructive randomized trial (n=168) from Brazil compares efficacy of hydroxychloroquine/chloroquine/ivermectin in severe Covid-19.

No control group, so only relative efficacy between the 3 drugs can be established.

And they are equally effective.

The authors should have stopped there, but being what many infatuated and/or biased scientific researchers are, they decide to overreach, go for a bigger prize and conclude than none of the drugs works in Covid-19.

So what control group are they going to use to demonstrate it?
The only analysis in the discussion part of the report is below.

Unspecified, undocumented, unreferenced.

Absolutely gigantic red flag. 🚨🚨🚨

(it is where I come to despair of peer-reviewers...)
Read 7 tweets