ice9 Profile picture
18 Nov, 8 tweets, 6 min read
Brazilian dutasteride outpatient RCT (N=130) for mild acute COVID-19:…

Mechanism is impairment of androgen-dependent TMPRSS2 expression ergo viral entry.

I have reservations about this approach, but efficacy is good at least.

Reference via @jamagalha
The paper includes further evidence from observational studies consistent with the RCT result.

It also makes some rather provocative hypotheses about regional susceptibility to the virus:

Male pattern balding may be a significant risk factor and varies widely by ancestry.
For another androgen dependent method of reducing TMPRSS2 expression, while also helping to protect against pulmonary edema, see also--


No trial results yet, but many proposal papers and excellent feedback from practitioners.
For a non-androgen dependent method of indirectly inhibiting TMPRSS2/13/11, see--

Bromhexine / ambroxol:

For doing so directly with small-molecule protease inhibitors, camostat is orally and commercially available, while nafamostat is mostly neither.
Possible roles for *soy isoflavones* in acute COVID-19:

The soy isoflavone and phytoestrogen genistein likewise downregulates TMPRSS2.

It also has a variety of anti-inflammatory effects directly relevant in moderate and severe COVID-19.
Estrogen protects mice against SARS-CoV:

COVID-19 retrospective study shows hazard ratio 0.29 for estrogen replacement in older women:…

Trials running for estrogen and progesterone in... male patients:…
SSRIs are associated with reduced COVID-19 mortality, with at least one successful RCT (fluvoxamine).

SSRIs have many relevant mechanisms. One is that they are weakly anti-androgenic:…….

And estrogenic:

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More from @__ice9

17 Nov
Discussion of antiviral properties of acid sphingomyelinase inhibitors vs. SARS-CoV-2 and others.

Examples: fluoxetine, fluvoxamine, flupenthixol, clemastine, dicyclomine, etc.

May inhibit endosomal entry, as one effect.

Fluvoxamine succeeded in RCT.
Note that sufficient concentrations for antiviral effects are likely not attainable at tolerable clinical doses of some.

Fluvoxamine and fluoxetine have shown clinical benefit at ordinary doses.

Flupenthixol is not hittable.
Amitriptyline also works well for preventing SARS-CoV-2 infection, apparently.…

Intriguing study design.

Volunteers were given amitriptyline, then epithelial cells were removed from their noses and inoculated with SARS-CoV-2. Infection was prevented.
Read 4 tweets
17 Nov
Please do not speculatively give linezolid or vancomycin as first-line monotherapy in literal first-glance triage protocols.

Some of us are awfully prone to getting MRSA SSTIs and would appreciate it if fallback antibiotics continue to actually work in the future.
At the very least, please recognize monotherapy as a key contributor to antibiotic resistance.

Add an antibiotic with an independent mechanism so the bacterial population cannot just evolve around it again.

True in more mundane situations as well.…
Read 6 tweets
16 Nov
I am not sure how best to say this, but:

The increasingly likely possibility that SARS-CoV-2 arose from a systematic gain-of-function study on the emergence of human pathogens from wildlife reservoirs does not invalidate the implications of the study.

It affirms them.
Bat caves are truly dangerous places, at manifestly global and historic scale.

The viral genomes recombined by the EcoHealth grant were not artificial.

They came from the cave that killed the miners and tourist and yielded RaTG13, and others like it.

It is imperative for human interaction with bats to be sharply curtailed, by government policy if necessary.

If emulating the virome of a bat cave in the lab gave us SARS-CoV-2, then that is damning evidence that this can and will happen again.
Read 4 tweets
15 Nov
Hospitals are getting full. There is still widespread practitioner ignorance about early treatment.

These are the antivirals proven to work in RCT against COVID-19 to date.

There are others that also look promising, but this is the short list.

Do with it what you will.
Addendum, as many replies mentioned other promising options that nonetheless still lack proper RCTs:

Each item on this list appears to have attainable EC90 based on pre-clinical data, and most have observational evidence in favor, but no RCT to date.
Also note the following options (not all of which are antivirals per se) are available OTC in at least some countries:

Read 8 tweets
14 Nov
Latest ivermectin COVID-19 RCT:

Enormous mortality reduction in severe COVID-19: crude relative risk ratio is 0.1.

Also reduced mortality to zero in mild cases and led to faster viral clearance.

To date, every single study on ivermectin in COVID-19 has been highly successful. ImageImage
See e.g. this thread for more ivermectin studies:

Here is a large thread containing a number of additional ivermectin studies--

Read 4 tweets
13 Nov
Recent RCT demonstrates reduced viral load in patients treated with ivermectin.…

Along with the post-exposure prophylaxis trials, this further indicates genuine antiviral activity in vivo for ivermectin (not merely anti-inflammatory). ImageImage
See here for a few other relevant studies:

The only study in vitro for ivermectin against SARS-CoV-2 used Vero cells and did not pre-treat at all.

This made it difficult to infer much about the effect during an ongoing repository infection in humans. Initial estimates looked unhittable.
Read 4 tweets

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