Quote from axil

In a small trial with a sample size of 80 subjects Favipiravir had a more potent antiviral action on SARS-CoV-2 than lopinavir/ritonavir.[30] In March 2020, Chinese officials suggested that Favipiravir seemed to be effective in treating COVID-19.[31]

From Japanese instruction leaflet: Favipiravir may have mutagenic effects and thus breast feeding is not allowed and of course also it may not be used for pregnant woman. Man are not allowed to have sex for a certain safety period due to the fact it has been found in seminal fluid.

Favipiravir has been developed to fight the influenza virus but due to the above its no allowed for prime medication in case of influenza unless all other medicaments do fail.

These are mild contraindication compared to the overall large positive effects. Fuji is ramping up production and also China has the right to produce a generic.

This looks like a lucky shot and we all hope that mild to medium progress cases can soon have access to it.

There is a separate therapy - an add-on - for strong infections but my wife could not yet find the details for the add-on.

I'm glad that a lot of people are trying different drugs - that seems to me the best way medium-term to fight COVID.

I'm still unsure about the hydroxychloroquine + X currently hyped treatment. It will be great to get some genuinely useful data and surely that should be soon. For example, here is an example of Australian doctors claiming (no data) that they have anecdotal good outcomes from CQ + an aniti-HIV drug and wanting to conduct a trial:

https://www.news.com.au/lifest…da0cff4fc4d2c5e51706accb5

AFAIK the anti-HIV drug here is not Arithromyin (not anti-HIV), but something else. There are a lot of existing licensed (and hence side effects known) drugs that exhibit antiviral characteristics against RNA viruses and any of them might possibly help with COVID, although there is absolutely no reason why they have to do this since anti-vitral behaviour is quite specific.

I'm pretty skeptical about any one of these "find a miracle drug" treatments, while thinking it likely that good drugs do exist and we will soon find them.

One point is that there are two separate issues:

• Suppressing the virus,
• Modulating the destructive cytokine storm that does so much damage.

In principle a decent treatment could come from either of these two things. The claim is that CQ can do both, but at the moment that is just a claim based on unreliable data.

I'd expect that modulating an out of balance destructive immune response would be possible with existing drugs: just a matter of finding what exactly will do that + still allow the right response response to kill the virus. We do now have a lot of candidates that can be used right away and have varying effects on immune response. I'm less sure that an effective COVID killer can be found, but we know people's own immune systems will do that given enough time.

So: while I'm with Jed and the "oh my God exponential increase + current mortality rate => we must all be tightly locked up" camp at the moment, one reason I see this as a good idea is that much better treatments could quite likely be only 8 weeks away. Let us stay safe for those 8 weeks!

If anyone worries trials will not be done, you will see rich individuals as well as governments throwing money on trials (but not necessarily the right trials). Note of caution. If you are a doctor on the front line the temptation to hope on minimum anecdotal data you have a miracle cure, and then the temptation to go public with it asking for a big trial, must be enormous. Suppose you have, worldwide, 10,000 such doctors trying ad hoc off label treatments. Well, something that is only a 1 in 10,000 chnace of hapenning will happen to one of them, who might proclaim, on the back of a statistical fluke, that they have found a cure. Just like these Australian guys. So caution is needed about any one of these results.

I realise that is no help at all for those who have COVID now: but it is great help for society.

THH

Quote from Alan Smith

https://www.theguardian.com/wo…ate-coronavirus-infection

Anti-inflammatories may aggravate Covid-19, France advises - French minister says patients should take paracetamol rather than ibuprofen or cortisone

lot of people take anti inflammatory meds for Gout, Arthritis, Ulcerative Colitis, Chrons etc

From 2015...

3D Printed Ventilator Manifold Might One Day Save Patients from Lung Damage

https://3dprint.com/45352/3d-printed-ventilator-manifold/

Drugs

Here is a published study of favipiravir in COVID patients - one of the possible anti-virals being tested.

18 March online publication.

Compare this with the Marseille results:

Similar: not randomised, not double-blind, similar very encouraging results

Different: more patients, more careful screening to reduce selection bias, better documentation of exact methodology, more explicit discussion of selection bias, includes CT conparisons

So while also a preliminary "be cautious" study, and for a drug we should maybe be more cautious about (not sure how to evaluate this) it is significantly more convincing than the Marseille study.

favipiravir is known teratogenic and therefore expected carcinogenic - hence caution needed in its use. But I guess people dying of COVID don't care about that much.

Quote from Alan Smith

Chloroquine AFAIK is an immune system moderator, hence it's use as a symptom-relief treatment for chronic arthritis.

Yes, it seems pretty plausible that Chloroquine can help by reducing cytokine storm, based on its known characteristics. But the details here: how much, in clinical use does this help significantly, will not be clear for a while. Enough positive for quite a lot of people to be trying it on anyone in hospital without any of the CQ contraindications I'd expect.

some of you here might want to trace this info, I cannot verify it yet and it is from a source not always trustworthy.

protease TMPRSS2

A clinically proven drug known to be active against TMPRSS2 was found to block SARS-CoV-2 infection and might constitute a novel treatment option

“Our results show that SARS-CoV-2 requires the protease TMPRSS2, which is present in the human body, to enter cells,” says Stefan Pöhlmann, head of the Infection Biology Unit at the German Primate Center. “This protease is a potential target for therapeutic intervention.”

“We have tested SARS-CoV-2 isolated from a patient and found that camostat mesilate blocks entry of the virus into lung cells,” says Markus Hoffmann, the lead author of the study. Camostat mesilate is a drug approved in Japan for use in pancreatic inflammation. “Our results suggest that camostat mesilate might also protect against COVID-19,” says Markus Hoffmann. “This should be investigated in clinical trials.”

Deutsches Primatenzentrum (DPZ)/German Primate Center

Publication: Hoffmann, M et al. (2020). SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically-proven protease inhibitor.

Reading the news in this article today is just painful. At this hospital in Italy patients over 60 are no longer being helped. It’s a wake up call for the rest of this world to stamp this thing out early with heavy testing and staying at home. No half hearted measures.

https://www.jpost.com/Internat…help-those-over-60-621856

And posted new cases today in the U.S. are approaching 8k. I want to believe in some strange way that this is not bad news because it means they are finally rolling out more high-throughput testing.

Italy’s number of new cases is actually down from yesterday, but it has been reported that they are no longer testing at the level they were because their health system is at a breaking point. Hopefully their number of daily deaths finds a way to go down.

https://www.worldometers.info/coronavirus/

I found this interesting, although it's just the abstract. If true, I'm supposing it is because PCR tests can amplify tiny contaminants.

From https://pubmed.ncbi.nlm.nih.gov/32133832/

Quote

Conclusions: In the close contacts of COVID-19 patients, nearly half or even more of the 'asymptomatic infected individuals' reported in the active nucleic acid test screening might be false positives.

Quote from Deleo

And posted new cases today in the U.S. are approaching 8k. I want to believe in some strange way that this is not bad news because it means they are finally rolling out more high-throughput testing.

I am afraid not. The total for today is now 13,958. Of that, 12,345 are in New York. In New York they are not doing high throughput testing. They stopped doing it a few days ago, because they do not have enough test kits or nurses to administer them. See:

New York City health department moves to curtail testing as pandemic overwhelms hospitals.

https://www.nytimes.com/2020/0…irus-new-york-update.html

The U.S. total is now 3 times higher than yesterday. OOPS. WRONG. I THINK THE WORLDMETERS DATA WAS WRONG FOR A WHILE, OR I MISREAD IT. Today's total as of 4:30 p.m.:

8,149

Yesterday: 4,824

That's a factor of 1.69, not ~3.00

It has been increasing 1.3 times per day for the whole month. It is now accelerating dramatically. As I said above, I do not think this is because of more widespread testing, because most of the increase is in New York where they only have enough kits and nurses to administer tests to patients in the hospitals. So, this is a real increase. It is what you expect from a completely uncontrolled natural epidemic. The curve goes up more and more steeply until the number of surviving immune individuals begins to slow it down.

If the rate slows back down to 1.3, and it continues at that rate for 1 week (until March 29), there will be 357,000 cases and 87,000 new cases per day. That is my simplified curve. However, even in New York, the most concentrated area of the epidemic, that will still not be a significant fraction of the population, so acquired immunity will not affect the curve. So it is a reasonable approximation. Again, this is the outcome assuming no changes in the rate. I am not saying "the rate will not change" or that it cannot change.

There is no indication the rate is slowing down. The Federal government is doing nothing to slow it down, as far as I can tell from news reports. The governors of California and New York are doing a lot, but no more than the Italian government did weeks ago. There has been no change in the rate of increase in Italy. The rate in Germany appears to have slowed dramatically.

No, wait. I was wrong about increased testing in New York. I should be more careful. Here is the latest from the New York Times:

New York has 15,168 confirmed cases.

Gov. Andrew M. Cuomo disclosed new statistics on Sunday that indicated that New York State now has roughly 5 percent of coronavirus cases worldwide.

The jump in the number of cases in New York stems from both the rapid growth of the outbreak and significantly increased testing in the state. Health officials emphasized that testing was revealing how quickly the coronavirus has spread.

There are now 15,168 confirmed cases of the coronavirus in the state, up 4,812 since Saturday, and 114 deaths, Mr. Cuomo said. About 13 percent, or 1,974 people in New York who tested positive for the virus, are hospitalized, Mr. Cuomo said.

https://www.nytimes.com/2020/0…irus-new-york-update.html

[Here is something we have discussed:]

New York has secured from the federal government trial drugs that it will begin testing on Tuesday, Mr. Cuomo said. They include hydroxychloroquine, zithromax and chloroquine.

“The president is optimistic about these drugs,” Mr. Cuomo said. “I’ve spoken with a number of health officials, and there is a good basis to believe that they could work.” . . .

[Here is more about testing:]

As of Sunday morning, 9,654 people in New York City had tested positive for the coronavirus, and 63 had died from complications related to it, city officials said. In New York State, 61,401 people have been tested for the virus, including 26,389 in New York City.

[My comment, as an amateur in statistics: You can see they are still mainly testing people they think they are sick, to confirm the diagnoses. That's vitally important! I am not saying that is a mistake. But, testing a sample of general population would also be good. By now they have tested 35,000 others who, it turned out, were not sick. I assume these were self-selected people who thought they were sick. Perhaps some had the seasonal flu? Anyway, 35,000 is a more significant sample of the general population than what New York or Washington state had a few weeks ago. A self-selected sample of people who are worried they are sick is a very biased sample. (I mean it is unrepresentative of the general population.) But you know how and why it is biased, so you can extrapolate roughly to the whole population. You can begin doing this by asking people "do you think you have the coronavirus?" and if they say yes, "have you been tested?"]

Treatment with hydroxychloroquine and azithromycin is an interesting but not completely proven possibility. However, in the USA, if your doctor wants to secure a small supply, at this time and subject to change, the drugs can be purchased from https://www.henryschein.com/us…es/physicians-office.aspx

An account and a medical or institutional license (hospital or clinic) are required. The drugs provided are FDA approved and USA legal as differentiated from the internet drugs coming directly from India. Packaging is US style, in bottles and not blister packs. About a week ago, I ordered 4 bottles of 100 tabs each, 200 mg each of hydroxychloroquine from this source. After being initially accepted, the order was rudely cancelled without comment. Today, the site software is automatically limiting orders to two bottles but states that these will be delivered (UPS second day air) in three days. Of course that could change. Azithromycin orders are being limited to a total of 60 tablets of 250 mg each. The hydroxychloroquine supposedly available will treat about six people and azithromycin about 8 - 10 if the doses given are the same as in the Marseilles paper (200 mg three times a day x up to 10 days for hydroxychloroquine and 500 mg first day followed by 250 mg for five days for azithromycin IIRC-- check me on this if you plan to do it).

ETA: Save 6 to 10 lives for less than $100? That would be nice. *IF* it's true.

As mentioned before, hydroxychloroquine and azithromycin while commonly used for decades (separately) both may have consequence to heart rhythm. This is particularly important because the elderly need treatment most but are also the most likely to have pre-existing heart probems. I can't get a clear read on how rare this problem might be however these papers may help.

https://www.pharmaceutical-jou…7.article?firstPass=false

https://journals.sagepub.com/d…/10.1177/2048872612471215

There are many unusual and very severe adverse reactions to hydroxychloroquine in the peer reviewed literature. But they seem to be quite rare. Most are in patients who have severe illness -- progressive rheumatoid arthritis and lupus for example -- and in most of these, the adverse effect develops over long periods of use.

One thing that can be done to mitigate heart hazards in older people is to check their EKG in general and the Q-T interval on the EKG in particular. If you have a little technical aptitude, you do not need a physician or a complicated machine to do this. You can Google it. And several inexpensive EKG devices which work with apps are available on Amazon. I have used these and they work well if you follow directions. Both can be used to measure and follow the Q-T interval in most patients.

https://www.amazon.com/Aliveco…ef=sr_1_3?keywords=kardia

https://www.amazon.com/AliveCo…Smartphone/dp/B07RQW6SD5/

ETA: https://en.wikipedia.org/wiki/QT_interval

Important disclaimer: I am not advocating do it yourself medical care. My suggestions are in view of a changing world and dire emergencies and will be entirely at your own risk. I did not write the book "Brain Surgery Self Taught for Fun and Profit." Nor "Medicine For Dummies." It takes typically 10 - 12 years after high school to (barely) become a practicing physician in the US. As always, it is strongly recommended that you contact your health care provider. Do not take matters into your own hands unless absolutely out of other options and even then... I have learned to my sorrow a few times along the way, that it is not difficult to do more harm than good.

Here is another modeling program, which is about a hundred times more sophisticated and realistic than my simple graph. It takes into account things like acquired immunity.

https://neherlab.org/covid19/

Set this for "United States." On the top left, set the "epidemiology" parameter to "Slow/North" and the projection for March 21 (yesterday) comes out 19,624 cases, 260 deaths. The actual total for yesterday was 24,207, 302 deaths. So, the model is remarkably close to yesterday with that setting.

[However, it shows only ~50,000 by April 1, and we are already past that. So I think the "Moderate/North" setting is more realistic. WRONG we are not past that. Maybe "Slow/North" is more accurate.]

This model and mine assume the control parameters will not change. That's unrealistic! We are not a flock of birds with no control over the epidemic. Of course the parameters will change as people are frightened and they begin to follow orders and stay in their houses. How much they will change I myself cannot predict. I hope epidemiologists can predict this, and advise government officials.

Obviously, the parameters could have changed completely, enough to extinguish the epidemic weeks ago in the U.S., if only our political leaders had learned from S. Korea and Japan. And learned what not to do from Italy. Alas, they did not, and now whatever happens, we will surely pay a high price. How high? This model predicts the peak in early June, with 1.7 million deaths by September. The epidemic is waning in September, but not over. . . But, I cannot figure out how to extend this graph.

[NOTE: Setting the parameter to "Slow/North" reduces deaths to 223,000 by Sept. 1. You can see the dramatic difference slowing things down can have.]