Covid-19 News

Quote from RobertBryant

Normally, vaccines go into human trials after tests for safety and effectiveness in animals. But the Moderna vaccine and another being developed by Inovio Pharmaceuticals in Plymouth Meeting, Pennsylvania, are being tested in animals at the same time as human phase 1 trials are happening. Inovio plans to begin its first human trial in April.

Right. That's what I thought. Maybe I read that somewhere.

We have no time to test for safety and effectiveness only in animals. We must be reckless. As I said, I personally would be willing to take this risk, so it is not as if I am saying: "someone else should risk his life and health, not me!" As things stand, everyone on earth is risking his or her life and health.

Landscape analysis of therapeutics as 21st March 2020

Quote from Ahlfors

Landscape analysis

preprints202003.0302.v1.pdf

Maybe sartans.. maybe metformin maybe viagra?"

Data... data... data... sine qua non

. For instance, drugs directly implicated in renin-angiotensin signaling (e.g., sartans) are known to increase
the SARS-CoV-2 host cell receptor expression ACE242
It is also uncertain if this effect might aggravate COVID19 or if, by modifying the UPR/autophagy flux,

these drugs might have a beneficial impact by, for instance, effectively blocking the virus entry.

Therefore, relevant preclinical, experimental tests and massive electronic health records (..

real-world evidence must be used to pre-screen them and check whether their effect

could potentially prevent, treat, or, on the contrary,aggravate COVID-19 before launching safe clinical trials.

To this end, we must rapidly evaluate the

COVID-19 prognosis of individuals taking these drugs, through an international effort to mutualize
and provide such patient data,

Quote from JedRothwell

I do not know enough about medicine to follow this discussion of hydroxychloroquine. I could not judge whether it might be effective. However, since it has been approved for other uses, I suppose it is reasonably safe in the correct dosage. Even if it does no good, I don't suppose it would do much harm. If doctors feel it helps, I would encourage them to use it. I would ask that it be used on me if I were sick. I understand that in normal circumstances you have to do double-blind testing and you have to be careful when deploying a new drug. You even have to be careful when using an old drug in new ways. But these are not normal circumstances. In this situation, I think we should put aside the rules and use whatever the doctors think is best. They may be judging by intuition, but the intuition of a professional is often a good thing to go by. You want ship captains and airplane pilots to pay close attention to their intuition.

We can always do double blind tests for a reserved set of people while many doctors outside the study go ahead and use the drug before the test results are in.

Since this situation is so extraordinary, I think we should skip some steps in the development of a vaccine, too. Or accelerate steps, even to the point of recklessness. As reported the other day, tests of vaccines on human volunteers has already begun. This might hurt the test subjects, but they are willing to take that risk. I would be willing too, even if they told me there is a significant risk of harm. In this case, the harm of delaying far outweighs the harm that a few dozen volunteers might suffer.

I believe in normal circumstances, they would not have started the human tests so soon. I guess they would still be inoculating mice or primates?

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Choloroquine has been around since the 1940’s I believe. So it’s well known. But in rare circumstances it can cause blindness and even death. It’s definitely not your run of the mill antiviral drug. It’s powerful stuff. See article below.

https://slate.com/news-and-pol…navirus.html?via=taps_top

The news from the U.S. is terrible. The U.S. is now #3 behind China and Italy. I have not looked closely, but I believe the sustained rate of increase during March has been the highest in the U.S. for any country at any phase of this pandemic. The rate for this month has been 1.3. It is accelerating to 1.5. I hope this is partly caused by increased testing, but I wouldn't know. I suspect that may not be the case because testing in New York has been suspended except for gravely ill people. There are still not enough test kits, and not enough protective equipment for the nurses administering the tests, so they have given up. 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

Today's U.S. new cases is 6,513, and that may not be the final tally. It is almost the same as Italy, 6,557. The rate in Italy is starting to come down. It 1.1. So, tomorrow the U.S. will have the highest number of cases, and in three days it will double to 12,000 per day. In few weeks the number of deaths will be about the same as Italy, about 800 to 1,000 per day. As people predicted, we were one or two weeks behind Italy.

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

If things do not change, by April 1, the U.S. will have more cases than the entire rest of the world combined: 473,000, and 9,500 deaths per day. By comparison, on average 6,000 soldiers were killed every day in World War I.

I am sure things will change somewhat, because people will be so frightened. But the curve may not bend down far. As things now stand, the peak will be in mid- to late-April. This is by far the most disastrous outcome there can be. At the peak there will be roughly 100 million sick people, 50 million new cases per day, and 2 million deaths per day. Soon after that the curve must start to fall as the number of survivors with natural immunity increases to most of the population.

If the curve can be reduced now, and the pandemic stretched out over time, many fewer people will die, for the reasons explained here already.

(Those numbers are from my simple graph, but sophisticated models at various sites done by experts roughly agree. Anyway, if only 500,000 people die per day instad of 1 million, it will hardly be less of a nightmare.)

The news from some other countries is a little brighter. Italy and Spain are stable. Germany is declining, 0.7 compared to yesterday, but this may be a one-time dip. Some other countries have had similar dips, or spikes. Ireland seems to have the pandemic under control. Japan reports 47 new cases, about the same number they have had every day this month. They have 55 "serious" cases (probably in ICU). South Korea has 147 new cases. Both countries can live with these numbers indefinitely. They are tracking and following up on ever case. The curves are starting to level off and even bend down everywhere in the developed world, except the U.S.

Let me once again say for the record -- since I might be dead in a few weeks -- that this never should have happened. It did not happen in Japan or Korea because their leaders believe in science, and facts, and numbers. It could have easily been prevented. It is entirely the fault of our political leaders, mainly president Trump.

Quote from JedRothwell

entirely the fault of our political leaders,

The USA is not alone..

and neither is their leader ..in fallibility

I will go today Chinatown to buy some rice.. the stuff from China is only 1$/kg for some reason

"In God we Trust"

Quote

"Everybody is using it now off-label. We have a surge of coronavirus 19 patients throughout the metropolitan area of New York. And the problem is these patients are coming in quite sick and when they get to a very difficult respiratory status, doctors are using hydroxychloroquine with or without a drug called zithromax or azithromicin, and that's showing tremendous activity. And we have not had a death in our hospital. We have probably close to 100 patients and not had any deaths. But I've talked to many of my colleagues at other hospitals in New York and they also are using hydroxychloroquine although the supplies are running down, so any kind of supplements to those supplies will be much appreciated. . . in the trenches we're all using it, especially for desperately ill people . . . we think it works in two ways, as you know the death rate goes up as the age goes up, and what I think is the more mature your immune response is, the more likely you are to have a cytokine storm, which means that people with viral pneumonias die because their lungs fill up with fluids largely from an immune response, and this drug works not only inhibiting virus replication, but also inhibits the immune response so you don't get the tremendous amount of inflammation. That's why the drug is also used in rheumatoid arthritis and lupus"

That is very very encouraging if accurate... ... but not a study. It is especially gratifying if it works on very sick patients since that did not seem to be what the French study examined. However, I forgot who said it on the news today, maybe the governor, but New York is funding a study ASAP. They have a lot of cases and deaths. Hopefully, it will be properly designed.

Quote

But in rare circumstances it can cause blindness and even death.

Blindness is usually a long term side effect however some retinal damage may take less time so caution is warranted in people who already have glaucoma or retinal/macular degeneration.

The most immediate concern for short term use is heart rhythm disturbances, some of which can kill. Certain types of heart disease predisposes to this and zithromycin also causes the same problems so probably enhances the ones caused by chloroquine.

Quote

or instance, drugs directly implicated in renin-angiotensin signaling (e.g., sartans) are known to increase

the SARS-CoV-2 host cell receptor expression ACE242

It is also uncertain if this effect might aggravate COVID19 or if, by modifying the UPR/autophagy flux,

these drugs might have a beneficial impact by, for instance, effectively blocking the virus entry.

Therefore, relevant preclinical, experimental tests and massive electronic health records (..

The relevant angiotensin variant is angiotensin II type 2. I already cited this at least twice. ACE inhibitors and ACE receptor blockers (ARB's) affect mostly A-II type 1 and NOT type 2 so they would have little or no effect on coronavirus binding sites. One place this idea was proposed was a discussion by a whacko who thought the virus was synthetic and included HIV sequences deliberately inserted. This and the ACE inhibitor/ARB idea were strongly refuted by genuine experts on that site in the comment section. Please try to keep up. If someone is taking ACE inhibitors or ARB's for congestive failure or high blood pressure DO NOT STOP THEM except on advice from your doctor. Stopping them could cause a stroke, heart attack or death. I suggest you worry less about my credentials and pay more attention to the reliable sources I constantly cite and link.

Quote

I suppose it [chloroquine] is reasonably safe in the correct dosage. Even if it does no good, I don't suppose it would do much harm.

Chloroquine and derivatives are indeed safe-- as you say in correct dose but you left out "in people with healthy hearts, livers and kidneys." Especially hearts. Certain types of heart conditions are a very strong reason not to take chloroquine derivatives. This can be evaluated by a doctor with labs and EKG. In a dire situation where you don't have a doctor around (maybe because all are sick or busy) and someone is getting sick with what seems to be COVID-19 and this person is elderly, possibly with heart problems, giving the two drugs recommended recently becomes a really difficult decision. Faced with this, which I may well be, I would inform the patient and let them choose whether to risk the mostly untested treatment or not. And I would recommend starting with a small test dose of hydroxychloroquine (say 200 or 300 mg per day) and azithromycin at the usual dose without the usual loading dose (250 mg per day) for a day or two. In a patient who was going downhill fast with COVID-19 (high fever, serious difficulty breathing, no ICU, no ventilator, I would pull out the stops and give the full recommended doses. But not more. I really hope I never face that decision but I may have to make it, possibly in the near future, and it's terrifying.

OK Shane. I'll go this far. I have an M.D. from a major US University. I did one year of internal medicine residency at a large city university medical center and a two year postdoctoral fellowship also at a major center. I also have varied experience with basic and applied research in medicine and biophysics. I was an assistant professor of medicine and assistant dean at a US medical school. I served many years as a medical consultant for several different government departments over time. I did not do patient care after my year of residency but the consulting work involved extensive reviews of medical records and, with a team, the interface and resource design of a computer software system for that government entity. I maintain a current medical license and DEA (narcotics) certificate. I have authored technical reports, peer reviewed papers, and slews of internal documents for companies and government.

There is more but I always emphasize sources, references and links and I don't expect anyone to believe me because of my training and experience. This is a very serious emergency and those who don't recognize it are doing their neighbors and their country a major disservice. Promoting poorly sourced and/or whacky ideas at a time like this can very harmful, even deadly, to others.

https://www.businessinsider.co…irus-what-it-means-2020-3

Quote

The FDA is allowing two drugs to be used for 'compassionate use' to treat the coronavirus. Here's what that means.

Far as I know, remdesivir is not easy to find yet. Hydroxychloroquine and azithromycin can be prescribed for off label use without FDA approval. Compassionate use permits from the FDA for specific patients are not hard to get in reasonable cases. I got one once for an experimental drug for a cancer case. The only problem is that reporting requirements are burdensome and you really have to comply if you ever expect to need another permit.

Shane D. I don't know for sure for right now, but a few years, I found that it applied to any very sick patient who a) was at a very real risk of dying and b) was not responding to conventional treatment. They didn't try to break your ass about it as long as you explained it well. It could be different now, it's a different FDA head. If I was cornered, I would just claim off label use which is a matter of judgement. Remdesivir is experimental so I don't know if off label use applies (probably doesn't) but it does for the other already accepted and FDA certified drugs.

SOT, I had a heart attack around 6 years ago. I just completed a stress test and they said my rest ejection fraction was borderline, but under stress my heart did well, with good results in every other measure. I am quite active otherwise. I assume a conservative chloroquine dose would be safe? I used to take losartan but don't much anymore as I have been measuring my blood pressure and it is usually normal or barely above normal. Thanks for the free medical advice

The beneficial effect of sartans versus prils in reducing mortality has always been dubious..

Although ARBs(sartans) are commonly promoted versus ACEIs(prils) to reduce blodd pressure/mortality following heart attack

to physicians by " ARBs are ACEIs without coughing"

I once went to a workshop full of physicians (and only one pharmacist= me) where

the speaker described the misinfo about ARBs

as

"ARBS are ACEIs with coffin."

As long as your BP is down I wouldn't advise any BP med..and not any ARB

Well done in getting your BP down..

https://www.racgp.org.au/afp/2…ovascular-risk-reduction/

https://en.wikipedia.org/wiki/Favipiravir

Favipiravir

On February 2020, Favipiravir was being studied in China for experimental treatment of the emergent COVID-19 (novel coronavirus) disease.[7][8] On March 17, Chinese officials suggested the drug had been effective in treating COVID in Wuhan and Shenzhen.[9][10]

SARS-CoV-2 virus disease

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]

Japanese flu drug 'clearly effective' in treating coronavirus, says China

https://www.theguardian.com/wo…ng-coronavirus-says-china

See from 4:08

Shane D.

Emotional times ...

Strive to read academic papers [not the devil, all in all], respect the dead avoiding nonsense, and wait the tide.

Italy 12 - 21

12 15113

13 17660 1,168

14 21157 1,198

15 24747 1,169

16 27980 1,130

17 31506 1,126

18 35713 1,133

19 41035 1,149 Avg [12-20] = 1,153

20 47021 1,145 [21 > 53839 / 6818]

21 53578 1,139 [22 > 61049 / 7471] <<< no licorice here

12-21 9 +354,51%

[22-01 9 > 189942]