Viral Facts

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Just interesting. I have no predictions about the results. Especially, since a definitive answer is likely to come from this large study. Results expected this summer which is unheard of for a study like this.

It is of note that Remdesivir is an IV medication and Gilead Sciences has no plans for making a pill that could be used as prophylaxis or early treatment.

I would like to add this caution. Nisser mentioned prolongation of the QT interval. This risk is greater when azithromycin (Z-Pak) is added. From the FDA: “Use with caution ……during concomitant administration with QT interval prolonging drugs such as azithromycin and some other antibacterial drugs.”

The article is behind a Medscape paywall (or signup at least) so a link will not be helpful:

[i]"In perhaps the fastest-moving, large prophylaxis trial, researchers at Duke University are leading a $50 million collaboration across hundreds of American health care systems, which will test 15,000 volunteers. Half the health care workers will take hydroxychloroquine, and half a placebo. Other drugs could be added to the study if they prove promising for preventing or lessening infection, says Adrian Hernandez, the trial’s principle investigator.

The trial is being launched by PCORnet®, the National Patient-Centered Clinical Research Network, a network of health care systems that have come together over the last few years to plan and conduct research trials. Although the collaboration predates COVID-19 by nearly five years, this is precisely the kind of situation it was designed to address, says Hernandez, adding that he hopes the network will soon be able to test COVID-19 vaccine candidates as well."[/i]

Lopinavir and Ritonavir prophylaxis also being tested in France:

“In France, researchers are running a trial with 1,200 health care workers to test prophylactic use of hydroxychloroquine or a combination of two HIV drugs, Lopinavir and Ritonavir, which failed as a treatment in people with severe COVID-19 infections but may work as prevention. It is expected to take 6 months.”

54

https://abc11.com/amp/coronavirus-drug-covid-19-malaria-hydroxychloroquine/6079864/

55

Fascinating.

There is a growing body of thought that some of the disease process in some Covid-19 is related to tiny blood clots. These tiny clots (microthrombi) mean there is reduced blood flow to the air sacs in the lung, and so they have problems oxygenating their blood.

This theory is borne out by the fact that autopsies of Covid-9 bodies have found a high percentage of pulmonary hemorrhaging. That’s weird. And also small thrombi in the periphery of the parenchyma! This might also explain why heart disease is such a risk factor in Covid-19 patients.

…

56

Chaim,

I think you are right about this being a problem for COVID-19 patients. I think you are probably referring to disseminated intravascular coagulation (DIC).

Paradoxically, these people develop bleeding problems as all of their clotting factors get used up creating intravascular clots. The problem is devastating. It carries a terrible prognosis and is not limited to COVID-19 patients. So I had a healthy fear of this problem even before I heard of COVID-19.

I do not have full access to this journal article but here is a copy of the “take home message:”

[i]"TAKE-HOME MESSAGE

The authors of this retrospective analysis evaluated coagulation parameters in 183 patients admitted with the severe novel coronavirus COVID-19. Median age at admission was 54 years, and 71.4% of non-survivors developed overt disseminated intravascular coagulation (DIC), with a median time from admission to DIC of 4 days. Only 0.6% of survivors developed DIC. On admission, non-surviving patients presented with higher D-dimer levels, prolonged PT, and aPTT compared with surviving patients.
In patients with COVID-19 infection, the development of coagulopathy and overt DIC appears to be associated with a high mortality rate. Larger analyses confirming these findings and investigating both the pathophysiology and impact of correction of coagulopathy on mortality are warranted."[/i]
– Curtis Lachowiez, MD

57

Doc,

Here are the autopsy reports.

In what may be related news, there is a small but growing group of physicians who believe that ventilators are not the best treatment for the ARDS (Acute Respiratory Distress Syndrome) seen in Covid-19 patients.

from here :

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In relation to the above, an article from the NY Times: What Doctors on the Front Lines Wish They’d Known a Month Ago

59

Media is so good at sensationalizing. Proning is nothing new; it’s a common ICU technique to recruit sick lung tissue. I’m sure it was tried day 1 everywhere.

60

Hi Nisser,

Yes! Certainly not new for patients already on a ventilator.

Here is a meta-analysis of 2,129 patients (already on a respirator or intubated) with acute respiratory distress syndrome from 2017: Prone Position for Acute Respiratory Distress Syndrome. A Systematic Review and Meta-Analysis.

Here is a good controlled study published in the New England Journal of Medicine from 2013 (again of patients already intubated): Prone Positioning in Severe Acute Respiratory Distress Syndrome

Best,

Jim

61

Unfortunately not everyone has been able to make it to the hospital. If this is well-known this is the kind of information that needs to be disseminated but for some reason isn’t.

62

https://www.statnews.com/2020/04/16/early-peek-at-data-on-gilead-coronavirus-drug-suggests-patients-are-responding-to-treatment/

63

https://emcrit.org/pulmcrit/pulmcrit-eleven-reasons-the-nejm-paper-on-remdesivir-reveals-nothing/

The quality of the paper in NEJM is absolutely shameful; shame on the editors for letting this through. I wouldn’t let this be published in the Journal of Scandinavian potato farming.

64

Ivermectin is showing to be very promising for treatment of Covid 19. 70% reduction in deaths for those treated with it in a study.

Newspaper article
Paper

65

Thanks Chaim. Very interesting study.

I thought this was a good review of some other medications with varying potential: JAMA Review Article

Best,

Jim

66

[quote]

Thanks Chaim. Very interesting study.

I thought this was a good review of some other medications with varying potential: JAMA Review Article

Best,

Jim
[/quote]Thanks. I skimmed through it. Interesting. At the risk of sounding like a broken record, why did this review omit zinc from its discussions about findings for the HCQ/azithromycin regimen? It’s almost like there is a bias against minerals and in favor of pharmacological treatments.

As someone who did not have formal training in medicine, but has experience in vetting studies, I love to see all kinds of spaghetti thrown at the wall (assuming there is some putative theory and low risk to the patient), find what sticks with a very open mind, try to figure out why it worked, and then run better studies using the exact same regimen which was reported to have success.

67

Don’t know but someone I read who looked at the way zinc supposedly works with HCQ was skeptical about the mechanism put forth. He thought the theory of HCQ acting as an ionophore was dubious because the dosage necessary in his opinion would be too high to work as theorized in real life. He said it was far more likely that HCQ if effective worked by raising the pH of the cell.

But I doubt anyone really knows.

Other drugs have backers willing to fund studies.

What I am curious about is whether South Korea and Malaysia which I have heard it implied were using HCQ and zinc in combination are having success and why we aren’t hearing anything from them. Their death rates are pretty low.

68

This is not a knock on medical professionals. I believe that medical professionals as a group are among the smartest and most dedicated people around. But I see this in all disciplines. People focus too much on theories and not on data. My investment results have gone up exponentially once I started building my theories around the data instead of the other way around.

Two of the most successful clinical trials included zinc in the regimen. Yes, those clinical trials had flaws. But the results were so good that even after adjusting for the flaws the results were still extraordinary. Yet, instead of trying to replicate the exact same regimen, I was seeing a lot of studies that took out zinc, or tried using HCQ in patients presenting with ARDS, then reported less than stellar results, and these studies were used to prove that HCQ doesn’t work.

Why not try to replicate exactly what worked using well designed studies?

I believe that at this stage, theory is secondary. Data is first. But I can throw out a theory to explain why HCQ would help zinc. The CEO of the company that did the modern research on Cloroquine says that Cloroquine is metabolized by the same enzyme in the liver as azythromycin. Presumably HCQ is also metabolized by that same enzyme. If so, then the effective dosage of HCQ is amplified when taken in conjunction with azythromycin. This may explain some things.

Let’s build theories around the data and not the other way around.

69

I was buying stocks aggressively throughout this entire crisis, and now even more so.

1-hour discussion with 2 doctors:
-As data comes in, the virus is no worse than the flu.
-The models vastly over-predicted the deaths, even the models that included social distancing.
-Quarantining the sick is effective. Quarantining the healthy does not help.
-Quarantining the healthy weakens their immune system. When the economy opens back up, there will be a surge in sick people.
-Economy shut-down is causing a rise in domestic violence, drug abuse, alcoholism, suicide, and these are “significantly more detrimental” to society than the virus.
-Doctors are pressured to inflate the numbers of death due to covid 19.

https://www.facebook.com/KGET17News/videos/537566680274166/?v=537566680274166
(I was able to watch the video without logging into facebook).

What the heck do I know, I’m just a random guy on the internet, but I maintain that this media-driven panic is an excellent buying opportunity, and in a few months, the media cycle will move on to the next hot topic. Of course, the obvious caveat is that whatever you are buying must survive long enough to benefit from the rebound.

70

Hospitals are being rewarded for declaring Covid-19

https://www.usatoday.com/story/news/factcheck/2020/04/24/fact-check-medicare-hospitals-paid-more-covid-19-patients-coronavirus/3000638001/

71

I know why I don’t read this forum. Looks like a medical forum with more “experts” debating posting random articles. How is this relevant to investing?

72

Some hope for a vaccine (NY Times):

In Race for a Coronavirus Vaccine, an Oxford Group Leaps Ahead
As scientists at the Jenner Institute prepare for mass clinical trials, new tests show their vaccine to be effective in monkeys.

https://www.nytimes.com/2020/04/27/world/europe/coronavirus-vaccine-update-oxford.html