Sunday, March 29, 2020

Surviving the Coronavirus: Part 8

Evil China Government Edition

Those of you previously familiar with the august blog realize that American governments (at federal, state, and local levels) are far from being exceptions to my skeptical scorn. The Skeptical Juror blog has, until this coronavirus crisis, focused on the great harm our governments (at the federal, state, and local levels) have inflicted on some of our fellow citizens. Some of those who allegedly serve us, far too many of them, have carelessly, foolishly, and all too often intentionally used our legal system to bring down great harm, even death, on the innocent among us.

It should therefore come as no surprise to my ever dwindling list of followers that I will make no skeptical exception for those who govern the Chinese people. I do not trust the Chinese government any further than I can throw it. In this specific case, my metaphor server is not failing me. I cannot throw the Chinese government even an angstrom; I trust the Chinese government not even a whit, whatever the hell a whit is.

I'll waste just a bit of textual white space to make a lame effort to calm all the hair-trigger racist-labelers out there. I have no unique animus or dislike of the Chinese people. They are my fellow Earthlings. I feel a kindred spirit with them knowing that, in both absolute and percentage numbers, they suffer far greater harm (than we do) at the hands of those who allegedly serve us.

With that background, in that context, I herein discuss a report from China claiming that hydroxychloroquine is not effective as a treatment for the Wuhan coronavirus. The report is mostly in Chinese, and my skills in that regard are somewhat limited. The abstract, however, is in English. I'll therefore provide a condensed version of the abstract so that you can consider it yourself, kinda like a pop quiz, before I tell you why I am skeptical of it.

Sharpen your pencils, gather your wits about you, and prepare to focus. Here we go.
Objective: To evaluate the efficacy and safety of hydroxychloroquine (HCQ) in the treatment of patients with common coronavirus disease-19 (COVID-19). 
Methods: We prospectively enrolled 30 treatment-na├»ve patients with confirmed COVID-19 after informed consent at Shanghai Public Health Clinical Center. The patients were randomized 1:1 to HCQ group and the control group. Patients in HCQ group were given HCQ 400 mg per day for 5 days plus conventional treatments, while those in the control group were given conventional treatment only. [...] 
Results: One patient in HCQ group developed to severe during the treatment. On day 7, COVID-19 nucleic acid of throat swabs was negative in 13 cases in the HCQ group and 14 cases in the control group. The median duration from hospitalization to virus nucleic acid negative conservation was 4 days in HCQ group, which is comparable to that in the control group, 2 days. The median time for body temperature normalization in HCQ group was 1 day after hospitalization, which was also comparable to that in the control group. Radiological progression was shown on CT images in 5 cases of the HCQ group and 7 cases of the control group, and all patients showed improvement in follow-up examination. Four cases of the HCQ group and 3 cases of the control group had transient diarrhea and abnormal liver function. 
Conclusions: The prognosis of common COVID-19 patients is good. Larger sample size study are needed to investigate the effects of HCQ in the treatment of COVID-19. Subsequent research should determine better endpoint and fully consider the feasibility of experiments such as sample size.
Bonus points to those of you who were skeptical of the integrity of my condensed version of the report's abstract. Gold stars to those of you what actually compared my condensed version with the actual abstract. You were probably shocked when you realized that I removed some percentages, ranges, and statistical confidence levels without noting the omissions with bracketed ellipses. I did so [I lamely claim, after the fact] solely in a good faith effort to make my condensed version of the paper's abstract more readable and understandable to the reader and understander. Also, the delay provided you with time to consider your skepticism, presuming you have any.

Here are the issues that jumped out at me.

#1. Why only 30 patients? Wuhan alone has tens of thousands of cases that could be studied, and China has apparently been routinely using chloroquine in some form as part of their treatment. So why only 30 patients? Why not a huge observational study of documented cases across China?

#2. What were the demographics of the test and the control groups? I realize you said that you randomized them between the two groups, but you didn't give us the demographics of the starting pool of 30 patients. Did you take them all from a senior citizens center? That seems doubtful, since the fatality rate probably would have been higher. Did you take them all from a youth athletic club? Given that all but one of the patients responded well to whatever treatment was provided, I'm going to guess that the test population consisted largely of younger people.

#3. And just how many times did you randomize before you settled on your test and control groups?  Only once? More than once? Be honest with us. This issue relates back to issue #2. What was the demographics of your final test and control groups? How did they compare to one another? Was either group representative of the entire population?

#4. What the hell was the "conventional care" provided to the control group? You never mentioned that. Based on your own test results, I think we want whatever you were giving to them.

I became aware of this report a few days ago. Since I had written several times of some version of chloroquine as being a good candidate for a possible treatment, "my top pick" as I recall, I pondered about writing a post presenting contradictory evidence.

"Write the post," said the little devil on my right shoulder, accusing me of confirmation bias should I not."

"Ignore that bastard," said the little devil on my left shoulder, accusing me of carelessly spreading false information should I write of the report.

"You're tired of writing these posts," said the little devil in my left ear. "Do some of the other stuff you have to do. Do something you want to do. Take some time for yourself. You deserve it."

"You have an obligation," said the little devil in my right ear. "You didn't have to start this series, which you repeatedly refer to as an august series, even though most your readers have no idea what you mean by that. You can't just stop now, as things are getting worse, just before they will get real bad, just when you might make a difference, even if only an itsy bitsy, teeny weenie difference."

So I listened to the devil in my left ear, and I went and worked on my impending series of books about Louise Conan Doyle being the actual author of the Sherlock Holmes adventure. Yesterday was the most pleasant, least stressful day I've had in a while. I took some time for myself. I deserved it.

I have this nagging guilt problem though. I still have database design work I should be doing to generate an income, which I still need. I still have several tons of work to do on a specific wrongful conviction case that I've been trying to correct for over a decade. I still have responsibilities to help prepare and protect those close to me from the coronavirus onslaught that is rapidly approaching. And I still have this blog post to write, since the readership has increased slightly and must be waiting with baited breath with bated breath anxiously.

Also, and this is the factor that finally compelled me to write this post, I've come across an 80-page Norwegian paper that describes how broadly, persistently, and effectively China is using chloroquine as a treatment. In my quick summary of that lengthy paper, China not walking the talk. They are telling others that hydroxychloroquine is not worth using, but they are using it themselves, big time.

The paper is entitled "Essential Takeaways from China’s Response to COVID-19." It is authored by Yun Zhou (biomedical Researcher from Wuhan, living in Norway), Dr. Niels Chr. Danbolt (MD, professor, University of Oslo), and Stefan Krauss (MD, professor, University of Oslo). I present their key points, strategy, and additional point below. I excise some of their footnotes and parentheticals. Other than that, everything that follows, beneath the divider, is theirs, not mine. See the original if you prefer. Otherwise, continue reading this most august blog post to the end.

I congratulate the authors on their paper, their professionalism, and their effort to save lives.

*******

Key points:

1. The morbidity and mortality rates are so high that the virus causes the healthcare systems to be overwhelmed. The virus must be contained, and that explains the massive Chinese response with extensive quarantine measures.

2. While an approved drug for COVID-19 treatment does not exist, some drugs appear to be effective in treating the disease. One of these is the malaria drug chloroquine (both the phosphate version, and the hydroxy-variant). Chloroquine appears to be most effective if given early in the disease when symptoms are mild. This was reported in Chinese newspapers and other state-controlled media as early as early February 3, 4. Chloroquine is the drug most often mentioned in Chinese newspapers. It simple and fast to produce in large quantities and its side effects are well known and controllable.

3. For patients not tolerating or responding to chloroquine, three other drugs have been tried: Remdesivir, Lopinavir/Ritonavir and Umifenovir (Arbidol). All of these have moderate to severe side-effects, they are less studied, and they are more expensive to produce.

4. Chinese authorities have, according to our open-source intelligence, placed large orders on chloroquine, and we have got the impression that they maybe using this drug on a vast scale. Guangzhou Baiyunshan Guanghua Pharma has resumed full production capacity and has a daily capacity of 2 million tablets, suggesting that the Chinese authorities believe that chloroquine is effective.

5. A key point is that Western publications have not caught up with the above information as it is only available in Chinese. The authors of this memo are concerned that Western authorities (e.g. CDC and WHO) are unaware of important information that can be used to effectively deal with the COVID-19 pandemic. Information on the potential benefits of chloroquine for treatment of COVID-19 mediated disease is beginning to appear in Western media.

6. To what extent chloroquine treatment has been a key factor in the apparent Chinese success in fighting COVID-19 is unknown, but the evidence for a key role of chloroquine in this epidemic is compelling and needs to be investigated.

7. Our sources indicate that chloroquine administered at a sufficiently early stage may lower the number of patients that will require hospitalization.  In fact, this is what the Chinese have tried to do. Early treatment of infected people in Wuhan City reduced the percentage of severe conditions from 38% to 18%. In contrast, when the disease has progressed into a serious condition requiring intensive care admission and artificial ventilation, the treatment is less effective and a significant number of patients will die.

To summarize:

a. There is an existing drug, well tested, well documented and with manageable side effects, which is neither exceptionally expensive nor difficult to produce and is fairly effective if administered at the correct time.

b. In order to maximize the effectiveness of chloroquine it will be necessary to identify infected patients as early as possible through extensive testing with a rapid turn-around time.

8. There are also rumors that chloroquine may prevent the development of the disease if given at smaller doses to asymptomatic individuals.  If this is correct, then prophylactic treatment of people at risk (e.g. health personnel and individuals with underlying conditions) may be possible.

9. A high percentage of infected people may be absent from work for months and the Chinese are becoming stricter with respect to declaring an infected patient disease-free. Effective March 6th, 2020, they only release infected patients from quarantine after they have developed COVID-19 neutralizing antibodies. Infected patients with no or minimal antibody response are kept in quarantine as there is increasing evidence that they continue to shed virus and therefore can infect others. We have also been told by friends in Wuhan that China is considering 4 weeks of quarantine rather than the current recommendation of 2 weeks.

10. There are speculations that some patients die from an uncontrolled immune response (a.k.a. “cytokine storm”) and the immune suppressing drug Tocilizumab is being tested to prevent or stop this serious complication.

11. There are discussions whether ADE (antibody-dependent enhancement) may complicate vaccine development and pose a significant risk if reinfection occurs with a mutated virus.

12. Because the disease originated in animals, it may be worthwhile to check whether domestic animals need protection.

Potential strategy implications based on the above findings:

1. More resources need to be allocated to learn more about what has actually happened in China and what the Chinese have learnt from it. Relevant agencies should search Chinese sources and also interview Chinese doctors and other relevant persons. This latter part may be somewhat challenging, for obvious reasons.

2. The capacity for early diagnosis need to be radically expanded and combined with a decentralized access to relevant drugs (including chloroquine phosphate and/or hydroxychloroquine). The majority of the infected may then be able to treat themselves at home under remote medical guidance. This could have major implications because the number of patients admitted to hospitals would decrease and fewer people would need long sick-leaves. This in turn would also reduce the infection rate among healthcare workers.

3. The production of chloroquine in sufficient amounts to cover the entire US population, and hopefully also those of US allies, should be contemplated. At present, we are dependent on the Chinese for production both of chloroquine and the central materials needed to make it.

4. The West should increase own production of a panel of anti-viral drugs and antibiotics. Anti-viral drugs reported by the Chinese and others to be effective, are not available in sufficient quantities.

An additional point:

It is currently speculated whether chloroquine is able, not only to cure, but also prevent the onset of a Corvid-19 infection. How can we get an indication if it can work prophylactically? Patients suffering from rheumatoid arthritis and patients with systemic lupus erythematosus are often receiving hydroxy-chloroquine to keep the disease in check. If these patients do not get infected (or have a reduced risk to get infected) with coronavirus, then a likely interpretation is that chloroquine may have a protective effect. We got the following information from a hospital in Wuhan: "In the early stage of the study group, through the clinical analysis of 178 patients with new coronavirus received by the hospital from December 2019, it was found that none of them has systemic lupus erythematosus. After that, in the consultation of 80 patients with systemic lupus erythematosus treated by dermatology department of the hospital, it was found that they were not infected with new coronavirus pneumonia."

This is at current only an indication. We therefore propose that the US authorities explores health registries to identify a potential connection between hydroxychloroquine treatment and Covid-19 prevalence. Information could be gained within days. Particular good sources may be European countries and South Korea, but also China. If hydroxychloroquine has a protective function, we may -in combination with traditional measures (quarantine etc.) – be able to bring the transmission rate below 1 (each infected will infect on average less than 1 other person) and the epidemic may be contained in short time.

Friday, March 27, 2020

Surviving the Coronavirus: Part 7

How Bad Could It Be? Edition

In Part 3 of this august series, the part that I have recently labeled as the Diamond Princess Edition, I respond to the claim of a Stanford epidemiologist that perhaps, maybe, kinda, the coronavirus is not so bad after all. In summary of that edition, the Stanford epidemiologist made a needlessly crappy assumption, ended up with a needlessly crappy result, and needlessly crappily misinformed his readership. I've since seen his needlessly crappy result quoted by others hoping that they can hope this problem away.

Today I see some similarly crappy analysis by John Lee, writing for The Spectator: "How Deadly is the Coronavirus? It's Still Far from Clear." John Lee doesn't claim to be a Stanford epidemiologist. Instead he claims to be "a recently retired pathologist and a former NHS [Britain's National Health Service] consultant pathologist." I guess I'll be punching up, again.

In my apparently-not-so-humble opinion, the former NHS consultant pathologist goes off the rails early in his article when he writes:
The simplest way to judge whether we have an exceptionally lethal disease is to look at the death rates. Are more people dying than we would expect to die anyway in a given week or month?
Apparently, woefully, the recently retired pathologist failed to read Part 1 of this august series, the part that I have recently labeled as the Deadly Peril Edition. Had he, he would have understood that the death rate, more properly the case fatality fate (CFR), is only one of two critically important pieces of information we need to make a first order assessment of how bad a pandemic might be. The recently retired pathologist made the same stupid mistake as did the Stanford epidemiologist. Both considered the CFR; neither reasonably quantified the eagerness with which the Wuhan coronavirus spreads.

Because I have higher regard for the intelligence and moxie of my readers than the former NHS pathologist apparently has for his, I'm not going to sugarcoat it. One can make a first order assessment of how bad a pandemic might be once one knows two characteristics of the bug: the CFR and Ro, also known as R zero or R naught, also known as the basic reproduction number, also known (by me) as the starting reproduction number.

The reproduction number tells us how many uninfected people an infected person will infect. The reproduction number varies over time depending on the number of people who are immunized (naturally or artificially) and on social behavior response. While the reproduction number is greater than 1, the number of infections will grow. When the reproduction equals 1, the number of infections will remain constant, as new cases exactly equal the number of cases resulting in cure or death. While the reproduction number is less than one but greater than zero, then the number of infections will fall. When the reproduction number equals zero, the bug can no longer spread.

If the bug can no longer spread because society has reached herd immunity (naturally and/or artificially) then the reproduction number will be permanently equal to zero. If the bug is no longer spreading because people are hiding in nooks and crannies (as they should until a decent treatment is available), then the reproduction number will be temporarily equal to zero. The bug is still out there, lurking, waiting for people to re-emerge, waiting for winter weather, waiting for people to stop wearing masks and stop washing hands. As long as the bug is out there, and as long as we don't have natural and/or artificial herd immunity, the reproduction number will increase, flatten, and decrease in waves as environmental and social conditions allow.

In terms of assessing the potential mortality of a virus or a bacteria, we are interested in a specific reproduction number. We are interested in Ro, the starting reproduction number, the value as it exists early on, when people don't recognize the disease as a pandemic in the making, before people begin to scrub up, mask up, hide in the nooks and crannies, before they become immunized, naturally or artificially. We can estimate Ro for an specific disease based on the experience of a specific population. Based on the unfortunate specific population of the Diamond Princess floating petri dish, the estimated Ro of the Wuhan coronavirus is 2.28. (See Diamond Princess Edition.) Based on the unfortunate specific population of Wuhan, where the coronavirus first struck with fury, the Ro is 2.28.

Once we have the starting reproduction number, we can determine the percentage of the population that will have to become immunized (either by surviving the infection or getting an effective vaccine) in order to created herd immunity and permanently drive the final reproduction number to zero. As I explained in the Deadly Peril Edition, the calculation is simple.
Herd Immunity Fraction = 1 - 1/Ro
Since I would somewhat rather be labeled a shipist than a racist, I'll use the Diamond Princess Ro for the calculation. If the Ro is indeed 2.28, then 56% of us must survive an infection or be effectively vaccinated so that we can all benefit from herd immunity.

Now that we have the starting reproduction number, which gives us the herd immunity fraction, can we begin to make sense of the case fatality rate. I'll use a CFR of 0.77%, based on the South Korea experience. (See Deadly Peril Edition.)

Assuming no vaccine, then 56% of a given population must get infected in order to create herd immunity, and 0.77% of those infected will die. To express this in the form of an equation (just this once, I can stop whenever I want, I swear) I'll introduce a new term that I will call the Potential Death Toll Fraction, to which I will assign the acronym PDTF.
PDTF=Herd Immunity Fraction x CFR = 0.56 x 0.0077 = 0.0043 = 43%
"Hello. I'm The Skeptical Juror and I'm an engineer. I haven't formulated an equation since my last post."

Without identifying the loopholes in the coronavirus, and without leaping through them, then the PDTF for any given population is 43%. Given that the population of the good ol' USA is around 325 million, the PDT is 1.4 million fellow Americans dead of the virus. Given that the population of the good ol' Earth (my favorite planet) is 7.5 billion, then the PDT is 32.2 million fellow Earthlings dead of the virus.

That's nothing to sneeze at, even though sneezing is not one of the symptoms of the disease.

Here's the good news. The PDT (potential death toll) need not equal the ADT (actual death toll), and it certainly won't. To fight back, and to save more than a million American lives (and tens of millions of our fellow Earthlings), we need to:

1. Flatten the hell out of the curve. Those of us most likely to succumb to the disease and those of us most likely to spread it to others must head for, and remain in, our nooks and crannies.

2. Make available an effective treatment / cure. There are some candidate treatments out there. We need to test the most likely of them quickly. If they fail, we need to be ready with more to quickly test and distribute.

3. Develop an effective vaccine. All the smart people say this is a year to 18 months off. We can't wait that long. That's why we need the effective treatment quickly, conventional protocols be damned, full speed ahead.

If someone sees a better path forward, please let me know. Do not, however, be like the Stanford epidemiologist or the former NHS pathologist. Do not talk to me about just the death rate. I'm sick and tired of hearing about just the death rate. Talk to me about both the CFR and the R, and how we can reduce both of those deadly numbers.

Wednesday, March 25, 2020

Surviving the Coronavirus: Part 6

Don't Die! Edition

There are now various geezers senior citizens out there talking about how they are willing to risk death if it means saving other lives by saving the economy. In other words, more specially in my words, they are willing to take a bullet for the team by stupidly not flattening the curve as much as they could. Glen Beck has just recently volunteered for the heroically-foolish geezer ranks, though he admits to not quite yet being a geezer.
I mean, I'm in the danger zone. I'm right at the edge, I'm 56. In Italy they're saying if you're sick and you're 60, don't even come in. So, I'm in the danger zone. I would rather have my children stay home and all of us who are over 50 go in and keep this economy going and working, even if we all get sick, I would rather die than kill the country. 'Cause it's not the economy that's dying, it's the country. 
It's a noble thought, but it's stupid. It's exactly the wrong thing to do. And if only not-quite-a-geezer Beck had been reading this august blog, he would have known better.

Consider, for example, my sister. She is not "right at the edge" of the danger zone; she's 70; she can see the edge of the danger zone only if she squints. She's been insulin-needles-several-times-a-day since she was a teenager. She is now battling a theoretically controllable form of leukemia, one that was diagnosed on the anniversary of the day her husband died of cancer, at home hospice. Her battle with leukemia, coupled with some mistakes at a hospital, has left her with reduced liver, kidney, and lung function. She could, in a foolish act of heroism, not isolate herself. She could Glen Beck it, go out and about, economic guns ablazing, trying like hell to stimulate the economy, trying to save it, trying to save the country.

But she shouldn't, and she doesn't, and I love her for it.

Instead, she isolates herself so that she doesn't catch the disease, so that she doesn't infect others, so that she doesn't get transported to the hospital, so that she doesn't add to the burden that most hospitals will soon be facing, so that she doesn't deprive someone else of the medical care that might save their life. She flattens the curve as much as she can so that we can hang on until we have an effective treatment, so that we can save a million lives.

Glen Beck, apparently, doesn't believe in exponential growth. Things aren't so bad today, he seems to reason, and they might be worse tomorrow, but that still won't be so bad. He's dead wrong if he thinks anything like those thoughts I have improperly attributed to him.

People simply can't think in terms of exponential growth. To see exponential growth in effect as it pertains to the the coronavirus, take a peek at the following numbers, if you dare. They show the total confirmed cases in the U.S. at the end of each Tuesday.

Jan. 14  — 0
Jan. 21  — 1
Jan. 28 — 5
Feb. 4   — 11
Feb. 11  — 14
Feb. 18 — 25
Feb. 25 — 59
Mar. 3   — 125
Mar. 10  — 1,004
Mar. 17  — 5,902
Mar. 24 — 53,478

Do you want to make a guess at how many cases there will be next week? I'm going to guess that there will be somewhere between and quarter and a half million, and still accelerating. Do you want to make a guess at how many will be out there the week after next? How about the week after that?

We're starting to hear of infections among celebrities and politicians. Soon we'll be hearing of infections closer to home, among people we know. Soon thereafter, we may begin hearing of deaths among people we know, and love.

We're certainly going to be hearing of hospitals struggling to get through this. If we're not careful, we're going to hear horror stories of people dying in hospital hallways and waiting rooms, or in tents or makeshift triage shelters.

So, Glen Beck, don't go out and about. Recognize that the most vulnerable of us out there are the ones who must most thoroughly isolate, since we are the ones most likely to overburden our health care system, since we are the ones most likely to take others with us to the grave.

So, kind and gentle geezer readers, do not model your behavior after Glen Beck, who can sit behind a microphone in a home studio if he so chooses. Model yourself after my sister, who sits alone, heroically, with a smile and a sense of humor.

Stimulate the economy as she does. Purchase things, but purchase them from home. And leave a really nice tip for the younger, less-at-risk, less-likely-to-need-the-hospital generation. And thank them, sincerely, for their service.

Stimulate the economy as The Skeptical Spouse and I do, because we can still afford it. We are paying for routine services even when those services cannot being supplied. Today, we will be sending checks to the two small business people who routinely cut our hair. The checks are in the guise of informal, unwritten (probably-won't-be-strictly-enforced) gift cards for future redemption.

Stimulate the economy as best you can, given your unique set of circumstances. But, if you are a geezer, particularly if you are even more of a geezer than Glen Beck, don't be foolishly heroic by rushing headlong into a viral machine gun nest when an Abrams tank could do it more safely.

Be like my sister.

Sunday, March 22, 2020

Surviving the Coronavirus: Part 5

Chloroquine Edition

Yes, it's all over the news now. Apparently someone read Part 2 and/or Part 4 of this august series, acted on it/them, and now the world is saved.

Perhaps I overstate the matter in one or two tiny aspects, but there is certainly good news afoot.

150 million or so doses of chloroquine (or some variant thereof) are being promised by various manufacturers. China's protocol calls for 2 tablets per day for 10 days. The 150 million doses would be good for 7.5 million cases. South Korea's protocol calls for 1 tablet per day for 10 days. The 150 million doses would be good for 15 million cases.

I've come across a nice looking site out there called Spin, Strangeness, and Charm. It's not a site about sub-atomic physics, as most of you immediately presumed. It is instead about media and political spin, the strangeness of the world around us, with a sprinkling of charm to keep everything in perspective. It's running frequent updates regarding the coronavirus, the updates seem to be rational and well informed, and everything there is free, so good on the fine folks at Spin, Strangeness, and Charm.

In a very recent post, "COVID19 update: a brief look at three possible drugs," TFF at SSC embedded a video from the questionably-named medical site medcram.com. Personally, I don't like combining thoughts of medical treatment with the word cram. The fine folks at Medcram, though, were apparently using "cram" in the sense of "cramming for a test." The site's banner reads "Medical Videos and Lectures Explained Clearly." Their underline, unlike mine, is hand-drawn, bold, colorful, and eye-catching. But I digress.

The video was quite well done. 17 minutes or so long, as I recall. When I attempted to play it a second time, it wouldn't play. I received an error message. When I tried to play it a third time, I got an error message. When I tried to play it a fourth time (and I really did do that), I got an error message. My guess is that Part 2 and/or 4 of this august series indirectly but eventually led to so many Google hits for "chloroquine" that the Medcram server was overwhelmed.


Somehow, astoundingly, blessedly, the server serving this site has been able to withstand the traffic. But I digress.

As a public service, I'll try to summarize the Medcram video, since you can't watch it yourself. (I just tried to view it again. Same result. Perhaps I'm part of the problem.) Since I'm not a doctor, physician, epidemiologist, biomedical researcher, or involved in any fashion whatsoever in the medical field, I may get things a bit wrong here and there.

Hang on. Buckle up. Here we go.

A virus is a strange creature, not at all like a human, or even a human cell. Instead of multiplying through dividing, as do our cells, it replicates itself inside our cells only after creating something that scientists cleverly call replicase. Wikipedia, which I can still get to, describes replicase in simple, understandable fashion.
RNA-dependent RNA polymerase (RdRP, RDR) or RNA replicase is an enzyme that catalyzes the replication of RNA from an RNA template. This is in contrast to a typical DNA-dependent RNA polymerase, which catalyzes the transcription of RNA from a DNA template.
The coronavirus, and others of its evil ilk, have a loophole that we might be able to jump through. Coronavirus replicase hates zinc, because zinc kills coronavirus replicase. Good for us, bad for them. Don't go rushing to your store for zinc tablets, though, because our cell walls will not allow zinc to pass through without an appropriate escort. (The clever among you can now see where this is going.) Our cell walls, however, allow zinc to pass IF the zinc is escorted by Chloroquine!!!!!

If this works in practice as well as it works in the video, which is not working at the moment, then here's how you can survive the coronavirus. Have a medical profession administer chloroquine, or one of it's even better variants, make sure your cells are smart enough to allow the zinc to enter if escorted by chloroquine, watch the coronavirus already in your cells wither on the vine (my metaphor server is obviously down), get better.

But wait, there's more. The fine doctor in the fine video pointed out some very interesting comparisons between the outbreak in South Korea and the outbreak in Italy. Both countries have similar populations, 51 and 60 million respectively. Both countries have similar infections per million people. HOWEVER, the South Koreans have an order of magnitude fewer deaths AND more than an order of magnitude fewer instances of critical cases per infection.

Though the video doctor did not say so directly, it seems to me that the differential rates of critical cases per infection rules out the primary reason being differences in age distribution, testing, social distancing, wearing face masks, etc. There seems to be some difference in how the patients are treated after they have been infected. One difference is that the South Koreans have apparently been treating their patients with chloroquine while the Italians apparently have not.

The video doctor actually expressed cautious optimism that chloroquine will prove in practice to be an effective treatment. He did caution that we have been fooled before by early promising results, and that is all we have now for chloroquine. I already pointed out (in Part 4 of this august series) that the HIV drug that was once thought promising, and was being used in China, has since been shown in better controlled testing to have no effect.

As far as I am concerned, the best strategy for surviving the coronavirus, both as an individual and as a nation, is to flatten the hell out of the curve while quickly identifying and making widely available an effective cure. The chloroquine may be that effective cure. If not, we need to quickly move on to the next best candidate in the long list.

We need to save both our lives and our economy. To save us and it, we absolutely must quickly discover and widely distribute an effective cure. There is no other good option.

Thursday, March 19, 2020

Surviving the Coronavirus: Part 4

I begin with a quick review of previous posts in this series.

Part 1: I describe the potential magnitude of the problem if we don't "flattening the curve" and quickly find an effective treatment.

Part 2: Brits say that we Yanks will suffer more than a million dead, even with "flattening the curve." They fail, however, to consider effective treatments. I discussed two possible effective treatments. 

Part 3: As a recovering engineer, I take issue with a Stanford epidemiologist regarding the significance of the Diamond Cruise experience.

Now on to Part 4, in which we look at some exceptionally exciting news in the world of effective treatments.

Recall that in Part 2, I described two existing drugs, one for malaria and one for HIV, both of which looked promising as potential treatments for coronavirus. I declared the malaria drug as my top pick and the AIDS drug as a runner up. I will give you an update on those two before moving on to more candidates.

My runner up, the HIV drug, appears to no longer be in the running. We learn of that in the disappointing article "HIV drug combo fails as treatment for severe COVID-19 in China study."
A pill containing two HIV drugs that was touted as a potential treatment for the novel coronavirus was not effective, according to a study released late on Wednesday in the New England Journal of Medicine. 
A test in Chinese patients with severe COVID-19 disease found the 99 who received AbbVie Inc's Kaletra, a combination of lopinavir and ritonavir, fared no better than the 100 who received standard care. [...] 
The lopinavir-ritonavir combination also produced more side effects, prompting the treatments to be halted in 13.8% of patients.
On the very bright side, my top pick, the malaria drug chloroquine / hydroxychloroquine, seems to have considerably opened its lead over the 50 or so other contenders in the race for an effective treatment / cure. Several papers detailing good success in separate human trials are here and here. China, South Korean, and Belgium are already using the medication in practice, not just in trials. The drug may have preventative as curative potential. The U.S. authorities have knocked down bureaucratic hurdles and the medication will be used in human trials and/or actual practice within a matter of days. Bayer is preparing to donate the a large quantity of the medication. (Good on Bayer.)

Also in the running is a Japanese flu drug favipiravir. According to an 18 March 2020 article in the The Guardian:
Medical authorities in China have said a drug used in Japan to treat new strains of influenza appeared to be effective in coronavirus patients, Japanese media said on Wednesday. 
Zhang Xinmin, an official at China’s science and technology ministry, said favipiravir, developed by a subsidiary of Fujifilm, had produced encouraging outcomes in clinical trials in Wuhan and Shenzhen involving 340 patients. “It has a high degree of safety and is clearly effective in treatment,” Zhang told reporters on Tuesday. 
Patients who were given the medicine in Shenzhen turned negative for the virus after a median of four days after becoming positive, compared with a median of 11 days for those who were not treated with the drug, public broadcaster NHK said. 
In addition, X-rays confirmed improvements in lung condition in about 91% of the patients who were treated with favipiravir, compared to 62% or those without the drug. [...] 
Doctors in Japan are using the same drug in clinical studies on coronavirus patients with mild to moderate symptoms, hoping it will prevent the virus from multiplying in patients. But a Japanese health ministry source suggested the drug was not as effective in people with more severe symptoms. “We’ve given Avigan to 70 to 80 people, but it doesn’t seem to work that well when the virus has already multiplied,” the source told the Mainichi Shimbun.
Meanwhile, the ebola drug remdesivir may have already saved the life of an American dying of coronavirus. I excerpt from the Wikipedia article.
Remdesivir [...] is a novel antiviral drug [...] developed by Gilead Sciences as a treatment for Ebola virus disease and Marburg virus infections. [...] 
In response to the 2019–20 coronavirus outbreak induced by coronavirus SARS-CoV-2, Gilead provided remdesivir for a "small number of patients" in collaboration with Chinese medical authorities for studying its effects. 
Gilead also started laboratory testing of remdesivir against SARS-CoV-2. Gilead stated that remdesivir was "shown to be active" against SARS and MERS in animals. 
In late January 2020, remdesivir was administered to the first US patient to be confirmed to be infected by SARS-CoV-2, in Snohomish County, Washington, for "compassionate use" after he progressed to pneumonia. While no broad conclusions were made based on the single treatment, the patient's condition improved dramatically the next day, and he was eventually discharged. 
Also in late January 2020, Chinese medical researchers stated to the media that in exploratory research considering a selection of 30 drug candidates, remdesivir and three other drugs, chloroquine, lopinavir/ritonavir and favipiravir, seemed to have "fairly good inhibitory effects" on SARS-CoV-2 at the cellular level. Requests to start clinical testing were submitted. On February 6, 2020, a clinical trial of remdesivir began in China. 
On 17 March 2020, remdesivir was provisionally approved for use for COVID19 patients in a serious condition in the Czech Republic. 
On 18 March 2020, the first Italian COVID-19 patient was successfully cured with remdesivir in Genoa.
So, as this series draws to a close, I want to summarize what I consider to be our best strategy for surviving the corona virus.

1. Flatten the hell out of the curve. Keep the hospitals from becoming overwhelmed. Geezers and other high risk individuals should be particularly disciplined about their social distancing. The young whippersnappers, who are at the lowest risk, should carry the burden of keeping essential distribution systems in place.

2. Crank out, in record time, an effective treatment.

Most of us have no way of contributing to item #2. All of us can contribute to item #1. That is why I have broken my indefinite sabbatical from this site to write this series. We need to recognize that we face a deadly foe, and we need to pitch in to combat it in whatever fashion we can.

As a society, we are responding in spectacular fashion. Nice job, everybody.