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.

Wednesday, March 18, 2020

Surviving the Coronavirus: Part 3

Diamond Princess Edition

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

In Part 1, I introduced the concepts (and an itsy bitsy teeny weenie bit of math) behind the spread of a virus. I predicted that, left unchecked by anything other than natural herd immunity, 1.6 million of us Americans would die.

In Part 2, I tooted my horn that I had beat the Brits to press by one day, conceded that they carried their work substantially further than I had mine, and then offered what I believe to be our only hope to avoid hundreds of thousands of deaths. We need to hunker down while we get an effective treatment widely distributed. The two leading candidates are a malaria drug and an AIDS drug.

In this Part 3, I want to consider an article arguing that the Diamond Princess experience indicates that we, both as a nation and as a planet, are over-reacting to the virus.

From Wikipedia, we get a nice overview of the Diamond Princess and its unfortunate transformation into a gigantic, floating, petri dish.
Diamond Princess is a British-registered cruise ship owned and operated by Princess Cruises. She began operation in March 2004 and primarily cruises in Asia during the northern hemisphere summer and Australia during the southern hemisphere summer. [...] Diamond Princess and Sapphire Princess were both built in Nagasaki, Japan by Mitsubishi Heavy Industries. [...]
Diamond Princess (ship, 2004) - cropped.jpg
2,670 Passengers + 1,100 crew (nominal)
On 20 January 2020, an 80-year-old passenger from Hong Kong embarked in Yokohama, sailed one segment of the itinerary, and disembarked in Hong Kong on 25 January. He visited a local Hong Kong hospital, six days after leaving the ship, where he later tested positive for COVID-19 on 1 February. On its next voyage, 4 February, the ship was in Japanese waters when 10 passengers were diagnosed with COVID-19 during the 2019–20 coronavirus outbreak.
The ship was quarantined on 4 February 2020 in the Port of Yokohama in Japan. The infections included at least 138 from India (including 132 crew and 6 passengers), 35 Filipinos, 32 Canadians, 24 Australians, 13 Americans, 4 Indonesians, 4 Malaysians, and 2 Britons. Home countries arranged to evacuate their citizens and quarantine them further in their own countries. As of 1 March, all on board including the crew and the captain had disembarked.
As of 5 March 2020, at least 696 out of the 3,711 passengers and crew had tested positive for the virus. On 6 March, the death toll reached 7.
The Diamond Princess based article that has drawn my attention and prompted this post is "A fiasco in the making? As the coronavirus pandemic takes hold, we are making decisions without reliable data" by John P. A. Ioannidis, an epidemiologist at Stanford University. (Uh oh!) For those of you keeping track, I am seriously outgunned here. I am not an epidemiologist. I don't even play one on television. I am but a self-admitted recovering engineer. "Hi. I'm the Skeptical Juror, and I'm an engineer. I haven't solved an equation in three days."

I extract the Stanford epidemiologist's article below. I emboldened the portion where I think he makes a mistake so glaring that even a recovering engineer might catch it.
The current coronavirus disease, Covid-19, has been called a once-in-a-century pandemic. But it may also be a once-in-a-century evidence fiasco. At a time when everyone needs better information, from disease modelers and governments to people quarantined or just social distancing, we lack reliable evidence on how many people have been infected with SARS-CoV-2 or who continue to become infected. Better information is needed to guide decisions and actions of monumental significance and to monitor their impact. […] 
The one situation where an entire, closed population was tested was the Diamond Princess cruise ship and its quarantine passengers. The case fatality rate there was 1.0%, but this was a largely elderly population, in which the death rate from Covid-19 is much higher.
Projecting the Diamond Princess mortality rate onto the age structure of the U.S. population, the death rate among people infected with Covid-19 would be 0.125%. But since this estimate is based on extremely thin data — there were just seven deaths among the 700 infected passengers and crew — the real death rate could stretch from five times lower (0.025%) to five times higher (0.625%). […] 
If we assume that case fatality rate among individuals infected by SARS-CoV-2 is 0.3% in the general population — a mid-range guess from my Diamond Princess analysis — and that 1% of the U.S. population gets infected (about 3.3 million people), this would translate to about 10,000 deaths. This sounds like a huge number, but it is buried within the noise of the estimate of deaths from “influenza-like illness.” If we had not known about a new virus out there, and had not checked individuals with PCR tests, the number of total deaths due to “influenza-like illness” would not seem unusual this year. At most, we might have casually noted that flu this season seems to be a bit worse than average. The media coverage would have been less than for an NBA game between the two most indifferent teams.
He bothered to extract a case fatality rate (CFR) from the Diamond Princess petri dish, but then he simply assumed that 1% of the U.S. population gets infected. Perhaps if he had read my first post in this series, he would not have made such a silly careless self-reinforcing mistake. He might have instead homed in on this tidbit from my earlier august post.
According to the International Journal of Infectious Diseases, the estimated Ro value for the Wuhan COVID-19 coronavirus, based on the Diamond Princess Cruise Ship trip to hell, is around 2.28.
Then, with the R zero value of 2.28 (which the International Journal of Infections Diseases derived from the Diamond Princess petri dish), the epidemiologist could have made a first order estimate of the percentage of U.S. infections as per my earlier august post.
Thanks to the wonders of mathematics, we can estimate the percentage of the population that must become immune to provide our entire herd with herd immunity. The equation is A = 1-1/Ro, where A is the herd immunity threshold (as a percentage of the population) and Ro is the reproduction number that you now understand so thoroughly and so well. Given that we have no vaccine, and probably will not soon have a vaccine, we are going to calculate the number of Americans who will have to get sick, survive, and develop a natural immunity. 
The next paragraph is rated S, for shocking. Get ready. Brace yourself. Here we go. 
If the starting R value for the coronavirus is indeed 2.28, as the poor folks aboard the Princess Cruise Line Ship have helped establish, then we will reach the herd immunity threshold once 56% of the population has been infected and has survived. Given there are 325 million of us here in the good ol' USA without a vaccine, then 182 million of us are going to have to get sick and survive.
Given that the herd immunity threshold is equal to the number of expected infections within a population, assuming the virus is left to its own devilish devices, then the Diamond Princess experience tells us that the percentage of the population that could be infected is 56%, not 1%. For those of you who might be particularly disinclined towards math, my engineering estimate is 56 times greater than that of the Stanford epidemiologist. My engineering estimate may be wrong, certainly, but at least I provide some basis for it. The epidemiologist simply said "If we assume."

Please do not include me as part of that scholarly pronoun.

If, instead, we derive both a case fatality rate (CFR = 0.625% as per the epidemiologist) and a starting reproduction number (Ro = 2.28 as per the IJID) from the Diamond Princess experience, then we're looking not at 10,000 deaths, but 1.1 million deaths. That, I am certain, would draw more media coverage than "an NBA game between the two most indifferent teams."

As I made clear in my first two posts of this series, our best strategy is to flatten the hell out of the curve and work like hell towards mass distribution of an effective treatment, at least two of which may be on the way.

As I pointed out in Part 2 of this series, the 31 authors from the Imperial College of London followed close on my heels in predicting more than a million deaths in the U.S. Their calculation was even more frightening, though, since it presumed serious flattening-the-curve efforts such as those now in effect within the U.S.

Since the Brits actually presented some defensible basis for their numbers other than "If we assume," I spent no time trying to dispute them. Instead, I faulted them just a wee bit for failing to even mention the possibility that cheap, effective treatments seem to be on the horizon.

According to the "we do not simply assume" Brits, we have to get even more aggressive at flattening our curve. I'm concerned that articles such as that of the Stanford epidemiologist do just the opposite.

[Addendum]
I meant to include this thought in the original post, but the sun got in my eyes, or some other equally lame excuse.

One might argue that 56% infection rate cannot be correct since only 18% of the 3779 pax and crew (nominal) aboard the Diamond Princess got infected, despite close quarters.

One might respond that the Diamond Princess was quickly quarantined, internally and externally, once the initial infection was recognized. One might therefore argue that the Diamond Princess experience demonstrates the importance of flattening the curve as soon and as much as possible, reducing the infection rate from 56% to 18%, saving two-thirds of the 21 lives that would have otherwise have been lost.

The correct lesson from the Diamond Princess experience might be exactly the opposite of that being taught by the Stanford epidemiologist.

Tuesday, March 17, 2020

Surviving the Coronavirus: Part 2

In the first post of this series, I discussed the potential harm that might be inflicted on us by the coronavirus, described several strategies for fighting back, and described a Machiavellian approach for reducing deaths in the US from more than a million to less than one hundred thousand. The entire post presumed the availability of neither a vaccine nor an effective treatment. I predicted I would discuss those issues in my next post, and it looks like I was correct, at least about discussing vaccines and treatments. Well, at least about discussing treatments. I will do that soon, but first ...

I published my first post in this series on 15 March 2020. The next day (16 March 2020, for mathematically resistant among you),  Imperial College of London published its 20-page, 31-author paper, "Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand." The 31 authors also described the grave nature ignoring the virus, estimating a  potential, unmitigated death toll of 2.2 million for the US and 510,000 for Great Britain. The 31 authors are, of course, arguing (as I did) that we should mitigate the impact of the virus.

Just as I did, the Brits described two basic approaches to mitigating the virus. First is what they call the suppression model, what I called the early mammal hunker down strategy, what China seems to have pulled off in the real world. The suppression model involves extreme measures in identifying and isolating each and every possible case. The Brits recognized not only the social cost of such extreme measures, they recognized, as I did, a fundamental problem with the strategy. The government needs to keep its populous hunkered down and suppressed until a vaccine arrives, since the population did not develop herd immunity as 0.77% of them died off.

The second strategy identified by the Brits, the one they call mitigation, is what we Yanks are calling "flatten the curve." The Brits studied five mitigation scenarios, ranging from what I'll call "those who show symptoms should just stay home" to "kinda like what the Yanks are doing right now." The Brits estimated, for each scenario, how many hospital beds would be required. The most aggressive mitigation scenario, the "kinda like what the Yanks are doing right now" scenario, was the best at flattening the curve. (Yea! We're number one.) Even those results, however, were quite disturbing. (Uh oh.)
Perhaps our most significant conclusion is that mitigation is unlikely to be feasible without emergency surge capacity limits of the UK and US healthcare systems being exceeded many times over. In the most effective mitigation strategy examined ... the surge limits for both general ward and ICU beds would be exceeded by at least 8-fold under the more optimistic scenario for critical care requirements that we examined. 
Yikes!
So how many of us might, uhm, er, uh, succumb?
In addition, even if all patients were able to be treated, we predict there would still be in the order of 250,000 deaths in GB, and 1.1 - 1.2 million in the US.
Yikes!
So what do the 31 authors suggest we do?
We therefore conclude that epidemic suppression [China, early mammal hunkering down] is the only viable strategy at the current time. The social and economic effects of the measures which are needed to achieve this policy goal will be profound. Many countries have adopted such measures already, but even those countries at an earlier stage of their epidemic (such as the UK) will need to do so imminently.
Yikes!
So how long would we have to be hunkered down and suppressed, as in  China?
To avoid a rebound in transmission, these policies will need to be maintained until large stocks of vaccine are available to immunise the population – which could be 18 months or more.
Holy Cow!
A year and a half of Chinese-like suppression / enforced hunkering OR more than a million of us die.

While I don't disagree with their numbers, I politely suggest that the 31 authors have overlooked another strategy, one I've been hinting at during my previous writing on this subject. We need an effective treatment for coronavirus, and we need it toot friggin' sweet.

Fortunately, there is good news, very good news, out there. 

There are several safe medications already available for other illnesses that have a pretty good chance of working on the coronavirus. I'll give a brief description of the two leading contenders, beginning with my top pick ...

From Wikipedia, Chloroquine is a medication used to prevent and to treat malaria in areas where malaria is known to be sensitive to its effects. [...] Common side effects include muscle problems, loss of appetite, diarrhea, and skin rash. Serious side effects include problems with vision, muscle damage, seizures, and low blood cell levels. It appears to be safe for use during pregnancy. [...] It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system. It is available as a generic medication. The wholesale cost in the developing world is about $0.04. In the United States, it costs about $5.30 per dose. [...] In late January 2020 during the 2019–20 coronavirus outbreak, Chinese medical researchers stated that exploratory research into chloroquine and two other medications [to be named herein later] seemed to have "fairly good inhibitory effects" on the 2019 novel coronavirus. [...] On 19 February 2020, preliminary results found that chloroquine may be effective and safe in treating COVID-19 associated pneumonia. [...] The Guangdong Provincial Department of Science and Technology and the Guangdong Provincial Health and Health Commission issued a report stating that chloroquine phosphate "improves the success rate of treatment and shortens the length of patient’s hospital stay" and recommended it for patients diagnosed with mild, moderate and severe cases of novel coronavirus pneumonia.

Regarding that precious malaria drug, from "An Effective Treatment for Coronavirus (COVID-19)"
Recent guidelines from South Korea and China report that chloroquine is an effective antiviral therapeutic treatment against Coronavirus Disease 2019.  Use of chloroquine (tablets) is showing favorable outcomes in humans infected with Coronavirus including faster time to recovery and shorter hospital stay.  US CDC research shows that chloroquine also has strong potential as a prophylactic (preventative) measure against coronavirus in the lab, while we wait for a vaccine to be developed.  Chloroquine is an inexpensive, globally available drug that has been in widespread human use since 1945 against malaria, autoimmune and various other conditions.

The runner up, so far, is ...

From Wikipedia: Lopinavir/ritonavir [...] is a fixed dose combination medication for the treatment and prevention of HIV/AIDS. It combines lopinavir with a low dose of ritonavir. [...] It is taken by mouth as a tablet, capsule, or solution. [...] Common side effects include diarrhea, vomiting, feeling tired, headaches, and muscle pains. Severe side effects may include pancreatitis, liver problems, and high blood sugar. It is commonly used in pregnancy and it appears to be safe. [...] It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system. The wholesale cost in the developing world is $18.96 to $113.52 a month. In the United States it is not available as a generic medication and costs more than $200 for a typical month supply as of 2016. [...] Lopinavir/ritonavir has been studied for its anti-coronavirus activity. As such, in late January 2020, Chinese medical researchers began exploratory research considering a selection of 30 drug candidates, three of them, remdesivir, chloroquine and lopinavir/ritonavir, seemed to have "fairly good inhibitory effects" on SARS-CoV-2 in cell culture. Requests to start clinical testing were then submitted. Trials are ongoing.

Regarding that precious HIV drug, from "COVID-19 Drug Therapy — Potential Options":
Therapies evaluated in human clinical trials during previous coronavirus outbreaks [...] Lopinavir; ritonavir in conjunction with ribavirin [an anti-viral drug] and corticosteroids [...] 21-day adverse outcome rate: 28.8% for historical controls and 2.4% for treatment group.

At the moment, it seems as if the only thing standing between the lofty, large-brain humans and the lowly, no-brain coronavirus is the rapid, widespread distribution of an effective treatment. Existing malaria and HIV drugs look promising as treatments. The malaria drug looks like it might even prevent infection.

So ...

Stay calm and keep flattening the curve until our government cuts through the red tape and makes plentiful an effective treatment / prophylactic.

We gonna get through this.

Sunday, March 15, 2020

Surviving the Coronavirus

Deadly Peril Edition

Though I have been busy working to resolve wrongful convictions, I have not been posting about wrongful convictions on this once august site, due to priorities and time constraints.

Though I am now, as you can see with your own eyes, publishing a post on this once august site, it is not about wrongful convictions. Instead, as a public service, I am presenting my thoughts on how we, individually and as a society, might best survive the COVID-19 / Coronavirus pandemic.

I'll begin by pointing out that I am not an epidemiologist, a doctor, or a health care professional of any sort. Instead, I was once an engineer, and I now claim to be a recovering engineer. "Hello. My name is TSG, and I'm an engineer."

The Skeptical Spouse assures me that I will never recover. The fact that I am publishing this article weighs heavily in her favor.

Several recent technical articles have prompted me to think through the mathematics of surviving a pandemic. I will extract interesting and useful tidbits from some of the articles. I'll throw an itsy bitsy tiny weenie bit of math your way. I'll explain the math for those of you who are not recovering engineers. Hopefully, if I do this well, we might actually, in all seriousness, save a life or two. That's why I am resurrecting and redirecting this once reasonably well visited site.

The first article of interest is a pre-print, non-peer-reviewed paper enticingly titled, "Trends and prediction in daily novel coronavirus infection in China, Hubei Province and Wuhan City; an application of Farr's law." Dated 15 February this year, when 793 new cases were reported in Wuhan City, the authors predicted that new cases would drop to zero by 8 March, just three weeks out. According to a Reuter's article that I dug up, as of 5 March there were zero new cases in all of Hubei Province, which includes Wuhan City.

That was a spectacular prediction, certainly worthy of some consideration.

The authors made their prediction shortly after the rate of new cases each day had peaked. That allowed them to use Farr's Law to predict a "zero-new-cases" date. William Farr (1807-1883) was a British epidemiologist who observed that, during an epidemic, the rate of new cases tends to follow a normal bell-shaped curve. Since then, Farr's Law has been applied with reasonable success to analysis of a number of epidemics including smallpox, flu, and AIDS.

The authors who applied Farr's Law to the coronavirus outbreak at Wuhan city provided both tabulated data and plots for Wuhan City, the remainder of Hubei Province, and all of China. I show their plot for Wuhan City below. The blue line shows the actual number of new reported cases. The orange line is the author's best projection of how the future rate of new cases would develop in Wuhan City. The authors gave a 25% chance that new cases would develop more slowly than the comforting gray line, and a 25% chance that cases would explode faster than the scary yellow line.


The cases haven't peaked in the U.S., not by a long shot, so we can't yet apply Farr's Law of to make a guess at how bad things might become in our country, the good ol' US of A. What the plot does show is, that by applying extreme measures quickly, a country has some hope of limiting the damage that can result from the virus.

The second article provides the best quantified overview of the coronavirus pandemic that I have come across so far. It is by Our World in Data, which begins its article with the organization's mission statement: "The mission of Our World in Data is to make data and research on the world’s largest problems understandable and accessible." As a recovering engineer, I like that. I'll use some of their data as I describe a simplified mathematical model for the contagion, beginning ...

Now!

One of the most important numbers in epidemiology is the reproduction number, represented by the letter R. The number is defined as the average number of secondary cases generated by one primary case. If on average, one person infects two others, then R is equal to 2. If R is greater than 1, then the epidemic will spread. If it is much greater than 1, then the epidemic will spread quickly.

To get a sense of how serious the coronavirus might be when compared to other viral outbreaks that mankind has survived, we can compare their Ro values. (Ro is pronounced R zero or R naught, depending on your side of the pond.) Ro is the reproduction number at the beginning of the outbreak. For previous viral outbreaks, I rely on the classic paper by BMC Infectious Diseases, "Estimates of the reproduction number for seasonal, pandemic, and zoonotic influenza: a systematic review of the literature." From that august paper, I find the following:

The median Ro value for seasonal flu was 1.28. Seasonal flu kills between 3,000 and 49,000 people in the US each year.

The median Ro value for the 2009 swine flu was around 1.46. That animal named flu left 12,000 dead in the US.

The median Ro value for the 1957 Asian flu was 1.65. That non-geographically named flu left 115,000 dead in the US.

The median Ro value for the 1968 Hong Kong flu was 1.80. That non-geographically named flu left 110,000 dead in the US. 

The Ro value for the 1918 Spanish flu was also around 1.80. That non-geographically named flu left 675,000 dead in the US.

According to the International Journal of Infectious Diseases, the estimated Ro value for the Wuhan COVID-19 coronavirus, based on the Diamond Princess Cruise Ship trip to hell, is around 2.28.

According to the august medical journal The Lancet, the estimated Ro value for the Wuhan COVID-19 coronavirus, based on the China experience, is around 2.5. 

Yikes!

If you are not yet worried, you should be, at least a teeny weeny bit. You absolutely should not panic, but you absolutely should force yourself to read this lengthy august article to its dramatic conclusion.

For an epidemic to recede, its R value, its reproduction number, must somehow drop below 1.0. Anthony Farr's bell curve will peak when R falls to 1.0, and the rate of new cases will drop when R falls below 1.0. Because we need to keep R as low as possible, we should more carefully consider the reproduction number.

Left to its own evil devices, a pandemic will burn itself out by creating so many survivors that the entire society reaches a herd immunity threshold. At that point, R goes to 1. As still more and more people survive the infection and develop a natural immunity, then R falls below 1, the herd immunity becomes more robust, and pandemic blessedly withers.

Thanks to the wonders of mathematics, we can estimate the percentage of the population that must become immune to provide our entire herd with herd immunity. The equation is A = 1 - 1/Ro, where A is the herd immunity threshold (as a percentage of the population) and Ro is the reproduction number that you now understand so thoroughly and so well. Given that we have no vaccine, and probably will not soon have a vaccine, we are going to calculate the number of Americans who will have to get sick, survive, and develop a natural immunity.

The next paragraph is rated S, for shocking. Get ready. Brace yourself. Here we go.

If the starting R value for the coronavirus is indeed 2.28, as the poor folks aboard the Princess Cruise Line Ship have helped establish, then we will reach the herd immunity threshold once 56% of the population has been infected and has survived. Given there are 325 million of us here in the good ol' USA without a vaccine, then 182 million of us are going to have to get sick and survive. If the starting R value is 2.5, as the poor folks in Wuhan have helped establish, then 60% or us are going to have to take one for the team. That's 195 million of us.

Yikes!

There's an important caveat here. A really important caveat. We need people to survive to create our herd immunity. We don't need people to die. We don't want people to die. We want to minimize the number of people who die. And there is plenty within our power to do just that.

Pandemics are at their worst, by far, when the number of cases overwhelm the medical care capabilities of a country or community. China, obviously having prepared for a serious epidemic, built two temporary hospitals and put them into operation in slightly more than a week. Italy, far less prepared, was completely overwhelmed. The stories coming out of Italy are horrific beyond any words that I want to write.

The OECD (Organization for Economic Cooperation and Development) informs us that, at the outbreak, China had 4.3 hospital beds per 1,000 people; Italy had 3.2. South Korea and Japan had 12.3 and 13.1, respectively. The United States, by comparison, has 2.8.  Less than Italy!!

Yikes!!

Now you can see why the strategy here, in the good ol' USA, is to "flatten the curve." Lots and lots and lots of people are going to contract the disease, but we don't want them to all contract the disease at once. We want to spread the infections out over time. Dr. Anthony Fauci, who appears to be the well-informed, calm, level-headed professional orchestrating the US response, explains it this way.
If you look at the curves of outbreaks, they go big peaks, and then come down. What we need to do is flatten that down. That would have less people infected. That would ultimately have less deaths. You do that by trying to interfere with the natural flow of the outbreak.
I think Dr. Fauci meant to say "fewer people" and "fewer deaths" rather than "less people" and "less deaths," but I quibble. More to the point, I think that Dr. Fauci was careful to follow "less infected" with a period rather than "at any point in time." It's not at all clear that the "flatten the curve" strategy is intended to lead to fewer infections. It is clear that the strategy is to spread those infections out over time, so that our hospitals can manage the most severe cases.

There are now many images out there showing the "flatten the curve" concept in graphical format. I offer one of them below.


Notice that the generic red and blue curves follow William Farr's Law. New cases appear slowly at first, intentionally, to lure the sleepy populace into a sense of complacency. Then the rate of new cases increases very rapidly, until the rate levels off because the stupid virus overdoes it and creates herd immunity. Thereafter the rate of new cases decreases rapidly. Finally, the rate of new cases approaches zero, and we tally the dead.

It is clear that, if our national strategy is to be successful, the peak of the blue zone will require fewer than 2.8 hospital beds per 1,000 people. What is left unsaid from the chart is how high the peak of the red curve might be. That peak might be very, very, excruciatingly high. As a recovering engineer, I suggest all such charts should, in the future, be labelled "Caution. Not drawn to scale." I'll go first.


For emphasis, I used red lettering, all caps, and exclamation marks. You can't miss it.

Also left unsaid by the chart, though suggested by it, is that the "flatten the curve" strategy will not necessarily reduce the total number of infections. Instead, the strategy is focused primarily on reducing the total number of deaths. By not overwhelming the healthcare system, we can reduce the number of deaths while the virus runs its course, but runs it more slowly.  The chart needs further clarification. I'll go first.


Warning! I may be wrong with my next observation. I might be way off base. If I am, I ask that any highly-qualified epidemiologist reading this post politely correct me in the comments.

I suspect that the "flatten the curve" strategy is actually the "best path to herd immunity since we won't have a vaccine for a while" strategy. The authorities simply refuse to use my more appropriate name for the strategy because it is a bit too long, not quite as snappy, and a whole lot scarier. I suspect they want to ease us into the herd immunity realization slowly, so that they can flatten the curve.

Flattening the curve is not the only strategy out there. There is, or at least was, what I'll call the impenetrable barrier strategy. Don't let any cases into the country and no one will get sick. In today's world though, that simply wasn't possible. The reason for restricting travel is not to prevent entry of the virus, but to slow it down, to flatten the curve.

There is one other strategy. I'll call it the "early mammal hunkering down" strategy. To explain it, we need to go back 65 million years to the age of the dinosaur. (You should keep in mind that your tour guide is neither a paleontologist nor an evolutionary biologist.) Way back then, the earth was very much like a giant, spherical Thomas's English Muffin with lots of nooks and crannies. Early mammals, with their disproportionately large brains, were smart enough to hide in the nooks and crannies, thus to keep from being eaten by the dinosaurs, with their disproportionately large teeth, small brains, and tiny arms. In this insightful analogy, the early mammals were today's humans and the dinosaurs were the coronavirus. Completing the analogy, the early mammals decided to hunker down and stay hunkered down until a vaccine, in the form of a giant meteorite, hit the planet and wiped out the the dinosaurs, a.k.a. the coronavirus. Then the early mammals unhunkered and evolved into us. That's the only reason you're able to read this. Q.E.D.

Again I may be wrong, but it seems to me that China is aggressively pursuing the "early mammal hunkering down" strategy. It's like Whac-A-Mole. Knock down every case that pops up. Don't let cases spread. You must literally bar people in their apartments, with metal bars outside their doors so they can't leave until some government official remembers them (with a bureaucratic "Oops!") and chooses to remove the bars.


You must literally drag people from their homes and families to quarantine locations, where they will be released only when and if the government decides you are to be released.

 

Under a government that assigns a social score to each of its citizens, it must be quite easy and socially responsible for panicky and vengeful individuals to see that any unwanted person is barricaded or extracted.

There are massive downsides to this early mammal hunkering down approach, even beyond the grave issue of social cost. Among the massive-est of downsides is the possible cratering of the economy, darkening the skies with gloom and impoverishment, increasing rather than decreasing the death and misery taxes, fees, and surcharges that will be extracted by the virus.

And, to top matters off, the early mammal hunkering down approach may have a fatal flaw. To the extent that the aggressive response rapidly shuts down the virus, the society that is being forcibly hunkered cannot develop herd immunity. Once the hunkering conditions are relaxed, and the mammals begin to reappear from their nooks and crannies, the virus is still out there, at least somewhere on the same planet, lurking, waiting, searching for the tiniest hole in the not-so-impenetrable barrier. The recently unhunkered populous will need to be forcibly hunkered down again, and again, and again. Rinse, lather, repeat. Over and over. Ad nauseam.

I suspect, therefore, that China's early mammal hunkering down strategy is coupled with some wishful thinking, which might come true. Their strategy may indeed lead to the minimum number of lives lost IF a vaccine or an effective treatment appears soon.

In the US, the strategy is to implement far less harsh measures that will flatten the curve. We don't want to drive the curve too quickly all the way back to zero. We want to flatten the curve. It's all about flattening the curve. Flatten the curve and save lives. Flatten the curve and develop herd immunity. Flatten the curve, but not at full speed ahead, rather at one-half or one-quarter speed ahead. If a vaccine or an effective treatment appears soon, that will be great. If not, we will develop herd immunity and move on with our lives without the dismal prospect of recurring infections.

Now, just in case the discussion has been insufficiently depressing, we will now plumb the depths of discouragement by considering how many of us might succumb as we develop our herd immunity. Bear in mind that it is not necessary that anyone at all die for us to achieve herd immunity. Sadly,  tragically, some people certainly will die of the disease, and many people may. Their deaths, however, will have little or no impact on the rate at which we develop herd immunity.

What we need to do, as individuals and as a society, is figure out how to minimize the number of deaths while we develop our herd immunity. I'll begin by using the wonders of math to estimate the worst case scenario, then we'll look at how we can improve on that number. Be forewarned, the worst case scenario is really bad. Also be fore-encouraged, because we can and will do much better than the worst case.

We already know, based on our deep understanding of Ro, that 60% of us must get infected and survive so that we, as a society, can develop herd immunity. We only need multiply our total population of 325 million by 60% and then by the case fatality rate (CFR) to get an estimate of how many of us will die along the way. To know the CFR, you have to know both the number of deaths cause by the disease (relatively easy to obtain) and the number of people who have survived or died of the infection (much harder to obtain).

Because South Korea has such an effective testing system in place, it is probably best to base a CFR on their numbers. As of 11 March 2020, South Korea had reported 7,755 cases and 60 deaths. That's a CFR of 0.77%. Multiply that by 60% of 325 million and were looking at 1.5 million dead.

Yikes!

We need to reduce that number, big time. Big, big, big time. We can begin by focusing on a coronavirus loophole. The coronavirus loophole is that it kills a disproportionately high number of old folks, such as your beloved Skeptical Juror and his beloved Skeptical Spouse. So widely recognized is this loophole that a few millennials have labelled the disease as a "boomer remover." While it's clever, it is not particularly helpful. Words can still hurt.

Business Insider has been more helpful and less hurtful. They published the Korean CFR by age group. I present that useful chart below.

covid 19 death rate by age south korea 3 11 20

There's very good news. Young children and adults seem to be at little risk of dying. That is not always the case with a pandemic. Children are frequently at greater risk than other groups. Furthermore, the 1819 Spanish flu took out young adults at a disproportionately high rate, just when World War I was taking them out almost exclusively on the battlefield and in military hospitals.

There's still more good news in the chart. Middle age adults seem to be faring reasonably well. Those people beneath fifty are no greater risk than the general population is during a regular seasonal flu.

Now, if we can determine the age distribution within the U.S., we can perform the dreadful task of distributing the 1.5 million deaths by age group, assuming each group was infected at the same rate. The good folks at statisa.com provide a chart that gives us the insight we need.


The data are reportedly accurate as of 1 July 2018. The numbers in the horizontal bars are in millions for both men (blue) and women (black). The total population based on summing of all the values in each of the horizontal bars is 327.14 million. I've been assuming a population for the U.S. of 325 million.

So that you won't have to, I've aggregated the numbers into age ranges matching those used to report the South Korean CFR values by age range. Now, to serve you even better, I've put it all together, below, to calculate the number of U.S. deaths by age required to get us to herd immunity, assuming 60% of each population group will be infected.

0-29 years: 127.5 million x 60% for herd immunity x 0% CFR = 0 deaths
30-39 years: 43.69 million x 0.6 x 0.001 =   26,214 deaths
40-49 years: 40.46 million x 0.6 x 0.001 =   26,076 deaths
50-59 years: 42.83 million x 0.6 x 0.004 = 102,792 deaths
60-69 years: 37.41 million x 0.6 x 0.015 = 336,690 deaths
70-79 years: 22.66 million x 0.6 x 0.043 = 584,628 deaths
80 +   years: 12.68 million x 0.6 x 0.072 = 547,776 deaths

The not so grand total is 1,622,376 Americas dead of coronavirus. That number is reasonably close to the 1.5 million deaths calculated by multiplying 60% of our total population by the CFR for all of South Korea, 0.77%. The "slight" difference (of 122,376 deaths) is apparently due to slightly different age distributions between our two countries. I'm afraid that the higher number, the one based on population distribution, is more defensible from a mathematics standpoint.

From here, you can see the coronavirus loophole. If we somehow infected only the youngest among us, then the total number of deaths would be greatly diminished. We need 60% of 325 million to get infected and survive. We have 127.5 million with a CFR of zero, and 84 million with a CFR of a flu-like 0.1%. To ruthlessly reach our herd immunity level with the fewest number of deaths, we would ruthlessly infect everyone under 29 years of age and 81% of those between 30 and 49 years of age. The total number of people infected would be just over the magic number of 195 million. The number of deaths would be:

0-29 years: 127.5 million x 100% for herd immunity x 0% CFR = 0 deaths
30-39 years: 43.69 million x 0.81 x 0.001 =   35,389 deaths
40-49 years: 40.46 million x 0.81 x 0.001 =   32,772 deaths

The still not so grand total would be 71,161 Americans dead of coronavirus. That's only 4.4% of the 1.6 million that would die in the absence of such a ruthless loophole approach.

There are a number of assumptions involved with this ruthless loophole calculation, and the resulting 71,000 dead is almost certainly too low, even ignoring the moral implications.

In the real world, Americans are already beginning to recognize the coronavirus loophole. They can't quantify it, but they are nonetheless already acting on their intuitive feel. The older among us are more aggressively quarantining themselves than are the younger. The younger among us are stepping to the plate. They are, for example, the primary shoppers / drivers for services such as Instacart that bring groceries and supplies directly to one's doorstep. Some of them have taken to wearing masks and gloves, for the betterment of all involved, but their smile and enthusiasm is still obvious.

Yesterday, as the Skeptical Spouse and I returned from a safe outing, our younger neighbor approached us and volunteered to do any shopping we might need. I informed him that we were already well prepared. I thanked him. I asked him if he offered because he recognized that we (the Skeptical Spouse and I) are part of a high risk group. He acknowledged that was the case. I thanked him again for his thoughtfulness and compassion.

So ...

My prediction right now is that, in the absence of a vaccine or an effective treatment, somewhere between 75 thousand and 1.6 million of us Americans will succumb to the coronavirus, even if we flatten the curve. So too will too many others from other countries. We humans are an ingenious lot, though. When we cease our bickering and marshal our resources against a common enemy, we are formidable.

In upcoming posts, I will address the promise of vaccines and effective treatments. I will offer thoughts on how you, as an individual, can pitch in.