Author: chogan@directresearch.com

Ionophore transmitting metal ion across cell membrane.  Source:  Wikipedia

I’m going to keep updating this continuously, so you might check back in a few hours.

Back in Post #562 (March 19 2020), I reviewed the evidence for hydroxychloroquine, as one of three drugs that might prove useful for COVID-19.  Search “An old drug that works in vitro (in a test tube).  Not yet proven in humans, but it sure looks like it ought to work”.  I was flip enough to describe it as “Golly, that’s like “take two aspirin and call me in the morning.”“.

It certainly had potent anti-viral properties in vitro against SARS (2003) and SARS-CoV-2 (COVID-19).  The drug was already known to concentrate in certain organs, including the lungs.  A small study in France suggested some efficacy in humans.  The Chinese had included it as one of very few drugs approved, in that country, for COVID-19.

All the elements of likely effectiveness were in place.  (And, separately, as it turns out, virtually all of those older-line malaria drugs, and the current malaria drug of choice, also have significant anti-viral properties, suggesting some underlying mechanism behind all of them. )

So I’ve been looking for further evidence to pop up.

There are now two separate reports — case studies from one physician, and professional society endorsement — suggesting that it does work.  It’s well worth your while to check out both of them.  One physician says that the drug must be used with zinc to be effective.  That’s a new one on me, and I’d love to understand what the presumed mechanism of action is there.

First, here’s an LA physician.  He’s the guy who says, combine with zinc.  His results sound a little too good to be true, based on the efficacy of other anti-virals in late-stage illness.  But you never know.  I’m going to spend a little time to see if I can track down the presumed mechanism that involves zinc.

Second, here’s no less an authority than the American Thoracic Society of New York (a physician professional society) endorsing off-label use for severely ill COVID-19 patients.  (The actual guidance document, referenced there, is literally from the American Thoracic Society.)

Just thought I’d pass along a little good news for a change.  And let you know that, despite what you may read, yes, there was a good chance this would work.  But nobody anticipated the results that the LA doctor reported, with combined with zinc.  Don’t get your hopes up, but he does seem to be a legit doc, legitimately taking care of COVID-19 patients.

Be aware that there are also studies showing no effect.  So the evidence is far from crystal clear.  No less an authority than Dr. Anthony Fauci says we should not assume that this is a “knockout drug”.

But I have to say, for that LA doc to say — eight hours later the patients taking the drug in combination with zinc were symptom-free.  That’s a strong claim and is easily tested.  And a requirement for requirement that something else be present — something already found in varying levels in the body — would be a plausible way to explain variations in success rates across studies, and then a claim of huge impact with explicit supplementation.

Update 1:  Well, about that zinc thing.  Sure enough, there was already a clinical trial underway using a combination with zinc.  The don’t do stuff like that at random, so presumably some smart cookie had some understanding of probable mechanism of action.  That was an observational trial for using this drug prophylactically (to prevent healthcare workers from getting coronavirus).  But at the bottom of the listing is a raft of scholarly articles on this.

Update 2:  And here’s an MD from New York who, separately, identified this drug, in combination with zinc, as an effective medication at preventing hospitalization of COVID-19 patients.  It’s always good to see some independent confirmation, even if it’s just a series of 200 cases for one physician.

OK, weirdly, zinc does in fact bind to hydroxychloroquine.  That’s been flagged as a potential drug-drug interaction.

And, it does potentiate the uptake of zinc by human cells, and that response is unique to zinc (as opposed to other metals.).

Apparently the FDA quietly approved the use of hydroxychloroquine for COVID-19 more than week ago, on an emergency basis.  I didn’t know that.  So it’s not even an off-label use now.

Aha!  Here’s an explanation for a potential mechanism right here, based on a couple of scholarly studies — read the comments.  If true, hyroxycholoroquine’s main role in humans is as a zinc ionophore — something that transports zinc ions across the cell membrane and therefore substantially raises within-cell zinc concentration.  Heck, it’s already been demonstrated in vitro. 

Ah, here’s what an ionophore is.  Interestingly, Wikipedia does not list a single zinc ionophore.

Based on this, if it really is the zinc, any consumable zinc ionophore that concentrates in lung tissue would be helpful.  Makes me wonder if there others that are as effective as hydroxycholorquine.  Makes me wonder if the reason that all those old-line (and current) anti-malarials have the same underlying mechanism of action.

Hilarious:  Quercitin is a zinc ionophore.  That’s a flavonoid, which you first met in my post on folk medicine (Post #552).  In fact, that’s the single most common flavonoid in the diet.  I think I’ll get my order in at Amazon before that’s vacuumed off the shelves.  Pretty sure I’ve got some zinc pills around here somewhere …

Two other zinc ionophores I’ve never heard of, but in vitro anti-viral activity was demonstrated.

So in addition to “eat your fruits and vegetables” (flavonoids), we can add green tea (epigallocatechin-gallate, another flavonoid) and zinc pills to my roster of folk medicines.

That’s not medical advice.  That’s just what I’m going to do, based on the observation that zinc supplementation apparently greatly enhances the effectiveness of hydroxychloroquine, and that zinc apparently does show in-vitro anti-viral effectiveness, if it can be transported into cells in high enough concentration.

Probably can’t hurt, if done in moderation.  Might help.  Why not?

1:  Total tests required = number of batches, plus all persons in one batch.

Batches = 500/10.  Persons in a batch = 10.  So:

1A: (500/10) + 10 = 50 + 10 = 60 tests needed under TTTT.

1B: 500 – 60 = 440 tests saved.

1C:  440/500 = .88 = 88% reduction in tests

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2)  Total tests required = number of batches, plus all persons in one batch.

2A: T = (E/N) + N

2B:  E = 500, N = 10, T = (500/10) + 10 = 60.

3)  Optimum batch size is the square root of total employment E

3A)

T = E*N^-1 + N  (formula from step 2)

dT/dN = -1*E*N^-2 + 1 (calculate the first derivative (slope) with respect batch size).

Now minimize the number of tests by finding the point where the derivative is zero.

-1*E*N^-2 + 1 = 0  (Set derivative to zero).

-1*E*N^-2 = -1  (Subtract 1 from both sides).

E*N^-2 = 1 (divide by -1).

E = N² (multiply through by N-squared).

N = SQRT(E)  (Take square roots)

The optimum batch size is the square root of total hospital employment E.

Second derivative is positive by inspection, so this is a minimum.

3B)  For Euler Hospital’s 500 employees:

Optimum batch size:  SQRT(500) = 22.36

Number of tests = 2*SQRT(500) = 44.72

Ignoring rounding.

4)  Download this Excel file: TTTT numerical analysis

The answer is somewhere between 22 and 23 for the optimum batch, requiring a around 44.73 tests.  So that matches the calculus result to within rounding error.

5)  Gauss Hospital in Binary, Arkansas.

5A) 2*SQRT(256) = 32 tests required for optimized TTTT

5B)  Gauss hospital should consider using a binary search instead.  At each step, divide the employees in half, test both halves, and repeat on whichever half tests positive.  Employees at each phase:

1. 256, divide in two, test both
2. 128, ditto
3. 64, and so on …
4. 32
5. 16
6. 8
7. 4
8. 2

5C) On the eight tier, you have two employees, you test them both, and one of them is positive.  You have a total of 8 tiers (8 rounds of testing), each tier requires two tests, so this requires a total of 16 tests.

6) It matters much more to larger hospitals.

Flat-footed testing of every employee required E tests.  Optimized TTTT requires 2*SQRT(E) tests.  Calculate the ratio of the two — the smaller that is, the more that optimized TTTT saves you, in percentage terms.  Either calculate that for a few different values of E (numerical analysis approach), or inspect the derivative of that with respect to E (loosely termed here the calculus-of-variations approach).

Ratio = 2*SQRT(E) / E

Ratio = 2*E^1/2*E^-1 (re-expressed using exponent notation) 

Ratio = 2*E^-1/2  (when you multiply the numbers, you add the exponents)

dRatio/dE = -E^-3/2  (take the derivative, and note that it is always negative)

So the ratio falls as E gets larger.

Examples:

50 beds, ratio = .28, optimized TTTT requires 28% as much testing as the just-test-everybody approach.

500 beds, ratio = .09, optimized TTTT requires 9% as much testing.  (Recall from question 1 that standard TTTT had 88% savings, so standard TTTT only required 12% as much testing.  So, true to its name, optimized TTTT not only requires less testing than test-everybody, it requires less testing than standard TTTT).

5000 beds, ratio = .03, optimized TTTT requires 3% as much testing

7)  The worst-case scenario occurs if your infected employers are spread as thinly as possible across your population.

7A)  To find 2 infected employee:  50 batches, plus 10 in two batches = 70 total.

7B) To find 10 infected employees:  50 batches, plus 10 in 10 batches = 150 total

7B) To find 60 infected employees:  50 batches, plus 10 in … well, there’s only 50 batches so … that’s 550 tests?  No,wait, that’s dumb.  You end up having to test everybody anyway.  The batch tests are a waste.

Just test everybody from the get-go.  The answer is 500 tests.

8)  We’ve just shown that the TTTT method still functions, even if you have more than one infected employee, it just requires more tests.  And, it can be wasteful if you reach the point where you’re going to have to test every employee anyway.

Optimized TTTT simply wastes fewer tests in the case of 60 sick employees, because you only have 23 wasted batch tests.  But note that optimized TTTT, due to the higher batch size, becomes wasteful at lower infection rates.  With optimized TTTT, in this example, once you have 23 infected hospital employees, you end up testing everybody.

Binary search will eventually find everybody, but it is a total and hugely inefficient waste of time at high infection rates, because instead of performing two tests at each tier, you have to test every group.  It doesn’t let you discard groups of people until you get way down the tier structure.

Let me just hack through it with 32 sick employees at Gauss General.  Worst case scenario, it requires 190 tests.  You don’t rule out anyone until you get to the next-to-the-last tier.  If you knew the infection rate was this high, you’d just go straight to smaller batches (start at tier 6) and only use 128 tests.

1. 256, 2 batches, 128/batch, 2 tests required
2. 256, 4 batches, 64/batch, 4 tests required.
3. 256, 8 batches, 32/batch, 8 tests required
4. 256, 16 batches, 16/batch, 16 tests required
5. 256, 32 batches, 8/batch, 32 tests required  — at this point, every group has one.
6. 256, 64 batches, 4/batch, 64 tests required — half the test are now negative
7. 128, 64 batches, 2/batch, 64 tests required — you have isolated the 32.

 

Source:  Wikipedia.

I’m writing this one just in case your kids ever wonder what math is good for.

Germany has had a remarkably rational, effective, and organized response to the COVID-19 pandemic.  One thing I found out yesterday is that they test every hospital employee for the virus.

I was floored.  How can they do that? U.S. hospitals have about 5.2 million employees on payroll.  If you toss in volunteers, and physicians and others with hospital privileges, it’s safe to say that, in the U.S., you’d be talking about testing at least 6,000,000 people on a routine basis.

That would require about six times more tests than the US has done, in total, so far.  Just to do one round of testing on all US hospital employees. US public health labs have done fewer than 200, 000 test.  If you toss in a guess as to all the testing done in private labs, you’d still come up with somewhere in the neighborhood of 1,000,000.

How on earth can Germany do that, then?  I mean, sure, they probably have more test per capita than we do.  But, still, that’s a pretty big gap between what the entire U.S. lab system appears to be able to do, and what the Germans routinely do.

What’s their secret? Continue reading Post #605: Real-world word problems: Teutonic two-tier testing

I’m relying on the NY Times extract of the John’s Hopkins coronavirus counts, for this. Plus the 6 PM count as posted on the Hopkins map.

I added a seven day moving average to try to smooth out the day-to-day variations.  On any given day, that’s just the sum of counts for the last seven days, divided by seven.  Sometimes that lets your eye perceive any change in the trend that might otherwise get lost amid the daily ups-and-downs.  (But that smoothness comes at a cost of being “late”, in the sense that if there is some change, the seven-day moving average takes seven days to reflect that fully.)

For Virginia as a whole, by eye, we’re still in the “exponential growth” phase.  That gray line is “concave upwards”, like the side of a bowl.  And it could just be wishful thinking on my part, but the Fairfax seven-day moving average appears qualitatively different.  That looks concave-downward to me — like the peak of a hill. Starting to break away from exponential growth, by eye, sometime around 3/28-ish or so.

Obviously, that could be wishful thinking.  You eye can play tricks on you. And we’d need another week to at least to confirm it.  But for now, at least, Fairfax County does not appear to be experiencing exponential growth.  We’re getting more new cases each day, sure.  And total cases continue to rise.  But not, for the moment, at an accelerating rate.

Well, we’ll see.

Please wear a face covering of some sort when your are in public, near others.

 

Following on to my prior post, I’m already getting blowback because people think that any home-made masks need to go to hospital workers.   The upshot is that we’re going to have a bunch of older people, around Vienna, who refuse to mask up because they think they need to give any home-made mask to the local hospitals.

Let’s ask the Inova health care system.  We don’t even have to ask, because they’ve already addressed this issue.  Note the boldface.  That’s a dead giveaway that this issue has already become a nuisance for them.  They really, really don’t want you bothering them with your home-made mask.

They want your money.  They want your blood.  And if you have it, they will accept full, unopened boxes of genuine surgical masks and gloves.

They don’t want your homemade mask.  They have genuine N95s and surgical masks.  Even if we get to the point where they have to re-use N95s, those will be VASTLY BETTER than any mask your or I could make.  It would be frankly illegal for them to use home-made mask if they have any other alternative whatsoever.  If you look at CDC guidance on this issue, of all the things hospitals are allowed to do, use of homemade masks is dead last, following going bare-faced behind a face shield.

Use of homemade masks puts hospital staff at unnecessary risk, so long as there is any other alternative.  The only time hospitals can legally consider use of home-made masks is in the event that the only alternative would be to go bare-faced, i.e., literally no protection.

And now that a) everybody knows how to re-used N95s safely, and b) we are going to allow China to flood the US with cheap KN95s, not only does Inova not need your home-made mask, they will never need your home-made mask.

If you want to make a mask, absolutely the best thing you can do with it, in this situation, is wear it.

Rule #1:  Don’t be the dumbass who fills the next empty hospital bed.  Do what the CDC now tells you to do.  Wash your hands, keep your distance, no crowds, disinfect high-touch household surfaces, and so on.

And now they’re telling you to wear a mask when you go out of your house.  The best thing you can possibly do, right now, is to follow the CDC’s guidance.

Source: COMMENTARY: COVID-19 transmission messages should hinge on science. March 16, 2020, Lisa Brosseau, ScD, author, on line at the University of Minnesota Center for Infectious Disease Research and Policy.

In the illustration above, Person A has COVID-19 but doesn’t know it.  He’s talking loudly and at close range to person B, who soon will have COVID-19.  Person C is standing to the side, wondering why none of them are wearing masks.  Presumably, this snapshot was taken in an android nudist colony.

In all seriousness, go read that article if you want to know what’s probably going on with the continued spread of COVID-19.

Continue reading Post #602: Radical change in CDC guidance, and implications for your behavior.

Note to regular readers:  This is a compendium of everything I think I know about the current pandemic.  Some material repeats prior posts.  I am hoping to get wider distribution of this once it is finished.  But I have been told that this is a hard post to read.  All I can say is, read it anyway.

By Christopher Hogan, Ph.D.

If you don’t want to spend a month slowly suffocating to death, the CDC has a tip for you:  Wear a mask.  Wear one any time you’re around people other than your immediate family.  That won’t guarantee that you’ll avoid dying from COVID-19 (SARS-CoV-2), but it will improve your odds.  And it will improve everyone else’s odds as well.

Sure, you need to keep doing everything else that the Centers for Disease Control (CDC) has recommended.  Wash your hands and maintain your distance.  Wash your hands and avoid touching your face.  Disinfect commonly-touched surfaces in your home.  And then wash your hands again.  But now, in addition, wear a mask whenever you are around people other than your immediate family.

As I write this, it looks like we’re about a week away from inevitable mass deaths in New York City.  That’s going to happen when they run out of ventilators and they start just letting people die.  Not because they want to, but because there will be no other option.

We don’t know, yet, whether other parts of the country will end up in that position or not.  Including the Washington DC area.  We’ve taken the gamble that “social distancing” will break the back of this pandemic.  But in fact, nobody knows whether our “soft” approach to social distancing will slow the spread  enough.

In effect, we are in the middle of a vast experiment.  Performed ad-hoc, one city or state at a time.  And we’re the guinea pigs.

Or maybe sheep would be a better analogy.  Because, by and large, We the People have been sitting around, hoping that our various government leaders will solve this problem for us.  And we are now finding out that, outside of the US Army Corps of Engineers, not only is the Federal government not helping, it has actively been getting in the way.

In two critical ways, business-as-usual mistakes by two Federal agencies have made things vastly worse.  And those two key mistakes dovetail in such a way as to increase your risk of death materially.

But before I get into that, let me remind you of what, exactly, we’re talking about.  In so far as a person can know, absent first-hand experience.

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What will it be like to die from COVID-19?

The short answer is that it will take a while, you’ll be alone, and you’ll be on a ventilator as you slowly suffocate to death.  That means that you will be confused, unable to move and likely delirious when you are conscious.

And that’s the best-case scenario.  That assumes you get into a hospital, a ventilator is available, and the drug stocks hold out.

First, it will take a while.  World Health Organization analysis of the Chinese experience suggests that, among decedents, it typically takes two to eight weeks from diagnosis to death.  Given that this type of data typically has a “long right tail”, a good guess for the median would be about three-and-a-half weeks.  But that’s awkward to say, so let me just say “about a month”.

Second, you’ll be alone:  You’ll never see your family again.  Hospitals are no longer allowing visitors, almost without exception.  Looking at Inova as an example, they say they make an exception for (e.g.) some end-of-life situations.  But not in the case of COVID-19.

"Visitation will not be allowed for suspected or confirmed patients with COVID-19."

The upshot of that is that if you die in the hospital, from the time of admission to the time of death, you (or your loved one) will never see family or friends again.  You won’t have any way to know that, ahead of time, because you don’t enter the hospital expecting to die.  But that will be the outcome, after the fact.

Third, you’ll be on a ventilator for some time, with all that entails.  In most if not all cases, they have to dope you up, eventually, so you don’t “fight the ventilator”.  So, you’ll be not-quite-unconscious, and not-quite totally unable to move.  And being in that ICU environment for any length of time makes many people literally go crazy, as in, experience delirium (as in ICU psychosis).

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Two big mistakes.

OK, with that firmly in mind, let’s move on to the two big mistakes our Federal government has made.  So far.  And a third big mistake that we need to prevent. And then, finally, what we can do, for ourselves, as a sort of mid-course correction.

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Mistake 1:  The N95 mask shortage and the Food and Drug Administration rules

I used to be self-employed as a health economist.  And  I still get a lot of business-to-business emails.  One of those landed in my in-box yesterday.  It was a legitimate offer to sell me up to 5 million N95 and KN95 masks per month.  If I only need a few — 100,000, say — they could get them to me in three to five days.  Larger orders would take a bit. The masks cost about $3 each.  Free shipping.

My first thought was, what alternative universe did that come from?  All I read is that we have a huge shortage of those N95 masks.  So much so that it is our patriotic and ethical duty to leave those for the health care workers.  You, as a good citizen, need to accept a small additional risk of death, so that front-line health care workers and first responders don’t have to take a much larger risk.  Just look on Amazon, and you’ll see those clearly marked “Hands Off” for the general public.

If they’re in such short supply, how can this joker offer me 100,000 masks by next Wednesday?  (Not me personally, of course, he mistook my business as one that actually provides health care.)  And what the heck is a KN95, anyway?  I thought they were called N95.

Well, as it now turns out, it looks like that shortage was, in some large part, the result of our shooting ourselves in the foot.  And now, months into the US portion of the pandemic, the Food and Drug Administration has graciously, if ever-so-slowly and ever-so-grudgingly, decided to stop doing that.

The FDA would not allow Chinese-made N95-equivalent masks (“KN95”) to be used in US hospitals.  If you look at the full specs for N95 and KN95 (here, from 3M, in a .pdf), they are virtually identical.  I believe the FDA’s concern was not about the performance of the masks, but instead about the potentially insecure supply chain (i.e., you might get sold knock-offs).

But as of two days ago, the FDA changed its mind.  Apparently after numerous people yelled at them for the stupidity of their actions, including a petition that collected thousands of signatures of front-line health care personnel. Just read it on Buzzfeed.

And as a result, yesterday I got that email.  It was from a well-established firm whose main line of business is helping other companies sell to the Federal government.  They’re deal-makers, for want of a better term.  And right now, they’re in the business of arranging import of KN95 masks from China.  They were ready to go the day the FDA dropped the ban.  And I doubt that they were the only ones in that position.

So I expect our mask shortage to begin easing soon.  Through the simple expedient of buying them.  And it only took us a few months to think of doing that.  Better late than never, I guess.

For the time being, consumers should still refrain from buying them.  Leave what we have for health care workers and first responders.  For now.

And, as far as I can tell, anything you want to know about masks, that is known, you can find on the Smart Air website.  If you have a question, look there first.  I have no idea who those folks are, but I am glad they are sharing their knowledge.

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Mistake 2: CDC guidance and its misunderstanding of how COVID-19 spreads.

Let’s briefly review what has changed, now that the CDC has quietly added “wear a cloth mask” to its guidance to the public on dealing with COVID-19.

A week ago, CDC was saying that COVID-19 was primarily spread by droplet transmission from symptomatic individuals.  And so, in effect, stay out of range of droplets when an obviously sick person coughs or sneezes, and hey, you’ll be OK.  Keep your distance and wash your hands.  Social distancing will keep you safe, so there’s no need to wear a mask.

Anyone who was paying attention realized that couldn’t possibly be right.  You really couldn’t explain the spread of disease that way.  I mean, do you really think they let somebody who was coughing and hacking anywhere near the Prime Minister of Great Britain in the past few weeks?

Even for hoi polloi, that explanation wasn’t credible once social distancing was in place.  Based on the handful of shopping trips I have made in the past three weeks, nobody is stupid enough to be out in public with symptoms of COVID-19. The idea that this is mainly spread by people coughing and sneezing is just plain nuts.

Not-being-sick-in-public is now a rigidly-enforced social norm.  Last time I was in the Safeway, somebody, somewhere in the store, coughed.  And we shoppers reacted like a herd of startled deer.  Heads came up.  Eye contact was made.  Everybody made that little “wasn’t me” gesture.  These days, you’ll get some hard looks if you so much as clear your throat loudly in the grocery store.

Finally, just do the simple arithmetic.  COVID-19 has a median incubation period of 5 to 6 days, based on the Chinese experience.  In Fairfax County, my home, schools have been closed for more than three weeks now.  And yet, the count of cases continues to climb at an accelerating rate, with Fairfax expected to top 400 cases today.  Do the math.  We’re now seeing our third or fourth generation of new infections since the start of serious social distancing.  If “stay out of range when sick people cough” was all it takes, we wouldn’t be seeing this.

Today?  Now CDC says, well, maybe this is being routinely spread by asymptomatic individuals.  People who don’t look sick, feel sick, or sound sick.  Maybe you don’t have to cough or sneeze, because most people spew tiny droplets simply by talking.   And — not clear if they are saying it or not, but true nevertheless  — clearly some of this is aerosol spread, for which, indoors, there is no “out-of-range”.

And so, as their understanding of the facts has changed, the CDC has changed its mind.  Everybody needs to mask up in public.  Social distancing is not enough.  Particularly not when the head of the Chinese CDC called failing to require masks in public “the big mistake” that the US and Europe were making. Presumably, he would know.

So the CDC is finally getting it.  This disease is a lot easier to spread than they thought.  And it’s not being spread by obviously sick people.  So everybody needs to wear a mask, all the time, when you are in public around others.

In addition to droplet transmission, we need to start having public discussion of the potential for aerosol (airborne) transmission (particularly close-range aerosol transmission) and superspreaders.   Because at this point, it’s clear that the CDC isn’t going to be doing that despite clear evidence that it has occurred.  And, so, without an explicit warning from the CDC, we risk that it will continue to occur.

(If you read nothing else, go read the University of Minnesota, Center for Infectious Disease Research and Policy piece that explains the importance of close-range aerosol transmission.  My takeaway from that is that, arguably, the stupidest thing we can be doing, right now, is to stand six feet apart and talk at each other, loudly, with no masks on.)

Everyone needs to read about the safely-conducted, properly-socially-distanced, hand-sanitized, no-hugs choir practice that resulted in 45 infections and two  deaths (so far), out of 60-member choir.  That’s aerosol spread.  There’s no way to be sure, but that’s plausibly due to a single infected individual who was a superemitter of aerosols.

And that’s the kind of event that may continue to happen if we don’t educate ourselves about it. (But in groups no larger than ten, these days, in Virginia).  Because at this point it’s clear that the CDC isn’t going to do that for us.  Possibly for fear of panicking the public.  Possibly because they believe their epidemiological evidence rules that out as a common transmission route outside of the hospital.  (But inside the hospital is a different story.  The threat of aerosol transmission is the main reason they need those N95 masks instead of common surgical masks, and why the US Army Corps of Engineers has worked up an expedient way to convert hotel rooms to negative-pressure rooms for housing the overflow of COVID-19 patients.)

But we also have to say what needs to be said:  So far, the CDC has been dead wrong about how this virus routinely spreads.  They kept telling the public that coughing and sneezing by clearly sick individuals was the problem.  And so, social distancing and hand washing was the answer.  You can’t really blame the CDC, because droplet transmission by symptomatic individuals is what the WHO analysis of China (cited above) said.  But it’s still wrong.  And you have to wonder why, up to now, they continued to ignore the potential for widespread transmission by asymptomatic individuals.  Maybe the thought that was just too scary for us to handle?

In any case, however they got there, they have now come to realize that a lot of the spread must be via asymptomatic individuals. As had anyone else who has been paying attention.  Because nobody with symptoms of anything is going out in public any more.

But they’re still focused on droplet transmission, and they aren’t going to mention aerosol transmission.  Maybe that’s because they have evidence that strongly supports that.  Maybe they won’t mention it because they don’t want a run on the N95 masks needed to filter out aerosol-sized (five micron or smaller) droplets.  Or maybe because they think that’s just too scary for us to handle.  However you slice it, after this first about-face on the typical transmission route, I’m not sure it means anything that the CDC isn’t talking about aerosol spread.

The CDC is mum on this topic despite that certain knowledge that many historical and current contagious diseases were characterized by aerosol transmission.  Those include both bacterial disease such as tuberculosis and viral diseases such as Ebola and some forms of influenza.

And in this case, there’s an old saw that clearly applies.  It ain’t what you don’t know that gets you into trouble.  It’s what you know for sure that just ain’t so.  Every thinking American took the CDC guidance as an indication of what they knew about how this disease spreads.  And, as it turns out, that just wasn’t so.

If aerosol spread is a probable route of transmission, we’re unknowingly making a major public health blunder by standing around talking loudly to each other.  Speech generate large volumes of aerosol-sized (5 micro or smaller) droplets.  Loud speech generates more.  And singing generates those droplets at roughly the same rate that coughing does.  Which is, in all likelihood, how almost that entire choir got infected from a single choir rehearsal.

No mask that you can ethically buy right now will stop all, or even most, of those tiny aerosol droplets.  Your only option, for benefit of us all, is to try not to generate them.

So shut up when you are in public.  That’s advice the CDC needs to offer us, but can’t.  Because, for whatever reason, they won’t engage in public discussion of the potential for aerosol transmission.  We need to do that for ourselves.  So far,  “superspreader” events like that choir rehearsal are almost unheard-of.  Let’s hope it stays that way.

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The synergy of those two mistakes.

So now the CDC has added a wishy-washy bit of advice to their guidance to the public:  Wear a cloth face covering.  Wear a cloth mask, if you will.

Why cloth?  That pretty much means that every American has to make one, borrow one, or scrounge one up.  Is there something beneficial about cloth masks?  Do they perform well.

No.  The recommendation for cloth masks isn’t to protect you, the wearer, very much.  With luck, skill, and diligence, a face mask made out of cloth can be constructed so as to provide nearly as much protection to the wearer as a standard hospital surgical mask.  If you happen to make the right choice of fabric, you can filter out aerosol particles almost as well as a standard surgical mask.  But it’s a good bet that the typical cloth mask won’t come up to that standard.

Wearing a cloth masks probably does help protect others, in the event that you’re infected but don’t know it yet.  I keeps you from spreading disease by capturing or at least slowing the velocity of the droplets you emit.  So that’s a plus, and that’s the public health benefit.  But wearing a commercially-made mask would probably do a better job of that, too.

The guidance to use a cloth mask is there because the CDC is afraid of exacerbating the N95 mask shortage.  Commercially-produced masks are better (surgical mask), and sometimes vastly better (N95 respirator), than what the typical American is going to be able to whip up on the fly.  The guidance to wear a cloth mask is to keep the public from purchasing those “real” masks.

But no reputable seller has N95 masks for sale to the public.  Just look on Amazon.  See what Home Depot has done.  Any reputable entity that could channel a large number of such masks to the public has withdrawn those from the market.

And, see Mistake 1.  With the lifting of the ban on use of KN95 masks, and the realization that standard N95s and similar masks can be filter air effectively for vastly longer than a single use, with relatively little risk if appropriate protocols are adopted, it’s a fair bet that this N95 mask shortage is simply going to disappear as a factor in the future progress of this pandemic.

And yet, it’s the heart of current CDC guidance.  Will that change in the near future, if the mask shortage abates?  I guess we’ll see.

What has me truly irked, of course, is how the FDA exacerbation of the N95 mask shortage dovetails with the CDC decision not to recommend masks in public.  If you think about it, if these two agencies had done this differently, there’s some chance that we could have all been wearing KN95 masks whenever we were out in public.  Or, maybe, all the people in New York City could have been wearing KN95s whenever they were in public.  And maybe it’s not too late to make that happen.  Bet that would have altered the course of this some.

If the importation of large numbers of KN95 masks from China resolves the current N95 shortage, the next city to approach the situation that New York is in will have the opportunity to issue those effective, commercially-available masks to citizens and enforce wearing them in public places.  Before they run out of ventilators.

The whole point of an N95 mask (technically, respirator) is that, when properly worn, very little gets through it.  It’s effective at stopping even the most difficult-to-catch size of aerosol particle (0.3 microns).  Nothing is a perfect, but that’s (very nearly) as good as it gets.  (Unless you want to wear a half-face or full-face respirator.)  And that, and hand washing, and social distancing, would seem to up the odds of breaking the back of this pandemic.  If we can solve the current and apparently self-inflicted mask shortage, we need to start thinking of the strategic deployment of those masks to the citizenry, and enforcement of public mask use.

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Will vaccine development be the next big Federal mistake?

Edit:  Upon re-reading this the next day, I think I overstated the case for skipping Phase I trials in this emergency, slightly, so let me clarify.  But I still conclude that it would be smarter to proceed directly to Phase II, in terms of total lives lost.  You will need to read the rest of this section, then come back and re-read this. 

What I forgot in the first draft of this is that vaccine trials have a unique feature:  You can use the Phase I trial to see whether or not vaccine recipients develop the appropriate antibodies.  That can prevent you from going on to Phase II, and needlessly exposing a cohort of individuals to coronavirus with a vaccine that has no chance of success.  Further, if you move directly to Phase II, and expose the patients to disease, that would confound your ability to determine whether or not patients developed antibodies from the vaccine alone.

That said, somebody needs to do the estimate of total lives lost under two scenarios:  Business-as-usual:  Take the N months required for Phase I, and ultimately distribution the vaccine X + N months down the road.  Emergency approach:  Skip Phase I, and distribute it a X months down the road. 

To some degree, that calculation depends on what you think the state of the world will be X months from now.  That is, how many people you think will die in the period from X to X + N.  If you are convinced that this will be under control, you might judge that fewer lives would be lost under business-as-usual.  If not, you’d judge that fewer lives would be lost with the emergency method.

Given that the total number of people in the vaccine trial will likely number in the hundreds, while the number of people at significant risk of dying from COVID-19 will likely still be in (at least) the tens of millions, I’m almost sure that under any plausible scenario, fewer lives would be lost under the emergency methods that skips Phase I. 

That’s all I’m trying to say.  The text of my original post follows.

So far, there’s scant information available to the public on what the Federal government is doing to produce a vaccine.  But I can tell you, from what I’ve read, and based on what we’ve seen from FDA and CDC so far, I’m not betting on seeing one any time soon.

What sets me off on this topic is the report that the Federal government was starting Phase I trials of a vaccine.  To which I said, why in the hell are they doing that?  Allow me to explain.

Drug development goes through three phases.  Phase I simply tests whether or not the drug will kill you.  Is it safe?  It doesn’t actually do anything to test whether or not it works.  (Edit:  See above.  You do test development of antibodies.)  Phase II is where you start to test whether the drug works or not, and typically tries a few different dosing regimens to see what works best.  Then Phase III re-tests whether it works, using the most promising dosing regimen.

There’s no barrier to skipping Phase I.  If the proposed vaccine kills people, you’ll find that out in Phase II.  (Edit:  And so, if the vaccine could have been discarded as ineffective in Phase I, you risk needlessly killing some of the treatment group by skipping that, but gain lives saved by delivering an effective vaccine sooner than you otherwise would.) And normally, under business-as-usual, sure, you wouldn’t want to take a risk of killing a large number of people.  So you do a small Phase I trial first.  Take a few months, go slow, don’t push it.  Just on the off-chance that what you’ve developed is particularly deadly.

But in this case, every day that we don’t have a vaccine is a day that more people die.  What are we up to now, about a thousand a day?  Is that going to double or triple when New York City hits the wall?  How long is that going to go on?

Skipping straight to Phase II risks killing a few more people than you might have otherwise.  On the other hand, how many additional deaths will result from each additional day of delay in creating this vaccine?  Has anyone even bothered to do the cost-benenfit analysis of Phase I in this case? 

Or, as I suspect, is this just another example of a Federal agency that can’t shake itself loose from its business-as-usual attitude?  On the one hand, they realize this is a national emergency. They press forward with all due haste.  But on the other hand, it never even occurs to them to skip Phase I.  Or, if it does, the people making their decisions, within their own silos, are not being forced to see the big picture.

The question of how many deaths for each day of delay is not an idle one.  That will will depend on the state of the pandemic at the point when the vaccine is ready for distribution.  Maybe our current state and local experiments in social distancing will pay off, and nobody will be dying from this 12 to 18 months from now.  In that case, sure, take your time.  On the other hand, maybe we’ll never get this fully under control, and we’ll still be looking at 1000 deaths a day, 12 months from now.  In which case, in hindsight, this will be yet a third example of business-as-usual by a Federal agency being exactly the wrong choice.

So it’s a gamble, and I’m not sure our Federal government realizes it.  Phase I makes perfect sense — if you think all the dying will be over before the vaccine is ready.  Phase I is lunacy if you don’t.  If it were up to me, I’d hedge my bets in favor of developing this as rapidly as possible, just in case we’re still dying from this, in large numbers, a year from now.

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But back in the real world, citizens are not taking this seriously enough.

Based on my last trip to the grocery store, it’s clear that many people and some major corporations still haven’t gotten the message.  Yesterday, at my local Safeway, maybe a third of the employees were wearing masks.  And at least some employees were not maintaining social distance. I expected to see that sort of thing among the shoppers, and did.  Some people are hopelessly stupid and there’s not much you can do about it.  But I did not expect that from a major US corporation with a huge number of public-facing employees.

Just do the math:  My home, Fairfax County, has 400 known cases of coronavirus and about 800,000 adults.  Based on the recent daily growth, it’s fair to say we likely have at least one case of undetected coronavirus per 500 adults, right now.  That Safeway is the largest one on the East Coast, so I’m guessing they have 2000 people a day walk through there, even with this pandemic.  With those numbers, the odds are overwhelming that those Safeway employees are being exposed to coronavirus, right now, every day. 

And what do I see?  No masks, no sneeze guards at the registers, no enforcement of social distancing.  No nothing.  For the single largest grocery store in the area.

My wife called the manager to complain, and got a classic corporate non-response.  Safeway says its up to each individual employee to wear a mask or not.  A corporation with a huge public-facing staff, and their policy is, every man for himself.

I’m still trying to figure out whether they are unaware of the almost-certain daily exposure of their staff, or they just don’t care.  The only thing I know for sure is that I’m not going back there until this pandemic is over.  Maybe never.  And that’s from a loyal life-long Safeway shopper.

Doesn’t anybody get this?  We haven’t fixed it.  We hope we’ve fixed it, sure.  But there’s no guarantee that our various half-hearted attempts at social distancing will, in fact, work.  Look at what China imposed in Wuhan, then go to your local grocery store and see what’s going on.  The game isn’t over yet.  The fat lady has not yet sung.  I don’t think we’ve reached an inflection point (where the daily increase in cases begins to decline) in any US state yet.  For sure, we haven’t reached that in the Commonwealth of Virginia.

And the clerks at Safeway aren’t wearing masks.  Official corporate policy at the largest grocery store in the County is, eh, wear ’em if you want to.  This is so wrong.  We need to start thinking of getting ahead of the curve, not acting like a bunch of sheep.

So, for damned sure, I’m not going to spend another penny on a vendor who is too lazy, or too foolish, to require all public-facing personnel to mask up.  Not if I have any alternative.   I suggest that all of you do the same, and maybe that will speed them along toward eventually figuring this out.

We, as a country, are in the process of running out of hospital beds, masks, respirators, and staff.  As we scramble to build temporary hospital space, now more than ever, public health officials need to keep in mind the reverse of Roemer’s Law:  A bed not filled is a bed not built. 

We as citizens, have an obligation to ourselves not to be the moron who fills the next bed.  Morally, I’m a Darwin Awards fan.  I really have little objection to stupid people getting themselves killed for their stupidity.  But in this case, with beds and ventilators in scant supply, stupidity is going to kill a lot of innocent bystanders.  If our current lackadaisical attitude results in filling all the beds by the time I catch this disease, then I’m going to be the one left to suffocate slowly at home.

Unsurprisingly, I object to that.

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Summary:  What can you do?

Rule 1:  Don’t be the dumbass who fills the next available hospital bed.

The big change this week is that the CDC has finally figured out that this is being spread by people who are infected, but don’t have symptoms.  You need to act as if you are one of those people.  And you need to act as if everyone you meet outside of your immediate family is one of those people.

Outside of your home, treat yourself and everyone else as potential carriers of coronavirus.  Not because you’re paranoid.  But because its true.

First, minimize trips to public places.  Given the shortage of delivery slots for groceries, I’ve decided to continue grocery shopping in person.  And, while I’m there, I pick up a few things for relatives and neighbors.  There’s no sense having three people in the grocery store when it only takes one.

Two, do what the CDC tells you to do.  Wash your hands.  Maintain a 6′ distance.  Wash your hands.  Don’t touch your face. Wash your hands.  And if you even think you might be sick, stay home.

Three, wear a mask when you are in public around other people.  In particular, wear a mask whenever you find yourself talking to someone, in person, outside of your immediate family.

Fourth, unless and until the CDC can firmly rule out aerosol transmission of this disease, keep your voice down when in public.  Ideally, just keep your mouth shut, because talking releases large numbers of aerosol particles.

Fifth, wear the best mask that you own, right now.  If you don’t own one, ask around.  If you have to make one, there are plenty of plans available.  And I’ll give you my tip:  The smart people have figured out that the best possible material for use in an expedient (home-made) mask is the inside of a high-end furnace filter.  I’ve heard Filtrete 1900 or better.  I’d accept MERV-13 or better.  See Post #593 for details.  If you have access to materials like that, incorporate them into your home-made mask.

Sixth, if the importation of KN95 masks solves the mask shortage, the Federal government needs to step up and target any excess to hard-hit cities and towns.  And those cities and towns need to distribute those, and enforce public mask use by ordinance.

Seventh, urge your city or town to enforce public mask use by ordinance.

Eighth, boycott any business that does not require all public-facing employees to use masks, or a least puts them behind a sneeze guard or some other effective barrier.  In my area, it’s a sure bet that employees in the largest retail establishments are now being exposed to coronavirus on a daily basis.  Corporation who can’t figure that out don’t deserve your money.

Ninth, write your Congressman and urge all possible haste on vaccine development.  We really have no clue what things are going to look like a year from now.  Bureaucracies stick to business-as-usual unless and until somebody screams at them loudly enough.  Maybe we all need to start screaming.

Finally, consider establishing a mask-distribution program in your immediate area.  Mail-a-Mask, or some such.  People who have them, or have the skills to make them, offering them to their neighbors.

This is a followup to Post #583.

I emailed the people who run the Central Markets farmers’ market, and they will continue to hold their farmers’ market at the Holy Comforter church on Sundays.  The next date is now explicitly shown on their website.

If aerosol transmission of this disease actually does occur frequently, and vendors won’t wear masks, then an open-air market on a windy day is probably your safest bet for shopping, and long as the density of individuals is kept low.

If you go, you should wear a mask of some sort.  Get ahead of the curve.

On the plus side, the Safeway was nearly fully stocked.  Yes, they have bananas.  Produce was fully stocked.  Butter and eggs were there, but skimpy.  Milk was little moth-eaten, but anything you’d want, they had some.  Still light on cooking oil.  Rice was fine.  Poultry was still a little scanty (but they had chicken wings at $0.99/lb).

All in all, they are to be commended on getting on with their business.  Except for TP, the place looked more-or-less normal.

On the minus side, many employees were not wearing masks.  Many employees were not maintaining “social distance” from each other.

I mean, sure, I expected some of the customers to ignore the current CDC guidance.  And, in the past, because CDC said we didn’t need to wear masks in public, I could forgive stores that didn’t impose that on employees.  No matter how foolish I thought that was.

But now?  Grocery store clerks, including at checkouts, not wearing even a rudimentary mask? Other stores are at least putting up plastic guards between customer and checkout clerk?  Not here.

I am a loyal, lifelong Safeway customer.  When they shut their Vienna store, I dutifully began shopping at Pan Am.  And I’m not going back there until the epidemic is over.  Maybe not even then.  Not if I can find a store that will follow anticipate current CDC guidance.

Let’s briefly review what has changed.

A week ago, CDC was saying that COVID-19 was primarily spread by droplet transmission from symptomatic individuals.  So, stay out of range of droplets when an obviously sick person coughs or sneezes, and hey, you’ll be OK.  No need to wear a mask.

That obviously wasn’t right.   You really couldn’t explain the spread of disease that way.  I mean, do you really think they let somebody who was coughing and hacking near Boris Johnson?  I don’t.

Today?  Now CDC says, well, maybe this is being spread by asymptomatic individuals.  Don’t look sick, don’t feel sick, don’t sound sick.  Maybe you spew droplets just by talking.  No sneezing or coughing needed.  And — not clear if they are saying it or not, but true nevertheless  — clearly some of this is aerosol spread, for which, indoors, there is no “out-of-range”.

(If you don’t understand droplet versus aerosol, look them up in my prior posts.)

And so, the facts have changed, and the CDC has changed will soon change its mind.  Everybody needs to mask up in public.  Social distancing is not enough.  Particularly not when the head of the Chinese CDC called failing to require masks in public “The big mistake” that the US and Europe were making.

This disease has a median 5 to 6 day incubation period.  That’s the time lag between when you are infected, and when you feel ill.  Fairfax County Schools have been closed for 21 days now.  I assume we’ve all been doing our social distancing during that time period.  And today, Fairfax is set to record its 400th case.

Surely we can all do math here, right?  We are seeing new cases that had to have been infected way, way after the start of social distancing.  COVID-19 is still spreading, for now, despite social distancing. 

Doesn’t anybody get this?  We haven’t fixed it.  We hope we’ve fixed it, sure.  But there’s no guarantee that our various half-hearted attempts at social distancing will, in fact, work.  Look at what China imposed in Wuhan, then go to your local grocery store and see what’s going on.  The game isn’t over yet.  The fat lady has not yet sung.  I don’t think we’ve reached an inflection point anywhere in any US state yet (but I have not checked that). 

And the clerks at Safeway aren’t wearing masks.  So we are living by Rule #6:  Yes, the really can be that stupid.  Not the clerks.  I mean the people who run Safeway.

The CDC finally wised up.  We all need to follow the CDC advice.  The new advice, that reflects their current understanding of the facts.

Edit:  Well, I was not right.  I guess I read a description of what their advice might be.  But right now, the CDC is still kind-of, sort-of, maybe talking about someday asking (but not requiring) Americans to wear a mask in public.  I can’t even imagine what they are dithering about. But the bottom line is that they still have not modified their official guidance regarding use of masks in public places.

And here’s why they need to get on the stick.  My wife called the Safeway and talked to the manager, and he said that nobody had called for public mask use, so it’s up to each employee to do what they want with regard to mask or not.  That said, I’m sticking by my original conclusion.  We need to start thinking of getting ahead of the curve, not acting like a bunch of sheep.

 Again, do the simple arithmetic.  Fairfax has about 800,000 adults.  And as of today we’re likely to reach our 400th known can of COVID-19.  One in 2000 adults is known to have been infected.  Do you think 2000 adults shop at the Pan Am Safeway on a given day?  I’d bet so.  So, I’d say the odds are pretty good that the clerks in that store are getting exposed on a regular basis.  Day in and day out.  It’s really stupid not to provide them with some protection.  And it’s really stupid of me to shop at a store that does not provide and require at least some minimal protection for public-facing staff.

And, for damned sure, I’m not going to spend another penny on a vendor who is too lazy, or too foolish, to require all public-facing personnel to mask up.  Not if I have any alternative.   I suggest that all of you do the same, and maybe they’ll eventually figure it out.