Thursday, December 24, 2020

A Necessarily Incomplete Overview Of COVID-19 Vaccines

Being a post I wanted to expose on a private Facebook group originally, only here I can add links when needed, and update as well. As ever, I Am Not A Virologist, etc. Info here is culled from This Week In Virology, assuming I understand them correctly, the Milken Institute's vaccine tracker, and the London School of Hygiene & Tropical Medicine vaccine tracker.

  • The biggest gun out there right now is the mRNA approach used by Moderna and Pfizer/BioNTech. It consists of a nanoparticle container housing messenger RNA that eventually gets into your body’s cells. Once inside, the mRNA instructs your cells to manufacture a protein that looks like the “spike” protein from the disease — the protein SARS-CoV-2 uses to gain access to your body’s cells and eventually cause disease. Essentially, it tells your body to make a wanted poster, readying your immune system for real disease. 

    The super cool thing about mRNA is rapid turnaround. Once you have a virus sequenced, you can make a vaccine very quickly — Moderna had theirs two days after the Chinese published the genetic sequence. Everything else is safety/efficacy testing and approval. (You can read a very nice summary of how mRNA vaccines work here.)
  • Next is the vectored vaccine approach used by AstraZeneca/Oxford, their  ChAdOx1. That name is a portmanteau of chimpanzee adenovirus Oxford (1). Originally developed for MERS, it was hoped it would readily translate to SARS-CoV-2 (COVID-19). Basically, they take a virus, in this case a chimpanzee adenovirus known not to infect humans, slice out the gene sequence for replication, and add genes to express the SARS-CoV-2 spike protein. Their testing is not going well — looks like a 62% overall efficacy, with a mistake group getting a half-dose first at 90% efficacy — and lately have started doing trials with other vaccines as a means to hopefully still be useful. My take on this is that such vaccines are functionally dead ends, because you can’t know whether the immune system is learning the vector proteins or the target protein(s), so a second injection might be useless. This in fact is why some vectored vaccines use a second viral backbone for the second shot. The Johnson & Johnson and Russian (Gamaleya's "Sputnik") vaccines are also vectored, and we shall see whether the former encounters the same problem.
  • On to the inactivated vaccines. This is one of the oldest types of modern viral vaccines, including the polio, rabies, and annual influenza inoculations. Basically, you grow active virus in a medium (typically chicken eggs, but others are used) and then "inactivate" it. (Viruses aren't alive, but they can be made to fall apart by heat or chemical means.) This process leaves you (hopefully) with the outer proteins that the immune system needs to know about without all that infectious virus. These have a spotty record, which is part of the reason why, when you get one that does work, it becomes enormous news, as with the Salk polio vaccine (though there were other reasons for that). The inconsistent efficaciousness is also part of the reason we do extensive testing on vaccines. Sinopharm (the Chinese state entity) is using this approach and licensed theirs months ago. As you can imagine, I do not have a lot of faith in their trials or data.
  • Protein subunit vaccines are by far the most popular approach with this disease, and is currently used in vaccines for shingles, hepatitis B, and human papilloma virus. Sanofi Pasteur is the most prominent name going to war with this approach, but a number of Chinese entities are also doing this. Basically, all this does is create the proteins of interest (here, the spike protein) and inject them straight into patients. It can produce a really strong immune reaction to the one protein in question, which is why it should in theory work well for SARS-CoV-2. (Coronaviruses tend to genetic stability because they have a proofreading ability most viruses lack.) The bad news for the US and Sanofi is that they had to pause their trials because the target population of people 65 and over did not respond well to the vaccination
Stay tuned, kids.

Don't Panic About The New UK Coronavirus Strain

 As ever, I use the word "strain" in the title here with some hesitation, because it hasn't been shown (yet) conclusively to affect pathogenicity or transmissibility, but some very good stuff in yesterday's This Week In Virology Episode 697. This doesn't cover all of it, but it hits the big points I think people are most interested in:

  • Increased transmissibility has not been conclusively shown but the genomic data is suggestive. The mathematical models can be tweaked to show any result, and don’t take into account founder effects or population-level changes that might be affecting transmission.
  • Spike protein changes are sufficient to require new primers for PCR tests, so they have had to rely on other genes for diagnosis.
  • The spike protein change is NOT enough to alter antibody response. This has been verified in animal models. Existing vaccines will most likely work fine on the new variant.
  • Underdiscussed: the ORF8 deletion may make a less-virulent disease course. (SARS-CoV-1 had one midway through that outbreak with that consequence.) It’s not that the disease is intrinsically more transmissible, but if you don’t feel sick you’re more likely to be out and shedding virus. We do not definitively know this to be the case at this point, however. 
Update 2020-12-29: I wanted to address a point that @politicalmath raised on his recent Substack post on COVID-19 strains; the consensus on TWiV seems to be that the US does much less viral sequencing than they do in the UK, although it’s unknown if what we do is enough to adequately assess spread by particular isolate. In any case, he links to a useful new (to me) site that tracks viral spread, Nextstrain.org. Bookmarked.
 
Update 2020-12-30: It was pointed out to me on Twitter that the strain is actually called B.1.1.7, which "has an unusually large number of genetic changes, particularly in the spike protein". I'm still not terribly worried about antibody response to this variant, for several reasons:
  1. It's not clear that this has enough difference from other isolates to prevent existing vaccines from mounting an effective immune response.
  2. We have known for months that other (possibly zoonotic) coronaviruses leave antibodies capable of reacting with SARS-CoV-2. It doesn't have to be perfect to work.
  3. If B.1.1.7 is really a major shift, changing the mRNA vaccine to include the new spike protein should be a simple thing that could be turned around rapidly. (Of course, that assumes the FDA will allow an altered vaccine to be delivered without widespread testing first.)

Saturday, October 31, 2020

Some Thoughts On The COVID-19 Mid-Term

 

 Cut-and-paste from a comment elsewhere on a news story about Dr. Fauci's remarks on the timetable for a return to "normal", and expanded on here. Particularly, this graf:

"I mean, if normal means you can get people into theater without worrying about what we call a 'congregate setting.' Superinfections. If you can get restaurants to open at almost full capacity, if you could have sporting events to be able to be played with spectators, either in the stands or in the arena, then I think that's going to be well, well into 2021 and perhaps beyond. I think one of the things that will be clear that our sensitivity to the potential devastating effects of a pandemic will be extraordinarily heightened. And I don't think that we will have the normal way of interacting with each other, particularly in the sense of wearing masks, which I think will become very commonplace as it is in many countries in Asia, even outside of the context of a pandemic outbreak. Again, I think it's many months."

We’re probably looking at a widely-deployed vaccine in the mid-2021 timeframe. Do not be surprised to see this pushed back as failures occur among the front-running vaccine candidates.
 
We will not know the durability of the immunity it confers. In that regard, it will be a phase III test (the actual term used by vaccinologists is phase IV). We may need to get revaccinated as often as twice yearly, forever. I am modestly hopeful on that front, because SARS-CoV-1 reactive T-cells have been documented as long as 17 years after infection. If T-cell immunity is the primary response, we could be golden.
 
We know that B-cell (antibody) immunity declines rapidly. A recent large-scale UK study showed antibody prevalence dropping from 6% to 4.4% in three months. This is strongly suggestive that we should not expect sterilizing immunity from a vaccine, but only protection from disease. This is not an uncommon outcome. The injected Salk (inactivated virus) polio vaccine has this effect also.
 
Because we will not get sterilizing immunity, we cannot rule out disease transmission even among the vaccinated. And because a vaccine will only confer protection on a (large) fraction of individuals, viral transmission will continue. The hope is that viral loads among the infected-but-vaccinated will be sufficiently low so as to reduce or eliminate transmission, but we cannot count on it.
 
So I can see what Fauci’s saying as not improbable. Masks, occasional lockdowns (hopefully becoming more infrequent as we find out how effective the vaccine(s) is/are) and other measures will probably continue to be necessary for a while.


Monday, October 19, 2020

We’re Gonna Be Doing This For A Long Time: Enola Holmes

 I have had my problems with the social justice types in Hollywood, and mainly because they tend to be entryists. Because they do not have good, original stories to tell, they take up and ruin beloved franchises, viz. Ghostbusters, and to a lesser degree, Star Wars. Enola Holmes doesn’t quite fit that category; it’s more of a cinematic hermit crab, occupying the shell of a beloved franchise. We see almost nothing of her older brother, Sherlock (Henry Cavill), and so the eponymous Enola is mostly on her own when their mother disappears.

The exceptionally talented Millie Bobby Brown plays the title role, fresh off an extraordinary run as the psionically gifted Eleven in the Netflix series, Stranger Things. But as with Hailee Steinfeld’s gobsmacking entry to the screen with the 2010 remake of True Grit, it’s hard not to question Brown’s subsequent choice of vehicles. In this case, much of it comes off as cliché — particularly her willingness to engage in hand-to-hand combat with a larger and older man. She’s an expert in jiu-jitsu, we learn, but it goes on. She outwits her famous brother (who comes off as a bit of a dunderhead). You expect more given the actress, but ... it’s almost a Mary Sue character. There’s too many of those already.

Tuesday, September 15, 2020

Summary of TWIV 663, "The Joy of Vax": About Accelerated Vaccine Approval

 A summary of Alan Dove's segment of This Week In Virology episode 663, "The Joy of Vax", relating to the status of COVID-19 vaccines, as bullet points. He attended a webinar from the National Adult and Influenza Immunization Summit regarding COVID-19:

  • Top level executives from eight of nine companies the furthest ahead in vaccine trials participated (Astra Zeneca declined, for the obvious reason that they had halted their trial): Pfizer, Moderna (CEO participated), Novavax, Inovio, Medicago, Sanofi Pasteur, J&J, and Merck.
  • "We're all in this together". Cooperation among competitors is significant.
  • Prevention of disease is the primary goal, not sterilizing immunity.
  • The bar is set for a minimum of 80% efficacy. (FDA will accept anything over 50%, but the Bill & Melinda Gates Foundation has set 80% as a minimum.)
  • Because the goal is protective immunity, it's not clear that sterilizing immunity will occur. Therefore, it's quite likely that even vaccinated individuals could act as asymptomatic carriers. This will have consequences for health care workers and the general population.
  • "Herd immunity" therefore doesn't have the meaning people suppose it does, because vaccinated asymptomatic carriers can still spread the virus. We need new language to explain how this works. Infection is different from disease.
  • Consequently, we will need testing to prevent transmission, even with a vaccine.
  • All vaccines are two-dose regimens. (Merck believes theirs could be a single-dose.) All expect full approval, but plan on Emergency Use Approval. If you get a vaccine in 2021, it will likely be on an Emergency basis.
  • Many of the vaccines will require adjuvants which will need to be added to the vaccine on-site. This is not a problem in the US and Europe, but will be a big problem in developing countries. The plan is to eventually reach single-dose distribution.
  • Scaling is enormous. Sanofi, which regularly provides 100M flu vaccines per year, is building out for a billion doses for COVID-19. "People are building entirely new facilities for this stuff."
  • Storage will be a non-problem in the western world, but the extreme cold needed (-70C) for mRNA vaccines (Moderna) will be a problem for the developing world. This is a conservative estimate, and research is ongoing for higher temperatures.
  • Cross-testing of vaccines is not occurring, so you will need to get the second shot of whatever vaccine you started with to get the benefit.
  • Population diversity is a problem in some cases. (Moderna has slowed their trial because they don't have enough African-Americans in their control group.)
  • Efficacy is assumed to begin 10 days after the second dose. If someone gets sick after the first dose, it does not count.
  • Consequently, it's unlikely there will be good data on any vaccine until mid-November. But Pfizer's CEO thinks there will be enough data to say whether a vaccine works by Halloween.
  • Worst-case scenario is a vaccine that actually makes infection worse (as the dengue vaccine).
  • Protection (from disease) is still important even if a vaccine doesn't provide sterilizing immunity, because you could still prevent hospitalization.


Saturday, August 22, 2020

The Epidemiologist And Thief

Michael Osterholm of U. Minnesota's Center for Infectious Disease Research And Policy (CIDRAP), and the Minnesota Federal Reserve Bank President Neel Kashkari came out in an editorial in favor of a renewed and stricter set of lockdowns to address the spread of COVID-19:
To successfully drive down our case rate to less than one per 100,000 people per day, we should mandate sheltering in place for everyone but the truly essential workers. By that, we mean people must stay at home and leave only for essential reasons: food shopping and visits to doctors and pharmacies while wearing masks and washing hands frequently. According to the Economic Policy Institute, 39 percent of workers in the United States are in essential categories. The problem with the March-to-May lockdown was that it was not uniformly stringent across the country. For example, Minnesota deemed 78 percent of its workers essential. To be effective, the lockdown has to be as comprehensive and strict as possible.
But how to pay for this? Isn't keeping people alive during this new lockdown going to be terribly expensive? They have an answer for this (emboldening mine):
This pandemic is deeply unfair. Millions of low-wage, front-line service workers have lost their jobs or been put in harm’s way, while most higher-wage, white-collar workers have been spared. But it is even more unfair than that; those of us who’ve kept our jobs are actually saving more money because we aren’t going out to restaurants or movies, or on vacations. Unlike in prior recessions, remarkably, the personal savings rate has soared to 20 percent from around 8 percent in January.

Because we are saving more, we have the resources to support those who have been laid off. Typically when the government runs deficits, it must rely on foreign investors to buy the debt because Americans aren’t generating enough savings to fund it. But we can finance the added deficits for Covid-19 relief from our own domestic savings. Those savings end up funding investment in the economy. That’s why traditional concerns about racking up too much government debt do not apply in this situation. It is much safer for a country to fund its deficits domestically than from abroad.
Such savings are not the government's to spend, though, unless
  1. the government confiscates such savings, or
  2. taxes them at a very high rate.
Joe Biden has lately said he would institute such a lockdown if scientists recommended it ("I would listen to the scientists"). This has already happened. Given the printing press approach to buffering the population from the consequences of COVID-19, it's unlikely the fiscal oppression approach will get traction, but it's far from guaranteed.

Monday, August 10, 2020

Michael Mina: Diagnostic And Surveillance Tests Need Different Kinds Of Regulatory Approval

Buried in this Harvard Magazine article is a point that I didn't emphasize enough in my previous article on COVID-19 rapid/cheap testing, and that is: diagnostic and surveillance tests are different beasts with different requirements, but the FDA currently treats both identically (emboldening mine, as per always):

Mina has been predicting the advent of more widely available, cheaper tests for months. But those tests have not materialized, largely because of regulatory risk, he says: manufacturers cannot meet Food and Drug Administration (FDA) templates for test sensitivity that use PCR as the standard. The FDA—whose approval process is stringent because it is designed to test the efficacy of clinical diagnostics—has no jurisdiction over public-health testing. But at the moment, there is no alternative regulatory process for tests designed to ensure population-level wellness—such as a certification program that might be run through the Centers for Disease Control (CDC), the agency charged with safeguarding the public health.

“It is time to stop allowing diagnostic definitions to get in the way of absolutely essential public-health interventions,” says Mina, for whom explaining the distinction between the two types of test, and the different ways they can be used, has been an uphill battle. But it is one that he desperately hopes to win—and that the country needs him to win—for public-health measures to stand a chance of reining in the outbreak as schools and other institutions move toward reopening this fall.
It's probably asking too much to have the FDA make a whole different track for surveillance tests on the fly like this, but clearly something has to give.

At Last, Something Approximating A Plan In Portland

I recently despaired at the problem of Black Lives Matters offering no policy directions to improve policing and diminish police abuse of blacks. It therefore came as welcome news when I found out about Reimagine Oregon's surprisingly meaty list of policy demands, particularly their section on police divestments. A great deal of this has already been accomplished in some form or another (banning the use of chokeholds, mandated duty to report/intervene in cases of violence, making officer disciplinary records visible to the public) with many other particulars still on the table. Some correspond to reforms I have already proposed, but many strike me as commonsense beyond those:
  • Prevent contract arbitration from limiting disciplinary action.
  • Demilitarize the police, including ending (a) tear gas use, (b) sound cannons, and (c) flashbang grenades. (a) will be extremely difficult to implement (crowd control is still a legitimate function of government), but the other two ((b) especially) are so overused as to be serious problems.
  • Decriminalize public transportation fare evasion.
  • Prohibit public transportation fare evasion as justification for search warrants.
  • Remove sworn and armed officers from public university campuses. This is probably unlikely to happen, and in any case, how much of a problem does this realistically present? University campuses are hardly a hotbed of crime to begin with.
  • Ban the receipt of militarized equipment (1033 transfers). This is well overdue.
  • Reconsider personnel public records requests. Police disciplinary records need to be public. Despite a nearly 60-year-old Supreme Court case, Brady v. Maryland, that has frequently been read to imply that police disciplinary records germane to court proceedings must be made available to the defense, it is frequently flouted in practice.
  • Consider the laws that allow expunction [expungement] without costs for people with no convictions in a certain number of years.
  • End 48 hour rule that delays police officer questioning after a charge of excessive force is raised.
  • Eliminate qualified immunity, duh.
There are other items aimed at the county and municipal levels, but this strikes me as a fine first crack at achievable line-items. The biggest single item missing, and the hardest one to implement, is ending police unions. The question in my mind is whether the Portland protesters have anything whatsoever to do with this group.

Saturday, July 18, 2020

How Cheap, Daily Tests Could Stop The Spread Of COVID-19 — If The FDA Will Let Us

Thursday's Episode 640 of This Week In Virology had some astonishing remarks from Michael Mina, who lately has had a paper published advocating that rapid throughput is more important than high sensitivity when it comes to COVID-19 surveillance tests.

1. Viral Load Ramps Up Early And Declines Slowly

COVID-19 viral load expands rapidly — in a matter of hours — after initial infection.

2. The Window Of Infectiousness Is Brief [EDIT: If Caught Early], Only 2-3 Days In Most Cases


3. High-sensitivity tests are expensive, and have long throughput times.


Early tests from the CDC and WHO were designed to be as sensitive as possible. A large part of this was because it was thought that infection buildup took place over days, and thus the need to capture early, lower viral loads. But because the buildup is so rapid, it avails us little. More, because the reagents are so expensive, it is uneconomical to do the tests. Conventional PCR nasal swab tests are expensive, costing "from $50 to $150" each. Mina states that such tests "often have sample-to-result times of 24-48 hours". In the real world of limited lab capacity, I have heard of delays of as much as eight days.

4. Low-sensitivity, rapid, cheap daily tests can work to prevent disease spread.


Because of the rapid acceleration of viral growth early in the infection cycle, a surveillance test needs to only detect a relatively high amount of virus. These tests should be cheap — cheap enough for everyone to use daily, and capable of being mass-produced in the billions.

The good news is that such tests already exist:
E25Bio, Sherlock Biosciences, Mammoth Biosciences, and an increasing number of academic research laboratories are in the late stages of developing paper-strip and other simple, daily Covid-19 tests. Some of the daily tests are in trials and proving highly effective.

The strips could be mass produced in a matter of weeks and freely supplied by the government to everyone in the country. The price per person would be from $1 to $5 a day, a considerable sum for the entire population, but remarkably cost effective.
The bad news is that the FDA still looks at this problem from the standpoint of regulatory certainties, and the understanding we had of disease mechanics back in March. In TWIV 640, Mina participated in the following exchange:
Michael Mina: ... [H]igh-frequency testing using a less sensitive test goes much further than low-frequency testing using the best test in the world. We pretty much found that if you test less than ... every two weeks, you're not going to be able to contain pathogens.... What I would suggest is we have really cheap, low-sensitivity, from a molecular perspective, low-sensitivity tests that are a dollar, that people take every day. And so then it doesn't have to catch you in your incubation period, it doesn't have to catch you 20 days later, it just has to tell you the morning of that you have enough virus that you could be transmitting.

Rich Condit: Do such tests exist? Or will they?

MM: You know, they do. So this is the other bit that really led to that. They do exist, and I've been advising a lot of companies on their reagents and their tests and their test characteristics that might be needed. And the most frustrating thing for me is that these tests exist, but they're all getting slammed. Especially when they look at what happened with Abbott IDnow getting slammed for having a sensitivity that's a few Ct values worse than PCR, which is nothing. If you have a sensitivity that gets you to a Ct value of 36, great, that's amazing. But these companies are shaking in their boots, saying we can't go to the FDA, we can't try to market this test yet, because its sensitivity is three orders of magnitude worse than PCR, analytically, on the molecular level. And so I've been saying this: the FDA and the CDC and the NIH have to change their messaging. They have to say, look, there is actually a technology — that a test could exist right now — I have some sitting in my office next to me — they're paper strips. They're just little pieces of cardboard printed with monoclonal antibodies that can pick up an antigen. Essentially a lateral flow assay, can be printed in the millions, and could probably be done by the federal government and be funded by the federal government.
Mina's faith in the FDA et al. to manufacture anything is suspect given the CDC's role in delaying a working test back in February, but the funding part is much more likely. This sounds promising, which means it will all but certainly be ignored.


Thursday, July 9, 2020

No Concrete, No Foundation, Or, "Awareness" Is Not Enough

About a month ago, I ran into Shaun King's widely-disseminated tweet about voting response to police brutality:
This was, I think, the first sign of a possible awakening (and no, I don't think the Republicans are a particularly good answer here). The fact that these things keep happening in Democratically-run cities and states is an indicator that the rot is substantially more difficult to excise, and that the affiliations in multiple dimensions will make this harder still.

Forcing politicians to implement reform in the face of entrenched interests will require sustained political agitation, and an agenda of reforms to agitate for. This brings me to the subject of this piece, Black Lives Matter, the formal organization. It surely has been front and center in many aspects of the current crisis. Formed in the wake of the George Zimmermann acquittal in 2013, the protests of the Michael Brown shooting in St. Louis the following year garnered the nascent organization national recognition. But in that time, they have not set up a national 501(c)4. There is accordingly no IRS 990 history to analyze. The PAC registered under that name raised a grand total of $500, and has since been dissolved. As donations to BLM itself all go through ActBlue (itself a 501(c)(3) charity with over $1M in assets according to its 2017 990), there is no visibility to that money beyond what ActBlue provides. (At the time of writing, I have a request into that organization for BLM's finances, but have received only a robot response.)

You will seek in vain for actual policy at BLM's website. Their "What We Believe" page is a litany of sophomoric college intersectional babble, full of nonsense like
  • "We are self-reflexive and do the work required to dismantle cisgender privilege"
  • "We build a space that affirms Black women and is free from sexism, misogyny, and environments in which men are centered."
  • "We disrupt the Western-prescribed nuclear family structure..."
  • "We foster a queer‐affirming network."
This is not terribly surprising coming from people whose founders in fact include actual Marxists. But nowhere there will you find a proposal for dealing with police violence against black people. BLM, the organization, has lost sight of the main goal everyone assumes they are after: the end of disproportionate police violence against black people.

Contrast this void with CHAZ/CHOP's demand list. Yes, they're silly. Despite the repeated assurances this isn't what the phrase "defund the police" means, they "demand abolition. ... This means 100% of funding, including existing pensions for Seattle Police." But at least, they provide a set of specifics. You could also look at the NAACP, whose strategic plan is full of airy nothings ("A chance to live the American Dream for all", "A free, high-quality, public education for all", etc.), but at least they point in the direction of goals. You can't fix what you can't identify.

This is in some way ironic, because only five years ago, BLM had actually launched Campaign Zero, which offered tangible and plausible ideas to stop police violence (h/t Coyoteblog). But that seems to have since gone nowhere. Campaign Zero's parent organization, We The Protesters, has a 2017 990 (the last year I could find) detailing $484,588 of support in that year, with no distributions over the period 2015-2017. But where are they? Has anyone heard from them, at all, since the George Floyd protests started? They have been a cipher. "Activist" groups like Black Lives Matter, at least the formal entity, have invested much in protesting and public displays, but show almost no interest in why police violence against black people is so widespread, nor in concrete solutions to fix that problem.

Update: I forgot to add this Washington Free Beacon piece about Shaun King sending money from Real Justice PAC to his own company.  While this is not, by itself, proof of malfeasance, it sure looks fishy.

Saturday, July 4, 2020

The Childish, Utopian "Defund/Abolish The Police" Movement Will Fail

There are a number of silly, non-solutions being proposed lately, particularly police defunding. The Minneapolis City Council recently elected to disband their department, a futile and childish measure. Scott Greenfield's sensible take shows exactly what's on the line for the comfortable people making such demands:
But there will still be crime, because people will still be people just as they’ve always been people. Not every garage will be broken into, but some will. Are you willing to let it slide? Don’t call the cops as they won’t come. Don’t complain that they aren’t on the streets, as the twelve cops left on the force are busy busting stare rapists who are traumatizing strong and fierce women survivors.

How exactly this theoretical scheme that aspires to be “transformative” is supposed to work is anybody’s guess at this point. It’s not as if anybody has thought of any this through, and given the tendency to make word salad for dinner, it’s not as if their supporters demand specifics rather than meaningless vagaries about whiskers on kittens.

But Lisa Bender came the closest to spilling the beans when she told her constituents, flat out, that if they aren’t willing to take a garage break-in for the team, then they might as well wear Klan hoods. And if they break-in to your comfortable white privileged house after the garage has been emptied, who will you call?
There will always be simple, easy, wrong answers, and this is one.

Saturday, June 27, 2020

The Hucksters Con The Con Man: Viral Inactivation In A Phoenix Church Ain't All That

Trump's Tulsa rally having proven a disappointment (supposedly because of ticket sales from people hoping to minimize attendance), he moved on to a Phoenix church. Said church assured its membership that they had a state-of-the-art air purification system:
June 23, 2020 – On Sunday we made a post for our congregation to inform them we are doing everything we can to foster the cleanest, safest environment as we resume church services. We have heard Coronavirus and COVID used interchangeably. Our statement regarding the CleanAir EXP units used the word COVID when we should have said Coronavirus or COVID surrogates. We hope to alleviate any confusion we may have caused. We have done our best to direct all CleanAir EXP questions to the company executives who are best suited to answer and have provided the following clarity; CleanAir EXP is at the forefront of air and surface purification testing and technology – it is our understanding that they tested with a third-party Certified Biosafety Laboratory on the best coronavirus surrogates available. The company found that their technology leads to a 99.9% elimination of airborne coronavirus surrogates. So while they do not eliminate COVID-19, their coronavirus surrogate testing results are significant for the future of clean air.
We’re proud to be their customer! This is one of many examples of how we’re committed to fostering the cleanest, safest environment for our church congregation and facility event rentals.
So, how do it work?
When particulate levels reach an unacceptable amount, the sensor activates the EXP Purification Unit installed in the air duct of your HVAC system. ... These high-energy oxygen ions help cluster particulates together. This clustering effect allows your existing air filter to capture microscopic particles that would normally pass through.
In other words, the system generates ozone that is recirculated through the HVAC system (which can't possibly harm asthmatics at all) only when the sensors detect too many particulates in the air. In other words, by the time the system kicks in, viral particles have already spread.

What's ironic here is that a recent Nature paper found that far-UV light inactivates SARS-CoV-2 analogues (beta-HCoV-OC43, a virus that causes the common cold, and alpha HCoV-229E). This process "would result in ~90% viral inactivation in ~8 minutes", which isn't great for enclosed public spaces, but better than nothing. The manufacturer, Ushio, appears to be the first to market with a far-UV lamp of any kind for public space use. Something like this might make a substantial difference in disease spread, but once again, we don't have solid evidence that's the case. Inactivation in the lab is one thing, in indoors human settings another. The Phoenix church looks like they got conned by someone repurposing an anti-allergen system as sterilizing. (In fairness, ozone will inactivate viruses, but the time appears to be much longer [47-223 minutes] than for far-UV light.)

Sunday, June 21, 2020

The Case Against Cloth Masks

I have been a substantial advocate for mask-wearing in public places, even unto wearing cloth masks as a substitute for the much more effective N95 respirators. I even for a time sewed a number of cloth masks from the HK Mask site pattern. Much of this was based on research showing that surgical masks could reduce influenza transmission, and even homemade masks could be of some help in reducing disease spread.

Without getting too much into the weeds, it's useful to pause a moment and describe what it is we're trying to measure and do. Slate Star Codex in March ran a very good summary of the scientific literature regarding mask-wearing and why one might or might not choose to wear masks. The first order of business is defining how transmission occurs:

Epidemiologists used to sort disease transmission into three categories: contact, droplet, and airborne. Contact means you only get a disease by touching a victim. This could be literally touching them, or a euphemism for very explicit contact like kissing or sex. Droplet means you get a disease when a victim expels disease-laden particles into your face, usually through coughing, sneezing, or talking. Airborne means you get a disease because it floats in the air and you breathe it in. Transmission via “fomites”, objects like doorknobs and tables that a victim has touched and left their germs on, is a bonus transmission route that can accompany any of these other methods.

More recently, scientists have realized that droplet and airborne transmission exist along more of a spectrum. Droplets can stay in the air for more or less time, and spread through more or less volume of space before settling on the ground. The term for this new droplet-airborne spectrum idea is “aerosol transmission”. Diseases with aerosol transmission may be spread primarily through droplets, but can get inhaled along with the air too. This concept is controversial, with different authorities having different opinions over which viruses can be aerosolized. It looks like most people now believe aerosol transmission is real and applicable to conditions like influenza, SARS, and coronavirus.

Sifting through the papers, Scott Alexander writes,
I think the evidence above suggests masks can be helpful. Masked health care workers were less likely to catch disease than unmasked ones. Masked travelers on planes were less likely to catch disease than unmasked ones. In per protocol analysis, masked family members are less likely to catch disease from an index patient than unmasked ones. Laboratory studies confirm that masks block most particles. All of this accords with a common-sense understanding of droplet and aerosol transmission of disease.
And that's where I was as of March.

Never before in my 45 year career have I seen such a far-reaching public recommendation issued by any governmental agency without a single source of data or information to support it. This is an extremely worrisome precedent of implementing policies not based on science-based data or why they were issued without such data. ...

... When people state that CDC recommends cloth face mask use you have to understand there was much more going on than science and public health protection with this recommendation. I urge you go online to the CDC website yourself and you’ll not find one piece of information supporting that cloth masks are effective in reducing respiratory virus transmission.
Osterholm flat out accuses the CDC's stance change coming, in part, from arm twisting. ("Well, I signed [the MASKS4ALL open letter recommending public mask wearing] because of pressure from peers"). There's a great deal more there, which I recommend everyone read or listen to. I find him persuasive on the state of ignorance we live in regarding the efficacy of masks (and how much they can help in situations likely to transmit infection), but I will continue to wear masks in public and recommend others do as well.

Thursday, June 18, 2020

The Missing Space Between "Believe All Women" And "Believe Women"

I was seriously considering writing a rejoinder to the silly claims that #BelieveWomen didn't in fact mean #BelieveAllWomen coming from Susan Faludi in the NYT and Monica Hesse in the Washington Post. We are to believe these days that, apparently now that Joe Biden is the presumptive Democratic nominee, Tara Reade's accusations meet with condemnation and contempt if they aren't outright ignored.

Luckily for me, Cathy Young in Quillette wrote a fair piece examining Reade's accusations. She found them as vaporous as I do, unearthing a trail of exaggerations from a "serial fabulist", while noting Biden's hypocrisy in endorsing the convict-upon-accusation standard implicit in the "Dear Colleague" letter.) Excerpt:
Even leaving aside general questions about Reade’s credibility, some of which are discussed below, her specific story about Biden never made much sense. Reade has offered several iterations of what happened to her in 1993, when she was a staff assistant in then-Senator Biden’s office. According to the most recent and damning version, first made public less than two months ago, Biden pushed her against a wall, kissed her, got his hand under her skirt and jammed his fingers inside her—all this in a public space in the Russell Senate Office Building, in a hallway where she had seen him talking to someone else moments earlier. (She claims that Biden steered her to a “side area,” but no one has been able to find an alcove or other space in the building’s hallways that would offer the required level of privacy.)
 

Friday, June 5, 2020

Democrats' Tough Road Ahead To Diminish Police Violence

Trump provides a convenient scapegoat for a lot of sins on the national scene, but it's significant that George Floyd was killed by a blue city police force in a blue state. (Both Minnesota senators are Democrats, and Minnesotans have not sent a Republican to the Senate since Rod Graham retired in 2001. Tim Pawlenty, the last Republican governor, ended his term in 2011. The office has been held by Democrats ever since, including the current governor, Tim Walz. The mayor of Minneapolis, Jacob Frey, is likewise a Democrat, albeit as a member of the uniquely Minnesotan Minnesota Democratic–Farmer–Labor Party.) There's a number of reasons for that, and why these killings keep happening in such places. In some cases, Democrats are in a particularly bad position to implement needed changes:
  1. Ending qualified immunity. Among these, this is the least likely to result in division. Justin Amash has lately announced a bill to end the disastrous judge-made doctrine of "qualified immunity". This makes it difficult to pursue civil rights cases against police unless someone else has shown there was a pattern of such abuses. Because of the Catch-22 of qualified immunity, it is almost certain such cases will never proceed. Recently, the Supreme Court refused to hear one egregious case, which means legislative action is necessary. Justin Amash recently drafted a bill on the subject, and has lately found a Democratic co-sponsor in the House, Ayanna Pressley (D-Mass).
  2. Ending 1033 transfers and demilitarizing the police. There is substantial evidence that giving military-grade hardware to police increases civilian casualties. New efforts to dramatically reduce these transfers have lately started from Rand Paul (R-KY) and Brian Schatz (D-HI), but the problems there are the usual ones of politicians not wanting to look soft on crime, and lobbying efforts by the powerful Fraternal Order of Police (which, see below). In fact, it's never been safer to be a cop, and this military hardware is counterproductive to actual policing.
  3. Ending the War On Drugs. A study that came out last year purported to show that, once you controlled for violent situations, the number of black people shot was on a par with the overall population rates. Yet this contains a significant, circular flaw. Drug prohibition has chased procurement and distribution of some drugs underground. Accordingly, contract disputes become deadly. The mass of drug enforcement takes place selectively in predominantly black neighborhoods.

    Ending this will not be easy. Joe Biden, the Democrats' standard-bearer going into November, shows why: he has been one of his party's most enthusiastic drug warriors. While the terrain has changed since the Reagan administration, the appetite for meaningful reform has mostly been piecemeal and incremental.
  4. Reducing the scope of the law. The more laws there are, the more to enforce, and the more need for police interactions with the public. This can have fatal consequences — and there are no better examples of this than Eric Garner, whose cigarette sales evaded New York's insanely high taxes. Those taxes, since raised yet again, are a strong Tell that the technocratic Democratic Party is of no mind to dial back such laws, and indeed still thinks mankind is perfectible by way of the legislature.
  5. Ending police unions. This is the biggest nut, and the one the Democrats will have the most trouble with. Democrats' historic affinity for unions, and public employee unions particularly, will make a showdown with the Fraternal Order of Police all but impossible. The squabble a few years back over private prisons shows how this is likely to unfold: on the one hand, yay that organizations like CoreCivic have had fewer prisoners sent their way, with the recognition that private entities shouldn't create incentives to jail people; yet there is no analogous understanding that public employee prison guard unions spend vastly larger sums on lobbying to the same effect.

    As noted above, police unions oppose not only demilitarization, but also ending asset forfeiture, body cameras, and in California, a public records law that would provide much more transparency to police activity. For all these reasons, Peter Suderman at Reason has called for an end to police unions, on some very solid grounds:
    Forthcoming research out of the University of Victoria's economics department finds that the introduction of collective bargaining produces somewhat higher compensation for police officers. It does not correlate with a reduction in total crime—but it does eventually correlate with higher numbers of killings by police, especially of minorities.
Not even Wisconsin Governor Scott Walker, alleged scourge of public employee unions, had the guts to apply public employee union restrictions to police and fire unions. Democrats are in even worse shape, with stronger headwinds. The median Hillary voter is a greater danger to black people than even the Klan, nowadays.

Update 2020-06-10: Scott Greenfield, from a couple days ago:
Also, more from Jacob Sullum in Reason: banning chokeholds, use-of-force restrictions, making it easier to fire bad cops, increasing police transparency, and abolishing qualified immunity.

Sunday, May 31, 2020

Were Minneapolis Rioters Locals Or Imports?

The mayor of Minneapolis initially claimed that everyone arrested during the recent rioting was from outside the area, which would be a spectacular claim if true. Unfortunately, it turned out this was not the case, something the local Fox affiliate discovered when they looked at the Hennepin County jail log:
Of the 45 people arrested for rioting, unlawful assembly, stolen property, burglary or robbery on May 29 and May 30 so far, 38 had Minnesota addresses, according to publicly available jail records reviewed by FOX 9.
I did my own look at the numbers, and the Fox 9 figures check out. Miscommunication? Wishcasting? Who knows, but quite a pratfall to have to walk that back. I had thought at first maybe outsiders were being routed to other jails, but the about-face indicates the initial reports were wrong all along.

Update 2020-06-01: Churning some more numbers from the data set I picked up yesterday:
  • Of the 74 people arrested on riot-related charges (as set out in the Fox 9 criteria), 63 were from Minnesota.
  • Of those 63 Gopher Staters, 36 were from the Twin Cities, but 27 — nearly half — were from other towns. Violence tourism is apparently a Thing.

Sunday, May 24, 2020

Re: “Science By Press Release”

I have written skeptical comments about Moderna’s press release announcing success for their SARS-CoV-2 vaccine, but a listener letter from Episode 617 of This Week In Virology has backed me off a little from that position. I quote the letter in full here:

Jon writes:

Dear professors,

For background, I’m a mathematical physicist by training, but I invest in small biotechs as a hobby.    I remember first hearing about mRNA vaccines on a TWIV circa 2012 when I was driving to the Buffalo airport, and surprising my brother-in-law (a prof at MD Anderson in infectious disease) that something like that could work.

However, I have a bone to pick with you guys about your coverage of Moderna’s decision to issue its press release.  For reasons not widely appreciated in academia, brief press releases of so-called “top line data” are a standard and necessary practice, not something that Moderna has schemed up.

Unlike academic researchers, publicly traded companies are ethically and legally bound to consider at what point withholding trial results becomes unfair to either new or existing shareholders, especially when issuing new shares, as Moderna is now doing.   (The $483M the government is chipping in sounds like a lot, until you consider that they are already ramping up in a hurry to manufacture 1B doses/year, all of them still subject to clinical risk.)  Furthermore, as you know, a full release may jeopardize the investigator’s ability to publish the results or present them at academic conferences. (Note that this study was conducted in collaboration with the National Institute of Allergy and Infectious Disease).

The relevant legal issues are explained in the security and exchange commission (SEC) exceptions to the embargo policy of the annual American Society of Clinical Oncology annual conference website.  The conference website states:

After the abstract is submitted to and prior to the abstract information being publicly released in conjunction with an ASCO Meeting, the author, coauthors, sponsor of the research, journalists, and others must not
  • make the information public, or provide it to others who may make it public (such as news media),
  • publish or present the information or provide it to others who may publish or present it,
  • use the information for trading in the securities of any issuer, or provide it to others who may use it for securities trading purposes.
with an exception for minimal “top line” data releases required to fulfill SEC regulations.

SEC [securities and exchange commission] Exceptions

A publicly traded company may determine that it is legally required to disclose certain data or other information from a confidential abstract in advance of the public release date to satisfy requirements of the U.S. Securities and Exchange Commission or a corresponding regulatory body in a country where the company’s stock is traded (collectively, “SEC”). This need typically arises when there is a substantial likelihood that the information would be considered by a reasonable investor in the company to significantly alter the total mix of information made available to the investor.

In general, the abstract is still eligible for inclusion in the ASCO Meeting provided that the company submits to ASCO, in advance of the release, a letter signed by the company’s legal counsel that contains the abstract title, indicates the format/nature of the public disclosure, and advises that (a) public disclosure of the information is necessary for the company to comply with applicable securities laws, and (b) the information disclosed is the minimum necessary for such compliance…..

The emphasis was added by me.  So professors shouldn’t blame the corporate world for the brevity of press releases, unless they’re willing to forgo giving presentations! Science and Nature are also well-known sticklers as well.

More vitally, in the case of COVID-19 we are no longer waiting for phase 3 data to be published before we build factories and ramp up production.  It is therefore is entirely appropriate from an economic viewpoint that investors and others get an early peek at the interim data to decide where to allocate capital.  (I also worry that hackers will get at the data for insider trading if it isn’t released publicly ASAP.)

I should also point out that the company gave a fascinating and still-available 1-hour public webcast (slides + audio, slides only)  to discuss the release, which included a Q&A from big investment companies.   Later that day there was another webcast from an investor conference, again publicly available.  Don’t be put off by the websites asking for an email, just put “small investor” in the “occupation” box (and a fake email address if you like) and they won’t bother you.  (I presume their lawyers might have required them to collect email addresses in case they accidentally made a gross misrepresentation, because I’ve never gotten spam from such webcasts in the companies I follow.) 

Sincerely,

Jon

Wednesday, May 20, 2020

Distribution Shifts and Demand, Not Hoarding, Is Causing COVID-19-Related Shortages

Shortages, gluts, and the concomitantly higher (in most cases) prices for certain goods continue with no end in sight:
Yet, as Will Oremus writes in Medium, in the case of toilet paper, the problem mainly is one of distribution channels:

In short, the toilet paper industry is split into two, largely separate markets: commercial and consumer. The pandemic has shifted the lion’s share of demand to the latter. People actually do need to buy significantly more toilet paper during the pandemic — not because they’re making more trips to the bathroom, but because they’re making more of them at home. With some 75% of the U.S. population under stay-at-home orders, Americans are no longer using the restrooms at their workplace, in schools, at restaurants, at hotels, or in airports.

Georgia-Pacific, a leading toilet paper manufacturer based in Atlanta, estimates that the average household will use 40% more toilet paper than usual if all of its members are staying home around the clock. That’s a huge leap in demand for a product whose supply chain is predicated on the assumption that demand is essentially constant. It’s one that won’t fully subside even when people stop hoarding or panic-buying.
In other words, there is no easy way around this. With eggs, retailers are even taking a loss on pricing. This is largely due to commercial egg producers trimming flocks after a brutal 2019 where they "on average lost 2.7 cents per dozen eggs produced". And this despite cost decreases in feed and fuel, two of the biggest costs of the egg industry. It will take a substantial increase in the size of laying chicken flocks to make up the difference, yet as Bob Krouse of MPS Egg Farms says, "Once we're through the coronavirus, it'll be back to business as usual" — that is, he's not expanding.


Sunday, May 17, 2020

Spanish COVID-19 IFR

Well, that's terrifying (as usual, emboldening mine):
Torcuato writes:
Dear Twivers,

The Spanish Government has just announced the initial, preliminary results of its ENECOVID 19 serologic survey for SARS-cov-2. It is based on random, representative sample of over 60000 people selected by the Instituto Nacional de Estadística (akin to the US Census Bureau).  Rigorous stuff.

Everyone had a “quick” antibody test and most also consented to blood draws for an Elisa test (only a quarter of the samples have been analyzed so far though, so the Elisa results do not feature in the preliminary analysis). These will be repeated two more times, in 3 and 6 weeks’ time.

Formal publication is expected soon, but here are some highlights (alas, sans confidence intervals):

-Overall IgG prevalence of 5% nationally.

-Significant variation across provinces (from 1.6% to 14.2%).

-Among people who reported experiencing anosmia at some point in the previous two months, IgG prevalence is 42% (!).

The infection mortality rate was not specified, but here is my back-of-the-envelope calculation:

-Given that the population is 47 million, about 2,35 million are estimated IgG positive.

-PCR-confirmed deaths stand at 27100 (as of 5/13), but there is unaccounted for excess mortality (6000 as of 4/28), so actual number could be as high as 33000.

-If we are not too fuzzy, this gives a rate between 1,15% and 1,4%.

As a note, they mentioned in the press conference that in those individuals with Elisa already performed, the two kind of tests agreed 97% of the time, if I recall correctly (given the low prevalence, presumably they agree on a lot of true negatives). Official press note in Spanish:
https://www.isciii.es/Noticias/Noticias/Paginas/Noticias/PrimerosDatosEstudioENECOVID19.aspx
This is probably the highest IFR (infection fatality rate) I have seen published anywhere.

Saturday, May 9, 2020

Lockdown Or Not, Here We Go

Copied and lightly edited from a Facebook comment of a day or three ago.
 
In the stupid wars between Team Open Everything Up Yesterday (which, in practice, seems to have few adherents) and Team Stay Locked Down Until All Vital Services Are Closed And Everyone Dies Of Starvation Or Cholera, it seems to me the message needs to be something like:

Once containment was no longer possible, we switched to mitigation. That meant "flattening the curve" to prevent overloading our hospitals and (hopefully) allowing them to treat patients not infected with COVID-19. We have largely achieved that.

However, we can't stay locked down forever. The economy is the means by which we survive. The plan from Team Lockdown appears to keep it throttled indefinitely until ... what? Until we get a vaccine? What if we never get one? What if it takes four years (a typical vaccine development-to-deployment timespan)? What if it takes a decade? What is our goal then? In that light, indefinite shutdown is a demand for impoverishment if not outright death. We cannot print money forever without consequences. As the slow-motion closures of the meatpacking industry show, there are real and even mortal threats to society if the *only* weapon in our arsenal is the shutdown.

Simply put, we have to stay open, in some wise. Cellphone data makes it clear that people are leaving home in large numbers. Not all will participate with a reopening, even if given the clearance to do so. Restaurants particularly will be brutalized by the coming months: it is unlikely people will patronize them as they did before, and with restaurant margins being so thin to begin with, a reduction to half or third capacity is simply business failure by another name. We could say much the same of many other personal services requiring close contact (nail salons, hair salons, massage parlors, etc.).

There will be deaths. We must be frank on this point. And, we cannot dismiss them lightly, as do the people who say, "COVID-19 kills fewer people than heart disease did last year (and is unlikely to reach that total), so why are we so concerned about it?" It has already killed nearly as many people as suicide in all of 2019 last year*. Should we take these presumptive (but unknown) deaths more seriously because of that?

Parting thoughts:

  • Everyone should wear masks in public, no exceptions. If you're asthmatic and can't wear one, you're already in a high-risk group for COVID-19 complications and shouldn't be in public to begin with.
  • Keep the most vulnerable quarantined.
Here we go.

* 47,173 deaths by suicide as of 2020-05-09 from the CDC website, versus 47,128 from COVID-19 (provisional).

Friday, April 3, 2020

The Long, Hard Climb To Increasing N95 Mask Availability

The calls to get President Trump to use the Defense Production Act to force manufacturers to make more ventilators, and more protective clothing for medical personnel (and others) have increased over time, viz.:
Etc., etc., etc. It seems pretty commonplace that it's just assumed that commanding such a thing will make it so, as Sarah Silverman:

Of course, the obvious rejoinders to this are that
  1.  The T-shirt manufacturers have a week (at least) to churn those out, and
  2. N95 manufacturers (and consumers) have to deal with the FDA.
The exact reasons for commanding N95 masks to exist are, at the moment, fairly obvious:
 But as ever, it's easier said than done. The Canadians, rightly fearing today's announcement of a US export ban, have struck out on their own to manufacture a domestic N95 mask. Only trouble is, virtually the entire supply chain is beyond their grasp as well. "[I]n just over two weeks, the McMaster project quickly evolved from establishing a manufacturing method for surgical and more sophisticated N95 masks to building an entire supply chain from the bottom up."
The biggest challenge: finding the basic material to make the masks. A proper N95 mask the kind that can filter out droplets containing viruses such as COVID-19 requires a unique material, specifically a “meltblown, non-woven polypropelene” with narrow fibre diameters and a specific pore size.

Any company that can make the fabric — there are manufacturers in China and the U.S. — has already been flooded with phone calls. Others are operating within countries, like South Korea, that have placed specific export bans on the material.
So the core of the N95 mask needs a product that the Canadians can't make at the moment; every scrap made is already spoken for.
So in the meantime, the materials team has turned its attention to exploring whether other possible fabrics could be sourced and treated to perform as well.

That requires testing — another key bottleneck in the process. Until recently, most masks were tested in the U.S., said Preston, and some cannot be tested in Canada at all. Though McMaster sent some initial prototypes to a facility in Utah — that lab is “no longer accepting international orders,” added Selvaganapathy.
They seem to be optimistic about getting over this hump — they claim to be "very close" to getting a domestic surgical mask — but an N95 mask "will take more time". The expertise and equipment aren't easy to come by:
“What this is is a brutal education in the reality of supply chains,” [Simon Evenett, University of St. Gallen professor of international trade and economic development] said. “That’s what policymakers are getting.”
While we can expect 3M to add new capacity in addition to doubling its annual US production, and Honeywell and smaller players to expand or build out new factories, the larger of those at least have some of the necessary knowledge already on-staff. The team at McMaster University have no such experience. People like Silverman or the writers at the NYT and WaPo, who have most likely never trod a factory floor in their lives, believe in magic wands that don't exist.

Who Eats Dogs? Don't Say "Chinese A**holes" Or Facebook Censors You

So, this happened in a private Facebook group yesterday. To the question, "Who eats dogs?" I provided this response, and then the Overton window slammed shut on my keyboard:


Yes, it's now the case that Facebook has decided that discussions of Chinese eating habits — the proximate origin of the COVID-19 virus — are off-limits. This is, to put it mildly, insane. "Respectful" means we can't swear? The hell, Zuck. This is part of a general campaign Facebook appears to have started five years ago (at least) in which they decided to purge content the Chinese Communist Party wanted silenced, including video of Tibetan monks self-immolating to protest CCP repression.

Wednesday, March 25, 2020

CNN: Exterminators Of Hope

A few days back, I noticed a CNN "fact check" that was such an exemplar of entirely irresponsible and politicized journalism that I felt it meet to comment in this space about it. Recently, French doctors in a small-sample-size trial (n=20) summary wrote of their clinical success: "Despite its small sample size our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin."

This amounted to excellent news, at least for those of us who like actual good news about pandemics. (There is a recent report coming from China that another small sample randomized test does not show the same results.) Meantime, the CDC noted that "[b]ased upon limited in-vitro and anecdotal data, chloroquine or hydroxychloroquine are currently recommended for treatment of hospitalized COVID-19 patients in several countries." But you would not get that story from CNN, which downplayed the work being done elsewhere:
Chloroquine has not been approved by the FDA to treat the coronavirus -- and nor has any other drug, the FDA made clear in a post-briefing statement that said "there are no FDA-approved therapeutics or drugs to treat, cure or prevent COVID-19." Because chloroquine has been approved for other purposes, doctors are legally allowed to prescribe it for the unapproved or "off-label" use of treating the coronavirus if they want. But its safety and effectiveness has not been proven with regard to the coronavirus. FDA Commissioner Dr. Stephen Hahn, speaking after Trump at the briefing, said that chloroquine would be tested through a "large, pragmatic clinical trial" with coronavirus patients.
Here, the FDA and CDC speak in the same generalities one does when there aren't any pandemics involved, i.e. the same kind of thinking that delayed a US COVID-19 test by nearly a month. The combination is in fact going to those sorts of clinical trials, which are expected to conclude in 2022. But for now, CNN sees fit to omit the French work from their pretend "fact check" because it goes off narrative. Anything that gives people hope is disarming a weapon against Trump, and it must therefore be minimized if not eliminated. This foolish politicization will have consequences; we have already seen one in Nevada, where Democratic governor Steve Sisolak has barred physicians from using hydroxychloroquine to treat COVID-19 anywhere but in hospitals.

Update: It's important to note that Trump's initial comments were (mostly) comparatively anodyne (emboldening mine):
"It's shown very encouraging -- very, very encouraging early results. And we're going to be able to make that drug available almost immediately. And that's where the FDA has been so great. They -- they've gone through the approval process; it's been approved. And they did it -- they took it down from many, many months to immediate. So we're going to be able to make that drug available by prescription or states," Trump said.

He added: "Normally the FDA would take a long time to approve something like that, and it's -- it was approved very, very quickly and it's now approved, by prescription."
The approval speed was irrelevant for drugs already on the market. What was not forthcoming was whether this amounted to an on-label use, which, as stated above, won't be known for two years.

Wednesday, March 18, 2020

From The Virology Trenches: Squandered Chances By The FDA and CDC

A pretty good story from the trenches (written by someone at a local public health agency) regarding the early days of the CDC and FDA in the COVID-19 testing saga, and their role in fumbling the tests. The transcript begins at about 1:25:20; all errors are mine. Italics are what I assume is text from the letter's author; emboldened text is my emphasis, and anything in [square brackets] is my own commentary/editorial simplification as well.
Brenner writes: "Hi, TWIV team. Long-time listener. I started in academics after a PhD and a post-doc. I went into public health. I hear in the podcast that there isn't much information on the current COVID-19, or as I prefer to call it, SARS-2-CoV test [Ed. note: CDC seems to be calling it SARS-CoV-2], so let me give you the background. ... The CDC originally came out with a real-time reverse transcription PCR RTRTPCR. It had three targets, all in the N-gene. Why the N-gene when everybody else uses Spike? Your guess is as good as mine. And she gives a link. They sent out ... they sent the test out to 99 different public health labs. Of the 99, only five could make the assay work. 94 labs ... could have the N3 probe react to something in the HSC late in the reaction, causing a late positive CT for the HSC probe two [too?]. That's getting a little dense. Basically, ... test didn't work.  They got false positives. The CDC said they were gonna replace just the N3 primer probe set, but that the other two should be good to go.
A week passed. The CDC was still working on it. Were they going to change the sequence? No one knew what the problem was. However, in situations like this, laboratories cannot just adjust a protocol. We are required by CLIA, FDA, and just about every other alphabet soup agency to do the test as it is written.

A second week passed, and in a very surprising turn of events, the [Association] of Public Health Laboratories, who work very closely with the CDC getting a myriad of assays and programs up and running, wrote a harsh letter to the FDA asking them to loosen requirements for emergency authorized testing. Days afterwards, the CDC said, you only had to use the first two N-primer probe sets. They remanufactured and sent new lots out to the labs in about a week. Basically, we never speak of the N3 primer probe again....
Update 2020-03-21: Rereading this, I came to the incredible realization that there were not two but three weeks before the test could be properly performed. Insane.