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.