Results for “rapid tests” 76 found
The Poop Detective
Wastewater surveillance is one of the few tools that we can use to prepare for a pandemic and I am pleased that it is expanding rapidly in the US and around the world. Every major sewage plant in the world should be doing wasterwater surveillance and presenting the results to the world on a dashboard.
I was surprised to learn that wastewater surveillance is now so good it can potentially lock-on to viral RNA from a single infected individual. An individual with an infection from a common SARS-COV-2 lineage like omicron won’t jump out of the data but there are rare, “cryptic lineages” which may be unique to a single individual.
Marc Johnson, a virologist at the University of Missouri and one of the authors of a recent paper on cryptic lineages in wastewater, believes he has evidence for a single infected individual who likely lives in Columbus, Ohio but works in the nearby town, Washington Court House. In other words, they poop mostly at home but sometimes at work.
Twitter: First, the signal is almost always present in the Columbus Southerly sewershed, but not always at Washington Court House. I assume this means the person lives in Columbus and travels to WCH, presumably for work. Second, the signal is increasing with time. Washington Court House had its highest SARS-CoV-2 wastewater levels ever in May, and the most recent sequencing indicates that this is entirely the cryptic lineage.
Moreover the person is likely quite sick:
Third, I’ve tried to calculate how much viral material this person is shedding. (Multiply the cryptic concentration by the total volume). I’ve done this several times and gotten pretty consistent results. They are shedding a few trillion (10^12) genomes/day. What does this tell us? How much tissue is infected? It’s impossible to know for sure. Chronically infected cells probably don’t release much, but acutely infected cells produce a lot more. I gather a typical output in the lab is around 1,000 virus per infected cell. If we assume we are getting 1,000 viral particles per infected cell, that would mean there are at least a billion infected cells. The density of monolayer epithelial cells is around 300k cells/sq cm. A billion cells would represent around 3.5 square feet of epithelial tissue! Don’t get me wrong. The intestines have a huge surface are and 3 square feet is a tiny fraction of the total. But it’s still a massive infection, no matter how you slice it….My point is that this patient is not well, even if they don’t know it, but they could probably be helped if they were identified.
…If you are the individual, let me know. There is a lab in the US that can do ‘official’ tests for COVID in stool, and there are doctors that I can put you in contact with that would like to try to help you.
So if you poop in Columbus Ohio and occasionally in Washington Court House and have been having some GI issues contact Marc!
Hat tip to Marc for using the twitter handle @SolidEvidence.
Testing Freedom
In the latest Discourse Magazine I discuss the FDA’s long-standing fear and antipathy toward personalized medical tests and how this violates the 1st Amendment.
In 1972, the FDA confiscated thousands of home pregnancy tests, declaring that they were “drugs” meant to diagnose a “disease” and thus fell under the FDA’s regulatory dominion. The case went to the U.S. District Court for the District of New Jersey, and Judge Vincent P. Biunno ruled that the FDA had overstepped. “Pregnancy,” he said, “is a normal physiological function of all mammals and cannot be considered a disease … a test for pregnancy, then, is not a test for the diagnosis of disease. It is no more than a test for news….” As a result of Judge Biunno’s ruling, home pregnancy tests are easily available today from pharmacies, grocery stores and online shops without a prescription.
These days, debates over home pregnancy tests from the 1970s seem anachronistic and paternalistic. Yet the same paternalistic arguments appear again and again with every new testing technology. In the late 1980s, for example, the FDA simply declared that it would not approve at-home HIV tests, regardless of their safety or efficacy. As with pregnancy tests, the concern was that people could not be trusted with information about their own bodies…the first rapid at-home HIV test was developed and submitted to the FDA in 1987 [but] it took 25 years before the FDA would approve these tests. (Now, you can easily buy such a test on Amazon.)
…The FDA has a vital role in ensuring that tests are clinically accurate—tests should do what they say they do. Tests don’t need to be perfectly accurate to be useful (think of thermometers, personality tests and tire pressure gauges), but if a test advertises that it measures HDL cholesterol, it should do that within the tolerances the firm promises. The FDA has the technical knowledge to ensure that tests work, and that’s a skill that Americans value from the agency.
What Americans don’t want is to be told they can’t handle the truth. Yet when it came to at-home tests such as pregnancy tests, HIV tests and genetic tests, that’s exactly the reasoning the FDA used—and continues to use—to suppress information. The FDA should ensure that tests are safe, but “safety” means physical safety. The FDA may not declare a product unsafe because it might produce dangerous knowledge. Patients have a right to know about their own bodies. Our antibodies, ourselves. The FDA has authority over drugs and devices but not over patients.
Judge Biunno had it right back in 1972 when he said that diagnostic tests produce “news.” Test results, therefore, are a type of speech that fall under the First Amendment right to freedom of speech. The Supreme Court has repeatedly rejected restrictions on freedom of speech based on “a fear that people would make bad decisions if given truthful information”; thus, FDA restrictions on tests based on such fears are unconstitutional. The question of whether consumers will respond “safely” to test results is no more relevant to the FDA’s regulatory authority than the question of whether readers will respond safely to political news published in The New York Times. The FDA does not have the constitutional authority to regulate news.
The FDA’s Lab-Test Power Grab
The FDA is trying to gain authority over laboratory developed tests (LDTs). It’s a bad idea. Writing in the WSJ, Brian Harrison, who served as chief of staff at the U.S. Department of Health and Human Services, 2019-2021 and Bob Charrow, who served as HHS general counsel, 2018-2021, write:
We both were involved in preparing the federal Covid-19 public-health emergency declaration. When it was signed on Jan. 31, 2020, the intent was to cut red tape and maximize regulatory flexibility to allow a nimble response to an emerging pandemic.
Unknown to us, the next day the FDA went in the opposite direction: It issued a new requirement that labs stop testing for Covid-19 and first apply for FDA authorization. At that time, LDTs were the only Covid tests the U.S. had, and many were available and ready to be used in labs around the country. But since the process for emergency-use authorization was extremely burdensome and slow—and because, as we and others in department leadership learned, it couldn’t process applications quickly—many labs stopped trying to win authorization, and some pleaded for regulatory relief so they could test.
Through this new requirement the FDA effectively outlawed all Covid-19 testing for the first month of the pandemic when detection was most critical. One test got through—the one developed by the Centers for Disease Control and Prevention—but it proved to be one of the highest-profile testing failures in history because the entire nation was relying on the test to work as designed, and it didn’t.
When we became aware of the FDA’s action, one of us (Mr. Harrison) demanded an immediate review of the agency’s legal authority to regulate these tests, and the other (Mr. Charrow) conducted the review. Based on the assessment, a determination was made by department leadership that the FDA shouldn’t be regulating LDTs.
Congress has never expressly given the FDA authority to regulate the tests. Further, in 1992 the secretary of health and human services issued a regulation stating that these tests fell under the jurisdiction of the Centers for Medicare and Medicaid Services, not the FDA. Bureaucrats at the FDA have tried to ignore this rule even though the Supreme Court in Berkovitz v. U.S. (1988) specifically admonished the agency for ignoring federal regulations.
Loyal readers will recall that I covered this issue earlier in Clement and Tribe Predicted the FDA Catastrophe. Clement, the former US Solicitor General under George W. Bush and Tribe, a leading liberal constitutional lawyer, rejected the FDA claims of regulatory authority over laboratory developed tests on historical, statutory, and legal grounds but they also argued that letting the FDA regulate laboratory tests was a dangerous idea. In a remarkably prescient passage, Clement and Tribe (2015, p. 18) warned:
The FDA approval process is protracted and not designed for the rapid clearance of tests. Many clinical laboratories track world trends regarding infectious diseases ranging from SARS to H1N1 and Avian Influenza. In these fast-moving, life-or-death situations, awaiting the development of manufactured test kits and the completion of FDA’s clearance procedures could entail potentially catastrophic delays, with disastrous consequences for patient care.
Clement and Tribe nailed it. Catastrophic delays, with disastrous consequences for patient care is exactly what happened. Thus, Harrison and Charrow are correct, giving the FDA power over laboratory derived tests has had and will have significant costs.
Clement and Tribe Predicted the FDA Catastrophe
Laboratory developed tests are not FDA regulated–never have been–instead the labs are regulated under the Clinical Laboratory Improvement Amendments (CLIA) as overseen by the CMS. Laboratory developed tests are the kind your doctor orders, they are a service not a product and are not sold directly to patients. Labs develop new tests routinely and they do not apply to the FDA for approval. Despite this long history, the FDA has claimed that it has the right to regulate lab tests and they have merely chosen not to exercise this right for forty years. In 2015, Paul Clement, the former US Solicitor General under George W. Bush, and Laurence Tribe, considered by many to be the leading constitutional lawyer in the United States, wrote an article that rejected the FDA’s claims writing that the “FDA’s assertion of authority over laboratory-developed testing services is clearly foreclosed by the FDA’s own authorizing statute” and “by the broader statutory context.”
Despite lacking statutory authority, the FDA has continued to claim it is authorized to regulate laboratory tests. Indeed, a key failure in the pandemic happened when the FDA issued so-called “guidance documents” saying that any SARS-CoV-II test had to be pre-approved by the FDA. Thus, the FDA reversed the logic of emergency. In ordinary times, pre-approval was not necessary but when speed was of the essence it became necessary to get FDA pre-approval. The FDA’s pre-approval process slowed down testing in the United States and it wasn’t until after the FDA lifted its restrictions in March that tests from the big labs became available.
Clement and Tribe rejected the FDA claims of regulatory authority over laboratory developed tests on historical, statutory, and legal grounds but they also argued that letting the FDA regulate laboratory tests was a dangerous idea. In a remarkably prescient passage, Clement and Tribe (2015, p. 18) warned:
The FDA approval process is protracted and not designed for the rapid clearance of tests. Many clinical laboratories track world trends regarding infectious diseases ranging from SARS to H1N1 and Avian Influenza. In these fast-moving, life-or-death situations, awaiting the development of manufactured test kits and the completion of FDA’s clearance procedures could entail potentially catastrophic delays, with disastrous consequences for patient care.
Clement and Tribe nailed it. Catastrophic delays, with disastrous consequences for patient care is exactly what happened.
Addendum: See also my pre-pandemic piece on this issue, Our DNA, Our Selves.
Why the defenses of Australia do not persuade me
Alex laid out some complaints about Covid policy down under, I have been receiving emails and tweets arguing the following:
1. Australia is choosing a perfectly acceptable point on the liberty vs. safety frontier.
2. The Australian decision to do extreme lockdowns is democratic, and most Australians support it.
And sometimes I see a third point, which as far as I can tell is true:
3. Australia doesn’t have much in the way of ICU excess capacity, so a Covid surge would hit the country especially hard.
I think those responses, however, are missing the point of the critique. I would stress that if Covid risk has you with your back against the wall and the government is forcing extremely restrictive measures on your citizenry, you should be implementing the following in an urgent manner:
a. Twice a week rapid antigen tests for everyone. (Plenty of time to prep for this one.)
b. Much stronger incentives to vaccinate people more rapidly, including with the large stock (six million or so?) of AstraZeneca vaccines. Demand side incentives, supply side incentives, whatever can be done. Let’s throw the kitchen sink at this one. But as it stands, I just don’t see the urgency.
c. Mobile monoclonal antibody units, as they are used in Florida (modest progress here).
d. Maybe other emergency measures too? I’ve been hearing for decades that Australia has such a great health care system so surely they can make lots of progress on these and other fronts?
As far as I can tell from this great distance, Australia is doing none of these. And, while there is some disquiet about lockdowns, few of its citizens are demanding that they do any of those positive measures. Not many of its well-known politicians are proposing those ideas either. (Please feel free to correct me if that is wrong!…but I just don’t see word of it on-line.)
If Australia implemented all of those policies, or even just one of them, they could attain a much better “liberty vs. lives” frontier, no matter where you think the government should end up on that frontier. They could save lives, and enjoy more liberty.
And that is the great shame and indeed I would say crime. There seems to be an incredible complacency that people in some parts of the country will put up with the current measures and not demand the government look for more practical measures to boost both liberty and security.
So when you write me and suggest “this is democratic and the people approve,” yes that is exactly the problem.
Saturday assorted links
1. Private insurers are now picking up less of the tab for Covid-related hospital stays.
2. Claims about vaccine efficacy, useful. And further claims about boosters. The correct final picture here still is not clear to me.
4. Progress in the use of monoclonal antibodies. Sadly: “For the administration, mum’s the word on monoclonal antibodies, rapid home tests, high quality masks . . . anything except vaccines,” Eric Topol, founder and director of the Scripps Research Translational Institute, said in an email. “Which is wrong, since we need every tool in the kit to effectively take on delta; we’re not doing that well at all.”
5. What academia used to be like. Before the internet, that is.
6. Jerry Brito on the coming regulatory challenge for crypto.
Our Regulatory State Isn’t Learning
Delta is the fourth wave of covid, and amazingly the US policy response is even more irresolute than the first time around. Our government is like a child, sent next door to get a cup of sugar, who gets as far as the front stoop and then wanders off following a puppy.
The policy response is now focused on the most medically ineffective but most politically symbolic step, mask mandates. An all-night disco in Provincetown turns in to a superspreader event so… we make school kids wear masks in outdoor summer camps? Masks are several decimal places less effective than vaccines, and less effective than “social distance” in the first place.* Go to that all night disco, unvaccinated, but wear a mask? Please.
If we’re going to do NPI (non pharmaceutical interventions), policy other than vaccines, the level of policy and public discussion has tragically regressed since last summer. Last summer, remember, we were all talking about testing. Alex Tabarrok and Paul Romer were superb on how fast tests can reduce the reproduction rate, even with just voluntary isolation following tests. Other countries had competent test and tracing regimes. Have we built that in a year? No. (Are we ready to test and trace the next bug? Double no.)
What happened to the paper-strip tests you could buy for $2.00 at Walgreen’s, get instant results, and maybe decide it’s a bad idea to go to the all night dance party? Interest faded in November. (Last I looked, the sellers and FDA were still insisting on prescriptions and an app sign up, so it cost $50 and insurance “paid for” it.) What happened to detailed local data? Did anyone ever get it through the FDA’s and CDCs thick skulls that even imperfect but cheap and fast tests can be used to slow spread of disease?
…And then we indulge another round of America’s favorite pastime, answers in search of a question. Delta is spreading, so… extend the renter eviction moratorium. People who haven’t paid rent in a year can stay, landlords be damned.
All true. I got dispirited on testing. It’s insane that we don’t have cheap, rapid testing and good ventilation ready for a new school year. As I wrote about earlier, even the American Academy of Pediatrics is shouting from the rooftops that the FDA is deadly slow. The eviction moratorium is a sick joke. Just a backhanded way to redistribute wealth without a shred of justice or reason. Disgusting.
Here’s one more bit (but read the whole thing there is more.)
To learn from the mistakes, and institutionalize better responses would mean to admit there were mistakes. One would think the grand blame-Trump-for-everything narrative would allow us to do that, but the mistakes are deeply embedded in the bureacracies of the administrative state. Unlike bad admirals in WWII, nobody less than Trump himself has lost their job over incompetent covid response. The institutions have an enormous investment in ratifying that they did the best possible job last time. So, as in so many things (financial bailouts!) we institutionalize last time’s mistakes to keep those who made them in power in power — which means we do not learn from mistakes.
Why I am not entirely keen on the Great Barrington Declaration and AIER
More people are asking me about my attitudes toward Great Barrington and AIER, including David Henderson in this post (which also has a good transcript of my remarks to Russ Roberts). Earlier I wrote a conceptual critique of the Great Barrington Declaration, but today I would like to make some more targeted remarks. I didn’t do this when speaking to Russ because I feel they require direct quotation and documentation, which one cannot easily do in a podcast. And in general I don’t like to write posts “attacking people” (way oversupplied on the internet), but in this case libertarian sympathies are so split that a kind of a wake-up call is needed.
Let me first say that if you are libertarian, and would like a libertarian response to the pandemic, and you find Alex and me not libertarian enough, read the Ryan Bourne book from the Cato Institute. You may not agree with everything in there, but it has no “gross errors” and no “biomedical weirdness.” And people, the Cato Institute really is libertarian. They once hired David Henderson as chief economist.
As for the AIER, read this Jeremy Horpedahl thread and click through appropriately, here is the Sam Bowman-produced part of the thread. Conspiracy theorist and shall we say “speculative thinker” Naomi Wolf is now a senior researcher at AIER, please do read her tweets. 5G conspiracy theories? Vaccine nanoparticles that make you travel back in time? “Not kidding” she wrote, and the general weirdness extends far beyond that, to some of her books as well. Or try this “externality denialism” from just a few days ago: “Your vaccine status makes no difference to others.” Her pinned tweet casts suspicion on Bill Gates, and refers to “global treason.”
I say it is a mistake to let such a group set the libertarian agenda or indeed any agenda, even if you favor very rapid reopenings and are very critical of lockdowns. I implore you to think very seriously about what is going on here.
Going back to the GBD proper, which again is sponsored by AIER, here is co-author Sunetra Gupta:
“What we’ve seen is that in normal, healthy people, who are not elderly or frail or don’t have comorbidities, this virus is not something to worry about no more than how we worry about flu,” professor Gupta told HT.
Nope, almost 600,000 U.S. deaths later. Or how does this Gupta claim look?:
‘Why would you arrest transmission?’ she asks. ‘To wait for a vaccine? You cannot get rid of it.’
What would Benjamin Netanyahu say? Or Gupta in May: “Covid-19 is on the way out.”
The best of them is probably Jay Bhattacharya, with whom I often agree, and who, as far as I can tell, has no track record of blatantly false predictions. Yet even he cannot avoid a tinge of biomedical weirdness.
Why was Bhattacharya on the advisory board of the anti-vax group Panda? I am reluctant to play the “guilt by association” game here, but I think there is a broader pattern of these writers simply being wrong about the science, and their associations reflecting that.
I agree with his WSJ critique (with Kulldorff) of vaccine passports. Still, he comes up with some literally true but misleading sequences such as:
The idea that everybody needs to be vaccinated is as scientifically baseless as the idea that nobody does. Covid vaccines are essential for older, high-risk people and their caretakers and advisable for many others.
I wonder why cannot he bring himself to say that “the average social value of a 16-year-old getting vaccinated is strongly positive”? (And we are running significant tests to lower the remaining uncertainty, and if it is merely adenovirus platforms you worry about well say that.) Instead he has to walk around the issue and play down the value of near-universal Covid vaccination. You might think that is all the fault of the editorial chopping board, but it seems to be a broader and more consistent pattern with this group.
Take Hulldorff’s now-famous tweet “Those with prior natural infection do not need it [Covid vaccines]. Nor children.” “Need?” — OK, I get it, demand curves slope down. But again, his tweet is not nearly as good or as accurate a message as “the average social value of a 16-year-old getting vaccinated is strongly positive.” There is good evidence that the vaccines provide better protection than does natural infection, especially against the Covid variants, and it is established that infected younger persons can carry Covid to the unvaccinated, of which there will always be quite a few, most of all globally. Furthermore, non-vaccine methods of achieving herd immunity are looking worse, due to the spread of variants and areas such as Manaus, which seem to have high rates of reinfection. And have I mentioned that hospitalization rates for the young are rising? (We are not sure why.)
Is it so great that 38.9% of Marines are refusing to take the vaccine? (no). Or have these writers looked into the huge success that is Gibraltar?
Why take this weird, hinky attitude toward the science for no good reason? It’s as if — when it comes to vaccines — they deliberately talk in an Alice in Wonderland universe without self-awareness of that fact.
No matter what your associations may or may not be, getting people vaccinated with quality vaccines is the #1 issue right now and it is the path back to liberty most likely to succeed and prove sustainable. If you are not really enthusiastic about that, I think, frankly, that you are out to lunch.
In praise of Alex Tabarrok
Here’s a question I’ve been mulling in recent months: Is Alex Tabarrok right? Are people dying because our coronavirus response is far too conservative?
I don’t mean conservative in the politicized, left-right sense. Tabarrok, an economist at George Mason University and a blogger at Marginal Revolution, is a libertarian, and I am very much not. But over the past year, he has emerged as a relentless critic of America’s coronavirus response, in ways that left me feeling like a Burkean in our conversations.
He called for vastly more spending to build vaccine manufacturing capacity, for giving half-doses of Moderna’s vaccine and delaying second doses of Pfizer’s, for using the Oxford-AstraZeneca vaccine, for the Food and Drug Administration to authorize rapid at-home tests, for accelerating research through human challenge trials. The through line of Tabarrok’s critique is that regulators and politicians have been too cautious, too reluctant to upend old institutions and protocols, so fearful of the consequences of change that they’ve permitted calamities through inaction.
Tabarrok hasn’t been alone. Combinations of these policies have been endorsed by epidemiologists, like Harvard’s Michael Mina and Brown’s Ashish Jha; by other economists, like Tabarrok’s colleague Tyler Cowen and the Nobel laureates Paul Romer and Michael Kremer; and by sociologists, like Zeynep Tufekci (who’s also a Times Opinion contributor). But Tabarrok is unusual in backing all of them, and doing so early and confrontationally. He’s become a thorn in the side of public health experts who defend the ways regulators are balancing risk. More than one groaned when I mentioned his name.
But as best as I can tell, Tabarrok has repeatedly been proved right, and ideas that sounded radical when he first argued for them command broader support now. What I’ve come to think of as the Tabarrok agenda has come closest to being adopted in Britain, which delayed second doses, approved the Oxford-AstraZeneca vaccine despite its data issues, is pushing at-home testing and permitted human challenge trials, in which volunteers are exposed to the coronavirus to speed the testing of treatments. And for now it’s working: Britain has vaccinated a larger percentage of its population than the rest of Europe and the United States have and is seeing lower daily case rates and deaths.
Pandemic sentences to ponder
Of course, there are national health systems in Canada, Mexico, England, and France, among many others, and the uniformity of failure across this heterodox group suggests that structure may have made less of a difference than culture.
“One of the common features is that we are a medical-centric group of countries,” says Michael Mina, a Harvard epidemiologist who has spent the pandemic advocating for mass rollout of rapid testing on the pregnancy-kit model — only to meet resistance at every turn by those who insisted on a higher, clinical standard for tests. “We have an enormous focus on medicine and individual biology and individual health. We have very little focus as a group of nations on prioritizing the public good. We just don’t. It’s almost taboo — I mean, it is taboo. We have physicians running the show — that’s a consistent thing, medical doctors across the western European countries, driving the decision-making.” The result, he says, has been short-sighted calculations that prioritize absolute knowledge about everything before advising or designing policy about anything.
…in East Asia, countries didn’t wait for the WHO’s guidance to change on aerosols or asymptomatic transmission before masking up, social-distancing, and quarantining. “They acted fast. They acted decisively,” says Mina. “They made early moves. They didn’t sit and ponder: ‘What should we do? Do we have all of the data before we make a single decision?’ And I think that is a common theme that we’ve seen across all the Western countries—a reluctance to even admit that it was a big problem and then to really act without all of the information available. To this day, people are still not acting.” Instead, he says, “decision-makers have been paralyzed. They would rather just not act and let the pandemic move forward than act aggressively, but potentially be wrong.”
This, he says, reflects a culture of medicine in which the case of the individual patient is paramount.
Here is more from David Wallace-Wells, interesting throughout and with a cameo from yours truly.
FDA Postpones Inspections Delaying New Drugs and Creating Shortages of Old Drugs
NYTimes: The Covid-19 pandemic has forced the Food and Drug Administration to postpone hundreds of drug company inspections, creating an enormous backlog that is delaying new drug approvals and leading the industry to warn of impending shortages of existing medicines.
…In an interview, F.D.A. officials said they sharply curtailed the inspections to protect their investigators, following guidelines from the Centers for Disease Control and Prevention, which discouraged federal employees from travel during the pandemic.
But some people in both industry and public health communities say that federal drug inspections are essential, and that the agency should bypass travel restrictions by taking precautions, including wearing proper personal protective equipment.
…In interviews, F.D.A. officials denied that the dramatic drop in inspections has slowed drug approvals. But a number of drug companies, including Spectrum Pharmaceuticals, Biocon Biologics and Bristol Myers Squibb, has issued statements noting deferred F.D.A. action because of the agency’s inability to conduct inspections.
In October, Spectrum announced that the F.D.A. had deferred action on its application for Rolontis, a treatment for cancer patients who have a very low number of certain white blood cells, because it could not inspect the manufacturing plant the company uses in South Korea.
In late December, Biocon Biologics notified shareholders that the F.D.A. deferred action on its joint application with Mylan for a proposed biosimilar to Avastin, a cancer drug.
Bristol Myers Squibb announced in November that the F.D.A. would miss its November deadline for taking action on a lymphoma treatment, lisocabtagene maraleucel because it could not inspect a third-party Texas manufacturing plant. The agency eventually did complete its inspection and approved the drug last month.
Grocery store workers are working, meat packers are working, hell bars and restaurants are open in many parts of the country but FDA inspectors aren’t inspecting. It boggles the mind.
Let’s review. The FDA prevented private firms from offering SARS-Cov2 tests in the crucial early weeks of the pandemic, delayed the approval of vaccines, took weeks to arrange meetings to approve vaccines even as thousands died daily, failed to approve the AstraZeneca vaccine, failed to quickly approve rapid antigen tests, and failed to perform inspections necessary to keep pharmaceutical supply lines open.
I am a long-time critic of the FDA and frankly I am stunned at the devastation.
New CRISPR-based COVID-19 test uses smartphone cameras to spot virus RNA
This one brings us closer to the Star Trek medical universe:
Scientists at UC Berkeley and Gladstone Institutes have developed a new CRISPR-based COVID-19 diagnostic test that, with the help of a smartphone camera, can provide a positive or negative result in 15 to 30 minutes. Unlike many other tests that are available, this test also gives an estimate of viral load, or the number of virus particles in a sample, which can help doctors monitor the progression of a COVID-19 infection and estimate how contagious a patient might be.
“Monitoring the course of a patient’s infection could help health care professionals estimate the stage of infection and predict, in real time, how long is likely needed for recovery and how long the individual should quarantine,” said Daniel Fletcher, a professor of bioengineering at Berkeley and one of the leaders of the study…
The new diagnostic test takes advantage of the CRISPR Cas13 protein, which directly binds and cleaves RNA segments. This eliminates the DNA conversion and amplification steps and greatly reduces the time needed to complete the analysis.
“One reason we’re excited about CRISPR-based diagnostics is the potential for quick, accurate results at the point of need,” [Jennifer] Doudna said. “This is especially helpful in places with limited access to testing or when frequent, rapid testing is needed. It could eliminate a lot of the bottlenecks we’ve seen with COVID-19.”
In the test, CRISPR Cas13 proteins are “programmed” to recognize segments of SARS-CoV-2 viral RNA and then combined with a probe that becomes fluorescent when cleaved. When the Cas13 proteins are activated by the viral RNA, they start to cleave the fluorescent probe. With the help of a handheld device, the resulting fluorescence can be measured by the smartphone camera. The rate at which the fluorescence becomes brighter is related to the number of virus particles in the sample.
And:
Now that the CRISPR-based assay has been developed for SARS-CoV-2, it could be modified to detect RNA segments of other viral diseases, like the common cold, influenza or even human immunodeficiency virus. The team is currently working to package the test into a device that could be made available at clinics and other point-of-care settings and that one day could even be used in the home.
“The eventual goal is to have a personal device, like a mobile phone, that is able to detect a range of different viral infections and quickly determine whether you have a common cold or SARS-Cov-2 or influenza,” Fletcher said. “That possibility now exists, and further collaboration between engineers, biologists and clinicians is needed to make that a reality.”
I recall once asking Silvana Konermann: “What am I going to buy at the CRISPR store?” Well, this is what you are going to buy at the CRISPR store.
Here is the article. And funded by Fast Grants, I am happy to say. Quite the week for science, yes?
Where We Stand
There is good news and there is bad news.
Let’s start with the good news.The early results from the Pfizer vaccine are very good, 90% efficacy. That will probably fall a bit but it’s very good news not just for the Pfizer vaccine but for most of the vaccines in the pipeline which target the spike protein.
The Pfizer vaccine does require very cold storage which means it won’t work for large parts of the world. A distribution plan is in place for most of the United States and Pfizer already has 50 million doses, which can cover ~25 million people, in storage.
Many thousands of people are dying every week so Pfizer should apply for and the FDA should issue a EUA without further delay.
One issue is, given limited supply, how to distribute the vaccine. I have suggested we randomize distribution across hospitals, police and fire stations, and nursing homes (see also my piece in Bloomberg with Scott Kominers, The Case for a COVID Vaccine Lottery.) A vaccine lottery is fair, it will make distribution easier by limiting the number of vaccination locations and it will in essence create a very large clinical trial. With millions of participants we will be better able to make fine distinctions between the vaccine’s safety and efficacy in different populations and the results will come in quickly. Thus, if we randomize and collect data, limited capacity has a silver lining.
Second issue. Manufacturing capacity. Pfizer will have enough capacity to produce 1.3 billion doses in 2021 which sounds like a lot but it’s a two dose vaccine and there will be losses in distribution so maybe 500 million people vaccinated. We need to vaccinate billions.
The cost to the world economy of COVID is in the trillions so we want to vaccine a lot faster. Faster than private markets are willing to go. There are other vaccines in the pipeline but we still need to ramp up capacity. Increasing capacity is something that Michael Kremer, Susan Athey, myself and others at Accelerating Health Technologies have been working on since the beginning of the crisis. It’s not too late to do more.
Third issue is testing. Trump got it into his head that more tests means more cases when in fact a lot more tests means fewer cases. There is a Laffer curve for testing. Our failure to get ahead of the virus with tests has meant hundreds of thousands of excess deaths. We are still failing this test. Winter is coming. Infections and deaths are both rising.
Biden won’t be president until late January but there are things he can do now. In particular, Congress already allocated $25 billion to testing in April—that was far too little. We spent trillions on relief and comparatively little fighting the virus. But here is the real shocker, most of the $25 billion allocated in April hasn’t been spent. Let me say that again, most of the money allocated for testing in April has not been spent. Biden can signal today that that money and more will be spent. He can also signal, as in fact he has, that he wants rapid antigen tests approved.
Rapid antigen tests are cheap, paper strip tests that can check for infectiousness and are ideal to getting things like the schools running again.
Even if we start vaccinating this year, we won’t vaccinate a majority of the US population until well into 2021. That’s true but what’s underappreciated is that testing, masks, social distancing and vaccines are complementary. The more people are vaccinated, for example, the greater our testing capacity rises relative to the population at risk.
The pandemic is getting worse not better but we did flatten the curve, albeit imperfectly, and now if we can summon the will, we have the tools including rapid antigen tests, vaccines and monoclonal antibodies to really crush the virus.
The Beginning of the End?
It’s taken far too long and it’s still not FDA approved for at-home use or for asymptomatic individuals but the new $5,15-minute, easy to use, Abbott test and the Trump administration’s promise to purchase 150 million of them is a big deal. Abbott has been building capacity for months according to their lead scientist interviewed in the Atlantic by Alex Madrigal and in a few weeks will be producing 50 million tests a month:
Madrigal: Fifty million tests a month is a huge number. That’s more than twice the number of tests the U.S. completes in a month. How did you ramp up production so massively?
Hackett: This was the challenge of this program. We needed some sort of reliable testing that could be affordable and that doesn’t require instrumentation. You need scale. The more frequently you could test people, frankly, even tests with lower sensitivity would be very effective at identifying people quickly and slowing the spread. As we were developing the test, there were people working in parallel looking at supply chain and logistics. Abbott took a lot of risk—hundreds of millions of dollars were spent building two new manufacturing facilities focused solely on those tests. We hoped we could come to a solution that would be where we needed it from an overall accuracy perspective, but if you weren’t building capability simultaneously, there was no way it could be the answer.
The US has performed about 80 million tests since the pandemic began, so an additional 50 million tests a month is a big increase in capacity. As noted, the test is not approved for at-home use but it’s a CLIA-waived test which means that a doctor’s office, a CVS or Walmart clinic, even a school nurse could qualify for a waiver and perform the tests. The test is not approved for asymptomatic individuals but I suspect that won’t mean much in practice, it can be prescribed off-label although the fact that a prescription is required is limiting. I hope the necessity for a prescription will be lifted as we get more experience with these tests. False positives (~1.5%) are low and by taking the strain off the PCR system we can improve triage and afford to do more double checks. False positives will be more of an issue as we wipe out the virus but that will take time.
I hope these tests will open up air travel within a month or two. I also hope to see more of these types of tests approved. Derek Lowe has more technical details.
It won’t be all smooth sailing, Abbott may not be able to produce as much or as quickly as they say they can and quality in the field may fall. The government may distribute the tests poorly. The virus could pickup in the fall, as in 1918. I expect more problems and challenges but we now have a chance to get ahead of the virus which is very welcome news.
Addendum: This type of public-private partnership with private firms building capacity in advance of approval for tests and vaccines on the foundation of government push and pull funding is exactly the structure that the Accelerating Health Technologies team has been recommending both to the US government and to governments around the world.
Shoring Up the Vaccine Supply Chain
Supply chains were hit hard early in the pandemic. Disinfectant couldn’t be produced because of a lack of bottles, tests couldn’t be processed because nasal swabs or PPE wasn’t available, the decline of passenger air traffic hit commercial delivery and so forth. I worry about forthcoming stresses on the vaccine supply chain. Billions of doses of vaccine will be demanded in the next year and a lot will depend on complicated supply lines including cold storage, air traffic, styrofoam, vials, bags, needles and many other inputs. Companies and the awesome team at CEPI (give them all a Nobel prize) are planning for vials and needles and other inputs but there are many non-obvious inputs higher up in the supply chain that also need shoring up.
Writing in Bloomberg, Scott Duke Kominers and I look at some of the odder inputs to vaccines like horseshoe crab blood, shark livers and the vaccinia capping enyzme, VCE. We are actually not too worried about horseshoe crab blood and shark livers as these are used in other industries. Shark livers, for example, are used to produce a lot of cosmetics so we should be able to divert supply as needed. VCE, however, is rarer.
DNA and mRNA vaccine technologies have shown promising results, and two of the leading vaccine contenders, from Pfizer Inc. and Moderna Inc., use mRNA technology. But mRNA has never been used to produce a commercial vaccine for humans, let alone at scale. And scaling these technologies may not be easy. In particular, mRNA degrades rapidly. To prevent this, it must be “capped” by a very rare substance called vaccinia capping enzyme.
Just over 10 pounds of this VCE is enough to produce a hundred million doses of an mRNA vaccine — but the current manufacturing processes for VCE require so much bioreactor capacity that making 10 pounds would cost about $1.4 billion. More important, global bioreactor capacity cannot support production at that level while also producing other vaccines and cancer-fighting drugs.
If we work hard now, we may be able to find more efficient means of producing VCE. Expanding bioreactor production and repurposing bioreactors from existing large-scale industrial applications will also help to lessen the pressure on the supply chains for multiple types of vaccines.
In addition to supply chains per se we also face the problem that companies are not raising prices enough. Ironically, this means that we need more public investment.
Of course, we might think that private companies would have incentives to coordinate supply chains themselves — and to some extent, they are doing so. But many have pledged to keep their vaccine prices close to costs, both out of altruism and because they may fear public backlash (or legal action) if they’re perceived as “price gouging” in the middle of a pandemic. And if companies don’t stand to profit much from Covid-19 vaccines, then they don’t have much incentive to invest in increasing capacity. In short: If prices can’t rise, then the only way to encourage companies to invest more in production is to reduce their costs — and that means we need public investment.
More generally, it’s not too late to be building more vaccine capacity and to repurpose bioreactor capacity from non-GMP sources, perhaps including veterinary and food sources. There are lots of vaccines in development. The science is promising. We need to take action now so that we can deliver on that promise.
Read the whole thing.