Results for “nasal” 27 found
Wednesday assorted links
1. Russian billionaire wants to buy cancelled Confederate statues.
3. Where are the missing right-wing firms? And Arnold.
6. An evidence-based return to work plan.
7. The nasal spray, which will be entering clinical trials.
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.
Save Grandma, Save the Economy
The meat supply is starting to fail. Meat processing factories seem especially susceptible to COVID-19 probably because of mist, chilled air circulation, the creation of aerosols and close worker contact. What other industries could be affected? What would happen if the energy, transportation, or pharmaceutical sector failed? We aren’t even sure which industries are critical. Who would have thought that nasal swabs would be a critical industry? In researching vaccine production I was stunned to learn that glass vials may be a bottleneck. Glass vials! How then do we best protect the workers in our critical industries? Should everyone else practice social distancing, closing of non-essential firms and work from home or should everyone else return to work as if everything were normal?
Social distancing, closing non-essential firms and working from home protect the vulnerable but these same practices protect workers in critical industries. Thus, the debate between protecting the vulnerable and protecting the economy is moot. “Lockdowns” protect vulnerable people and protect vulnerable industries. Save grandma, save the economy.
The point is simple but made formally in Social Distancing and Supply Disruptions in a Pandemic by Bodenstein, Corsetti and Guerrieri.
Abstract: Drastic public health measures such as social distancing or lockdowns can reduce the loss of human life by keeping the number of infected individuals from exceeding the capacity of the health care system but are often criticized because of the social and economic costs they entail. We question this view by combining an epidemiological model, calibrated to capture the spread of the COVID-19 virus, with a multisector model, designed to capture key characteristics of the U.S. Input Output Tables. Our two-sector model features a core sector that produces intermediate inputs not easily replaced by inputs from the other sector, subject to minimum-scale requirements. We show that, by affecting workers in this core sector, the high peak of an infection not mitigated by social distancing may cause very large upfront economic costs in terms of output, consumption and investment. Social distancing measures can reduce these costs, especially if skewed towards non-core industries and occupations with tasks that can be performed from home, helping to smooth the surge in infections among workers in the core sector.
Addendum: I wrote “lockdowns” because I am in favor of getting back to work with mass testing and safety protocols so I don’t think that a “lockdown” is necessarily the optimal policy. Indeed, I think we could get the meat processors back up and running with testing at the door and safety protocols. But we are not having a rational discussion about the tools and the investments that we need to reopen the economy. Instead, the people protesting to reopen the economy are also protesting against the use of a key tool to reopen the economy, masks! Welcome to crazy town.
Are humans constantly but subconsciously smelling themselves?
Here is the opening of a lengthy abstract of a new paper by Ofer Perl, et.al., and it may help explain why it is so hard to avoid touching your face:
All primates, including humans, engage in self-face-touching at very high frequency. The functional purpose or antecedents of this behaviour remain unclear. In this hybrid review, we put forth the hypothesis that self-face-touching subserves self-smelling. We first review data implying that humans touch their faces at very high frequency. We then detail evidence from the one study that implicated an olfactory origin for this behaviour: This evidence consists of significantly increased nasal inhalation concurrent with self-face-touching, and predictable increases or decreases in self-face-touching as a function of subliminal odourant tainting. Although we speculate that self-smelling through self-face-touching is largely an unconscious act, we note that in addition, humans also consciously smell themselves at high frequency.
File under Questions that are Rarely Asked, via Michelle Dawson.
Spit Works
A new paper finds that COVID-19 can be detected in saliva more accurately than with nasal swab. As I mentioned earlier a saliva test will lessen the need for personnel with PPE to collect samples.
Rapid and accurate SARS-CoV-2 diagnostic testing is essential for controlling the ongoing COVID-19 pandemic. The current gold standard for COVID-19 diagnosis is real-time RT-PCR detection of SARS-CoV-2 from nasopharyngeal swabs. Low sensitivity, exposure risks to healthcare workers, and global shortages of swabs and personal protective equipment, however, necessitate the validation of new diagnostic approaches. Saliva is a promising candidate for SARS-CoV-2 diagnostics because (1) collection is minimally invasive and can reliably be self-administered and (2) saliva has exhibited comparable sensitivity to nasopharyngeal swabs in detection of other respiratory pathogens, including endemic human coronaviruses, in previous studies. To validate the use of saliva for SARS-CoV-2 detection, we tested nasopharyngeal and saliva samples from confirmed COVID-19 patients and self-collected samples from healthcare workers on COVID-19 wards. When we compared SARS-CoV-2 detection from patient-matched nasopharyngeal and saliva samples, we found that saliva yielded greater detection sensitivity and consistency throughout the course of infection. Furthermore, we report less variability in self-sample collection of saliva. Taken together, our findings demonstrate that saliva is a viable and more sensitive alternative to nasopharyngeal swabs and could enable at-home self-administered sample collection for accurate large-scale SARS-CoV-2 testing.
The FDA has also just approved an at-home test collected by nasal swab, a saliva test should not be far behind.
Hat tip: Cat in the Hat.
The Roadmap to Pandemic Resilience
Led by Danielle Allen and Glen Weyl, the Safra Center for Ethics at Harvard has put out a Roadmap to Pandemic Resilience (I am a co-author along with others). It’s the most detailed plan I have yet seen on how to ramp up testing and combine with contact tracing and supported isolation to beat the virus.
One of the most useful parts of the roadmap is that choke points have been identified and solutions proposed. Three testing choke points, for example, are that nasal swaps make people sneeze which means that health care workers collecting the sample need PPE. A saliva test, such as the one just approved, could solve this problem. In addition, as I argued earlier, we need to permit home test kits especially as self-swab from near nasal appears to be just as accurate as nasal swabs taken by a nurse. Second, once collected, the swab material is classified as a bio-hazard which requires serious transport and storage safety requirements. A inactivation buffer, however, could kill the virus without killing the RNA necessary for testing and thus reduce the need for bio-safety techniques in transportation which would make testing faster and cheaper. Finally, labs are working on reducing the reagents needed for the tests.
Understanding the choke points is a big step towards increasing the quantity of tests.
Supply curves slope upward, Switzerland fact of the day, and how to get more tests done
Under Swiss law, every resident is required to purchase health insurance from one of several non-profit providers. Those on low incomes receive a subsidy for the cost of cover. As early as March 4, the federal health office announced that the cost of the test — CHF 180 ($189) — would be reimbursed for all policyholders.
Here is the article, that reimbursement is about 4x where U.S. levels had been. The semi-good news is that the payments to Abbott are going up:
The U.S. government will nearly double the amount it pays hospitals and medical centers to run Abbott Laboratories’ large-scale coronavirus tests, an incentive to get the facilities to hire more technicians and expand testing that has fallen significantly short of the machines’ potential.
Abbott’s m2000 machines, which can process up to 1 million tests per week, haven’t been fully used because not enough technicians have been hired to run them, according to a person familiar with the matter.
In other words, we have policymakers who do not know that supply curves slope upwards (who ever might have taught them that?).
The same person who sent me that Swiss link also sends along this advice, which I will not further indent:
“As you know, there are 3 main venues for diagnostic tests in the U.S., which are:
1. Centralized labs, dominated by Quest and LabCorp
2. Labs at hospitals and large clinics
3. Point-of-care tests
There is also the CDC, although my understanding is that its testing capacity is very limited. There may be reliability issues with POC tests, because apparently the most accurate test is derived from sticking a cotton swab far down in a patient’s nasal cavity. So I think this leaves centralized labs and hospital labs. Centralized labs perform lots of diagnostic tests in the U.S. and my understanding is this occurs because of their inherent lower costs structures compared to hospital labs. Hospital labs could conduct many diagnostic tests, but they choose not to because of their higher costs.
In this context, my assumption is that the relatively poor CMS reimbursement of COVID-19 tests of around $40 per test, means that only the centralized labs are able to test at volume and not lose money in the process. Even in the case of centralized labs, they may have issues, because I don’t think they are set up to test deadly infection diseases at volume. I’m guessing you read the NY Times article on New Jersey testing yesterday, and that made me aware that patients often sneeze when the cotton swab is inserted in their noses. Thus, it may be difficult to extract samples from suspected COVID-19 patients in a typical lab setting. This can be diligence easily by visiting a Quest or LabCorp facility. Thus, additional cost may be required to set up the infrastructure (e.g., testing tents in the parking lot?) to perform the sample extraction.
Thus, if I were testing czar, which I obviously am not, I would recommend the following steps to substantially ramp up U.S. testing:
1. Perform a rough and rapid diligence process lasting 2 or 3 days to validate the assumptions above and the approach described below, and specifically the $200 reimbursement number (see below). Importantly, estimate the amount of unused COVID-19 testing capacity that currently exists in U.S. hospitals, but is not being used because of a shortage of kits/reagents and because of low reimbursement. This number could be very low, very high or anywhere in between. I suspect it is high to very high, but I’m not sure.
2. Increase CMS reimbursement per COVID-19 tests from about $40 to about $200. Explain to whomever is necessary to convince (CMS?…Congress?…) why this dramatic increase is necessary, i.e., to offset higher costs for reagents, etc. and to fund necessary improvements in testing infrastructure, facilities and personnel. Explain that this increase is necessary so hospital labs to ramp up testing, and not lose money in the process. Explain how $200 is similar to what some other countries are paying (e.g., Switzerland at $189)
3. Make this higher reimbursement temporary, but through June 30, 2020. Hopefully testing expands by then, and whatever parties bring on additional testing by then have recouped their fixed costs.
4. If necessary, justify the math, i.e., $200 per test, multiplied by roughly 1 or 2 million tests per day (roughly the target) x 75 days equals $15 to $30 billion, which is probably a bargain in the circumstances.
5. Work with the centralized labs (e.g., Quest, LabCorp., etc.), hospitals and healthcare clinics and manufactures of testing equipment and reagents (e.g., ThermoFisher, Roche, Abbott, etc.) to hopefully accelerate the testing process.
6. Try to get other payors (e.g., HMOs, PPOs, etc.) to follow CMS lead on reimbursement. This should not be difficult as other payors often follow CMS lead.
Just my $0.02.”
TC again: Here is a Politico article on why testing growth has been slow.
Pooling to multiply SARS-CoV-2 testing throughput
Here is an email from Kevin Patrick Mahaffey, and I would like to hear your views on whether this makes sense:
One question I don’t hear being asked: Can we use pooling to repeatedly test the entire labor force at low cost with limited SARS-CoV-2 testing supplies?
Pooling is a technique used elsewhere in pathogen detection where multiple samples (e.g. nasal swabs) are combined (perhaps after the RNA extraction step of RT-qPCR) and run as one assay. A negative result confirms no infection of the entire pool, but a positive result indicates “one or more of the pool is infected.” If this is the case, then each individual in the pool can receive their own test (or, if we’re getting fancy [read: probably too hard to implement in the real world], perform an efficient search of the space using sub-pools).
To me, at least, the key questions seem to be:
– Are current assays sensitive enough to work? Technion researchers report yes in a pool as large as 60.
– Can we align limiting factors in testing cost/velocity with pooled steps? For example, if nasal swabs are the limiting reagent, then pooling doesn’t help; however if PCR primers and probes are limiting it’s great.
– Can we get a regulatory allowance for this? Perhaps the hardest step.Example (readers, please check my back-of-the-envelope math): If we assume base infection rate of the population is 1%, then pooling of 11 samples has a ~10% chance of coming out positive. If you run all positive pools through individual assays, the expected number of tests per person is 0.196 or a 5.1x multiple on testing throughput (and a 5.1x reduction in cost). This is a big deal.
If we look at this from the view of whole-population biosurveillance after the outbreak period is over and we have a 0.1% base infection rate, pools of 32 samples have an expected number of tests per person at 0.0628 or a 15.9x multiple on throughput/cost reduction.
Putting prices on this, an initial whole-US screen at 1% rate would require about 64M tests. Afterward, performing periodic biosurveillance to find hot spots requires about 21M tests per whole-population screen. At $10/assay (what some folks working on in-field RT-qPCR tests believe marginal cost could be), this is orders of magnitude less expensive than mitigations that deal with a closed economy for any extended period of time.
I’m neither a policy nor medical expert, so perhaps I’m missing something big here. Is there really $20 on the ground or [something something] efficient market?
By the way, Iceland is testing many people and trying to build up representative samples.
Emergent Ventures prize winners for coronavirus work
I am happy to announce the first cohort of Emergent Ventures prize winners for their work fighting the coronavirus. Here is a repeat of the original prize announcement, and one week or so later I am delighted there are four strong winners, with likely some others on the way. Again, this part of Emergent Ventures comes to you courtesy of the Mercatus Center and George Mason University. Here is the list of winners:
Social leadership prize: Helen Chu and her team at the University of Washington. Here is a NYT article about Helen Chu’s work, excerpt:
Dr. Helen Y. Chu, an infectious disease expert in Seattle, knew that the United States did not have much time…
As luck would have it, Dr. Chu had a way to monitor the region. For months, as part of a research project into the flu, she and a team of researchers had been collecting nasal swabs from residents experiencing symptoms throughout the Puget Sound region.
To repurpose the tests for monitoring the coronavirus, they would need the support of state and federal officials. But nearly everywhere Dr. Chu turned, officials repeatedly rejected the idea, interviews and emails show, even as weeks crawled by and outbreaks emerged in countries outside of China, where the infection began.
By Feb. 25, Dr. Chu and her colleagues could not bear to wait any longer. They began performing coronavirus tests, without government approval.
What came back confirmed their worst fear. They quickly had a positive test from a local teenager with no recent travel history. The coronavirus had already established itself on American soil without anybody realizing it.
And to think Helen is only an assistant professor.
Data gathering and presentation prize: Avi Schiffmann
Here is a good write-up on Avi Schiffmann, excerpt:
A self-taught computer maven from Seattle, Avi Schiffmann uses web scraping technology to accurately report on developing pandemic, while fighting misinformation and panic.
Avi started doing this work in December, remarkable prescience, and he is only 17 years old. Here is a good interview with him:
I’d like to be the next Avi Schiffmann and make the next really big thing that will change everything.
Here is Avi’s website, ncov2019.live/data.
Prize for good policy thinking: The Imperial College researchers, led by Neil Ferguson, epidemiologist.
Neil and his team calculated numerically what the basic options and policy trade-offs were in the coronavirus space. Even those who disagree with parts of their model are using it as a basic framework for discussion. Here is their core paper.
The Financial Times referred to it as “The shocking coronavirus study that rocked the UK and US…Five charts highlight why Imperial College’s research radically changed government policy.”
The New York Times reported “White House Takes New Line After Dire Report on Death Toll.” Again, referring to the Imperial study.
Note that Neil is working on despite having coronavirus symptoms. His earlier actions were heroic too:
Ferguson has taken a lead, advising ministers and explaining his predictions in newspapers and on TV and radio, because he is that valuable thing, a good scientist who is also a good communicator.
Furthermore:
He is a workaholic, according to his colleague Christl Donnelly, a professor of statistical epidemiology based at Oxford University most of the time, as well as at Imperial. “He works harder than anyone I have ever met,” she said. “He is simultaneously attending very large numbers of meetings while running the group from an organisational point of view and doing programming himself. Any one of those things could take somebody their full time.
“One of his friends said he should slow down – this is a marathon not a sprint. He said he is going to do the marathon at sprint speed. It is not just work ethic – it is also energy. He seems to be able to keep going. He must sleep a bit, but I think not much.”
Prize for rapid speedy response: Curative, Inc. (legal name Snap Genomics, based in Silicon Valley)
Originally a sepsis diagnostics company, they very rapidly repositioned their staff and laboratories to scale up COVID-19 testing. They also acted rapidly, early, and pro-actively to round up the necessary materials for such testing, and they are currently churning out a high number of usable test kits each day, with that number rising rapidly. The company is also working on identifying which are the individuals most like to spread the disease and getting them tested first. here is some of their progress from yesterday.
Testing and data are so important in this area.
General remarks and thanks: I wish to thank both the founding donor and all of you who have subsequently made very generous donations to this venture. If you are a person of means and in a position to make a donation to enable this work to go further, with more prizes and better funded prizes, please do email me.
A report from the hospital front, from a reliable source
I visited *** Health Center in ***. They are not a hospital, more like an urgent care clinic funded by the city and state. They act as triage for three area hospitals, take vital signs, can write prescriptions and send serious cases to Hospital ERs. They have been overwhelmed with people worried about COVID-19…They had been testing people for the virus; they have run out of re-agent so they have stopped that….If they were provided with isolation beds and ventilators, could they take 20 patients? No, it is not in their license and an application to change their license takes two years. When NYC reaches maximum hospital capacity, this clinic will not be part of the solution.
I visited [underfunded public health consortium] in ***, which was at the forefront of the response to H1N1 in 2009 and Sandy in 2012. They typically see 150 ER patients a day; during H1N1 they averaged 350 at the peak; they think they will be over 1000 during COVID-19….There is no such thing as a “test kit” which tests for the virus; when people talk about those kits, such as those dropped onto that cruise ship, they are talking about a nasal swab packaged with some reagent, which is then mailed to a facility with a Polymerase Chain Reaction Machine that can look for the RNA from the virus.
You can find PCR machines on eBay for $25,000; such a machine is labor intensive and can do maybe 10 tests a day. The hospital complex I visited, which has been designated a testing center, has been swabbing about 200 people a day and receiving multiples of that number from other hospitals. The vast majority they are sending off to a federal lab. Two weeks ago the turnaround time was three days; now it is five to six.
There are much faster machines. The Roche Cobas 6800 can do 3000 tests a day with very little human interaction; it costs $500k a year to rent, which is way outside a poor hospitals’s budget (while still not providing sufficient testing for the receiving area in the coming months.) Outside their budget until today, when we gave that money (I specified first year only, though they should be sure to ask in a year) as part of a larger check. We also gave money for 10 transport ventilators with two ports, 20 isolation beds, the money to hire 14 nurses for round the clock coverage of those beds for 6 weeks, and other things that they need. Overall it was a $1 million check, with a promise to talk to them in a week to cover anything we might have missed and to talk to them whenever they ask during the crisis. Overall, I was pretty happy with the visit. They were stunned, they work in a bureaucracy where everything takes 3 years.
One thing that they can’t get enough of is N-95s [face masks]. The first thing that almost every doctor I talked to mentioned was the frustration at having to re-use N-95’s, not for multiple patients, but for multiple days.
Again, here are the Emergent Ventures prizes to encourage work to support work to fight the coronavirus, and please support them if you can.
Are the people in Middletown, Ohio “killers”?
As their budgets strain, communities have begun questioning how much money and effort they should be spending to deal with overdoses, especially in cases involving people who have taken near-fatal overdoses multiple times. State and local officials say it might be time for “tough love”: pushing soaring medical costs onto drug abusers or even limiting how many times first responders can save an individual’s life.
“It’s not that I don’t want to treat overdose victims, it’s that the city cannot afford to treat overdose victims,” said Middletown Council Member Daniel Picard, noting this industrial town in northern Butler County might have to raise taxes in response to the crisis.
Often, the only thing separating whether an overdose victim goes to the hospital instead of the morgue is a dose of naloxone, also known by the brand name Narcan, a medication that can reverse the effects of opioid overdoses.
Two doses of an injectable form of naloxone, Evzio, cost $4,500, up from $690 in 2014. The price of other forms of the drug, including the nasally administered Narcan, typically range from $70 to $150 per dose, officials say.
…Here in Ohio, first responders say it’s not uncommon for overdose victims to have previously been revived with naloxone at least a half-dozen times.
…Picard, the council member, has proposed a controversial three-strikes policy in which first responders wouldn’t administer Narcan to repeated overdose victims.
Here is the Tim Craig at WaPo story. I do not know what is the proper response to such opioid cases, or how much money should be spent. I do know that somewhere, somehow a line has to be drawn. And if you are reading a discussion of health care policy that does not acknowledge such a line, and set out possible standards for it, beware of sophistry and illusion.
Question of the day
John Kerry’s energy plan calls for reducing U.S. oil imports by two million barrels per day, roughly the amount the country brings in from the Persian Gulf. So how come Kerry is simultaneously blasting George W. Bush for not pressuring OPEC to sell us more oil?
That is Gregg Easterbrook. But in lieu of the resource pessimism in the rest of Gregg’s post, read Nick Schulz:
One way to determine if gas is too expensive is to compare it to other products to see how much bang you get for your buck. Sen. Kerry chose to speak in San Diego in part because that city has, according to Reuters, the highest gas prices in the country at $2.12 a gallon. So how does that compare with other consumer products like, say, the source of the Heinz-Kerry fortune: ketchup?
At the big-box retail outlets Sam’s Club and Costco, ketchup sells for about $0.04 an ounce or $5.12 a gallon – a little more than twice the price of gas.
But that’s not the best comparison. Americans typically don’t buy gas in bulk the way they buy foodstuffs at Costco. Ketchup at a retail grocery store is $0.16 an ounce meaning it rings in at an impressive $20.48 a gallon, almost ten times what gas costs.
Gas is also cheaper than orange juice ($6.64 a gallon), Snapple ($10.32 a gallon); olive oil ($51.04 a gallon), eye drops ($995.84 a gallon) and nasal spray ($2,615.28 a gallon) according to figures from the Department of Labor, Consumer Price Index.
Follow Nick’s links as well, including to Lynne Kiesling, keep scrolling to get her full treatment of this issue.