Category: Medicine

Rapid progress from Fast Grants

I was pleased to read this NYT reporting:

Yet another team has been trying to find drugs that work against coronavirus — and also to learn why they work.

The team, led by Nevan Krogan at the University of California, San Francisco, has focused on how the new coronavirus takes over our cells at the molecular level.

The researchers determined that the virus manipulates our cells by locking onto at least 332 of our own proteins. By manipulating those proteins, the virus gets our cells to make new viruses.

Dr. Krogan’s team found 69 drugs that target the same proteins in our cells the virus does. They published the list in a preprint last month, suggesting that some might prove effective against Covid-19…

It turned out that most of the 69 candidates did fail. But both in Paris and New York [where the drugs were shipped for testing], the researchers found that nine drugs drove the virus down.

“The things we’re finding are 10 to a hundred times more potent than remdesivir,” Dr. Krogan said. He and his colleagues published their findings Thursday in the journal Nature.

The Krogan team was an early recipient of Fast Grants, and you will find more detail about their work at the above NYT link.  Fast Grants is also supporting Patrick Hsu and his team at UC Berkeley:

And the work of the Addgene team:

When will discrimination against superspreaders arrive?

Garett Jones emails me:

How soon until superspreader discrimination studies becomes an academic field? Is it already, on a Straussian level?

Will employment discrimination law react quickly or slowly?

IIRC after 9/11 it took about a year for the left to start bringing up serious concerns about detainee treatment.

Perhaps social media and the naturally greater sympathy people may have toward probabilistic superspreaders will encourage a faster response to the injustice of treating people differently on the basis of personal E(R0 | Covid +).

This will shape the medium-term spread of Covid if it hasn’t already.

Nursing homes across nations

This is all from Michael A. Alcorn, from my email, no further indentation offered:

“Just to keep hammering on this nursing home point… I saw your Tweet about Eastern vs. Western Europe and decided to explore the nursing home angle there too. The WHO has data on the number of nursing and elderly home beds for different countries here. Unfortunately, the data only goes up to 2013-ish for many countries, but it’s suggestive nonetheless.

Italy and France were clearly trending up seven years ago in its number of beds… would be interesting to see if Italy had a similar jump to Spain at some point. The number of beds gives us a proxy for the number of people who are highly vulnerable to COVID-19. Obviously, these countries have different total populations, but I don’t think that should matter too much because I suspect nursing homes tend to be highly concentrated within countries (e.g., how many of France’s nursing homes are in the Paris metro?). Based on what I’ve read about nursing home staff often being low paid and so perhaps coming to work when sick and working at multiple facilities, I suspect nursing home density is nonlinearly related to the number of COVID-19 deaths in a country (especially when you account for some of the truly horrifying government decisions regarding nursing homes).

Here are those Nordic countries everyone likes to compare:

You can get exact numbers on the website, but Sweden had twice as many nursing home beds as Finland and three times as many as Norway. The ship might have sailed on what we can do to protect these vulnerable populations, but I would love to see a Fast Grant go towards investigating the COVID-19/nursing home tragedy.”

USA non-existing facts of the day

Want to know how many tuberculosis cases there were in the U.S. last year? Ask the CDC. Want to know about health-care-associated infections? Ask the CDC. It knows.

But ask how many Covid-19 tests have been done, and the CDC’s doesn’t have an answer. Want a daily update on how many people are getting hospitalized for Covid-19? The CDC isn’t tracking it. Want to know if social distancing is making a difference? The CDC doesn’t know.

During this pandemic, when accurate, timely, nationwide information is the lifeblood of our response, the CDC has largely disappeared.

The performance of the world’s leading public health agency has been surprising, and by that I mean surprisingly disappointing. When the outbreak began, the CDC decided to forgo using the World Health Organization’s testing kit for Covid-19 and build its own. The test it shipped out to states was faulty, creating problems that stretched for weeks and slowed response as states waited for replacement tests.

Here is more from Ashish K. Jha.  As I’ve said before, our regulatory state has been failing us.

Washington Post covers Fast Grants

Here is the opening:

Economist Tyler Cowen first sounded the alarm that America is unprepared for a pandemic in 2005, when he wrote a paper outlining ways the country should respond and, for a few years, ran a blog focused on the possibility of an avian flu outbreak.

Fifteen years later, as a novel coronavirus brings Cowen’s fears into reality, the George Mason University professor is trying to fix what he and others view as a structural problem impeding the scientific response to the crisis: the months-long application and review process scientists must endure to get their research funded.

Here is the full story by Will Hobson.  Recommended.

How tourism will change

That is the topic of my latest Bloomberg column, here is one bit:

Some of the safer locales may decide to open up, perhaps with visitor quotas. Many tourists will rush there, either occasioning a counterreaction — that is, reducing the destination’s appeal — or filling the quota very rapidly. Then everyone will resume their search for the next open spot, whether it’s Nova Scotia or Iceland. Tourists will compete for status by asking, “Did you get in before the door shut?”

Some countries might allow visitors to only their more distant (and less desirable?) locales, enforcing movements with electronic monitoring. Central Australia, anyone? I’ve always wanted to see the northwest coast of New Zealand’s South Island.

Some of the world’s poorer countries might pursue a “herd immunity” strategy, not intentionally, but because their public health institutions are too weak to mount an effective response to Covid-19. A year and a half from now, some of those countries likely will be open to tourism. They won’t be able to prove they are safe, but they might be fine nonetheless. They will attract the kind of risk-seeking tourist who, pre-Covid 19, might have gone to Mali or the more exotic parts of India.

And:

laces reachable by direct flights will be increasingly attractive. A smaller aviation sector will make connecting flights more logistically difficult, and passengers will appreciate the certainty that comes from knowing they are approved to enter the country of their final destination and don’t have to worry about transfers, delays or cancellations. That will favor London, Paris, Toronto, Rome and other well-connected cities with lots to see and do. More people will want to visit a single locale and not worry about catching the train to the next city. Or they might prefer a driving tour. How about flying to Paris and then a car trip to the famous cathedrals and towns of Normandy?

Maybe. But I might start by giving Parkersburg, West Virginia, a try.

Universities with Hospitals and Labs

Mitch Daniels, the President of Purdue, has outlined a preliminary plan to reopen involving test, trace and supported isolation on campus.

We intend to know as much as possible about the viral health status of our community. This could include pre-testing of students and staff before arrival in August, for both infection and post-infection immunity through antibodies. It will include a robust testing system during the school year, using Purdue’s own BSL-2 level laboratory for fast results. Anyone showing symptoms will be tested promptly, and quarantined if positive, in space we will set aside for that purpose.

We expect to be able to trace proximate and/or frequent contacts of those who test positive. Contacts in the vulnerable categories will be asked to self-quarantine for the recommended period, currently 14 days. Those in the young, least vulnerable group will be tested, quarantined if positive, or checked regularly for symptoms if negative for both antibodies and the virus.

This paper provides details on transforming a university lab into a testing center. In essence, a major university with a hospital (which Purdue doesn’t have) should be able to do it technically but to work to reopen for students it probably has to be a university located outside of a major urban area. Here are a few possibilities:

  • Baylor University
  • Vanderbilt University
  • University of Michigan, Ann Arbor
  • University of Virginia
  • University of Iowa
  • University of Utah
  • University of Alabama

Mitch Daniel also notes:

Our campus community, a “city” of 50,000+ people, is highly unusual in its makeup. At least 80% of our population is made up of young people, say, 35 and under. All data to date tell us that the COVID-19 virus, while it transmits rapidly in this age group, poses close to zero lethal threat to them.

which does seem to miss (ahem) an important group necessary for reopening.

My Conversation with Glen Weyl

I found it interesting throughout, the first half was on Covid-19 testing, and the second half on everything else.  Here is the audio and transcript.  Here is the summary:

Tyler invited Glen to discuss the plan, including how it’d overcome obstacles to scaling up testing and tracing, what other countries got right and wrong in their responses, the unusual reason why he’s bothered by price gouging on PPE supplies, where his plan differs with Paul Romer’s, and more. They also discuss academia’s responsibility to inform public discourse, how he’d apply his ideas on mechanism design to reform tenure and admissions, his unique intellectual journey from socialism to libertarianism and beyond, the common element that attracts him to both the movie Memento and Don McLean’s “American Pie,” what talent he looks for in young economists, the struggle to straddle the divide between academia and politics, the benefits and drawbacks of rollerblading to class, and more.

Here is one excerpt:

And:

And:

For me the most instructive part was this:

COWEN: What do you view yourself as rebelling against? At the foundational level.

But you will have to read or listen to hear Glen’s very good answer.

Definitely recommended.

Modeling COVID-19 on a network: super-spreaders, testing and containment

These would seem to be some important results:

To model COVID-19 spread, we use an SEIR agent-based model on a graph, which takes into account several important real-life attributes of COVID-19: super-spreaders, realistic epidemiological parameters of the disease, testing and quarantine policies. We find that mass-testing is much less effective than testing the symptomatic and contact tracing, and some blend of these with social distancing is required to achieve suppression. We also find that the fat tail of the degree distribution matters a lot for epidemic growth, and many standard models do not account for this. Additionally, the average reproduction number for individuals, equivalent in many models to R0, is not an upper bound for the effective reproduction number, R. Even with an expectation of less than one new case per person, our model shows that exponential spread is possible. The parameter which closely predicts growth rate is the ratio between 2nd to 1st moments of the degree distribution. We provide mathematical arguments to argue that certain results of our simulations hold in more general settings.

And from the body of the paper:

To create containment, we need to test 30% of the population every day. If we only test 10% of the population every day, we get 34% of the population infected – no containment (blue bars).

As for test and trace:

Even with 100% of contacts traced and tested, still mass-testing of just over 10% of the population daily is required for containment.

The authors are not anti-testing (though relatively skeptical about mass testing compared to some of its adherents), but rather think a combination is required in what is a very tough fight:

Our simulations suggest some social distancing (short of lockdown), testing of symptomatics and contact tracing are the way to go.

That is all from a new paper by Ofir Reich, Guy Shalev, and Tom Kalvari, from Google, Google, and Tel Aviv University, respectively.  Here is a related tweetstorm.  With this research, I feel we are finally getting somewhere.

Human Challenge Trials for vaccines

From an anonymous reader:

As you are of course aware, testing on vaccines for Covid-19 are beginning to be undertaken. The scientific community has seemingly decided that Human Challenge Trials (HCT) where test subjects are directly exposed to the virus following vaccination are unethical, instead using the typical protocol of vaccine/placebo inoculation followed by months of observation in order to observe effectiveness. This seems to me a grave moral error based on the following argument.

1) There exists a large cohort of young, healthy, fully informed, willing participants who would undergo HCT.

2) Given the mortality profile of this disease, these participants would be undertaking an exceptionally small mortality risk (perhaps 5-10 per 100k, based on data from Spain/Italy/NYC, assuming zero vaccine effectiveness).

3) Society deems acceptable other activities with much higher fatality risk (at least 5-10x) in both professional (soldiers, logging workers) and recreational (motorcycling, mountaineering) capacities.

4) HCT would speed up the vaccine testing process by many months, saving tens of thousands of lives and avoiding enormous economic damage.

5) HCT actually poses significantly less risk to participants in terms of allergic reaction or ADE risk compared to a standard testing protocol since the number of participants could be much smaller and they would be medically observed.

I fail to find any ethical justification for the current stance of the medical community, from either a utilitarian or deontological perspective, and believe a highly consequential error is being made. This error may be based on false analogies to past unethical testing practices in history where participants were not informed or willing and danger was significant. The current case bears no ethical resemblance, in my judgement, to these past cases.

The simplest model of such errors is that many members of the biomedical establishment do not wish to have bad feelings about any “sins of commission” and to see their status lowered as a result of “dirty hands,” and the readily criticized logistics of Human Challenge Trials.  Since HCTs do not “feel right” to them, they self-deceive into associating that feeling with a concern for the greater public good.

You should not be surprised to see grave moral errors committed in a crisis, however.  Our “mainstream” protection against grave moral errors, in normal circumstances, simply is that usually we are not given the opportunity to commit them.

I do understand that a Human Challenge Trial does not necessarily suffice to show that a given vaccine is safe.  Nonetheless it should be in the “armor of our discourse,” so to speak, as a morally acceptable alternative.  So if you are a biomedical professional, or a public intellectual, I hope you will speak up.

Here is a Matt Yglesias piece on the urgency of developing a vaccine as quickly as possible.  Eric Weinstein notes that women risk their lives every time they proceed with having children.

Early detection of superspreaders by mass group pool testing

Most of epidemiological models applied for COVID-19 do not consider heterogeneity in infectiousness and impact of superspreaders, despite the broad viral loading distributions amongst COVID-19 positive people (1-1 000 000 per mL). Also, mass group testing is not used regardless to existing shortage of tests. I propose new strategy for early detection of superspreaders with reasonable number of RT-PCR tests, which can dramatically mitigate development COVID-19 pandemic and even turn it endemic. Methods I used stochastic social-epidemiological SEIAR model, where S-suspected, E-exposed, I-infectious, A-admitted (confirmed COVID-19 positive, who are admitted to hospital or completely isolated), R-recovered. The model was applied to real COVID-19 dynamics in London, Moscow and New York City. Findings Viral loading data measured by RT-PCR were fitted by broad log-normal distribution, which governed high importance of superspreaders. The proposed full scale model of a metropolis shows that top 10% spreaders (100+ higher viral loading than median infector) transmit 45% of new cases. Rapid isolation of superspreaders leads to 4-8 fold mitigation of pandemic depending on applied quarantine strength and amount of currently infected people. High viral loading allows efficient group matrix pool testing of population focused on detection of the superspreaders requiring remarkably small amount of tests. Interpretation The model and new testing strategy may prevent thousand or millions COVID-19 deaths requiring just about 5000 daily RT-PCR test for big 12 million city such as Moscow.

Speculative, but I believe this is the future of our war against Covid-19.

The paper is by Maxim B. Gongalsky, via Alan Goldhammer.

A vaccine from Oxford?

In the worldwide race for a vaccine to stop the coronavirus, the laboratory sprinting fastest is at Oxford University.

Most other teams have had to start with small clinical trials of a few hundred participants to demonstrate safety. But scientists at the university’s Jenner Institute had a head start on a vaccine, having proved in previous trials that similar inoculations — including one last year against an earlier coronavirus — were harmless to humans. That has enabled them to leap ahead and schedule tests of their new coronavirus vaccine involving more than 6,000 people by the end of next month, hoping to show not only that it is safe, but also that it works.

The Oxford scientists now say that with an emergency approval from regulators, the first few million doses of their vaccine could be available by September — at least several months ahead of any of the other announced efforts — if it proves to be effective.

Here is more from the NYT.  I do not have a personal opinion on the specifics of this development, but it seems worth passing along.

The lockdown culture that is Singapore

S’porean man charged in court for leaving home 30 minutes before quarantine ended to get breakfast

And:

According to CNA, Tay is accused of leaving his home in Choa Chu Kang between 11:30am and 12pm, half an hour before his quarantine ended.

He thus breached his quarantine order by leaving his home to go to his neighbourhood shopping mall for breakfast without getting the permission of the Director of Medical Services, said the MOH release.

And:

The day prior, Thursday, Apr. 23, 34-year-old Alan Tham was sentenced to six weeks’ imprisonment for breaching his Stay-Home Notice (SHN) to eat bak kut teh.

To be clear, I am fine with Singapore doing this, but it hard to imagine the United States enforcing quarantine with the same vigor.  And on the other side, I might risk prison for laksa, but for bak kut teh?

For the pointer I thank Tuvshinzaya.  and Jeet Heer asks:

I have to confess I’m becoming more pessimistic since I don’t see much signs that most countries outside Asia & the Pacific are developing the testing-tracing-isolation capabilities needed. Am I wrong about this?

Model this, coronavirus stupidity edition

A [NY] state guideline says nursing homes cannot refuse to take patients from hospitals solely because they have the coronavirus.

Here is the NYT article, with much more detail.  Here is a previous MR post Claims About Nursing Homes.  Via Megan McArdle.

And from a formal study:

Twenty-three days after the first positive test result in a resident at this skilled nursing facility, 57 of 89 residents (64%) tested positive for SARS-CoV-2.

The Decline of the Innovation State is Killing Us

The latest relief bill contains another $320 billion in small business relief and $25 billion for testing. Finally, we get some serious money to actually fight the virus. But as Paul Romer pointed out on twitter, this is less than half of what we spend on soft drinks!!! (Spending on soft drinks is about $65 billion annually). Soda is nice but it is not going to save lives and restart the economy. Despite monumental efforts by BARDA and CEPI we are also not investing enough in capacity for vaccine production so that if and when when a vaccine is available we can roll it out quickly to everyone (an issue I am working on).

The failure to spend on actually fighting the virus with science is mind boggling. It’s a stunning example of our inability to build. By the way, note that this failure has nothing to do with Ezra Klein’s explanation of our failure to build, the filibuster. Are we more politically divided about PCR tests than we are about unemployment insurance? I don’t think so yet we spend on the latter but not the former. The rot is deeper. A failure of imagination and boldness which is an embarrassment to the country that put a man on the moon.

In Launching the Innovation Renaissance I said the US was a welfare/warfare state and no longer an innovation state. The share of R&D in the Federal Budget, for example, has diminished from about 12% at its height in the NASA years to an all time low of about 3% in recent years. We are great at spending on welfare and warfare but all that spending has crowded out spending on innovation and now that is killing us.