Immunity Passes Must Be Combined With Variolation

I wrote earlier that “recovered individuals have a kind of superpower and would be highly desirable workers.” Antibody tests will soon be able to identify these workers and that will help to reopen the economy because not only can these workers go back to work relatively safely they can also work relatively safely with those who are not immune, thus a kind of multiplier-effect for the workplace. Hence, Italy and the UK are talking about “Immunity Passes” that would allow (we hope) immune workers to go back to work.

One factor, however, which hasn’t been taken into account is that the demand to go back to work may be so strong that some people will want to become deliberately infected. If not done carefully, however, these people will be a threat to others, especially in their asymptomatic phase. Thus, if we use Immunity Passes they will need to be combined with variolation, infecting people with small doses of the virus to create immunity under controlled conditions, as suggested by Robin Hanson.

Hat tip for discussion: Rafael Yglesias.

Comments

Will Hanson get the Nobel, or tried at the Hague? Time will tell!

Has he volunteered yet for herd immunity? You don't need doctors just hang outside Helmhurst hospital in NYC, go sing at a megachurch, or get some bat soup in Chinatown.

As Hanson has emphasized, in order to be beneficial variolation has to be followed immediately with very careful isolation, preferably in a designated hotel/hospital facility. If you purposefully infect yourself and then just go about social distancing at the same level as the rest of the population, you're causing net harm. Furthermore, the sort of amateur deliberate infection you're suggesting wouldn't be at all reliable, so you would never know exactly when to stop attempting infection and start quarantine.

Because no such official quarantine facilities exists, private citizens cannot variolate safely. If such a facility existed, I'd volunteer to variolate.

Will there be state of the art sexbots employed?

@Jess Riedel - well said, though arguably getting a blood transfusion from somebody who survived Covid-19 might arguably (maybe, more research is needed) the the same as variolation. Recall in variolation you use a weakened form of the virus, such as the pus from cowpox/smallpox from nearly recovered patients.

Would *I* volunteer for herd immunity? Hell no. My hope is with my isolation, money and servants (I have some now) I can be in the happy 40% that doesn't need to be infected but free rides on the 60% who do get infected and develop herd immunity, and eventually the disease burns out. That's assuming C-19 is not like the measles, where due to R0 the herd immunity fraction of the population is not 60% but something like 95%. But so far C-19 seems not like the measles.

He Who Defends Everything, Defends Nothing.

Thank goodness for A, otherwise we'd need a whole industry of scientists and medical doctors trying to build safe vaccines to "build immunity." Unreal.

Make it official then. Put them up in a secure hotel, spray the virus up their noses yourself. Better yet, give them the vaccines first, see if they work.

I'd bet there is no shortage of people who are willing to be guinea pigs and risk getting a disease that is probably <0.01% fatal, with a majority of cases being asymptomatic, to get back to work. That is to say that the consequences of this massive lockdown are for most people more harmful than the virus itself (especially considering it had been running through the US at least two months before anyone knew to test for it).

You first, Herder. FYI variolation involves small, weakened live doses of the virus, compare to a vaccine, which involves inactive or killed viruses.

Cool story, Ed Jenner, but unless you're planning on losing a bunch of Boomers you'll need to work on the vaccines.

A true libertarian would want to ensure costs of the approach are internalized first, though. Who pays for hospitalization or ICU care of people who want to be deliberately infected? Should life insurance cover death benefits in the event they die? What about disability benefits if it turns out some infected people suffer permanent lung damage that limits their ability to work? If the costs of these risks were all priced out and passed along to volunteers, the number of such volunteers may be fewer than you think.

A true libertarian would be out in the streets right now (maybe figuratively) protesting the series of power grabs by the government that has caused him to lose his freedom and livelihood. Leave it to MR to conflate them with actuaries.

No, a true libertarian would be hoarding all the toilet paper to price gouge the local neighbors. It's so easy to clean out rural areas. They only have like one Walmart in 60 mile radius.

That is the ob of my local corner market, and the owner does a good job.

There is no way this disease is only 0.01% fatal. More than 0.01% of the total population has already died in Spain and Italy.

0.00000006% of the population of India has died. What's your point?

China's fatality rate is way lower than 0.01%.

Italy, NYC (and its CT and NJ bedroom suburbs), and Spain are extreme outliers. Even now, NYC subways are too-crowded and no masks.

Here's something. Early 5 April: USA 8,454 KIA; 330,000,000 population: ((8,454 / 330,000,000) * 100)) = 0.00256%, or three per 100,000. If you adjust for 60+ year-olds and those with existing, critical medical issues, the morbidity is much lower.

I'm thinking about my three sons, three daughters-in-law, and six grandchildren. American needs to get back to work ASAP. FYI I'm 70 with an underlying condition. So, I'll stay home, wash my hands, avoid close contact.

I thought you were happily going shopping just a few short days ago. What has changed - scared of the 'flu' you used to scorn? Maybe after becoming aware that drowning in your own lung fluids is probably worth avoiding, after mocking all those fearmongers and TDS victims who were attempting to reduce what NY is now experiencing?

Your nation-destroying lockdowns have been in force for three weeks and they are failing.

I know. I know.

It would be a gajillion times worse if we weren't wrecking the country.

Case fatality is highly stratified, with all age groups under 40 having a rate < 0.1%, but raising sharply by decade after 50 to a near 25% fatality rate above 80. Of course case fatality overstates the overall risk, as currently mostely severe cases are being diagnosed.

Presumably not many 80 year olds would choose to self infect. Rather than a general lockdown, a boomers only lockdown would save as many boomer lives, but also not destroy the economic future of the rest of the population.

... but 'Blackmarkets' will also arise in counterfeit “Immunity Passes”.

Politicians and economists seem to blithely ignore the whole issue of blackmarkets as draconian government Corona lockdowns on the economy.

"SpeakEasy" alcohol bars are already sprouting up in my county after government shutdown of all normal bars.
Blackmarket retail outlets for banned "non-essential" goods/services are also evident on small scale.

I live in downtown Chicago, a few blocks from Willis Tower (neé Sears). There used to be a bar here with an active whorehouse upstairs, but other than a very small coffeehouse that allows seated customers I know of no establishment operating outside the law. If there were a speakeasy here, I'd be there every day.

"some people will want to become deliberately infected"

That is a worse selection pool than drivers who think they'll make money with Uber. Or day trading.

IOW a few foolish people should not set policy.

Just so you know, the reason you support authoritarian technocrats like Elizabeth Warren is because you believe there are more than a few foolish people. You can stop pretending otherwise.

lol.

Do you think geniuses elected Donald J. Trump?

Because the rich desiring tax cuts got precisely who they wanted elected, compared to Sanders or Hellary..

The stock market crash is not really Trump's fault in the sense that this pandemic is global.

The rich always want tax cuts, that's a given. But what's interesting is the vibe they tapped and the alliance they formed with 'anti-elite' populists.

Think back a moment to the number of times Trumpists have called Tyler an 'elite' in these pages. It is not because he was born to wealth or power. Middle class background, education, teaching.

But somehow they chose the guy with gold furniture as their symbol of anti-elitism.

Or celebration of stupidity.

The rich will tap into any vibe that allows them to grow richer, whether religious fundamentalists like Falwell, gun lovers like Wayne LaPierre, or whatever media shills they can attract.

And Tyler is a variety of elite by most reasonable measures, before we started defining elite by the standards of lifestyles of the rich and famous, back in the Reagan era.

I was tempted to let that bad answer rot in the field.

But it might be useful to point out the source of your error.

It is not actually useful to declare that functional meritocracy is the same as plutocracy, or oligarchy.

Related, in terms of keeping our eyes on the ball:

"My dad’s an ER doctor. He just got off of a conference call. His hospital is cutting his salary - and everyone else’s that works on the front lines - because they’re losing money from non-COVID patients.

Cutting medical personnels’ salaries right now. I mean... what the fuck?"

https://twitter.com/CameronNBeach/status/1246183339364622336?s=19

It looks like our whole ER system is a big fraud. Suddenly people have less emergencies because they are scared of the virus, which means less money going to hospitals and healthcare workers. Similar to our unsustainable financial system that hit an all-time high in February that one month later is on life support needing a bailout.

This virus is like the tide that went out on our previously fake way of life. Putting a reality TV dotard in the White House who had no f*cking clue about public health even though that's his job is very fitting considering the long running joke we've played on ourselves in America.

Emergency rooms can be hazardous to your financial health. As anyone who's gone to an emergency room at an in-network facility only to find out later that all the physicians working there were out-of-network, and subsequencly received a stupendous balance-bill, would know.

So, if/when you start coughing and your fever spikes and you want to do the public-spirited thing by getting tested and isolating yourself if test positive for the virus, keep in mind that although your lab work may be covered you can stilla massive bill for services rendered should you present at an ER.

Sucker.

The government has heavily regulated the health care system and imposed the lockdown, and the left's impulse is to blame greedy corporations and whine about drowning government rather than drowning in government. If you want the health care system to focus on almost exclusively on the CCP-Coronavirus for the indefinite future, then put your money where your TDS mouth is and pay up.

TDS, eh?

"NEW: Inside the White House Situation Room yesterday, economic adviser Peter Navarro got into a heated dispute with infectious disease expert Dr. Anthony Fauci over the efficacy of the antimalarial drug hydroxychloroquine."

https://t.co/lvpf9HRxy5

File under sh*t you can't make up.

Yes, classic TDS. Change subjects to shiny TDS story that has nothing to do with the salary issue that you yourself raised.

@anonymous:

... Relax -- ObamaCare is still in effect.

Pelosi and the Democrats totally fixed the American healthcare system for all, under all circumstances; doctors and patients now get exactly what the Democrats delivered.

Obamacare was not a perfect solution to anything, but it's a complete lie that it's in full effect, or that it is fully supported.

https://www.cnn.com/2020/04/04/politics/health-care-covid-obamacare-republicans-trump-2020/index.html

Kind of a sick joke to pretend otherwise, right?

You are busy drowning the government in a bathtub, and as the government gasps and sputters, you say

"Why aren't you helping me with this pandemic?"

The bathtub-drowners aren't the ones who want or need government help. The "help", in fact, is unnecessarily impeding their daily lives. This is primarily a problem with blue areas, and one that is a long time coming at that.

That one I can let compost.

There's a rather obvious pattern here:

January: "it's only a China problem"
February: "it's only affecting parts of Europe and Asia"
March: "ok, it's affecting the U.S. but mostly New York, California, and Seattle"
April: ...

Since you're good at picking out obvious patterns you ought to be able to recognize the obvious fact that a disease is going to have a harder time moving through a population that has fewer contacts on a daily basis, which increases the probability that those who get it can isolate before infecting others. Combine that with the fact that the same group of people are more self-sufficient on average and it's not hard to imagine that they can get through this without a whole lot of outside intervention, as opposed to the cosmopolitan urbanites.

Or who knows, maybe the new 5%. This sort of speculation is just another fantasy, at least at this point. Preliminary data concerning antibody prevalence in a severely affected German area (Heinsberg) will be available in a week or two. No one is currently expecting even 5% of the population of the most severely affected area in Germany to have antibodies, but that is why testing is good. It allows for well founded policy decisions, as compared to whatever such posts as these represent.

Current numbers from Heinberg, population 254,000 - confirmed covid 19 infections on 3. April 2020: 1436. Using the Italian ratio of one known to 10 unknown, about 5.5% of the population has been infected. However, considering that there are still 626 infected people, the current (simplified) available work force is under 3%. Or less realistically, based only on confirmed cases (which one assumes would then be certified as infected and recovered quickly), .3%

And really, let us just at least get around to the next fall and winter before making uninformed guesses about immunity about a novel pandemic virus.

If variolation is so easy, how come nobody has done it yet? I barely see it discussed anywhere.

Go read the reports of 30 or 40-year-olds who have gone through a bad case of COVID-19. The idea is completely nuts.

To be fair, Hanson's whole shtick here is that deliberate variolation with low doses done right will reduce the percentage those bad cases at least 3 times.
Big if true but the question is - is it true?

I've seen nothing specifically on COVID, I think it is all extrapolation from other diseases.

The issue is about dosage level and symptom intensity. That data is very scarce at the moment.

There won't be any data on that unless they run human trials with dosage control during exposure.
This will not happen hence Hanson's proposal will never be adopted.
It's just another one of his fantasies where he proposes something that no sane person will adopt even if it is rational.

Another factor in proper variolation is location. Since COVID is a respiratory disease, you wouldn't deliberately infect someone, even with a weakened virus, via the respiratory system.

We will likely find out after the fact that most of the younger, healthy people who died from COVID were in situations where they were getting relatively large doses of the most active virus directly into the lungs. Under those circumstances, the immune system struggles to create enough antibodies before the fatal damage is done.

At least in the West, doctors and the associated regulatory authorities have a very strong aversion to taking direct action with the potential to injure otherwise healthy people: the whole "first do no harm" concept.

As of now, I don't think it's even the plan to intentionally expose vaccinated people to the novel coronavirus to speed up vaccine trials. (At least one bioethicist has argued that it should be done, but I'm pretty sure that's not the design of the trial underway in Seattle and Atlanta - https://www.kpwashingtonresearch.org/news-and-events/recent-news/news-2020/kaiser-permanente-launches-coronavirus-vaccine-study-seattle )

Secondary point even if someone thinks variolation is a good idea - there's an issue of resources and organization. The people who would implement such a variolation program are currently focused on dealing with treatment of *non-intentional* COVID-19 infection, whether that's direct care, testing, or treatment ideas (such as convalescent plasma treatment using blood donations from those who were already infected.)

For example, part of variolation would probably be quarantining the people who have been intentionally exposed. Any site being converted for quarantine, however, is being used for infected patients instead.

Having antibodies protects the recovered but can they still infect others? If so then we aren't out of the woods yet. I'm worried about the next wave of infections.

And the more people care about the economy or sports or going to church, the bigger the second wave will be.

Incubation period mean : 5.1 days. Most people not infectious 10 days after symptoms. Can be infectious before symptoms.
We can use a negative RT-PCR two days in a row to clear people

N N Taleb's reaction to hearing Robin Hanson's plan was to call him a dangerous lunatic and an example of an Intellectual Yet Idiot. Doesn't look like that has dissuaded Tabarrok or even made him consider the risks here.

What mortality rate would Tabarrok and Hanson predict from variolation? How many instances would there be of long-term damage to lungs, kidneys, the heart and brain? These were observed in multiple previously healthy patients.

https://amp.france24.com/en/20200402-for-some-survivors-coronavirus-complications-can-last-a-lifetime?__twitter_impression=true

How confident are Hanson and Tabarrok in pushing this as a policy response given they have practically zero knowledge of epidemiology, virology and public health?

Are they able to explain why variolation would work based on what they know about Covid-19's biology and etiology? Do they even know it's an RNA virus and not a DNA virus like smallpox?

Variolation is a small dose( the smallest actually) of a live virus, so it’s basically getting infected.
1- We know the people who recover from this virus get some immunity They produce antibodies and there’s no credible report of reinfection or at least it’s rare. In the case of SARS-Cov, recovered patients have antibodies for ~ 2 years. Infected patients also get immunity for 1 to 2 years for the other 4 less dangerous Coronavirus, so we can expect something similar for SARS- CoV2
Lasting lung damage is not the norm. It’s not from the virus but from the patient out of control immune system response (cytokine storm). This happens in some older patients with comorbidities. They’re not the candidates for variolation. He proposes healthy and young people. .

Yes, no young or healthy people have died or had lung damage. It just hasn't happened. Why can people not see this obvious fact?

I am sure you can find some cases Kevin, it's the frequency that's important and the underlying conditions of the patient. Those with lung damage are unable to tolerate the negative consequence of the immune response to infection. This happens with influenza too. They are typically much older people.
" We show that IAV ( type A influenza virus)-infected monocytes from older humans have impaired antiviral interferon production but retain intact inflammasome responses."
https://www.ncbi.nlm.nih.gov/pubmed/27102485

“Infected patients also get immunity for 1 to 2 years for the other 4 less dangerous Coronavirus, so we can expect something similar for SARS- CoV2”. Your source for this? I just listened to a podcast with 3 virologists who were pretty sure there would be no cross immunity.

Here is one paper that claims one year for 229E (alpha coronavirus)
https://www.ncbi.nlm.nih.gov/pubmed?term=6319590
Here is a paper for SARS that claims 2 years
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851497/

My reading of those papers is that they don’t deal with cross immunity but presence of antibody to the same virus over time.

I agree. It’s showing you can develop immunity to a coronavirus. We also know recovered Covid-19 patients don’t seem to get reinfected. All of this makes Covid-19 immunity ( at least for some period of time) likely.
At any rate, if no immunity is possible, this will be a problem for vaccines as well.

It seems as if the Swedes have already decided that not everyone will be given a chance to earn such a certificate, as is plain in the last line - "Stefan Hanson, a respected Swedish infectious diseases expert, said the situation was not lost in the whole country, with large parts of the south and north so far displaying low infections rates. “But in Stockholm it is fast becoming critical,” Hanson said. “There is a real risk now that cases will rise so high that the hospitals cannot cope. Treatment choices are already having to be made by biological age.”

This is literally a description of vaccination unless smallpox has made a recent comeback. In addition, the positive and negative predictive values of any antibody test as not fixed, but are dependent on technique and also the prevalence of immunity within the tested population. This is simply not a black-and-white result that necessarily correctly identifies immune persons.

Or, following the historical etymologic precedent that led to the words “variolation” and “vaccination” could this be described as...”coronation”? How much more appealing would that be?

the demand to go back to work may be so strong that some people will want to become deliberately infected.

Will that demand be by the employers or the workers? If by the workers, will there be any work to go back to? If by the employers, will they have the funds to pay the workers?

This comment is about virus testing not anti-body testing.

When you wanted to test everybody for the virus, you never answered my question why test at all ? While I think virus testing is useful for symptomatic people and for science volunteers, if you test everybody you learn something similar to what you learn from a general quarantine. Assume that a 20 day quarantine is weak proof of non-infection or immunity in connection to SARS-cov-2. These people can work. There will be some false negatives from this pseudo-test (quarantine) but these cases when discovered can receive the actual test and you can notify contacts for more actual testing. There will be false positives from this pseudo-test because the person actually has influenza. We want these people to stay at home regardless. They should notify their contacts and may be get SARS-cov-2 tested if we have the capacity. This pseudo-test requires fewer resources than testing everybody and the various lock-downs are an implementation of it.

In the case of virus testing everybody and the pseudo-test, the "badge" of non-infection is not reliable. You can be infected the minute after you receive your badge. I know you want to be able to virus test everybody and get a result instantly and to be able to do this frequently and I want that too. I just wanted to say that quarantine gives us similar information.

To me the cost of virus testing everybody is infinite presently because we cannot do it. The lock-down we can at a huge cost but less cost. I guess you're saying if we can virus test everybody instantly it's better than lock-down and of course that makes sense so never mind my comment.

Anyway the lock-downs are a sunk cost because we are already doing it so that diminishes the value of virus testing everybody.

May be a more useful comparison is resources to virus test everybody versus resources to do some science. It would seem we can do a lot of useful science on this virus one thousand times over for what it would cost to virus test everybody. I would opt for the science.

Variolation has a good chance of making things worse. Reading the commenter dmytryl on Hanson’s site led me to research “antibody dependent enhancement(ADE)” which is where a virus is made more dangerous by the presence of antibodies. From one paper:
“ The number of viruses for which ADE has been described is large and includes most prominently dengue virus, HIV, γ-herpes virus, influenza virus, murine cytomegalovirus (MCMV),foot and mouth disease virus, measles virus, coxsackievirus, Ross river virus, and aleutian mink disease parvovirus.”
See: https://www.sciencedirect.com/topics/medicine-and-dentistry/antibody-dependent-enhancement
Look for the paper entitled “Antibody-Dependent Cellular Phagocytosis...”

Or you can read up more on ADE in Wikipedia:
https://en.m.wikipedia.org/wiki/Antibody-dependent_enhancement

It’s possible but not proven. It seems to happen mostly for Dengue fever. At any rate it will be true of a vaccine too.
ADE seems to promote sustained inflammation. This by and large only occurs in older patients especially those with comorbidities, not the prime candidates for variolation.

Carl, the economists who have become internet doctors and virologists do not need medical knowledge. They have this figured out.

As for immune responses that go awry in the face of viruses, you left out a very pertinent virus from that list: SARS. It was found during vaccine development for SARS that the immune cells of vaccinated animals attacked the lungs. Subsequent work on a SARS vaccine may have overcome this, but we'll never know, because development was stopped.

We already know that COVID-19 fatalities are due to the host immune system overreacting and attacking the lungs. It may be an ADE response, or some other immune response gone haywire. We know that making a safe, effective vaccine won't be easy, because of the nature of this virus and they way it messes with the immune system. And we know that "variolation" as it is applied here is entirely speculative, as there is no evidence that a "lower dose" of virus leads to less severe illness. The way the virus reproduces, in all likelihood the initial dose is irrelevant. But hey, let's not let facts get in the way of a good fantasy.

Thank you Kevin

My son in law ER doc also mentioned that having and surviving covid with a lung infection might make you more susceptible to pneumonia or further damage from other respiratory illnesses later.

Thanks KevinK. That's, unfortunately, an excellent example of how the variolation strategy could backfire.

So how can variolation be performed DIY? How do you guarantee infection while precluding a high dose? Does anyone know?

Given the complete insanity of where we are today this may be the only way out.

Note this will increase the fraction of the population that will get the virus. A very funny outcome.

What’s the time lag between infection and a positive anti-body detection?

This study says 2weeks from symptoms to seroconvert. This is a problem that if we tested everybody today for antibodies, we’d only have a picture of the infection dynamics from mid March.
https://www.medrxiv.org/content/10.1101/2020.03.02.20030189v1

You can get this trip to Italy
You've always wanted

And

Have a job waiting for you
When you get back.

If you get back.

I've thought about this some more, and it's becoming clear to me. Imagine, all across the country, Hanson-Tabarrok Variolation Centers. They would have two parts - one, a kind of doctor's office, with strict infection control, since it's crucial that only a carefully controlled and tiny dose of virus is introduced to each volunteer. No one could enter until after they had tested negative, since bringing in not-yet-symptomatic but infected people into the H-TVCs would destroy the variolation protocol.

Perhaps each center would hire some experienced homeopaths, to take a drop of snot from an patient with a raging infection (off-site, of course), and dilute it down until there were a maximum of 10 viral particles per droplet. Each eager-to-work volunteer would then snort their variolated dosage and retire to a private isolation chamber (the second and larger portion of each H-TVC) to await their mild illness.

They'd be RT-PCR testing starting on day 2, once each day, and when they tested positive they'd continue to stay in their private chamber (no doubt watching MR University and contributing to this blog's comment section) till they no longer showed active virus in their system. Of course they'd have to show an antibody response, too. Then they would donate some plasma, 'cause they're all good citizens (this if for all the old people and work-shirkers). On their way out the door they pick up their engraved Variolation Certificate (TM), and hurry off to work.

If a volunteer fails to test positive after 4-5 days, they would snort a double variolation dosage, and repeat the testing while in isolation until it's all run it's course. Dosages would be increased until illness ensued, or the volunteer ran out of money to pay for the H-TVC protocol (of course these are free-market clinics - you don't get anything good for free).

The H-TVCs would need to be set up and staffed, thousands of them all over the country. This building/remodeling/staffing would be a real economic growth driver, in effect doubling the benefits to the economy of the H-TVCs. Perhaps this is the real genius. Even if it's a a lot of nonsense, and 10% of these variolated volunteers end up severely ill, with 1% of them dead or disabled, it will still have boosted the economy.

It'll be important for anyone volunteering for this idiotic scheme to agree that they would not take a hospital bed or an experimental drug away from someone who didn't insist on making themselves sick. That's only fair, and would absolve the Centers from being blamed for making the pandemic worse. So in addition to H-TVCs, we'll need to build special Variolation Hospitals, to treat the rare cases of variolation gone wrong. The homeopaths might be helpful here. Out-of-work economists could dress in white coats and play doctor all day long. It's a win-win-win.

The antibody test is only ~95% accurate. That's a huge error rate, given that <1% of the population is actually infected it means almost all positive are false (unless of course you already had a high chance of having it, but this applies if we start just broad testing of everyone).

There are NO 100% diagnostic tests for SARS-CoV-2. All of them have some variability. There is a Chinese pre-print I read the other day where they showed in the hospital the antibody test slight out performed the RT-PCR test they were using.

"given that <1% of the population is actually infected"

That's an assertion that may or may not be correct. Particularly in areas with the more severe outbreaks (Lombardy, New York City, parts of Spain, etc.), it's very plausible that the infection rate is well over 10%.

Over 1% of the U.S. as a whole (more than 3.3 million people) is also very plausible based on the potential (likelihood?) of relatively widespread introduction of the virus back in January.

Some other examples that support rates of over 1%:

- Iceland found prevalence of about 1% in a 2,000 person sample of totally asymptomatic people.

- Americans evacuated from Wuhan (and quarantined) at the end of January eventually tested positive at the rate of 0.9%.

- The entire Italian town of Vo (population 3,300) was tested on March 6. 2.7% of the population (90 people) tested positive. That occurred at a time when the province of which Vo is a part had only 198 confirmed cases in a population of 955,000.

Would it even be possible to carry out a small clinical study of variolation? Probably would need a few hundred volunteer subjects for statistical significance, some chance it doesn't work at all and in the worst case you incur single digit-death (if you survive you can go back to work, and if you die you die a hero). Best case scenario we discover an economy, life, and sanity saving procedure.

To me it makes sense on paper but I don't know if our political/scientific apparatus is equipped to make even a small deliberate sacrifice of life for utilitarian reasons.

Not to rain on the parade here but it took decades to come up with a vaccine for ebola. The SARS vaccine, I believe, never quite worked out. They've been punting around an HIV vaccine for decades as well. Ditto for Hep. C.

Not every virus is easy to develop a vaccine for and it would follow variolation is in the same boat. Has there been any record of anyone making themselves immune to HIV by getting exposed to it in small doses?

Most viruses are fought off by the immune system, but HIV attacks the immune system itself so people remain infected. With COVID-19, people either die or recover.

Right but it remains a fact that many viruses are not easy to develop a vaccine for, there are viruses where getting sick once does not give you immunity or only a very short term immunity and it would therefore follow variolation is a shot in the dark.

If the reality is variolation gives you immunity for two months, you could have a number of people walking around with "I'm immune, kiss me!" cards who go onto become superspreaders. In fact I could imagine a play where variolation makes one more likely to be asymptomatic but not necessarily immune from spread it for a long time.

True , there is some uncertainty but shutting down the economy for an indefinite period of time also counts as a shot in the dark experiment as to the consequences.
But most people have accepted it without a lot of forethought or afterthought.

Not quite. In terms of stopping the disease, this is all very old school. Humanity has been doing shutdowns since the beginning of time to deal with plague and other outbreaks. Doing less communicable things stops communicable diseases, no scientific question there.

You're saying the shutdown is an economic shot in the dark, I agree with you there. Although I'm not seeing much of a theoretical case that it is all that unknown. If two months from now things are ok and people want to sit in McDonalds and eat a burger, McDonalds stores are there and the seats are still there. Compounding an economic 'shot in the dark' with a medical 'shot in the dark' to undo potential side effects seems to me just adding risk on top of risk.

Asian countries have been burned before with outbreaks and they seem to have a set of protocols that have mostly worked pretty well that don't require cowboy attempts to shot cut cures with shots in the dark.

I think after SARS was eradicated , the momentum behind a vaccine search evaporated. HIV has the highest mutation rate of any biological entity ( 4* 10^-3 per base per cell) which makes it tough for a vaccine.
Covid-19 does not mutate as much. For comparison with HIV the influenza A virus has a mutation rate ~ 1000 times lower .

That's hopeful. I asked a virologist on another forum if she thought SARS was eradicated or is just dormant either in an animal population or passing quietly among humans. Never got an answer. I suppose it is possible SARS only exists now in labs and the actual virus has mutated into something that either no longer infects humans or doesn't cause illness hence no one is able to see it.

@Boonton
Regarding your question about whether anyone has been made immune to HIV by getting exposed to it in small doses:
I found evidence that the virus was made more infectious by the presence of virus specific antibodies. In other words, injecting a live vaccine like what is being proposed here might make the virus more, well, virulent.
See https://en.m.wikipedia.org/wiki/Antibody-dependent_enhancement for HIV
and
http://viruseradication.com/abstract-details.php?abstract_id=645
for the first SARS coronavirus.

Carl, variolation is basically an infection. There is the same clinical progression for a variolated person as for an infected person. There's no evidence that ADE is a big problem in the younger age group today in SARS-CoV2 infected people and there's no evidence they get reinfected and suffer serious consequences from having developed antibodies.
I am looking at the data from 12,250 deaths in Italy. The CFR is 0.05% for 39 and under and 0.01% for 29 and under. The general population mortality rate would be lower as not all cases are detected.
This is from a country with an overtaxed health care system.
There is no reason to think that deliberate infection would yield worse results. I am not specially advocating it, Hanson is. I am just pointing out we should not demonize it.
The paper you quote is an in vitro study, using SARS-CoV pseudoparticles ( particles made to look like a SARS-Cov virion ( with the S spike) but not the real virion and the author notes that " The ADE effect of SARS-CoV infection is controversial"
The Wikipeida article tells you that " ADE is common in cells cultured in the laboratory, but rarely occurs in vivo"
The reason ADE occurs generally is that conformally similar antibodies compete with correct antibodies to neutralize the virus. The former bind to the antigen but in such a way that it does not prevent the receptor binding domain of the virus to bind to its target cell receptor. In the process, it robs the correct antibody from occupying that site and neutralizing the virus.
One SARS-CoV2 paper hints this might have been happening in Wuhan when the mortality was high and antibodies from the common cold coronaviruses: 229E ,NL63 ,OC43 ,HKU1 from earlier infections may have competed with SARS-Cov2 antibodies.
At any rate, any vaccine would have the same problem.
HIV is a different type of virus with the highest mutation rate of any virus. It's perhaps no surprise that any vaccine could potentially generate ADE, because in a subsequent infection you might just get an imperfect antibody match to the mutated virus.
Here is the italian data on CFR from the Italian National Institute of Health. It's in italian but you can see the numbers
https://www.epicentro.iss.it/coronavirus/bollettino/Report-COVID-2019_2_aprile.pdf

Would you say then we should be able to get a reasonably safe and effective vaccine for this then?

I agree we shouldn't demonize the technique Hanson is advocating, it doesn't seem practical to me. We are going to set up special centers, deliberately infect a team of volunteers, wait 2 weeks then move onto the next round creating an immune army. In the meantime we can't get masks and gloves produced and in a few weeks a massive wave of currently infected is going to pass.

I think we probably will get a vaccine but it takes time. We''ll be lucky if it happens in 2020. Perhaps the mRNA vaccine from Moderna will work out. It's inherently safe and has the potential for rapid, inexpensive and scalable manufacturing. It's in Clinical trial phase 1
https://www.nih.gov/news-events/news-releases/nih-clinical-trial-investigational-vaccine-covid-19-begins
I agree the logistics of variolation scaled to whole country are not clear to me.

Strange dynamics. It's easy to see #survivorsclub travel junkies on instagram making use of their freedom, Corona parties in the cities, sad stories of actors and athlets who didn't make it despite their youth, exclusive two-week retreats on Bali with medical teams and ventilators, social justice debates on how those who don't go there take away hospitals' ventilators, how it is the uninformed/the well informed/the poor/the rich wo do it, etc. The debates on this might easily make abortion debates pale in comparison.

There's another twist: Individuals' incentives for variolation align too beautifully with societies need for big human samples for vaccine tests not to happen, so maybe it's just about channeling it well enough.

Also, be aware of the potential for burgeoning black markets for convalescent plasma transfusions, where receipt of these transfusions increases your antibody levels to the point where you can qualify for an immunity pass.

I wonder whether your health insurance will cover you if you deliberately infect yourself.

A practical question to ask,
But,
So far has not been asked by an economist.

The first word out of an economist's mouth:
Assume.....

Hi Alex,

I suggest an edit: Variolation with a weakly transmissible strain of SARS-nCOV-2.

Figures are looking good for Australia. Assuming we follow the same curve as China we'll go from close to 5,000 active cases to under 100 in two months. The US faces a far larger problem but if the US could be in a similar situation on a per capita basis in 3 months provided the spread is slowed. I hope it has been and we'll see it in the next set of figures, but even if they improve the US should still throw the kitchen sink at this. Australian restrictions are:

1. Social meetings limited to 2 people or family group +1. (Makes tracing easier.)
2. With obvious exceptions, stay at home except for work, education, exercise, or getting food/supplies.

That's the bulk of it. There is financial support for businesses to keep people employed even if they don't have much to do and if they have lost their jobs.

In case you think we're smart, we're still doing bloody stupid things like closing supermarkets over Easter so there will be crowds before and after the closings. Christ, you'd think in a multicultural society we'd be able to find someone to run the shops who doesn't believe in rabbits coming back from the dead.

"Must" is an awfully strong word to use when you have no medical background and are proposing a treatment whose benefits are totally speculative.

I find it amazing that people in certain bubbles laud Silicon Valley and public intellectual types promoting things that people on the front lines have been trying all along, sometimes while risking their own lives.

In the US, we just approved the first serology test. The US test, per Johns Hopkins , has a sensitivity of 93.8% and specificity of 95.6%. The CDC reports ~375k cases in the US, which must be an underestimate due to lack of testing and the lag between contracting COVID and displaying symptoms. Let's assume the undercounting is by a factor of 10x so that ~1% of the population has or has had COVID. If that's the case, then a random person who tests positive is 4.6x more likely to not have had COVID than to actually have COVID ! Of course, if you're getting a test for COVID now, you probably have had symptoms, so your base rate is higher. Therefore your chance of actually having COVID is higher than 20% if you have a positive test. Still, using a test like this to clear people to go back to work will be a poor decision until a large fraction of the population has had COVID so the base rates are higher, or we develop a better test. Therefore, we shouldn't count on being able to use serology tests in the near term to clear someone for work. P.S. If the undercounting factor is less than 10x, then the false positive rate would be even higher, so in this sense, the 10x undercounting is a conservative estimate.

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