COVID Transmissions for 2-7-2022
Flawed JHU study on lockdowns; first challenge trial shares results
Greetings from an undisclosed location in my apartment. Welcome to COVID Transmissions.
It has been 783 days since the first documented human case of COVID-19. In 783, Charlemagne’s second wife Hildegard died after giving birth to their ninth child. He quickly remarried to the daughter of a political ally.
Today we will examine a flawed study on the effectiveness of lockdowns against COVID-19, and also discuss a recently-concluded “challenge” study where people were infected with COVID-19 on purpose.
In today’s issue we also have the second installment of the paywalled “Other viruses” section. As always, COVID-19 information found here is free.
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Bolded terms are linked to the running newsletter glossary.
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Now, let’s talk COVID.
A flawed study on “lockdowns” out of Johns Hopkins University
Recently there has been news of a study out of Johns Hopkins University that found that what the authors called “lockdowns” prevented only a very small number of COVID-19 deaths. That study has not been peer-reviewed and has a lot of problems, so it doesn’t need to be shared here.
Instead, I would like to link you to a piece that collects expert critiques of the study in question, where it is pretty much demolished for using poor definitions of terms to come to a conclusion that does not align with reality. Here’s that: https://www.sciencemediacentre.org/expert-reaction-to-a-preprint-looking-at-the-impact-of-lockdowns-as-posted-on-the-john-hopkins-krieger-school-of-arts-and-sciences-website/
The biggest problem with the study is this, the authors’ definition of a “lockdown”:
the imposition of at least one compulsory, non-pharmaceutical intervention
By this definition, a place with a law that only unvaccinated people must wear cloth masks—not a very good COVID-19 preventive measure given where we are now—is “under lockdown.” This is despite the fact that everyone in such a locale has complete freedom of movement and all businesses are open.
By the definition used here, New York City and London have both been in continuous lockdown since early 2020.
Obviously that is pretty ridiculous, and I think it is important to call it out as such.
I also think it is important to emphasize that stay-at-home orders and other specific, lockdown-like interventions have been studied and generally the evidence shows they prevented COVID-19 deaths. Some links appear in this tweet:
The authors of the paper that I’m discussing here—who are not from the JHU school of public health, but rather are economists from elsewhere in the University—seem to have created a definition of lockdown so wide that it would necessarily include places that did almost nothing to prevent COVID-19 transmission. Under those circumstances it seems obvious that they would not find an effect, because their signal would be drowned out in a tremendous amount of noise. This far from the only problem with the work, too. It’s just the most glaring one.
So, if you see this research being bandied about, you now have the needed tools to push back against it.
Challenge trials
Challenge trials—studies where consenting subjects agree to become purposefully infected with an infectious agent, in this case SARS-CoV-2—are going forward in the UK due to the success of a small pilot study: https://news.yahoo.com/worlds-first-covid-human-challenge-073307667.html
The results of that study are currently in unreviewed preprint form and can be found here: https://www.researchsquare.com/article/rs-1121993/v1
Challenge trials can be an ethical minefield, but they are not without precedent. Generally, they are considered ethical under very strict conditions, but there is no hard and fast rule. Considerations that often make it onto the list in evaluating if running a challenge trial are:
What is the risk of long-term injury or death for the included subject population?
What is the likelihood that meaningful information will be learned from doing the study?
How common is the pathogen being used—ie, if the subjects are not enrolled in the trial, what are their chances of getting sick anyway?
What treatments and other preventative measures are available for the disease caused by the pathogen being studied?
Under these circumstances there are many pathogens that have been studied in challenge trials, ranging from noroviruses, which cause a transient and generally not life-threatening (but quite unpleasant) gastrointestinal illness1 to malaria, which is one of the oldest known human pathogens and causes a devastating disease that leads to billions of dollars in economic damage each year.2
Now, I’m not a bioethicist, but I can try to think like one for the purposes of this story. The risk of long-term injury or death from COVID-19 can be kept relatively small if the right patient population is selected and everyone is vaccinated as well as offered the best in medical care should they become ill (I will note that in this particular study, the participants were required to be unvaccinated, a design decision with which I disagree strongly). The pathogen is extremely common and I think the subjects are likely to encounter it in the world if they were not in the trial.
The real question here is: what valuable information could we get from doing such a trial?
Early in the pandemic we could have learned quite a lot of valuable information from the study that was conducted here. Specifically, this study looked at the minimum infectious dose of COVID-19, something that I think could have been valuable in understanding transmission dynamics and could have saved a lot of lives. Had this particular work been done in early 2020, I think it could have been really meaningful in terms of applicable interventions. Unfortunately, at that time we might not have known how to restrict the subject pool in a way that would adequately reduce risk. At this point, the information is somewhat useful still, but I’m not sure if the information gained at this stage is enough to justify the use of unvaccinated participants—particularly considering that it is not yet clear at this time if the patients have experienced any long-term effects like Long COVID. They are, by the way, being followed for a period of 12 months to examine these questions.
I think that at this point, given the number of people around the world who are still becoming infected with SARS-CoV-2 each day, there is not a lot of basic science benefit from a challenge trial that we could not get from observing actual patients.
That doesn’t mean, however, that I think challenge trials are utterly off the table. I think they have a real utility in the development of vaccines and antivirals. When it comes to medical interventions, I would rather study a drug in a group of humans than in a group of other animals. Animal studies are more misleading than human studies, even in highly restricted populations. In a challenge trial, we might be able to quickly resolve disagreements over drug mechanisms and efficacy, for example.
For the study of vaccines, we could be able to get a full picture of a patient’s response to vaccination, and then challenge them with the pathogen to see how that immune response impacts the course of disease. It would be great to be able to follow patients over time to see how drops in antibody levels might impact ability to prevent disease. It would be fantastic to develop correlates of protection against, say, infection, through these types of studies. We could also use such studies to test new vaccine technologies and new dosing schedules, removing a lot of the guesswork in that development process.
In this regard, I do see a way forward where challenge trials in the absolute lowest-risk consenting patients could be quite valuable. But the design has to be very careful, and the ethical questions need to be well-answered in advance.
Part of science is identifying and correcting errors. If you find a mistake, please tell me about it.
Though I can’t correct the emailed version after it has been sent, I do update the online post of the newsletter every time a mistake is brought to my attention.
No corrections since last issue.
What am I doing to cope with the pandemic? This:
Starting our baby on food
At the advice of our pediatrician, we’re trying out some foods with our daughter! We’re starting with simple grain-based baby cereals, but after that, we’re going to move to an important part of the Israeli diet: the peanut butter-flavored corn puff snack Bamba.
Bamba is famous in allergy and immunity research because it is incredibly common as a food given to infants in Israel, and consequently, the rates of peanut allergy in people in Israel are very low!
When you think about it, eating is a terrifying prospect for the immune system. Nearly everything we eat comes from a living thing3 that, ideally, is not of human origin4 and our immune systems have evolved specifically to kick off huge inflammatory responses when they detect life-based signals that are from foreign entities.
Early exposure to a potential allergen is important for preventing the development of allergic responses that target that particular thing. There is an entire system by which the body recognizes the proteins and sugars in the foods that we eat and adapts itself to not treat those proteins and sugars as dangerous threats.
Returning to the story of Bamba, the low rates of peanut allergy in Israel have taught us that if we expose babies to peanut-based allergens at specific critical points early in development (around 5-6 month of age), we can reduce the risk of the child developing an allergy. This approach may also work for common other allergens too. Of course, such an undertaking should only be considered at the advice of a pediatrician—and we’ve consulted ours.
To stay under the Gmail size limit, I’ve had to forgo copying reader comments on this issue. Go back to last issue to see some interesting discussion of treating anosmia as well as vaccinating against Omicron!
You might have some questions or comments! Join the conversation, and what you say will impact what I talk about in the next issue. You can also email me if you have a comment that you don’t want to share with the whole group, or if you are unable to comment due to the paywall in today’s issue.
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For those who won’t be continuing into the paywalled section below—as well as everyone who will—please know that I deeply appreciate having you as readers, and I’m very glad we’re on this journey together.
Always,
JS
