COVID Transmissions for 11-19-2021

The case for a live animal market origin of COVID-19

Nov 19, 2021

Greetings from an undisclosed location in my apartment. Welcome to COVID Transmissions.

It has been 733 days since the first documented human case of COVID-19. In 733, Charles Martel of France fought two battles against the rulers of the Duchy of Aquitaine, and we’re still not sure today who actually won! We think it was Charles, but, it’s a little murky.

Speaking of murky events in history—as it turns out, the second anniversary of the reported possible first case that I use as a milestone for the counter above came and went this past November 17th, and I did not even notice. However, I am beginning to wonder if that is the right date to use, as you will see from one of the stories I cover today—an attempt to trace the outbreak in Wuhan that started almost 2 years ago.

Also, I want to discuss a scientific paper that is being misused to further antivaccine cult lies. I don’t think it’s such a great paper, but its implications are being blown way out of proportion, and I want to arm you with some perspective.

Have a great weekend!

Bolded terms are linked to the running newsletter glossary.

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Analysis in Science traces first known COVID-19 case to Wuhan market

A peer-reviewed expert opinion piece that ran recently in Science magazine attempts to piece together the narrative of COVID-19 emergence in Wuhan in 2019: https://www.science.org/doi/10.1126/science.abm4454

The great thing about this article is that it is written by a real virus ecologist looking at real, confirmed evidence. This is not conspiracy theory-laden sleuthing based on misreadings of dubious “leaked” documents. Hard facts are assessed here by a person with expertise in those facts, whose work was then checked by four additional experts in those facts. This means we’re getting something here that we haven’t seen enough of in SARS-CoV-2 origin investigations: sober, open-minded assessment of things we are sure that we know in order to find an answer that we don’t yet know.

The author of this wrote it with a certain degree of bravery, because there are those out on the Internet who would seek to pillory anyone who writes anything suggesting that the Wuhan Institute of Virology (WIV) was not the source of SARS-CoV-2…despite there being no meaningful evidence of a connection.

Most arguments continue to be of the form, “WIV is in Wuhan and was doing bat coronavirus work, and this virus appeared in Wuhan.” As I’ve written before, this certainly allows for the possibility of a WIV origin, but is not evidence supporting that origin. The presence of WIV in Wuhan, where a bat coronavirus emerged, was a decision made because the Chinese government thought it would be a good idea to put a virological institute in a place where it might be likely for a virus to emerge. So there is a correlation between these two events, but that’s all.

Instead, the author of this piece chooses to focus on something we do know about: that the earliest cases in Wuhan were connected to the Huanan Seafood Market, one of several markets that we now know were engaging in live animal trade. Live animal trade was the source of the SARS-CoV-1 emergence event back in the early 2000s. As the article describes, this live market in Wuhan had inventory of animals that were also at the center of the original SARS emergence. SARS-CoV-2, with its wide host range, could easily have jumped to humans from such animals.

The thrust of this article—which you should really read—is that the cluster of cases that surrounded this market may well have been the original cases. The market may well be where the virus emerged. The article points out several reasons, and honestly, you should really just read it. I found this figure striking, however:

Image is a map of Wuhan with case reports superimposed on it. Blue cases are not definitively linked to the Huanan market and red cases are. The WIV campuses are marked on the map as well. Cases cluster close to the Huanan market, and not at all close to either WIV campus. Some cases connected to the market are found outside the city, also.

The upshot here is not to say that the Huanan market is the definitive origin of COVID-19. It may have been how the first case emerged, possibly coming in from outside the city. It may be how an animal was brought into the city that gave SARS-CoV-2 to multiple people. It may be the source of one of multiple introductions that share an animal or animal-human industrial source somewhere in the countryside. This is not definitive.

Still, the article makes a compelling case that Huanan market should not be dismissed as a central event in the emergence of COVID-19, and that scrutiny elsewhere may have deflected attention from the role of this location, and the importance of early cases linked to it.

I have more questions than I have answers at this stage. One question I have is whether the November 17th date that I have long used as the origin date of the pandemic is accurate any longer. The report of that case came from the South China Morning Post originally, and I don’t know of any academic confirmation of it. I’ve heard of other cases outside Wuhan, but this article does not mention those. I am wondering if perhaps I should adjust my date, and reset the clock, so to speak. What do you think?

At any rate, it remains that we have a lot of investigating that can be done into the origins of COVID-19. There are still data available and information can still be synthesized into an explanation that makes sense. Everyone wants to know where this virus really came from, and I think this article is a good, open-minded exploration of the facts.

Paper suggests that spike protein can disrupt DNA repair, doesn’t actually prove this happens

There is a paper going around that antivaxxers love: https://www.mdpi.com/1999-4915/13/10/2056

This paper appears in the open-access journal Viruses, which is a serious, peer-reviewed scientific journal that is sort of lower-tier within virology. To my knowledge it is not a great journal but it is not a bad one, either.

The paper in question suggests that the spike protein of SARS-CoV-2 can disrupt DNA repair mechanisms that are essential for the development of the unique immune cell repertoire that we develop in the womb and during early childhood. It does this using in vitro experiments. “In vitro” means “in glass,” which is to say in an experimental system that is artificial and does not use any free-living natural organism. It is a Latin term used in scientific papers, to distinguish from “in vivo” work, meaning “in life,” that is, in a living organism system. Other similar terms are “in silico,” for “in silicon,” aka “work done only on a computer,” and “ex vivo,” “after life,” for work exclusively done on deceased organisms.

In vitro work is exceedingly artificial. In this paper, the authors used a bacterial plasmid—a ring of DNA—that they had edited to express the spike protein, inserted it into human kidney cells that were transformed and immortalized in the 1970s and have been mutating into unrecognizability ever since, and used that plasmid to express levels of the spike protein that have nothing to do with any real-world expression scenario. They also did this with some other SARS-COV-2 proteins. The point I’m trying to make here is that this does not model any infection realistically in any way. It also doesn’t model vaccination with a vaccine that expresses the spike protein. It doesn’t model anything, really.

This is molecular work, being conducted in cells that have evolved over decades to grow in a 20% oxygen environment (aside from what’s in your blood, there is basically no oxygen inside your body, so that’s already very artificial), on a plastic dish, covered in vitamin-enriched fluid. These circumstances do not resemble real human conditions.

In their study, these authors showed that their system allows the spike protein to inhibit something called V(D)J recombination. V(D)J recombination is the mechanism by which each person develops a unique, random set of billions of immune cells that can target nearly any pathogen that exists now or might exist in the future. It happens in the bone marrow, early in life, and also in an organ called the thymus, which gradually atrophies by approximately the age of 20. V(D)J recombination happens long before the immune system responds to anything.

So why do we do this kind of work? Well, it’s a relatively inexpensive way to test hypotheses before we invest a lot of money into animal and human experimentation. Cells in these settings can be very misleading, and it’s often hard to reproduce experiments that are done between different labs because cells with the same names have sometimes mutated to be very different. Still, it can guide us into hypotheses that have to be confirmed in other models and other systems. These in vitro experiments are good at telling us things that virus proteins can do, so that we can design further experiments that assess whether they actually do these things in the contexts of real infections.

Now, I mentioned at the top that anti-vaxxers love this paper. Why? It has to do with a statement in the paper that never should have been printed:

Our findings reveal a potential molecular mechanism by which the spike protein might impede adaptive immunity and underscore the potential side effects of full-length spike-based vaccines.

This sentence is, frankly, complete BS. The supposition here is that somehow spike protein, in real life, actually inhibits V(D)J recombination and this somehow inhibits adaptive immunity, which would include things like antibodies.

There are so many things wrong with it. Firstly, inhibition of V(D)J recombination could only really matter if the spike protein were present in the thymus or the bone marrow in utero or in childhood. One of the reasons that immune cells develop in the bone marrow is that it’s so hard for things from the rest of the body to get in there. The stem cells in bone marrow are therefore in a privileged compartment that can keep them safe from signals from outside. In order for the spike protein to be having the effect these authors propose, it would have to be present in the right place, at the right time, in the right amount.

I already made the case that this experimental system almost certainly does not model the physiological amounts of spike protein that are produced in vaccination or infection. So we don’t have the right amount here.

We know that V(D)J recombination happens mostly during fetal development and childhood. We also know that children who get SARS-CoV-2 infection generally experience less severe disease than adults. It seems very unlikely that the spike protein is having this effect at “the right time,” based on this, during either infection or vaccination.

Lastly, it just doesn’t seem possible for spike protein to be getting into the right place to do this. The mRNA and adenovirus-vector vaccines are all sent right into the muscle. They don’t go anywhere near the bone marrow and they don’t produce spike proteins in a way that it seems possible for those products to get into bone marrow or the thymus. It just doesn’t make sense that this happens during vaccination. I might be convinced that this can rarely happen during infection, but the burden of proof would need to be quite high. But in vaccination? It doesn’t seem plausible to me.

So we have reason to doubt that the protein is present in the right amount, or at the right time, or in the right place, to do what these authors propose. All three of those things together make it sound unbelievable that this could ever really happen. That said, real-life, in vivo data trumps everything. So, what do we know about adaptive immunity to infection and vaccination?

We know:

Both can generate immune cell responses
Both can generate antibody responses

If the spike protein were meaningfully impacting V(D)J recombination in any population, these things would not be true in that population. The most likely population would be children, but we don’t see this effect in children, either when vaccinated or when infected. There are still immune cells and antibodies getting made. This has been extensively studied.

Basically, this sounds like a big “doesn’t happen” to me. It’s possible that maybe, rarely, this happens during active infection in very young people, but I don’t really know what it would mean for a transient infection to have this impact. In the long run, so much V(D)J recombination would have happened before, and would continue to happen after, the spike protein is present that I don’t see what difference this could possibly make.

My main feeling here is that there’s an interesting molecular finding—and maybe some weird details in the data to be further probed experimentally—but this isn’t a finding representative of real-world conditions, and never should have been published with any statements that imply it is.

To review, this is a phenomenon that only happens with artificial levels of spike protein, affecting a molecular process that has happened many times before a person is born, and that requires entry into a compartment where spike protein probably doesn’t go. Anyone suggesting that this matters for vaccination is writing fiction.

What am I doing to cope with the pandemic? This:

Getting our daughter vaccinated

Today, in advance of the Thanksgiving holiday, we took our daughter to the pediatrician for her first vaccines! She got initial protection from diphtheria, pertussis, tetanus, H. influenzae B, 13 kinds of pneumococcal bacteria, and rotavirus.

Image shows a light-skinned baby’s leg with a lilac-colored bandage bearing images of ice cream and candies on it. The baby is wearing a turquoise onesie and is laid out on a grey couch. In the background is an out of focus bag of farm share potatoes that yes, I really need to put away.

Back in the Middle Ages, half of kids (give or take) didn’t survive to adulthood. This was because of diseases that we now vaccinate against. Think of half the people you know. Without vaccination, they’d be in the ground and you’d never have met them. Or you would be, and same outcome.

I’m so glad we have these incredible technologies that can protect our children—and in particular, my daughter.

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.

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