COVID Transmissions for 2-23-2022
Ivermectin doesn't work, vaccines do--even if you got infected, and also if you didn't
Greetings from an undisclosed location in my apartment. Welcome to COVID Transmissions.
It has been 8001 days since the first documented human case of COVID-19. In 800, Charlemagne was crowned Emperor of the Romans by the Pope in St. Peter’s. This led, eventually, to the creation of the entity called the Holy Roman Empire, which pretended to be a successor to the Western Roman Empire, but really wasn’t that. The Byzantine Empire, which was in fact the actual remnant of the (Eastern) Roman Empire, had some choice words about this event. At any rate, this was a watershed year in European history and Charlemagne’s period was the closest that medieval mainland Western Europe came to unification under a single Empire.
Much like countries can merge together through conquest, viruses can merge cells together—we’ll talk about this in today’s Other Viruses section.
Today in COVID-19, results from a randomized trial on ivermectin, and an analysis of immunity in response to three exposures to the SARS-CoV-2 spike protein (whether from vaccination alone, or with infection included).
Also, for the paid subscribers, a discussion of respiratory syncytial virus and the mRNA vaccine that just entered Phase 3 trials to protect against it.
Bolded terms are linked to the running newsletter glossary.
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Now, let’s talk COVID.
Ivermectin really doesn’t work against COVID-19
I promised to continue monitoring the ivermectin situation until there were randomized clinical trial data available, and I have. Previously, I was saying that we did not possess evidence that ivermectin works, but of course as investigations have come in, it has become more apparent that it does not have an effect in COVID-19.
One recent study, published last week, demonstrated no effect of ivermectin on a variety of outcomes in COVID-19:
Among 490 patients included in the primary analysis (mean [SD] age, 62.5 [8.7] years; 267 women [54.5%]), 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk [RR], 1.25; 95% CI, 0.87-1.80; P = .25). For all prespecified secondary outcomes, there were no significant differences between groups. Mechanical ventilation occurred in 4 (1.7%) vs 10 (4.0%) (RR, 0.41; 95% CI, 0.13-1.30; P = .17), intensive care unit admission in 6 (2.4%) vs 8 (3.2%) (RR, 0.78; 95% CI, 0.27-2.20; P = .79), and 28-day in-hospital death in 3 (1.2%) vs 10 (4.0%) (RR, 0.31; 95% CI, 0.09-1.11; P = .09). The most common adverse event reported was diarrhea (14 [5.8%] in the ivermectin group and 4 [1.6%] in the control group).
To summarize, there was no significant reduction in:
Progression to severe disease
Rate of mechanical ventilation
ICU admissions
In-hospital death within 28 days of admission
For patients treated with ivermectin vs a placebo control. Also, there was a slight uptick in diarrhea, something that I’m sure you don’t want to see added to your COVID-19 experience if it doesn’t also come along with a benefit against the disease.
Readers, this is the profile of a drug that doesn’t work against COVID-19. Ivermectin continues to be a great drug against large parasite infections, but it doesn’t impact COVID-19.
You can read the study in JAMA Internal Medicine: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2789362?guestAccessKey=58760460-df0f-4790-9257-8f3682dca39b&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=021822
Three exposures to the SARS-CoV-2 spike protein elicit superior neutralizing immunity
This paper has some very detailed immunological explorations, but I think it’s a worthy read: https://www.nature.com/articles/s41591-022-01715-4#Sec15
Basically, what the authors asked here is this: Right now, we are exposing many vaccinated people to the SARS-CoV-2 spike protein 3 times, through vaccination + booster doses. There are other ways to be exposed to the spike protein 3 times—specifically, through infection. How does the response compare when those three exposures aren’t all vaccine-derived?
Well, the answer is…there really isn’t a big difference in neutralizing antibody titers among people with three exposures to spike, regardless of whether those exposures include infection or not. And, furthermore, the neutralizing response generated after these three exposures was reactive against all major variants of concern.
Now, neutralizing antibodies are important. I’ve said this before. But what I’ve also said before is that they are not the entire picture. So I have to put as a caveat on this whole thing that the finding here may not translate perfectly to the clinical experience. Maybe the vaccine does something that the infections don’t, or vice versa. I could envision either scenario.
Either way, I know that vaccination does not carry a high risk of death or permanent injury while infection with SARS-CoV-2 does. So what this tells me, in my personal opinion, is that I’d rather get my three exposures from vaccination.
On the other hand, there are people who got infected with Delta or Omicron variant viruses before they had the chance to get boosted. The paper has something to say about you, too:
I suppose this is somewhat reassuring if you got infected before you were able to get a booster, but it’s also reassuring, in my opinion, if you got a breakthrough infection after getting the booster, too. What we see here suggests that infection after vaccination, in general, offers an enhancement of response—except you also have vaccine-mediated protection from severe disease and death, as we well know from other data. While I still think getting 3 doses of vaccine is a good move, regardless of your past COVID-19 status, I think this shows that it is likely that continued exposures to the virus after those doses will reinforce our immune response to the virus. Since we don’t see more than three exposures here I can’t really guarantee that, but the results leave me feeling like as we continue through the pandemic, those who built a protective foundation with vaccination will be able to reinforce that foundation with additional immune training, either through boosters or through exposure.
Ideally the exposure option will be minimized, but since vaccination is highly protective, it is good to know that even breakthrough cases strengthen the foundation put in place by vaccines.
It’s an interesting paper overall, but that aspect in particular stood out to me.
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:
Wedding!
I attended a friend’s wedding over the long weekend. I feel like it is becoming more routine to attend these things now that the case background has faded somewhat and at least in my area, most people are vaccinated. Vaccination was required to attend, many people wore masks. I wore a mask as much as I could, occasionally taking it off to eat or drink. This isn’t ideal protection, but given the relative rarity of COVID-19 where I am, my relatively recent recovery from an infection with SARS-CoV-2, and the vaccination requirement, it was an item on which I was willing to be flexible. My thinking on that is most distinctly informed by how rare COVID-19 is near me right now. If it was more common, I might have followed a very different approach. I see the current state of things near me as a lull, not a permanent reduction.
Lots of interesting comments and discussion on the last issue. Here’s a taste of that (go over and read the full thing!), starting with a question from Peter:
The theories that the virus originated in the wild do not to me explain that the epicenter was in the same city with the leading virology lab. Mere coincidence?
As it turns out, I don’t think this was a coincidence—I think these facts are correlated. But, correlation isn’t causation, as I explain:
A good question, and not a coincidence at all actually--but in the other direction than what people might think.
The biosafety level 4 lab at the Wuhan Institute of Virology was conceived of as a facility that would be able to study zoonotic viruses. It was constructed in Wuhan specifically to be in a large urban area (thus, access and attractiveness for scientific talent) that also happened to be situated near enough to wilder areas to be able to conduct effective field work. This model has worked quite well for producing a much better understanding of bat viruses than we had when SARS-CoV-1 first appeared in the early 2000s. A couple of other considerations were key in the selection of Wuhan as the location--it is neither a major zone for floods or earthquakes that might compromise containment.
Chiefly, though, this was about having a high biosafety lab in a place where it would also be easy to recruit scientists and to do zoonotic virus field work. Of course this also means that Wuhan was a candidate city for the emergence of a virus like SARS-CoV-2 before the BSL4 lab was ever built, too.
All of that said, this doesn't preclude the possibility of this being a natural virus which was collected in the course of that field work and then accidentally released into the public.
What *does* seem to contradict that possibility is epidemiological analysis performed by Michael Worobey, who has shown a timeline of the first cases in Wuhan and demonstrated that they are geographically separated from the WIV, and centered more meaningfully around a particular seafood market which happened to be conducting illicit live animal trade. What Dr. Worobey has demonstrated does not definitively rule out a laboratory accident involving a natural virus, *but* it does create a narrative that better supports a spillover event unrelated to the laboratory.
We don't have a definitive answer here as to the events that led the virus from bats into humans. It looks quite likely that it happened in the seafood market, or as part of that market's operations. It remains possible that it also happened in the course of work with field samples at WIV as well, but this seems *less* likely.
What I can be pretty certain of is that this is a virus that *originated* in the wild, at this point--and everything I've discussed so far is just about how it transitioned from "the wild" to humans. A laboratory leak facilitating the transfer of a naturally-occurring virus to the general population, or a live animal market spillover event both represent the results of humans interacting with wild bats carrying a natural virus. Again, I think the market is most likely here, but I can't rule either possibility out.
What I feel more confident about ruling out is the possibility of intentional design of the virus. The sequence doesn't have any indications of that, it has features that suggest the contrary, and the papers I discussed in today's issue further reinforce the natural origins of the virus itself. I will note again, though, this isn't definitive. It's just a lot of very highly suggestive evidence.
So that leaves us mainly with the question of "How did the virus get from the wild to the city?" And that may be a lot harder to answer any time soon with a high degree of confidence, but the most likely answer from evidence so far is the seafood market. I'm hopeful we will learn more on this, but it may take a while.
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 a paywall.
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Always,
JS
