COVID Transmissions for 10-22-21
Greetings from an undisclosed location in my apartment. Welcome to COVID Transmissions.
It has been 705 days since the first documented human case of COVID-19.
Bolded terms are linked to the running newsletter glossary.
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Now, let’s talk COVID.
CDC recommends booster doses for Moderna and J&J vaccines, also endorses mixed-brand vaccination strategies
Today, the CDC completed a process that began at the FDA, leaving the door open for people in the US to get additional boosters of the Moderna and J&J vaccines.
For the Moderna vaccine, SpikeVax, the recommendation is limited in scope and applies only to certain high-risk people, and has two particular use cases.
Patients for whom a third dose is recommended if six months have passed from the completion of the first two doses are:
Those 65 years of age and older
People 50 and older with specific high-risk medical conditions or who live in long-term care settings
Certain others are told to consider a booster, in light of their individual risk (in other words, for these, getting a booster is a conversation to be had with their doctor):
People ages 18 to 49 with certain medical conditions
Any adults in professions or settings that expose them to particularly high risk
The J&J vaccine recommendation is, expectedly, more straightforward: anyone who got this vaccine as a single dose is recommended to receive a second dose at least 2 months later.
The CDC’s ACIP (American Committee on Immunization Practices) membership emphasized that patients who do not receive these boosters should still consider themselves fully vaccinated, which is something I found sort of odd. I believe that it’s clear for the J&J vaccine, at least, that a booster dose substantially improves immunity. The evidence for that is, in my opinion, of meaningfully higher quality than what was presented for Moderna or Pfizer’s vaccines, because it comes from a Phase 3 clinical trial conducted specifically to ask the question of whether a second dose improves efficacy for that vaccine. I might have recommended that the definition of “fully vaccinated” actually be changed for that product.
For the Moderna vaccine the evidence is more ambiguous, and the effectiveness of that vaccine remains higher. There, I do think it’s fair to say that people are still fully vaccinated even with just 2 doses. I might say the same for Pfizer’s product as well.
Lastly, the CDC has said that it is OK to mix vaccine brands for the purposes of these boosters. I discussed this in the last issue. I am still skeptical that we have sufficient data to support a mixed-brand, 2-dose J&J regimen. The J&J vaccine does not elicit nearly the same level of neutralizing antibodies as the mRNA vaccines, but it still provides meaningful protection. This suggests that it uses mechanisms other than antibody production to achieve this protection. But now, it is being recommended to give a booster dose that might be an mRNA vaccine on the basis that this boosts antibodies—with no information about the effect on other mechanisms. I am reluctant to say that this focus exclusively on antibodies is wise. I do think that an mRNA booster for the J&J vaccines is likely to improve protection, but I have seen no data confirming this.
For the two mRNA vaccines I think there’s a clear case for interchangeability for a third dose, so I don’t think that’s a big deal, as I mentioned last issue. The big difference between the Moderna and Pfizer offerings is dosage, and since Moderna boosters are at a reduced dose anyway, the differences is even less in this situation. I think it’s fine to get one or the other regardless of what the first two mRNA doses were.
Anyway, I think ultimately these recommendations were largely the right move on the part of ACIP, but I do have some questions about certain specifics that I’ve noted above. Still, generally speaking, I think this offers people in the US the opportunity to improve their protection against COVID-19 while restricting the number of booster doses distributed to those who have the most need to receive them.
Now we just need to vaccinate the rest of the world, too. Easy, right?
Update on the SARS-CoV-2 origins drama: a statement from the NIH director
While we have been focused on vaccines, some controversy and muckraking have been taking place in the world of SARS-CoV-2 origins. This all began several weeks ago when The Intercept obtained, through a FOIA request, some grant application and update documents that were created by a group called Eco Health Alliance (EHA) and the Wuhan Institute of Virology (WIV). These documents, which were hundreds of pages long, were misrepresented by The Intercept as containing what are called “gain of function” experiments. I need to state at the outset that nothing in the grants met the standard for being called gain of function (GOF).
Now, let me tell you what GOF means. When you’re working with viruses in the lab, you have several options for how you can understand their functions. One mainstay of virological work is to break the viruses you’re working with through mutation, and see how that impacts their life cycle; this is called a loss of function experiment. Another option, more recently available, is to try to make recombinant viruses that take different naturally-occurring sequences from different strains, and combine them into a single laboratory virus. This type of experiment is usually used to try and figure out why two strains might act differently from one another, and doesn’t involve creating any sort of new sequences—everything you have used is found in nature. This type of chimeric virus experiment is relatively commonplace these days. Lastly, there is a type of virological work where you creat an entirely new sequence variant that never existed in nature, in an attempt to add a function to the virus of interest. This is what GOF research is.
There are those who feel that GOF research is inherently dangerous. I am not one of them. I feel distinctly that the trillions upon trillions of virus particles that exist outside of laboratories and mutate every day are likely to have already tried anything we might attempt in the lab, and it’s hubristic to assume that an experiment that a scientist can do will somehow be cleverer than everything nature has already tried. However, I am not here to make the case for that today. What is important is that the accusation has been leveled that SARS-CoV-2 originated from GOF research being conducted by WIV and EHA in collaboration. This accusation is refuted by the grant materials.
This week, the outgoing NIH director Francis Collins addressed this in a statement: https://www.nih.gov/about-nih/who-we-are/nih-director/statements/statement-misinformation-about-sars-cov-2-origins
The EHA-WIV grants that were funded by the NIH involve surveillance looking for viruses in the wild, and then experiments in artificial mouse systems that involve virus sequences isolated from that surveillance. All of the sequences used are all distant relatives of SARS-CoV-2. Even in chimeric experiments, none of these could have given rise to SARS-CoV-2. None of the experiments detailed in the EHA-WIV grant materials are GOF experiments that could have altered these sequences to make them into SARS-CoV-2.
So, in other words, the NIH did not support GOF research through EHA and the WIV, despite politicized accusations that they did. If such research was conducted by EHA or WIV, it has been well covered-up by all of the dozens of people who would have been involved with it. A massive conspiracy would have to be at work to conceal that.
Unfortunately, it has also become clear that EHA was not entirely transparent or proactive in updating the NIH on its progress in this work. Virologist Dr. Angela Rasmussen explains this dimension of the problem in a Twitter thread:
You’ll need to click through to read the whole thing, but I think that Dr. Rasmussen explains a situation with a lot of subtleties quite well here. EHA acted inappropriately, but nothing they were doing was GOF research and none of it could have created SARS-CoV-2.
Speculation that they were doing work that could have done this is just that—and has no evidentiary support. Right now, the question of SARS-CoV-2 origins has become so overtly political, and so stymied by a lack of cooperation from Chinese authorities, that conspiracy theories and speculation abound, when the available facts suggest, as they always have, that the possibilities are as follows:
Most likely: introduction of the virus during a human-animal interaction in the wild
Possible, but less likely: introduction of the virus from animal meat or foodstuffs to humans
Possible, but less likely: release of a naturally-occurring virus during laboratory operations or field work being conducted to find pandemic-potential CoVs
Engineering of the virus remains a ludicrous idea. The sequences are so haphazard and random, so inelegant compared to what human science already knows can be done, that it is clear the virus emerged from nature. The origins question, and resulting investigations, now need to acquire evidence that tells us exactly how the virus came from nature into humans, but we do know what is most likely.
In order to acquire that evidence, honest investigations must be conducted in line with the principle that Dr. Collins puts forward in his statement:
This effort would benefit from less speculation and more scientific cooperation, especially from China, without which the SARS-CoV-2 origins will be impossible to identify.
If we get that cooperation, without breathless speculation, we have a chance at getting a good answer to the origins question.
What am I doing to cope with the pandemic? This:
Writing again
It must be odd that I’m saying I’m writing again, since I write to you three times a week, but what I mean is that I’ve returned to fiction writing. Some of you may be aware that I have had some very modest success as a writer of speculative fiction. It has been a while since I had what I felt were good ideas for fiction. I had trouble writing speculative fiction that wasn’t depressing after about November 2016, for some reason, and never felt like I could really envision a future that I wanted to write down.
It has taken a while to get back on the horse, abut I now feel like I have some ideas that are worth committing to paper. I’ve been working on that.
Unfortunately, I’m now without a writing critique group because my former one have all moved away from NYC, but I’m sure that’s a problem I can work on once I have some outputs that are actually worthy of critique.
Reader Sam commented about the possibility of mixed-brand vaccinations as a means to avoid the very rare myocarditis events that have been associated with mRNA vaccines:
Re: mixing J&J and mRNA vaccines -- assuming this combination does produce a durable immune response, I wonder if it might decrease the incidence of myocarditis reactions? Perhaps interesting in this regard is an article published last week (https://www.mdpi.com/2076-393X/9/10/1186/htm) suggesting a mechanism by which the reaction occurs, and recommending increasing the time interval between doses as a way to mitigate it.
This kicked off a whole discussion that involved others. I think what Sam is proposing is an interesting idea, but I also don’t think it’s clear that myocarditis requires 2 doses in order to happen. I don’t want to speculate on whether mixed-brand approaches might help here. But I did want to share a paper that provided a potential explanation for myocarditis events, and also may help explain why they are so rare:
I'm not sure whether myocarditis is necessarily caused by cumulative exposure, so I don't feel totally comfortable speculating. I am interested, though, in the following paper that suggests that inadvertent intravenous (rather than intramuscular) injection of the mRNA vaccines could give rise to myocarditis: https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab707/6353927
The intravenous vs intramuscular explanation (which is not necessarily mutually exclusive with what you shared, by the way) could explain why the event is so rare. It seems strange that cardiac inflammation would be caused, even transiently and in a very small subset of patients, by the injection of a small volume of mRNA into muscle. We know the mRNA is not very mobile and only persists for a couple of weeks, so if it is being properly injected into muscle, it shouldn't go anywhere, really, and the remote effect on the heart is at the very least surprising. In this explanation, accidental intravenous injection leads to dissemination of the mRNA more systemically, and when it reaches the heart it causes myocarditis. This doesn't sound too far-fetched to me, so I'd be interested to know if there is some way to further validate the hypothesis.
There was some more discussion subsequent to this, but if you’re curious about it, you can go check out the comments section for the issue right before this one.
On another thread, Carl Fink shared a story and some thoughts about issues with the Novavax vaccine, something I hadn’t heard about:
Did you see this story?
https://www.politico.com/news/2021/10/19/novavax-vaccine-rush-process-global-campaign-516298
Politico is claiming that Novavax still can't produce pure vaccine, and they predict that the FDA won't approve the Novavax product until next year at the earliest. I'm not totally persuaded (the story doesn't seem to know about their deal with the Serum Institute, for instance) but it's already crushing their stock price.
I’m not totally sure what’s going on there. Novavax has never brought a product to market before, and FDA standards are very high and can be difficult to meet. Perhaps Novavax will see more success with other regulatory authorities around the world. I really don’t know. However, their vaccine looks to be effective, so whatever the problems are, I hope they are surmountable.
You might have some questions or comments! Send them in. As several folks have figured out, you can also email me if you have a comment that you don’t want to share with the whole group.
Join the conversation, and what you say will impact what I talk about in the next issue.
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See you all next time. And don’t forget to share the newsletter if you liked it.
Always,
JS
The hypothesis that inadvertent IV injection is related to adverse events seems odd to me. I was explicitly taught not to aspirate for IM injections in nursing school. I don't think it's a widespread practice anymore (though I believe it used to be) and I have never seen anyone aspirate for a IM injection. Before we jump to this conclusion I'd like to see some evidence about the actual likelihood of an inadvertent IV injection.