Greetings from an undisclosed location in my apartment. Welcome to COVID Transmissions.
It has been 513 days since the first documented human case of COVID-19. In the year 513, the Byzantine general Vitalian began a revolt against Emperor Anastasius I.
I had intended to cover an Israeli report about the B.1.351 variant and vaccination in depth today, but the developments with the J&J vaccine required me to shelve that plan. Today, we’ll be discussing blood clots.
As usual, bolded terms are linked to the running newsletter glossary.
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Now, let’s talk COVID.
Johnson and Johnson vaccine in the US
Yesterday, the CDC and FDA issued a press release encouraging a pause in the rollout of the Johnson and Johnson COVID-19 vaccine, due to a rare pattern of unusual blood clots that may be associated with vaccination: https://www.cdc.gov/media/releases/2021/s0413-JJ-vaccine.html
This is a complicated development and I have spent a lot of time talking with various people about it. Vaccine dynamics and developments are one of those things that seem to turn everyone into an armchair biomedical scientist, and I’ve read some really bad takes on this today, most of them crafted on fundamental misunderstandings of what the FDA and CDC have recommended here. So, I want to clear some things up:
This is not a binding recommendation from either agency, and it is expected to be in place for a few days to a week; if someone still wants to administer this vaccine in the US, and they are a licensed medical practitioner, they are still allowed to do that
This statement is not an acknowledgement that the vaccine actually causes this safety outcome; one way that we can tell this is that the statement uses the term “adverse event” rather than “adverse reaction”—“reaction” is the word used when we know there is a causal relationship between the treatment and the adverse event
Very few patients have experienced this event; a total of 6 so far in 7 million vaccinees; there has been 1 death
The type of blood clot in question is unusual and particularly dangerous because it cannot be treated with the typical anticoagulant heparin; heparin can cause problems in cases with such blood clots; this event pattern really should not be compared to other blood clotting phenomena caused by other drugs or diseases
If you already received this vaccine, there is very little reason to be concerned about this; it will still protect you from COVID-19 and the blood clotting outcome is so rare that you are very unlikely to have it
So far, all of these clotting events happened within 2 weeks of vaccination, so it may be that this is a critical time window and once this amount of time has passed the already-small risk may go away—we will need to learn more, of course, but this appears to be the case
Those are facts, and now I’m going to start working in some opinion and analysis. What I find particularly concerning here is that this clotting event pattern is similar to what was recently observed in Europe for the AstraZeneca vaccine, which has some design commonalities with the Johnson and Johnson vaccine. While I am still unconvinced that there is a causal relationship between these events and the vaccine administration, the fact that it has been detected in the rollout of two vaccines sharing a similar design but not in other, distinct vaccines suggests to me that there may be a genuine signal here.
The problem is, it is very hard to decide how to approach the detection of such a safety signal. We have a global pandemic that is killing a very large number of people every day. The AstraZeneca and Johnson and Johnson vaccines are the two options that require the least stringent transport conditions and are also the least expensive. If there is a big problem with these vaccines, my first and foremost concern is what this means not for the US or Europe, but for the rest of humanity living in developing countries who will surely rely on these two options.
In the US, however, there is also a real ethical trade off here. So far, there are 6 cases in 7 million people, with one death. This is substantially fewer deaths than COVID-19 itself has caused over the period of time that the J&J vaccine was available. A cursory examination of the numbers would suggest that continuing to administer this vaccine is the choice that will preserve the most lives.
On the other hand, that cursory examination does not consider how little we really know about the event of concern here. Yes, we have detected 6 cases in 7 million doses, but that does not mean we have detected them all. That also doesn’t mean that 1 in 1.1 million is really the correct risk of this event; these numbers are extremely small and it is very early in monitoring for this vaccine, which has only been administered in the US for a matter of weeks.
Also to be considered in this equation is the fact that a very low proportion of the overall vaccine doses administered in the US each day are J&J vaccine doses. This option is fulfilling less than 5% of administered doses. This is partly because of ongoing manufacturing problems with the J&J vaccine that have kept supply lower than for other available options. Meanwhile, manufacturing capacity and supply of the Pfizer and Moderna vaccines has expanded tremendously.
As reported by NPR, at least one state that decided to suspend administration of the J&J vaccine was able to provide mRNA vaccine dose option alternatives to everyone already scheduled for a J&J vaccination. Even on the same day of the change. So, it is not clear that this will have such a substantial impact on the overall vaccination campaign’s progress. I’m sure there will be some amount of disruption, but I am not sure that it will have a large impact. The Biden Administration has made statements that they are confident they can still supply enough vaccine courses for every American even without the J&J vaccine.
Since I also do not feel confident about the risk of a bad clot outcome, I cannot immediately say whether I feel there will be bigger negative impacts from this “pause” recommendation than are being prevented by it. We do not know enough about this issue to be able to say for certain. What I do know is the kind of thinking that goes into this. In medicine, “do no harm” is taken with exceptional seriousness. It is considered much, much worse to provide a patient with a medicine that might kill them than to allow a potentially fatal disease to take its course. This is because when a medicine kills a patient, it is not a medicine; it is a poison. The line between “physician” and “assassin” is particularly fine, and most practitioners work very hard to avoid crossing it. While COVID-19 is deadly, we have other vaccines and also other measures to prevent contracting it, and we possess medicines that can improve survival if it is ultimately contracted. It is also not something that physicians intentionally give to their patients.
There is a whole other dimension to this, where if a safety signal is not taken seriously by regulators, there is a possibility that this will reduce the overall confidence of the public in vaccination for COVID-19. I am not sure how I feel about this argument. I think that the public is capable of making pretty good risk assessments when given the information that they need by honest communicators. The problems arise when a dishonest actor tries to manipulate situations like this one to undermine vaccine confidence. I suspect that this would happen whether the FDA took action or not, but I do think it matters to communicate a sense that the medical establishment is taking this seriously rather than dismissing it.
So, to sum things up, I feel that this nonbinding recommendation of a pause in administration is reasonable, particularly if it lasts only a few days.
That said, I want to also discuss what this recommendation means for the J&J product. In my day job as a pharmaceutical communications manager, I am bound by requirements of “pharmacovigilance (PV) monitoring,” which require me to notify my company of any safety event that I hear about within 24 hours. We take this pretty seriously, as does every pharmaceutical company.
When a safety signal is identified, it will trigger an investigation with the FDA involved. This investigation will assess whether the safety event is connected with the product, and also assess the risk posed by the safety event. This can be a grueling and long process; in this case, they are dedicating a lot of resources to keeping the process short.
The results of an investigation can take several forms. First, there might be no action taken because the safety signal might be determined to be unrelated to the treatment. Second, it’s possible that the product can be pulled from the market. This would be a disaster with respect to the J&J vaccine, because we really do need it globally in order to fight the pandemic effectively. Third, the product label might be modified to address the issue, either by restricting dosing, adding monitoring provisions, or changing the population of patients for whom the product is approved. Fourth—and this option may be in addition to a label change—a Risk Evaluation and Mitigation Strategy (REMS) requirement may be imposed, which usually requires the manufacturer to pay for some kind of grant-supported program to educate practitioners on safe product use.
I anticipate that either nothing will happen to the J&J vaccine, or there will be a change to its label to restrict the approved population or increase monitoring requirements. So far all of the blood clot cases in the US have happened in female patients between the ages of 18 and 48 years, but with such small numbers, it’s hard to say that this population represents the totality of people at risk. There are going to be some late nights poring over existing safety data at the CDC, FDA, and J&J over the next few days. I hope it really is that quick a turnaround.
For additional information, I recommend taking a look at this article from The Atlantic, which has some more commentary: https://www.theatlantic.com/science/archive/2021/04/jj-vaccine-pause/618591/
What am I doing to cope with the pandemic? This:
Getting back to cooking
I’ve finally gotten my kitchen fully set up!
Last night I made a maple-and-soy glazed Arctic char with rice and roasted Brussels sprouts. Those are regular staples for us, so no big culinary adventure there, but it’s nice to get back into the groove.
A reader, seeing that a donation had been made to charity in honor of the work I’ve been doing, asked me to list my preferred charities so that they might do the same. Here are the two options that I tend to suggest:
Medecins Sans Frontieres/Doctors Without Borders—a true powerhouse in global health, though I understand they have taken some political positions that some find distasteful
The West Side Campaign Against Hunger—this is a local charity to me that feeds people food, which is pretty important and has a huge impact
There were some other comment threads, but needing to write up and research the J&J situation has left me with really limited bandwidth. I will revisit these threads tomorrow and share.
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.
Also, let me know any other thoughts you might have about the newsletter. I’d like to make sure you’re getting what you want out of this.
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.
Correction: In yesterday’s issue I said “from humans to bats” when I meant “from bats to humans.” Oops. Thank you to those who pointed this out; it has been corrected in the online edition.
See you all next time.
Always,
JS
Possible way to make up for lost vaccine capacity if J&J (and AZ) become unusable: move EU and USA resources to support manufacture of the Novavax and CureVac vaccines. Both seem to have the high effectiveness of the Moderna and Pfizer entries and neither uses the adenovirus carrier that the AZ and J&J vaccines do.
Obviously, easier said than done, and you're right that the actual danger from the adenovirus-based vaccines is not really demonstrated, but ... people are not rational actors. Look at Australia, which has already stated a policy of not using adenovirus-based vaccines.