We have been reporting on the incidence of rare blood clots following the AstraZeneca vaccine in Europe. And now we have to report, just one week later, on a very similar situation with the Johnson & Johnson (J&J) COVID vaccine. In a joint statement from the CDC and FDA, they recommended pausing use of the J&J vaccine until reports of blood clots can be investigated. The situation is somewhat different now from one month ago with the AstraZeneca vaccine, but the dilemma is similar.
In a joint statement the CDC and FDA report:
As of April 12, more than 6.8 million doses of the Johnson & Johnson (Janssen ) vaccine have been administered in the U.S. CDC and FDA are reviewing data involving six reported U.S. cases of a rare and severe type of blood clot in individuals after receiving the J&J vaccine. In these cases, a type of blood clot called cerebral venous sinus thrombosis (CVST) was seen in combination with low levels of blood platelets (thrombocytopenia). All six cases occurred among women between the ages of 18 and 48, and symptoms occurred 6 to 13 days after vaccination.
This is very similar to the AstraZeneca cases – CVST associated with low platelets (a blood component that initiates clotting) mostly in younger women. The incidence here is a little less than one case per million vaccines, which is extremely rare, and only one death out of nearly 7 million. It’s difficult to estimate how many COVID deaths were prevented by these same vaccines, but it is at least in the thousands.
These reports presented a dilemma for the CDC and FDA. On the one hand, these are rare side effects, dwarfed by the benefits of the vaccine in the middle of a surge of a deadly pandemic, when we are in a race against the emergence and spread of more infectious variants. Also, recommending a pause in the J&J vaccine could increase vaccine hesitancy overall, including of the two mRNA vaccines (Pfizer and Moderna) that have so far had no serious side effects.
Arguing for the pause is the fact that these cases are similar to the AstraZeneca cases, and both of these vaccines are modified adenovirus vaccines (again, very different from the mRNA vaccines). AstraZeneca is a chimpanzee adenovirus and J&J is a human adenovirus, so they are different viruses, but the technology is similar. Further – the association with low platelets could suggest an autoimmune etiology, which is plausible following a vaccine. In fact a recent study published in The New England Journal of Medicine finds evidence for an autoimmune cause:
Vaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia.
They were also concerned with getting the word out to physicians as quickly as possible to be on the lookout for this syndrome, which needs to be treated differently than ordinary blood clots. And they wanted people who recently received the J&J vaccine to be on the lookout for any symptoms that might indicate CVST – severe headaches, confusion, dizziness, trouble speaking or difficulty understanding speech, numbness or weakness in the face/arm/leg, trouble seeing, trouble walking, loss of balance or coordination.
Finally they were concerned about the appearance of transparency, and that failure to act might sap confidence in the overall vaccine program. So they acted out of what they called “an abundance of caution”. They also did not ban use of the vaccine and the FDA did not revoke emergency use authorization. They simply recommended pausing use, and let the states decide how best to implement that recommendation.
The recommendation has attracted both praise and criticism. This is because they were dealing with a no-win scenario, especially when it comes to public perception and concerns about vaccine hesitancy. Whether they acted or not, the antivaccine forces on social media would exploit the situation to provoke as much fear and doubt about the vaccines in general as they can. There is no decision that would prevent this, so you might as well do what is best scientifically and then just explain the decision as best you can.
The scientific calculus is all risk vs benefit, and here the situation is very different from the AstraZeneca vaccine, which is critical to Europe’s vaccine strategy, especially in poorer countries. In the US most delivered vaccines are either Pfizer or Moderna, with J&J representing only 5%. Further, there are enough of the other two vaccines to meet demand and the ability to administer vaccines (enough for more than 3 million doses a day), so pausing or even eliminating J&J may have an insignificant effect on the vaccine program and not delay at all the date by which everyone who wants a vaccine will have it.
This is especially true after the Baltimore facility had to throw out a batch containing roughly 15 million doses of J&J vaccine because of contamination. Supplies of the vaccine were already short because of this.
This incident should, if anything, increase confidence in the vaccine program. There is an effective monitoring system that is capturing even very rare side effects from the vaccines. The Pfizer and Moderna vaccines have been out longer than J&J with many more doses given, and neither has been linked to any severe side effects. There is therefore extremely reassuring evidence for the safety of these vaccines, which also have extremely high efficacy.
The adenovirus vaccines are also safe and effective, but it increasingly seems like they can trigger a rare (about one in a million) autoimmune reaction in women less than 50. The medical community needs to know about this, how to recognize and treat it properly, and the general public needs to know in order to be vigilant about early symptoms. But the dilemma remains – in the middle of the COVID pandemic these vaccines will save thousands of lives for every one they take, and if we are careful we may be able to avoid any vaccine-related deaths. But we also know the public mostly does not make rational decisions based on math, and are more likely to avoid causing harm even if that passively allows a far greater harm to occur.
There are some compromises that could help. Giving the vaccine only to demographics that are not at high risk for blood clots, and not giving it to groups that are at risk for the clots but at lower risk from COVID. In the US the CDC and FDA are quickly reviewing the data and we will likely get more recommendations and actions soon. We are fortunate in that we have two other highly effective vaccines, and it seems plausible we can phase out the J&J vaccine with little impact. If necessary it can also be reserved just for populations at apparently low or no risk of developing the blood clots.
The situation is also another stark reminder of the persistent dangers to the public health of allowing gross medical misinformation to spread without consequences. Misinformation is a deeper pandemic, one which is much harder to treat.