An ongoing dialogue on HIV/AIDS, infectious diseases,
April 25th, 2021
The Decision on the Johnson & Johnson COVID-19 Vaccine Surprised Me — Here’s Why
The “pause” on the one-shot Johnson & Johnson (J&J) COVID-19 vaccine is over. Based on a further review of safety data that occurred on April 23, both the CDC and the FDA said the vaccine may resume here in the U.S., provided the label includes a warning about a serious, but rare, side effect — thrombosis with thrombocytopenia syndrome (TTS).
I confess this decision surprised me. My hunch was that they would advise limiting the vaccine in the U.S. to women older than 50, with no age criterion for men. Instead, it’s now available for all.
This was no doubt a tricky decision, one reflected in the 10-4 vote of the Advisory Committee on Immunization Practices (ACIP). When experts disagree, I find it useful to list those things we all can agree on:
- These are not your typical blood clots. TTS bears a strong resemblance to heparin-induced thrombocytopenia (HIT), with low platelets and development of antibodies to platelet factor 4. This “consumptive coagulopathy” has distinctive clinical features, is challenging to manage, and should not be treated with heparin — which can worsen the disease.
- The cases are very serious. Venous thrombotic events vary widely in severity; the clots in these TTS cases occurred in particularly bad anatomic locations, most commonly in the cerebral venous sinuses. Cerebral venous sinus thrombosis (CVST) can lead to permanent neurologic disability, require intensive care, or even be fatal. In the TTS cases, clots also occurred in other sites, and in the arterial system. From Friday’s ACIP meeting:
- They are rare. Nearly 8 million people have received the vaccine, and 15 of these distinctive clotting events occurred, for a rate of around 1 case per 500,000 people vaccinated. Additional cases may come to light, and apparently, around 10 are under investigation.
- The risk is higher in younger women. Thus far, all the cases occurring since the emergency use authorization (EUA) have been in women. The median age was 37 years (range 18–59). For women aged 18 to 49 years, the estimated TTS rate is approximately 1 per 140,000 doses — and potentially higher if more cases occur in this age group among the 10 or so being investigated. Plus, in hindsight, a 25-year-old man likely had a similar syndrome during the clinical trial.
- They occurred shortly after the vaccine. Median time to symptom onset was 8 days (range 6–15 days).
- Similar thrombotic events occurred with the AstraZeneca COVID-19 vaccine. This adverse effect is the primary reason some countries slowed the rollout of this vaccine globally or limited who should receive it. (The vaccine is not used in the U.S.) With the AstraZeneca vaccine, a broader demographic appears to be at risk. Both vaccines use an adenovirus vector strategy to deliver the SARS-CoV-2 spike antigen.
- No cases of TTS have yet occurred with the mRNA vaccines. While thrombotic events have been reported after the Pfizer or Moderna vaccines, none of the cases had low platelets or the other distinctive characteristics of TTS. Given the nearly 200 million doses of these vaccines already administered in the U.S. — with millions more globally — these are highly reassuring safety data.
- The J&J vaccine has several favorable characteristics. As a one-shot vaccine with less stringent storage requirements than the mRNA vaccines, it theoretically would be easier to give to a broader — and sometimes disproportionately at-risk — population. Specifically cited in the ACIP meeting included the homeless, rural residents, people in prison, disabled, homebound, or those with limited access to healthcare.
- We have a sufficient supply of mRNA vaccines to vaccinate all eligible adults in the United States. Given what India is going through right now, just writing this breaks my heart — but it’s true and must be considered in the risk calculation of using the J&J vaccine. Hence while the favorable characteristics of the J&J vaccine would make vaccinating the U.S. population easier, it may not be required.
- COVID-19 case numbers are falling in most of the United States. Even Michigan, the state with the recent marked surge, is fortunately now showing a sharp decline in case numbers. Again, this is critical when thinking about the risk calculation for someone choosing whether to be vaccinated and when.
The process by which safety issues come to light with these vaccines is truly impressive. These rare events triggered a thorough investigation, one in full public view with all the data shared. That’s a real win.
But let’s now consider an otherwise healthy young woman who wants a COVID-19 vaccine.
Give the availability of the mRNA vaccines, the falling case numbers nationally (and hence her reduced risk of disease), and the rare — but extremely serious — side effect of TTS that might occur with the J&J vaccine, under what possible circumstances should the J&J vaccine be the recommended approach?
If it’s a matter of convenience, I’d say it’s worth spending the time educating about how to get the two shots and avoiding the small risk.
If it’s a matter of lack of mRNA vaccine availability, I’d say fix the supply issue or outline where an mRNA vaccine is available.
But now? It’s possible that this young healthy woman might end up getting the J&J vaccine. And while the odds are overwhelmingly in her favor that everything will be fine, in practice, this would be giving a vaccine with a recognized safety issue when two highly effective and safe alternatives exists.
And the warning? I worry about women who lack the medical literacy to fully understand it, or the cultural authority to question what is being offered to them, or the forthrightness to request alternatives — or all of the above.
And that can’t be right.