COVID-19: What to think of the J&J vaccine?

I know, it’s been weeks since we’ve seen each other. Cue Barbara Streisand! “You don’t write me blogs…. any moooooooore.”

I’d like to say it’s because I was on my first worldwide blog tour, but really it was just about being busy. <Cue world’s smallest violin.>

I have heard from several readers who said that my blog convinced them and their friends and family to get vaccinated. Those words are humbling and also reflect an obligation I feel to you.

When I began this blog more than a year ago, I promised that I would always give the data straight to you along with my conclusion and what I would choose. Up until this point my statements have closely matched those by most public health officials. Today will be different, however.

I meant to get this post out some time ago, but (see above whine about being busy) couldn’t get the gumption going. My goal today is to review the data on the reports of blood clots with the J&J and Astrazeneca vaccines and give you my perspective on these vaccines. 

Background on the COVID-19 vaccines

The first two vaccines for COVID-19 were by Pfizer and Moderna and are mRNA vaccines, meaning they bring the code for the COVID-19 spike protein into your cells to produce immunity. The next two vaccines were produced by Astrazeneca and J&J and use replication-deficient adenoviruses, meaning they use viruses to bring the COVID-19 spike protein into your cells to produce immunity. These differences are important because although you can’t apply the data for the mRNA vaccines to the adenovirus vaccines, or vice-versa, I think it reasonable and necessary to apply many of the conclusions for one mRNA or adenovirus vaccine to the other vaccine in its same group.

Description of the blood clots

The blood clot syndrome described following both the Astrazeneca and J&J adenovirus vaccines is thrombosis with thrombocytopenia syndrome (TTS). For those of you not in the medical field, you may not recognize what appears to be a contradiction in terms. Thrombosis refers to blood clots, but thrombocytopenia (a low number of platelets in your blood) should lead to bleeding, not clotting. That is what makes this syndrome so odd. Patients have very low platelets but at the same time have serious blood clots. This is a key point: you’re looking for both of these characteristics at the same time.

These blood clots occur throughout the body with one of the most serious being a clot called cerebral venous sinus thrombosis (CVST). You don’t need to be a physician to see two concerning words in there — cerebral and thrombosis — a blood clot in your head.

Can TTS be treated?

Not all patients who develop TTS (whether due to vaccine or not) develop a serious blood clot. Sometimes the clot may be a relatively simple clot in the leg. But blood clots can be tricky to diagnose because patients at first may only have mild symptoms like a headache or abdominal pain.

Managing TTS is particularly tricky because it is rare and looks different than a usual blood clot. In addition, most “normal” blood clots are treated with a drug called heparin, which actually makes TTS worse, not better. 

So, you have a rare diagnosis that most physicians may not look for and that is worsened by the drug most physicians would think to use to treat blood clots.

Don’t blood clots occur in patients infected with COVID-19?

Yes, but the blood clots that occur in patients infected with COVID-19 occur in the presence of normal or high platelet counts, NOT low platelets. So we are talking about a fundamentally different syndrome than what we see in patients sick with COVID-19. In other words, the adenovirus vaccines are NOT causing a COVID-like syndrome.

How often does TTS and CVST occur in patients who have not been vaccinated?

TTS usually only occurs as an adverse reaction to a drug called heparin and is otherwise rarely seen. Similarly, CVST in the presence of thrombocytopenia is very rare and occurs in only about one in every million people in the U.S.

How often does TTS occur in patients who receive an adenovirus vaccine?

The United Kingdom and the European Union estimate that the Astrazeneca vaccine is associated with TTS in about eight to 10 individuals per million vaccinated people. The CDC estimates that the J&J vaccine is associated with TTS in about three individuals per million vaccinated people, but that rate is much higher in females (about eight per million vaccinated females), and even then is primarily seen in young females.

Do the vaccines cause TTS? Or is it just “noise”?

Note that I used the word “associated.” You’ve heard me say this before; we can’t say “caused” unless we have a randomized controlled trial. We are not going to have a randomized controlled trial of millions of vaccinated people, however. This is the best evidence we’re going to get. 

Those caveats aside, the rate of TTS in vaccinated people is roughly eight to 10 times greater than that expected in unvaccinated individuals. The data from the U.K., E.U. and the U.S. is consistent and compelling. Although we can’t say we “know” these vaccines “cause” TTS, the association is sufficiently strong that we must act as if this syndrome is caused by the adenovirus vaccines. 

But the Astrazeneca and J&J vaccines are different. Why are you lumping them together?

True, we can’t combine the European and the U.S. data because one data set is based on the Astrazeneca vaccine and the other data set on the J&J vaccine. That being said, however, based on the identical mechanism of action between the two vaccines, and the striking similarity of the cases of TTS seen on both sides of the Atlantic, I think it not only reasonable but necessary to use both data sets to inform our overall conclusion.

I say “necessary” because the U.S. has administered far fewer doses of the J&J vaccine than our friends across the pond have administered the Astrazeneca vaccine. Therefore, I think the Astrazeneca vaccine data give us an idea of what the U.S. data would look like in a larger J&J vaccinated population.

Who is most at risk for TTS?

Although cases of TTS have been reported following adenovirus vaccines in both men and women, and in all age groups, the greatest risk clearly occurs in females younger than 64 years of age. The risk in men and older women does not appear to be substantially different than in unvaccinated individuals.

What should someone do if they have received the J&J vaccine?

Look for headache, abdominal pain, confusion, or other potentially concerning symptoms within the one to two weeks following vaccination. If you notice any of those changes, especially if they are more significant than what you might normally experience, seek medical care and let your health care team know you received the J&J vaccine. 

Do the benefits outweigh the risks of the adenovirus vaccines?

Yes, the benefits of the adenovirus vaccines (the J&J one specifically here in the U.S.) outweigh the risks. But… (and yes, I mean that as a “but”) that is no longer the question that should be asked.

Well, what question should be asked Mr. Smarty Pants?

The question to ask is, in the context of the evidence of the safety and effectiveness of the mRNA vaccines, and the plentiful supply of those vaccines, in whom is the J&J vaccine still a reasonable option?

Note that question was not asked or answered by the CDC. The perspective of the CDC is far more broad than a single patient. In this blog post I related the story of a public health physician friend of mine who said “I’m a public health physician, which means I don’t care about the one patient.” He meant that statement.

So… in whom is the J&J vaccine still a reasonable option?

Males and older females who are opposed to receiving the mRNA vaccine, for example because they adamantly wish to receive only one shot.

So you’re saying you hate the J&J vaccine?

No, I don’t play the game that everyone seems to these days in everything from sports to politics. Very few things are a binary choice.

For the vast majority of patients, and certainly for the public at large, the risk of blood clots with the J&J vaccine is very small and clearly exceeded by the benefits of the J&J vaccine. And if this were December 2020, or if we didn’t have a surplus of the mRNA vaccines, I would recommend the J&J vaccine for many, if not all, patients. 

But neither of those caveats hold. The news reports and the vaccination data clearly indicate that although we are vaccinating tons of people, the number of new people getting vaccinated is declining. Most places have walk-in or same day vaccine appointments. I think the U.S. is at a fundamentally different place than it was even three months ago.

Although the adenovirus vaccines may yet be proven as effective as the mRNA vaccines, we know how ridiculously effective the mRNA vaccines are. Most importantly, however, the adenovirus vaccines pose a severe, albeit rare, risk that the mRNA vaccines do not. In fact, I am aware of no data indicating a severe safety risk with the mRNA vaccines. The anaphylaxis risk with the mRNA vaccines is very low, lower than the blood clot risk with the adenovirus vaccines, and is easy to spot (wait for 15-30 minutes after receiving the vaccine) and treat appropriately (standard health care procedures).

I’m NOT saying that people should NOT receive the J&J vaccine. I’m saying that I limit my recommendation for the J&J vaccine to a relatively small group of people: males and older females who are opposed to receiving the mRNA vaccines. If a young female said, “I’m either getting J&J or no vaccine at all because I despise needles,” then I would try to convince her to get a mRNA vaccine, but in the end I’d drive her to the vaccination site. I’m not losing sight of the big picture. Not getting vaccinated is worse than getting vaccinated with the J&J vaccine. 

Meanwhile I have no similar limitations to my recommendation of the mRNA vaccines. I was passionate in my advocacy for them in this post, and I stand by that enthusiasm. As long as supply remains high, my preferred COVID-19 vaccine (and I don’t think it’s a tough call) is either of the mRNA vaccines (Pfizer or Moderna).

Thanks for reading, I’ll try to write more soon, as soon as I get done playing my small violin.

Stay safe, and go make some lemonade.

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