UPDATED on 4/23: A few words about the Johnson & Johnson Vaccine

Dr. Van Yu, CUCS Chief Medical Officer

Just before 5PM this afternoon(4/23), the United States Advisory Committee on Immunization Practice (ACIP) voted 10–4 to approve this recommendation:

“The Janssen COVID-19 vaccine is recommended for persons 18 years of age and older in the U.S. population under the FDA’s Emergency Use Authorization.”

This means that the ACIP is recommending to the Food and Drug Administration (FDA) that the “pause” on the J&J vaccine be lifted without restrictions. The FDA will almost certainly accept this recommendation. This means that the J&J vaccine should be available for administration to any American 18 years of age or older again as soon as this weekend. Although there will likely not be any limitations on the vaccine’s use, the FDA will likely add a warning to the Emergency Use Authorization. The wording of this warning has not yet been worked out.

What was all the fuss about?

Last Tuesday, April 13, the Centers for Disease Control (CDC) and FDA “paused” the J&J vaccine after the Vaccine Adverse Event Reporting System (VAERS) detected 6 cases of a very rare and unusual clotting disorder in people who had recently received the J&J vaccine. The disorder, which is now being called, Thrombosis with Thrombocytopenia Syndrome (TTS), is a combination of blood clotting (a thrombosis is a blood clot) with low platelets (a thrombocyte is a platelet, “penia” means low).

What’s unusual about that?

A person who is having a clotting disorder usually has a high or normal platelet count. Platelets are one of the blood components that form clots. So, it’s really unusual for a clotting disorder to develop in a person with low platelets.

Why did this discovery lead to a pause?

Thrombosis with Thrombocytopenia Syndrome can result in blood clots in parts of a person’s brain which can be very dangerous. Of the original 6 people detected by the VAERS, one person died and one required ICU treatment. Furthermore, because the disorder is so unusual, it can be difficult to diagnose unless you are looking for it, and the treatment is counterintuitive (a common treatment of clots, a medication called Heparin, can make the condition worse). So, the CDC and FDA elected to pause the vaccine for 4 reasons:

  1. To carefully search for more cases to determine how prevalent the disorder is.
  2. To try to figure out how, or if, the vaccine is related to the disorder and what, if any, risk factors there might be.
  3. To alert medical providers about how to diagnose the disorder.
  4. To ensure that medical providers understand how to treat, and how not to treat, the disorder.

So, what has been determined?

In addition to the 6 cases detected by the VAERS, investigations since last Tuesday have uncovered 9 additional cases for a total of 15. 13 of these cases were in women 18–49 years old (out of 1.8 million doses). 2 cases were in women over 50 years old (out of 2.1 million doses). There were no cases in men (out of almost 4 million doses). Of the 15 people who have developed the condition, 3 have died, 7 are currently hospitalized, and 5 have recovered enough to be released from hospital. So, here are some rates to help you digest all this:

Rate of Thrombosis with Thrombocytopenia Syndrome in people who have had a J&J vaccine:

  1. Women under 50 = 7 in a million
  2. Women over 50 = 1 in a million
  3. Men = 0 in 4 million

Although it does appear that there is a real association between the J&J vaccine and this clotting disorder, the mechanism behind the association is still not understood (partly because it’s so rare). Furthermore, although it also appears that this affects women more than men (and may not affect men at all), the reason for that is still not understood.

And, by the way, there have been no cases of TTS in people who have taken the Pfizer or Moderna vaccines.

Why did 4 people vote against the recommendation?

It appears that all 4 people who voted against the recommendation actually do agree that the vaccine should be unpaused AND available to everyone, BUT they would have ADDED this to the recommendation:

“women aged <50 years should be aware of the increased risk of TTS, and may choose another COVID-19 vaccine (i.e. mRNA vaccine)”

So, where does this leave us?

If you received a J&J vaccine more than 3 weeks ago you have zero reason to worry about this clotting disorder. All the cases developed within 2 weeks of administration. If you received a J&J vaccine less than 3 weeks ago, I still encourage you not to worry. This disorder is super rare. If you have any of these symptoms seek medical care:

If you are a man and have not been vaccinated, the J&J vaccine still seems very safe and effective. If you preferred it over the Pfizer or Moderna vaccines then it seems to me it’s still reasonable to prefer it.

If you are a woman and have not been vaccinated, this clotting disorder does appear to be a real, albeit rare, risk. However, I do not think it’s unreasonable to choose the J&J vaccine. The risk of getting, and dying from, COVID-19 are still a lot higher than the risk of developing this disorder. The J&J vaccine is still the only single-dose vaccine available. On the other hand, you have options. It’s relatively easy to get a Pfizer or Moderna vaccine in New York City right now, and there have been zero cases of this clotting disorder associated with either of those vaccines.

This morning (4.13.2021), the United States Centers for Disease Control (CDC) and Food and Drug Administration (FDA) issued a joint statement calling for a “pause” in the use of the Johnson and Johnson (J&J) COVID-19 vaccine.

Out of the 6.8 million doses, the safety surveillance system has detected 6 cases of a rare and severe type of blood clotting condition. All 6 cases occurred in women between the ages of 18 and 48 between 6–13 days after vaccination. One of these women has died. The cases consisted of a combination of a scary-sounding condition called “cerebral venous sinus thrombosis” associated with a low level of blood platelets (known as thrombocytopenia). Now that this has been detected, CDC and FDA will try to determine if the vaccine is responsible, what the mechanism might be, how to monitor for it, and how to treat it.

Even if the vaccine is responsible, this would be a very, very rare side effect. There have been 6 cases in 6.8 million doses, so, it’s literally a one in a million occurrence. So, if you’ve already been vaccinated with the J&J vaccine, I encourage you not to worry. It seems you only have a one in a million chance of developing this problem. Furthermore, now that it has been detected, CDC has already issued some preliminary guidance about how to treat it.

If you have had the J&J vaccine within the last 3 weeks, be on the lookout for severe headache, abdominal pain, leg pain, or shortness of breath and contact your health care provider if you develop one of these symptoms. And remember, the J&J vaccine does provide excellent protection from COVID-19, which you have a much, much greater risk of getting sick from.

Over 100 million doses of the mRNA vaccines from Pfizer and Moderna have been administered with no evidence of this clotting condition. So that’s a rate of zero in 100 million.

This is exactly the way safety surveillance of vaccines is supposed to work. Since this appears to be a one in a million occurrence, it would have been unlikely to be detected in phase 3 clinical trials. Those trials included tens of thousands of doses. Not enough to detect a one in a million occurrence. That’s why the United States has a robust and elaborate safety surveillance system after vaccines are authorized. Catching something this rare is a testament to how sensitive this system is. I suspect what will happen now is that CDC and FDA will study this for a couple of weeks and then unpause use of the vaccine with new guidelines of how to monitor for this condition and treat it. In the mean time, everyone is working to try to replace any planned J&J doses with Pfizer or Moderna doses. So, stay tuned.

Here’s the official announcement from CDC and FDA: www.fda.gov/news-events/press-announcements/joint-cdc-and-fda-statement-johnson-johnson-covid-19-vaccine

One question people have about the J & J vaccine is whether it is not as good as either mRNA vaccine (Pfizer or Moderna). The short answer to that question is that I don’t know.

In phase 3 clinical trials, J & J had about a 70% “efficacy” while the mRNA vaccines had about a 94–95% efficacy. Seems pretty clear right? Not so fast.

Those phase 3 clinical trials were conducted in very different situations making them hard to compare. The mRNA vaccine trials were conducted in the United States over the summer when the prevalence of COVID-19 was relatively low and there were few if any variants transmitting in the States.

The J & J trial was conducted in the fall and winter, when the prevalence of COVID-19 was much higher, and trial locations included South Africa and South America, where there were a high level of variants transmitting.

That’s all to say J & J was up against a much more difficult environment, and still did really well.

Not a single person who got vaccine required hospitalization or died.

If Pfizer or Moderna had their trials in the same conditions, their efficacy measures would almost certainly not have been 94–95%. But we’ll never know. That is all to say that those efficacy numbers are not a fair comparison. Furthermore, all three vaccines are clearly very good.

What about the questions of whether two doses is better than one. Again the short answer is I don’t know. The second doses of the Pfizer and Moderna vaccines clearly make those vaccines better. Would the same be true if there was a second J & J vaccine? J & J is actually studying that. However, it’s not a foregone conclusion.

The J & J vaccine does work slightly differently that the mRNA vaccines (although the immunology of that is so complicated that I can barely understand it). So, I don’t think you can conclude that the J & J vaccine is half of a Pfizer or Moderna vaccine. Furthermore, the phase 3 clinical trials seemed to show that the level of protection of the J & J vaccine improved all the way out to 45 days after its single dose. There’s no data past that so for all we know it kept getting better after that.

The J & J vaccine does have the advantage of being only a single dose. So, it’s more convenient and your protection develops faster. Also, it seems that the adverse effects of the J & J vaccine are on average more mild compared to the mRNA vaccines.

I think the bottom line is still that all three vaccines are really awesome and better than we hoped for.

It really is amazing that 3 vaccines that are this safe and effective were developed in under a year. That’s a testament both to how advanced this science is and how well-conducted and supported those trials were.

And the timing could not have been better. One of the variants, B.1.1.7, the UK variant, which is quite prevalent in the city right now, if clearly more contagious and dangerous than the original virus, but all three vaccines seem to be just as awesome at protecting you from it as from the original. That is to say there is more of a reason now to get vaccinated than even a couple of months ago — the chance of getting COVID and dying from it is greater now than even in January.

So, my recommendation is to get the first vaccine you can.

Dr. Van Yu is the Chief Medical Officer at the Center for Urban Community Services | CUCS. He leads CUCS’s healthcare program, Janian Medical Care, which provides primary medical care, street medicine, and psychiatric care to homeless and formerly homeless individuals throughout New York City.

The Center for Urban Community Services | CUCS helps people rise from poverty, exit homelessness, and be healthy.