Science Corner: Slowing Down to Build Trust

The votes are in, the bracket is complete, and we have a most pressing science & faith question: How much should science inform religious practice? If I thought my seedings had any meaning, this would be a Cinderella story, the lowest seed in the Theology & Religion going on to take it all. Now that the results are known, I’ll work on getting you some answers to the last quartet of questions, so stay tuned for those. In the mean time, I had planned on bringing you some science news about honeybee communication. But in the spirit of last week’s posts about helping folks understand the COVID-19 vaccines, I thought discussing the latest developments were warranted.

First things first, a reminder that I am not a physician and cannot provide personal medical advice. Instead what I can offer is the perspective of a public health professional with a degree in immunology and infectious disease biology. Also, this is a developing situation, so the relevant public health recommendations may change. Having said all that, I know lots of folks have and will continue to have questions about the safety of the COVID-19 vaccines, so the overall conversation will remain relevant for the foreseeable future. And while I know that a blog post can only go so far in fostering trust and empathy, I also know there are folks looking for resources. This post may not substitute for an empathetic ear, but if after offering that empathetic ear you have a chance to answer questions, perhaps this discussion might provide some helpful input.

So what exactly happened? On Tuesday, April 13, federal officials from the FDA and CDC issued a recommendation to healthcare professionals to pause administration of the Johnson & Johnson (also known as Janssen, for the J&J division where it was developed) COVID-19 vaccine. (Update 4/26: After review, use of the vaccine has resumed in the United States with additional warnings and treatment information for this rare condition.) The emergency use authorization has not been revoked, and practitioners are still permitted to administer it if, in their judgment, the risk-benefit analysis for their patient works out positively. In practice, this has meant that public health officials in all states have also issued similar recommendations, and sites operated by or in cooperation with the federal government or state health departments paused their administration of that vaccine, while still offering the other two authorized vaccines where possible.

This decision was made in response to six cases of a specific blood clotting condition called cerebral venous sinus thrombosis, one of which was fatal. At this time, it is not known if the vaccine played a causal role or if this is a coincidence. What is known is that, at a rate of 1 death per 6.8 million vaccinated individuals, the risk of death from this condition as a possible vaccine side effect is much lower than the risk of death from COVID-19. We also know that the Johnson & Johnson vaccine is essentially 100% effective at preventing death from COVID-19. (I say “essentially 100%” because in the studies which measured efficacy, no vaccinated individual died from COVID-19, giving an estimate of 100% but the true value could turn out to be something like 99.9999%.) Based on those numbers, the Johnson & Johnson COVID-19 vaccine will save many more lives even if it does very rarely play a causal role in the development of blood clots.

Why take a pause then if the vaccine will still save lives? There are elements of due diligence and taking vaccine safety seriously. There is also the desire to save as many lives as possible. There are several options that could be considered and implemented via a short pause of a few days. All of the cases so far have been in women between the ages of 18 and 48, so recommendations could be changed to only administer either of the other two vaccines to women (or possibly all individuals) in that age range. Alternatively or in conjunction with that change, an adjustment could be made to lower the dose of the vaccine. Finally, this specific blood clotting condition needs to be diagnosed and treated differently than most other conditions involving blood clots, so further advisories and education materials could be disseminated to healthcare professionals to make sure they know what to look for and how to treat these blood clots, reducing the risk of severe outcomes should further patients develop the condition. Any or all of these actions could further reduce the risk associated with these blood clots while also saving lives by continuing to administer the vaccine.

In the mean time, there is no evidence that either the Moderna or Pfizer-BioNTech COVID-19 vaccines are associated with cerebral venous sinus thrombosis blood clots. Those vaccines have a very different formulation from the Johnson & Johnson vaccine, so it is plausible that they would have different side effects (if indeed the blood clots are a rare side effect of that vaccine). The Moderna and Pfizer-BioNTech vaccines consist of mRNA in tiny droplets of oily lipids, while the Johnson & Johnson vaccine contains an adenovirus that has been modified to also contain a SARS-CoV-2 coronavirus gene. Fortunately, the majority of the US vaccine supply comes from these mRNA vaccines, so many people can still be vaccinated during this pause and long-term projections of coverage should not be significantly impacted. For what it is worth, I received a waitlist dose of the Moderna vaccine last week, and I would not hesitate to do it all over again today if I had not already gotten that dose.

Finally, I’ve heard a number of people express concerns that these vaccines were developed too quickly. And so I wanted to say that, in my assessment, this pause and these blood clot cases are not evidence that the vaccines were rolled out too quickly. This condition is literally a one in a million proposition, and with just six events the need for a review was identified. The only way to identify such a rare outcome is to administer the vaccine to millions of people. It would be irresponsible to replace a phase 3 clinical trial involving tens of thousands of volunteers with one that involved millions. This is precisely why we scale trials the way we do. The first phase involves tens of people, so if there is a 1 in 10 side effect only 1-2 people are impacted. If we’ve ruled out the possibility of 1 in 10 side effects, we scale up to hundreds of volunteers to rule out 1 in 100 side effects up to roughly 1 in 1,000 side effects. If the vaccine passes that test, we scale up again. In this way, we keep the number of potentially impacted people as low as possible, in the single digits. And as we see in this case, even after clinical trials are over we continue to monitor vaccine safety so that 1 in one million or 1 in ten million side effects are found quickly. As I see it then, this pause is an indication that every effort is being made to provide a safe vaccine, not evidence that corners are being cut.

If you or someone you know has more questions or concerns about the vaccines, feel free to share them in the comments or stop by my virtual office hours, every weekday from 4-5pm EDT on this Google Meet: https://meet.google.com/jha-hrtb-pkd. I just ask that you RSVP–leave a name and/or e-mail address in the comments, a Twitter DM, or a Facebook message–so I know who to expect and let into the call.