On Tuesday this week, both the CDC and the FDA released recommendations to stop the administration of the Johnson & Johnson single dose Covid-19 vaccine after six young women developed a rare blood clotting disorder. This follows after an investigation was initiated by the European Medicines Association (EMA) where recipients of the vaccine were found to have blood clots. On Wednesday, this pause was extended for another 7-10 days.

In Perspective: More than 6 million doses of the J&J vaccine have already been administered but nonetheless 6 cases of severe blood clots were reported--with one person dying because of it and another in critical condition. One underlying similarity among the patients is that they had low platelets to begin with which might seem confusing but clots in patients with low platelet counts has been observed although not commonly in the brain and abdomen as we found in these cases.

For those with a medical background, this is assumed to be similar to a complication of heparin-induced thrombocytopenia (HIT) where in some individuals, the administration of heparin (blood thinner) can reduce the number of platelets significantly enough (>30-50%) within 10 days that then triggers a cascade of reactions ultimately leading to activation of antibodies (IgG) against PF4 that then result in thrombosis or clot.

Is it really similar? well so far as the recently reported cases of blood clots, patients had low platelet counts and increased levels of PF4 antibodies which is enough of a similarity but we do not know the trigger yet.

The majority of these patients and in patients with a similar blood clot reaction to the AstraZeneca vaccine, had high levels of platelet-factor-4 (PF4) antibodies. It is unknown what is the trigger for activation of these antibodies. Another similarity is that they were young women. In comparison, there have been no reports of blood clots in the more than 180 million doses of the Pfizer and Moderna vaccine. That vaccine supply is enough such that stopping the use of the J&J vaccine won't hurt the rate of vaccination in the US as the Biden administration explains.

"Johnson & Johnson vaccine makes up less than 5 percent of the recorded shots in arms in the United States to date. Based on actions taken by the President earlier this year, the United States has secured enough Pfizer and Moderna doses for 300 million Americans.” Jeff Zients, Biden's Covid-19 response coordinator said in a statement.

New visualization of the Covid-19 virus by @fusion_medical_animation

The Underlying Technology:
Both the Pfizer and Moderna vaccine are mRNA vaccines. In simplified terms, DNA makes mRNA and mRNA makes RNA which is then folded into proteins. The mRNA vaccine contains mRNA for the spike protein of the coronavirus. Our cells like dumb machines produce the spike protein and push it to their surface none the wiser. However, our body notices the spike protein and recognizes it as foreign, so it starts the build up of immune cells to destroy it. Once enough immune cells are created, we are officially vaccinated against the disease. The benefit of this approach is that mRNA vaccines don't have to use a live virus and the cells breakdown and get rid of mRNA soon after using it to make protein.

On the other hand, both the J&J vaccine as well as the AstraZeneca vaccine pack the genetic material, in this case DNA instead of mRNA, for the coronavirus spike protein into a disabled adenovirus. Adenovirus based vaccines have decades worth of research behind them while mRNA vaccines are relatively new. Adenovirus-based vaccines can survive in normal refrigeration compared to mRNA vaccines that require specialized cold storage for transport. Hence why these companies went with the tried and true approach.

AstraZeneca's vaccine also reported severe blood clots that are four times as frequent as J&J and it also was restricted in multiple countries after reports of blood clots were revealed two weeks following vaccination. Interestingly, the AstraZeneca patients also had low platelet counts and the majority were also young women.

Next Steps: Right now researchers are trying to figure out what caused the activation of PF4 in young women with low levels of blood clotting platelets. Hypotheses range from implicating the adenovirus or a portion of the genetic material packed into the adenovirus itself. Both are easily modified but would take several weeks to months to get through the supply chain to be administered to patients again.

**If you recently received the J&J vaccine (in the past 2 weeks) and have shortness of breath, chest pain, swelling, abdominal pain, or headaches and blurry vision then definitely seek medical assistance immediately.