EUA-Clots-Ethics...

1. EUA vs. FDA approval – what’s the difference? There is an interesting legal difference between an Emergency Use Authorization (EUA) and Federal Drug Administration (FDA) approval. When a drug has full FDA approval, colleges, employers, schools, hospitals and the military have the legal right to require the vaccine as a condition of participation, sometimes with the exception of a religious exemption. Schools, employers, hospitals and the military have required vaccines for decades, so this is nothing new. However, in the absence of FDA approval, and when a drug is only under the EUA, these legal mandates are not so clear. Most of what I have read suggests that the EUA alone does not give authority to require the vaccine. Of course, if an employer insists upon mandating the vaccine, the employee is not in a strong position. The EUA has only existed since 2001 -- developed after 9/11 so we could move quickly in the face of a national epidemic emergency. We are currently in a once in a century situation in which we have a lifesaving vaccine that needs to be used broadly in order for us to achieve herd immunity. I am personally in favor of employers, schools, and the military requiring this vaccine (with the exception for religious and medical exemptions) in the interest of public health. I am certain that some people will object to the requirement of taking a vaccine as a requirement for employment or attendance in school and there will be legal cases. Of course, if and when FDA approval occurs, the EUA issue will become moot.

2. Why is a vaccine induced clot different? The biology and pathophysiology of these vaccine induced clots in the veins in the brains of relatively young women are very uncommon and very different from typical blood clots. Typical blood clots happen in completely healthy persons from sitting in one place for many hours such as on an airplane. The risk with these clots is that they can dislodge from the leg and flow up into the lung causing a pulmonary embolism. Typical blood clots can also occur in persons with a hereditary clotting disorder, which is also fairly common. And finally, typical clots can occur in patients with cancer who develop a predisposition towards clotting. All of these clots can be treated with the usual blood thinners such as heparin and coumadin, in addition to some other drugs. None of these usual clots are typically associated with low platelet counts. In the cases of the Johnson & Johnson and AstraZeneca associated clots (and to a lesser extent Pfizer and Moderna), the unusual features of these blood clots include 1) the occurrence in pre-menopausal women some of whom were taking estrogen based contraception, 2) often showed clotting in the large vein in the brain called the cerebral sinus and 3) very low platelet counts. The theory is that these vaccines in approximately 39 cases out of 7 million doses, triggered an immune response in pre-menopausal women that looks like a syndrome in the medical world called TTP or thrombotic thrombocytopenic purpura. In these current clots there is a severe dysregulation of the immune system that results in antibody activation of platelets, clotting and then very decreased platelet counts that can then cause widespread bleeding. This is why heparin should not be used in these cases. Treatment of these blood clots can include intravenous immunoglobulin and high dose steroids as well as non-heparin anticoagulants. And why do these rare clots occur most frequently in pre-menopausal women? Though this is not proven yet, it has been known for a long time that estrogen contributes to the rare entity of cerebral vein sinus thrombosis (CVST). The exact reason for this is unknown. From a public health perspective, these blood clots are so rare that hopefully we will be able to return to the use of these vaccines as the risk of death from Covid is far higher than the risk of death from a vaccine induced blood clot.

 3. England trial – giving Covid to volunteers! The University of Oxford is conducting a trial – the only one like it in the world – where previously infected and recovered volunteers will receive a dose of Covid sprayed in their noses. Participants must be unvaccinated and have Covid-19 antibodies from a previous infection but be fully recovered and able to pass a rigorous health screening. The 64 persons aged 18 to 30 will remain in quarantine for 17 days after receiving the controlled dose of Covid. These volunteers will have subsequent antibody levels drawn, medically followed for a year, and receive $6917 for their trouble. This study will help us to understand more about how strong or weak natural immunity is when previously infected and recovered persons meet Covid again. The ethics of this trial are very interesting, and currently England is the only country in the world willing to pay volunteers to get voluntarily infected. I personally think the trial is ethical as the chance for serious infection is low and these young, healthy volunteers are entering into the trial of their own free will. Of course, some may question whether $6917 affects free will…