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Given all that we have discussed about COVID-19 vaccines over the past six months, you probably are not surprised to hear that scientists have confirmed the safety of COVID-19 vaccination in pregnant women, but now it’s official. In a large study published April 21 in the New England Journal of Medicine (NEJM), a group of experts in pregnancy, epidemiology, public health, infectious disease, vaccines, and immunology published results confirming that the two mRNA vaccines —produce by Pfizer-BioNTech and Moderna— are extremely safe when given to pregnant women. Working for the US Center for Disease Control and Prevention (CDC) and the US Food and Drug Administration (FDA), the authors analyzed data from the “v-safe after vaccination health checker” surveillance system, the v-safe pregnancy registry, and the Vaccine Adverse Event Reporting System (VAERS). Coming from 35,691 women ages 16 to 54 years, these data were analyzed to look for signals that the vaccines cause any adverse effects particularly in pregnant recipients. Of possible undesirable effects, the only one that the study identified as occurring more frequently in pregnant women than in non-pregnant women was pain at the site of injection. Meanwhile, other adverse effects connected with the vaccines, namely fever, chills, headache, and muscle aches, actually turned out to have occurred less in pregnant women. Meanwhile, there was no evidence of the vaccines increasing the risk of bad outcomes for the fetus, such as spontaneous abortion (miscarriage) and pre-term delivery.
Throughout the COVID-19 pandemic, much of the groundbreaking information in a kind science-by-press release manner, in which scientific manuscripts have been released as what are called “preprints”, whose methods and statistical analysis have not yet been peer reviewed, meaning not scrutinized yet by other experts with appropriate backgrounds who were not involved in the study. Peer review is a cornerstone of the scientific process and often, preprint manuscripts are later retracted, because reviewers have identified a problem with the study, or have recommended additional things for the authors to do before the manuscript can get published by the chosen scientific journal. In the setting of a pandemic, often it is acceptable clinical management can be influenced by pre-print data, but those data ultimately need to go through the peer review process. This makes the news about the NEJM study all the bigger.
The news about the mRNA vaccines came at a time when concerns about a type of blood clotting disorder —characterized by a low platelet count (thrombocytopenia) and thrombosis (clotting), particularly in the venous sinuses, a system of veins within layers of connective tissue that surround the brain— have led health authorities to pause administration of the Johnson and Johnson (Janssen) COVID-19. Like the AstraZeneca-Oxford COVID-19 that is being used in many countries outside of the United States, the Janssen vaccine is a viral vector vaccine. Its business end, a strip of DNA encoding the spike protein that SARS-CoV2 (the virus that causes COVID-19) displays on its coat and uses to infect body cells, is contained within an adenovirus that has been cleared of its usual DNA. This is different from the mRNA vaccines (Pfizer-BioNTech and Moderna), whose business end is a strip of mRNA contained within a lipid nanoparticle. Similar to the Janssen vaccine situation, concerns about possible clotting disorders also surround the AstraZeneca-Oxford vaccine, but risk vs benefit tradeoff for AstraZeneca works out in a way that makes it clear that older people definitely should receive the vaccine, while debate surrounds the tradeoff in younger people. In the case of the Janseen vaccine, at the time that I’m writing this, seven people in the United States have been reported to have suffered cerebral venous sinus thrombosis (CVST) with thrombocytopenia within a couple of weeks of receiving the vaccine. All of these cases —including two that were fatal— have been young to middle age females, meaning women of reproductive age, a characteristic that, by itself, puts them at elevated risk for developing CVST. Other factors increasing the risk for CVST and (more commonly) other clotting disorders include pregnancy, smoking, and —you guessed it— COVID-19.
As I pointed out in another recent post about the Janssen vaccine, we cannot say at this point that the Janssen vaccine caused the CVST. As the seven cases make the risk approximately 1 out of a million, which is lower than the risk of developing CVST from being pregnant, smoking, taking birth control pills, or having COVID-19, the pause is related to the fact that scientists have hypothesized a mechanism producing the clotting condition similar to that of rare condition in people receiving the drug heparin, called heparin-induced thrombocytopenia, which also can lead to CVST. As noted above, CVST is a very rare condition. Much more common, both in pregnant and non-pregnant individuals, is a condition called deep venous thrombosis (DVT) and a related condition called central venous thrombosis CVT. In DVT and CVT, heparin is the main treatment, but in heparin-induced thrombocytopenia, and in any clotting condition that includes thrombocytopenia, heparin makes the problem worse. Should the Janssen vaccine turn out to be the cause of the CVST, health authorities want to make sure that health care providers are up to speed with things; that way, in the event of cases of blood clots appearing different from the usual kind, they will do all of the needed testing and get any needed consultation from specialists, and not just automatically give heparin.
Now, in the United States, we have had the luxury to pause the Janssen vaccine, because we have a good supply of the two mRNA vaccines, and, in our most urbanized areas, also have the necessary deep freezers for storage and the logistical capability for transportation and distribution. On the other hand, the fact that the two mRNA vaccines require two doses, whereas the Janssen vaccine is a single dose, also is turning out to be important. Recently, the CDC reported that about 8 percent of those receiving the first dose of a Pfizer-BioNtech or Moderna vaccine have not shown up for a second dose. While there are data from Israel showing that, on a population level, having many people receive one dose of an mRNA vaccine is much better than having them receive no doses, this CDC report drives home the message of the potential value of the single dose regime of the Janssen vaccine. On top of this, in the United States, there are many settings, such as single-doctor practices in rural areas with limited or no cold storage, where the Janssen vaccine could be given out, whereas the mRNA vaccines would be more difficult. Add the advantage of the single dose regimen and the need for the Janssen vaccine becomes clear, even in the US. Such a need increases by orders of magnitude in other countries, particularly in India, where the pandemic is now orders of magnitude more out of control.