The COVID-19 mRNA Vaccine- Clinical Trials and Pregnancy

covid 19 clinical trials and pregnancy

How the COVID-19 mRNA vaccine works, why it’s not going to make you infertile, and why pregnant people are frequently excluded from clinical research

Both the Pfizer BioNTech and Moderna COVID-19 vaccines have recently been approved, ushering in a sense of potential hope for many. Despite ~95% efficacy and general safety, misinformation spread quickly about the COVID-19 vaccine much in the same way misinformation spread about the virus itself .

One claim stated the vaccine would cause antibodies against a protein called syncytin-1, which is essential to the formation of the placenta. Panic on social media ensued, mainly from those who were worried that the vaccine could render them infertile. While this claim is (thankfully) unfounded, clinical trials don’t exactly have a great track record with pregnancy and reproductive health. I’m breaking down how the vaccine works, why we don’t have any reason to worry about an immune response to syncytin-1, and the history of clinical trials in pregnancy.

What is an mRNA vaccine?

Most vaccines work by giving our bodies a weak or inactive version of the virus so we can recognize it and mount an immune response. mRNA vaccines work a little bit differently.

If it’s been a while since your last biology class- mRNA is “messenger RNA”. Let’s take a second to review this first. Your DNA, your genetic code, has the instructions to make every protein in your body. But DNA can’t actually do anything to make protein. This is mRNA’s role. mRNA is made from DNA through a process called transcription. mRNA then leaves the nucleus where the DNA is held, and undergoes splicing to cut it down to just what’s needed.

Think about it this way- when someone sends you a link to a recipe, you probably scroll through the annoying search-engine optimized parts about someone’s co-worker’s dog loving peanut butter and skip straight to the actual stuff you need to make it. The link still contains everything you need, but it also has useless info. This is basically what splicing does- cuts down your mRNA to just what is needed.

From this, an organelle called a ribosome reads the mRNA code, and tells another type of RNA (transfer RNA) which amino acid to bring along. Amino acids are added until the protein is complete.

For a more in-depth description of mRNA and why it’s useful, this is a solid (albeit dense) explanation.

Photo courtesy of RISE @ Duke University Medical Center.

The COVID-19 mRNA vaccine is cool because it essentially tells our body how to make a protein on the surface of the virus that causes COVID-19. This protein is called the “spike protein”. After vaccination, our bodies make this protein, and display it on the outside of our cells. Because this protein is not a protein our cells would normally make, our immune system recognizes that something is off, and begins to create antibodies. This way, if we do come across the virus, we know how to fight it.

Photo courtesy of BBC

Since the mRNA in the vaccine is only in the cytoplasm of the cell, it doesn’t impact our DNA in any way. Let me say it again: the COVID-19 vaccine DOES NOT change our genetic material.

Fertility concerns and syncytin-1

Regarding the viral (pardon the pun) posts about the COVID-19 mRNA vaccine rendering people infertile, there isn’t much to worry about.

Syncytin-1 is a cell-cell fusion protein that is necessary in fusion of the placenta. It’s essential to provide the embryo with nutrients. The spike protein on COVID-19 is also a cell-cell fusion protein . But that’s basically where the similarity ends.

On a basic level, you would want to see if the COVID-19 spike protein had any similar or overlapping genetic code (back to that mRNA making proteins) to syncytin-1. This is pretty simple to do with a tool called BLAST. With it, you can see if there are similarities between syncytin-1 (or, just for fun, the entire human genome), and the COVID-19 protein.

I spent every summer of college staring at BLAST to determine if genome sequences were similar among hundreds of samples. Happy to report that when looking at the COVID-19 spike protein and syncytin-1, for the first time ever, I saw the error message “No significant similarity found”. Just for fun, I took it one step further and found there’s no similarity between the COVID-19 spike protein and anything in the entire human genome. This suggests that any similarity between syncytin-1 and the spike protein is incredibly small, such that your body would not create an immune response against it.

Clinical trials and pregnancy

Although the concern about syncytin-1 is unfounded, clinical trials and pregnancy do have a relatively fraught record. Women in general have been excluded from clinical trials, but that’s a story for another article.

In the UK, anyone receiving the Pfizer BioNTech vaccine has been asked to hold off on receiving the vaccine if they are pregnant or expect to become pregnant within three months. Does this mean the vaccine isn’t safe for those who are pregnant or will soon be? Not necessarily. And the reasons why are… complex.

In 1954, a drug called thalidomide was created. It had sedative effects, but wasn’t in the category of barbiturates, which were known at the time to have side effects. As a result of its “fewer side effects”, it was marketed throughout the 50s and early 60s as a treatment for morning sickness. Its use as a hypnotic drug made it available over the counter.

It was used widely, but in 1960, it was revealed to cause severe birth defects or miscarriages. Grunenthal, the pharmaceutical company who had developed the drug, minimized these negative aspects. It took until 1963 to be withdrawn from the market in some countries.

The drug had never been tested on pregnant women during clinical trials, and the impact of the drug on fetal or maternal health wasn’t evaluated. Rather than just make sure that things were adequately tested before allowing them to go to market, the 1977 FDA guidelines essentially banned women of childbearing age (even if they were on birth control) from participating in Phase I or II clinical trials.

And thus began a legislatively-encouraged period of exclusion in medical research, where women were not part of the approval process, but were free to take a drug after it was approved. It wasn’t until 1990 that the Office of Research on Women’s Health was established at the NIH, and not until 1993 that a new guideline was created specifying that the population of study participants would reflect the population targeted after approval (this just seems like common sense, but ok).

In 1998 and 2000, this was again re-evaluated to allow the FDA to put studies on hold if researchers intentionally excluded people of reproductive potential, and they created regulations to require safety and efficacy data to be taken across a broad spectrum of minority and underrepresented groups. However, to this day, women are underrepresented in studies on cardiovascular disease, lung cancer, pancreatic cancer, and melanoma. 73% of drugs approved by the FDA between 2000 and 2010 included no clinical trial data about risk in pregnant women. A 2012 study found that 95% of industry‐sponsored clinical trials that included women of childbearing age specifically excluded pregnant women.

Although the exclusion of those of reproductive potential was, in theory, put into place to protect maternal and fetal health, the result was destructive. Drugs would make it to market without ever having been tested in populations that would eventually take them, resulting in essentially no supervision over potentially vulnerable populations.

The FDA’s regulations for testing on pregnant populations are pretty extensive. If a study does not meet these regulations (and the extensive IRB approval that often comes with it), anyone who is still under monitoring for the study cannot become pregnant. For studies to occur on pregnant people, it either has to be a product that is already approved in the “general” population or it must be the only treatment option available to the pregnant person (and have been tested in pregnant animals first).

For COVID-19 vaccines, this means that approving a vaccine for the general population was the primary goal, probably in an effort to avoid the numerous (and fairly justified) hurdles that come along with initial testing in pregnant populations. Only now that vaccines have been approved for the general public can studies on pregnant populations begin.

This is unfortunate, as many treatments for COVID-19 have also excluded pregnant populations. Pregnant people are at higher risk of COVID-19 complications than non-pregnant people in the same age category. But between 74 and 80% of studies on various treatments for COVID-19 have excluded pregnant populations despite low or no safety concerns of treatment during pregnancy.

The concerns about pregnancy and COVID-19 are certainly valid, but the concerns have less to do with the specific vaccines or treatment than they have to do with the fact that certain populations have been deliberately excluded from research across the board. As someone who relies on the value of thorough research and peer-review, this is unacceptable, but it is not an excuse to peddle misinformation (that lacks any empirical evidence).