S1E79 / Women’s Health: Fertile Ground for COVID Myths / Andrea Edlow, Stephanie Gaw, Alice Lu-Culligan, Leena Mithal, Steve Stecklow

Pregnant and lactating women have been sort of a taboo group to study for forever.

I think this is a general reflection of kind of how our society has treated women in the past and also these particular women's health issues.

The goal of COVID-19 vaccines in pregnancy isn't to protect the baby. The goal is to protect the mothers.

You're listening to Epidemic, the podcast about the science, public health, and social impacts of the coronavirus pandemic. I'm your host, Dr. Celine Gounder. Steve Stecklow is a Pulitzer Prize-winning journalist with Reuters. He's based in London. Earlier this spring, Steve and his colleague Andrew McCaskill wrote a report looking into the origins of one of the most harmful myths about COVID vaccines and the man behind it, Michael Yeadon.

So Michael Yeadon is a former scientist from Pfizer. Who'd worked in the UK from around 1995 to 2011. And he was an expert in allergies and respiratory diseases. But he's become this big figure in the anti-vax movement.

Yeadon wouldn't speak to Steve for his story, so some of the reporting was based on Yeadon's public Twitter account.

So in the beginning, interestingly enough, Dr. Yeadon's tweets, you know, he talked about how basically how the world needed a vaccine and that was one of the only hopes for it. This was back in March of last year. But by April, he started becoming more skeptical about vaccines and other things.

He then started to speak out against lockdowns in the United Kingdom. He became increasingly strident in his opinions. Those positions attracted more attention, and he started being interviewed on radio and TV.

He started making these predictions that there would be no second wave. And in the UK, there was a huge second wave. When we wrote our story in March, I think 80,000 more people had died during that second wave.

Steve says former colleagues of Yedon he interviewed for the story said they were surprised by his public comments on vaccines and pandemic controls.

He talks at some point about how his own family seemed disturbed by the things he was saying publicly.

Then Yedon went a step further.

So back in early December, Dr. Yeadon and a German doctor filed a petition with the European Medicines Agency calling for a halt for all clinical trials of COVID vaccines.

Yeadon's petition said they were concerned that the antibodies created by the vaccine could harm the placenta of a pregnant woman. The British government did not stop the trials, but news of the petition went viral. It quickly morphed into a rumor that COVID vaccines could make women infertile.

One month after he'd filed this petition, something like 1 out of 8 of people surveyed by Kaiser in, in the US said that they were concerned about or believed that the COVID vaccines cause female infertility.

Alice Lou Culligan started to hear these rumors too.

I think that it struck a chord because it was very pervasive and really hit my peer group quite heavily.

Alice is an MD-PhD student at the Yale School of Medicine. She studies the immunology of viral infections during pregnancy. Alice says she started to hear fears from young women about how vaccines could affect their fertility, but also nursing and menstruation.

One of my friends came forward and asked me what my thoughts were on vaccination because she was nursing her infant at the time, and she was on these mommy forums and saw a lot of really scary posts about how the vaccine would harm her child, in some cases potentially kill her child.

There is no evidence that COVID vaccines cause infertility or harm a child in the mother's womb. But the pandemic has underscored that pregnant and breastfeeding women are often excluded from clinical trials, including the COVID vaccine trials conducted in 2020.

So when a lot of these pseudoscientific theories started proliferating, we were already starting at a serious disadvantage by not having thorough safety data established and already conducted, or at least initiated.

So Alice decided to start studying the impacts of vaccines on women, including the myth about the vaccines causing infertility. In this episode, we're going to hear more about the research Alice and her colleagues did as we take a look at vaccines and women's reproductive health. We'll hear why it's so important for pregnant women to get vaccinated.

We know from large studies from the CDC that pregnant women who have SARS-CoV-2 are more likely to be admitted to the ICU.

What the latest science says about moms and vaccines There haven't been any warning signals yet from the thousands of women that have gotten the vaccine early in pregnancy.

And how the pandemic could be an opportunity to change the way clinical research is done in the future.

I think there's an opportunity to move away from thinking about these populations as vulnerable and instead thinking of them as populations that we can empower with research.

Today on Epidemic: COVID vaccines and women's reproductive health. For most of the 20th century, women were routinely left out of clinical trials. And this has important implications for how physicians treat their patients.

I think that women were being left out of trials because there were very rigid, very paternalistic guidelines that were in place expressly excluding women of childbearing potential from participating in trials. I do think these blanket policies came from a place of wanting to protect people, but unfortunately it also created huge disparities in information about these populations.

This is something I have personal experience with. When I was working with AIDS patients in South Africa in the 2000s, there was a lot we still didn't know about antiretroviral drugs in women. The clinical trials in which those drugs were studied didn't include a representative sample of women or racial and ethnic groups. That meant that if my patient was a non-white woman, I didn't have much hard data on how those HIV drugs might affect her differently than a white man. And when you add pregnancy to the mix, it's even more complicated.

So it was only in 1993 that Congress wrote into federal law the NIH inclusion policy that ensures women and also minorities had to be included in all clinical research.

Thinking back on that history, how does that make you feel that women were really left out of the scientific enterprise in many respects, not least of which was generating science around women and understanding women's biology? How does it make you feel that women were left out until 1993?

I mean, it's shocking. It's absolutely shocking. I think that to dismiss the biology of half of the population really shows what kind of system we were operating in during that time. So yeah, I think that having it be so recent really shows us that we have a long, long way to go and we really need to do a better job of promoting these issues far into the future because it really is a catch-up game at this point.

So Alice decided to start tackling some of the unanswered questions when it came to COVID and pregnancy. Including the myth about vaccines making women infertile, the same myth that started with Michael Yeadon last December. The myth has to do with a protein that's important in the formation of the placenta, syncytin-1.

There were some individuals early in the pandemic who perpetuated this myth that syncytin-1 looks a lot like the coronavirus spike protein, which of course the vaccines are designed to target. So these people argued that after vaccination, the body would inadvertently attack syncytin-1 in the placenta and not only the coronavirus. So the problem is, though, of course, there's just absolutely no biological basis for this theory.

Syncytin-1 and the spike protein just aren't that similar.

We teamed up with our collaborators who developed this method of detecting autoantibodies from patient sera. In a preliminary study there, we did not see any cross-reaction between patient sera whether they had COVID or had been exposed to the vaccine against syncytin-1.

Alice says a coronavirus spike protein and syncytin-1 are so different, the body's immune system simply won't confuse one for the other.

I think what's also particularly ironic about this myth is that the myth suggests that only vaccination would cause infertility. But if any of this myth were true, it would also follow that any SARS-CoV-2 infection could induce infertility because, of course, the virus itself is expressing spike protein.

Alice says this gap in logic reveals the myth as a piece of anti-vax propaganda.

It argues that this is something unique to the vaccine when it would be impossible that it would be unique to the vaccine. It should also happen with COVID infection as well, and that's just not seen.

So if infertility isn't a risk from SARS-CoV-2 infection or the COVID vaccines, what are the risks when it comes to pregnancy and COVID?

Yeah, that's a really important question.

This is Andrea Edlow. She's a maternal fetal medicine physician at Massachusetts General Hospital in Boston. Andrea also teaches at Harvard Medical School.

We know from large studies from the CDC that pregnant women who who have SARS-CoV-2 are more likely to be admitted to the ICU, to need a ventilator. So pregnancy definitely makes getting COVID-19 much more dangerous.

One of the reasons is that a woman's immune system is naturally suppressed during pregnancy. This is partly to help prevent the body from rejecting the fetus. But it can also make a pregnant woman more likely to get really sick if she gets an infection. The other risk has to do with how a baby inside the womb changes a woman's ability to breathe.

So the actual uterus that is enlarged pushes up the diaphragm, which is what you kind of need to drop down to take really nice deep breaths and kind of air out your lungs. And if the diaphragm can't physically drop as well because the uterus is higher, that is one aspect of why pregnant women are more predisposed to get severe lung illness. And that's part of the reason that if a pregnant woman gets SARS-CoV-2, she's more likely to need a ventilator.

And if the mother is sick, there's a risk that the baby will suffer in some way. Andreas says the studies so far suggest it's rare for a woman with SARS-CoV-2 infection to pass the virus on to her baby. But there are other risks that come with getting COVID while pregnant.

Having SARS-CoV-2 in general in pregnancy appears to be a risk factor for preterm birth. Some of the large population-level data suggests that the preterm birth rate is as high as 12% in women who have SARS-CoV-2 in pregnancy, and that's higher than the national average. So we're sort of attributing that to something about SARS-CoV-2.

These are just some of the reasons why a pregnant woman would benefit from protection against coronavirus. But because pregnant and lactating women were excluded from the clinical trials in 2020, there wasn't any hard data on how the vaccines impacted these women until Andrea and her team did their study.

We were primarily enrolling healthcare workers and any employees actually of the hospital who were interested in participating because those were the people who happened to be eligible to get the vaccine in Massachusetts at that time.

Andrea says when they announced the study, there was an outpouring of support and interest from women at Mass General. Nurses, food service workers, physicians, clerks, midwives. They all volunteered.

We were just so impressed with the willingness of people to participate in research that people were seeking us out. I mean, we were getting texts from people, emails, calls. People were contacting us through other people, like, my friend heard that you guys are doing a study and she works in the emergency 'She's breastfeeding.

Can she do it?' Why do you think they were so interested in participating in this study? Why was there so much enthusiasm for this?

I think that people just felt like immense relief and we just all felt really fortunate that we could start to have that anxiety lift, that we could do something proactive. And especially pregnant and lactating women who were living with that heaviness of always being worried that you were gonna infect your baby or infect your children that were already at home or your family members. And so I think it was a combination of just like feeling really joyful to let that anxiety lift and wanting to help other people with information.

Andrea's study collected blood samples before and after volunteers got their vaccine. They also collected samples from breastfeeding women. The results were stunning.

Antibody responses from vaccination were uniformly higher than the antibody responses that were attained from having natural COVID-19 infection during pregnancy. So when we looked across the pregnant, the lactating, and the non-pregnant groups who were vaccinated, all of their antibody titers were much higher than the titers that we saw in the blood of pregnant women who had COVID-19 in pregnancy.

She says the side effects of vaccination the women reported weren't unique— soreness at the injection site, fever, chills, and muscle aches. Only one participant reported an allergic reaction. Andrea says she hopes their research will encourage more pregnant women to get vaccinated.

Anytime that you're making a decision weighing theoretical unknown risks, you want to know, first of all, well, does it work in me? And so why would you, you know, take theoretical unknown risks if the vaccine wasn't going to work great for you? So I think that knowing that it works well is definitely going to help pregnant and lactating individuals. Make decisions around the vaccine better.

Andrea's research found that vaccines were just as effective in pregnant women, that the immune response from the vaccine was better than that from natural infection.

And then the third point is just kind of the concept of protecting two individuals.

We'll hear more about how moms who get vaccinated during pregnancy are able to protect themselves and their child from coronavirus. That's after the break. Lena Mithill is a physician scientist at Northwestern University and Lurie Children's Hospital in Chicago. Her focus is on pediatric infectious diseases. Lena agrees that pregnant women should get vaccinated first and foremost for their own health. But there are other advantages too.

A bonus to vaccination during pregnancy is antibody transfer to the infant.

A pregnant woman's antibodies are passed on to her baby through the placenta and breast milk. It's a natural way of protecting babies from infection when their own immune systems are still developing. This is why it's recommended that moms get a Tdap vaccine during their pregnancy. The antibodies a mom produces will transfer to the fetus and protect it from common childhood illnesses like whooping cough and diphtheria. But mRNA vaccines like those from Moderna and Pfizer had never been given to pregnant women before.

And so the question of what would be the transfer ratio and the efficiency of antibody getting to the baby through the placenta was unknown.

So Lena and her team set out to discover what level of protection the vaccines provided the fetus.

We found that as long as the vaccine was given greater than 2 weeks prior to delivery, that there were protective antibody levels in mom as well as in baby. And that the earlier in third trimester that the woman got vaccinated, the higher the transfer ratio and antibody level was in the baby.

Another way mothers can pass on antibodies and other protection against disease is through breastfeeding.

These are all kind of ways that Mother Nature has come up to protect a very vulnerable newborn from infections.

This is Stephanie Gau. She's a physician scientist at UC San Francisco, where she studies maternal health and infectious diseases. Just like pregnant women weren't included in the vaccine trials, neither were breastfeeding moms.

It was clear that there was no data for pregnant or lactating moms.

One of the common concerns Stephanie heard was if the mRNA vaccines were somehow passed on to the babies through the mother's milk.

There is still, I think, a lot of worry and anxiety amongst pregnant and lactating mothers that, you know, they're taking something that may be transmitted to the baby.

So Stephanie and her team started collecting samples from pregnant women and new moms who received either the Pfizer or Moderna vaccines.

We would take breast milk and blood samples from the mother before the first vaccine dose, before the second vaccine dose, and about 4 weeks after completion of the series.

So did you find mRNA from the Pfizer or Moderna vaccines in breast milk of women who'd been vaccinated?

No, we did not find any. We purified different parts of breast milk and looked at those specifically to increase our detection rate overall. And so in our PCR-based system, we did not find any evidence of the COVID-19 vaccine-related mRNA in the breast milk samples that we collected.

Stephanie says that with the evidence available, she recommends all pregnant and lactating moms seriously consider getting vaccinated.

We do still need to wait for, you know, data from the very early vaccinations, but there haven't been any warning signals yet from the thousands of women that have gotten the vaccine early in pregnancy. And it's a great way to, you know, as a, again, as a side bonus to protect your baby.

SARS-CoV-2 wasn't the first time Stephanie had to deal with an epidemic's impact on pregnant women.

When Zika first came out in 2016, I think it really brought to light how little we knew about infections in pregnancy and how little Brazil, we knew about how to protect moms.

Zika is a mosquito-borne illness. It can cause symptoms like fever and muscle aches. But it was also associated with birth defects, especially in Brazil. At the time, many questions went unanswered, like why some viruses can pass from mother to child.

With COVID-19, I definitely noticed, you know, that people brought up the question of pregnant women and the potential harm to the baby much earlier than I think they would have if we had not already lived through the Zika pandemic.

Zika and SARS-CoV-2 are just two examples of why Stephanie thinks pregnant and lactating women need to be included in more clinical trials.

We should be definitely including pregnant women in more research studies to understand how infections are dealt with during pregnancy and hopefully come up with new medications or vaccines or other strategies to prevent infection in the fetus.

Alice Lou Culligan agrees.

I think there's an opportunity to move away from thinking about these populations as vulnerable and instead thinking of them as populations that we can empower with research.

Concern for the mother and her unborn child have kept pregnant women out of clinical trials in the past. But women also need to be given the choice to participate in trials. The gaps in research caused by paternalistic or well-intentioned exclusions do a disservice to mothers and their children when they do need treatment. This is especially true now when a lack of data early on left physicians without hard facts to counsel their patients when it came to the vaccine's safety and efficacy for pregnant women.

I think that we need to start moving from a model of considering these folks as vulnerable populations to really more medically and scientifically complex cases. And I think there is an opportunity to be embraced there.

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