COVID-19 & Pregnancy — Interview with Victoria Male, PhD

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    As an expert on reproductive immunology, Victoria Male, PhD is an ideal scientist to address concerns about COVID-19, pregnancy, and vaccines. 

     

    MedCram Co-Founder and Producer, Kyle Allred, interviewed Dr. Male, a Faculty of Medicine and Lecturer in Reproductive Immunology at Imperial College in London. In this video, Dr. Male discusses the general impacts of pregnancy on a woman’s immune system, as well as concerns about vaccines impacting fertility. 

     

    Dr. Male answers a variety of questions about COVID-19, pregnancy, and vaccines (including trimester specific questions), how to navigate pregnancy and COVID-19 in the workplace, immunity and breastfeeding, and optimizing immunity while pregnant. 

     

    Watch the full interview here, or read through the transcript below. 

     

    You can also read more about Dr. Male here, and see her “Explainer on COVID19 vaccination, fertility, and pregnancy” here.

     

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    Kyle, MedCram Co-Founder and Producer: Dr. Male, you specialize in reproductive immunology at Imperial college in London, so you’re a great expert to talk to about a variety of questions related to COVID-19 and pregnancy: how safe are vaccines during pregnancy and what about breastfeeding questions as well? 

     

    But to start I’d like to ask you just a general question about what happens — if someone gets pregnant — what happens to their immune system? 

     

    Dr. Victoria Male, PhD: Yeah, that’s a really interesting question, and a long time ago in the 50s, it was suggested that maybe in pregnancy a woman’s immune system would be weakened to help her to tolerate the fetus, which is you know after all non-self, so it’s kind of in some ways a little bit like an organ transplant, but actually we now know that really the immune system doesn’t get suppressed during pregnancy, but it does get changed in some ways.

     

    So some people with certain kinds of autoimmune diseases that are really dependent on antibodies will find that their diseases get worse during pregnancy. So you’re getting a stronger antibody response, but people who have autoimmune diseases that more rely on things like T cells might find that their disease gets better during pregnancy. And similarly we see that pregnant women are more susceptible to some infectious diseases and for some infectious diseases, it makes no difference. And for some infectious diseases actually they seem to do a little bit better. 

     

    Kyle: I want to start right away with a rumor that’s been circulating a bit on the internet, and it’s about fertility and vaccines, specifically the COVID-19 vaccines. Is there any evidence that getting a COVID-19 vaccine reduces fertility for a woman?

     

    Dr. Male: No, there’s no evidence at all that this is the case, and we actually have several strands of evidence that it won’t reduce fertility. To me, probably the strongest strands of evidence are the people who got pregnant by accident during the trials, so in the trials pregnant women weren’t recruited and they asked people not to become pregnant during the trials but these things do sometimes happen. 53 people became pregnant unexpectedly — shall we say — and those people were equally divided across the vaccinated and the non-vaccinated groups, so clearly the vaccines aren’t stopping people from getting pregnant. And those people are being followed up quite carefully, and so far they’re all having normal pregnancies. 

     

    So again, we can say that the vaccines aren’t poorly impacting early pregnancy. We’re also beginning to see some people who are getting vaccinated just in the line of perhaps because they’re healthcare workers or or they’re on the front line and they’re also getting vaccinated shortly after– sorry getting pregnant shortly after they’ve been vaccinated. So really in people, it seems the vaccine is not stopping you getting pregnant at all if you want to get. If you want to not get pregnant, you need to use a contraception and we also have evidence from animals that the vaccine doesn’t stop them getting pregnant either. 

     

    Kyle: Do you know how that rumor got started about the COVID-19 vaccines reducing fertility in women? 

     

    Dr. Male: I think I know exactly how it got started, although of course it’s difficult to be sure, because a lot of things circulate for a long time on the internet. Before they necessarily come to the attention of people who can really fact check them, but we think that what happened was a man called Michael Yeadon, who about a decade ago was employed by Pfizer for about six years so there was that aspect to it. He was suggesting that there’s a certain amount in common between the spike protein of SARS-CoV-2, or what we would call COVID-19, and a protein in the placenta, which is called syncytin-1, and he was proposing that because there are some similarities between these, that antibodies that attach to the spike protein of SARS-CoV-2 might attach to proteins in the placenta and that might cause reduced fertility. 

     

    Now as it happens, we really have quite strong evidence that this won’t be the case, because there’s really not very much similarity between the spike protein and syncytin-1. And also I know some people at Yale, Alice Lu-Culligan, who’s in Akiko Iwasaki’s lab, have actually made the effort and taken antibodies from people who’ve had COVID-19 and seen if they bind to this protein, and they don’t. So, it was a theoretical concern, and we have good evidence to suggest that it won’t happen. But because of the way that this was reported, it was said “oh expert who’s working at Pfizer says that this is a big concern.” That is really I think why it took off and although the report was taken down quite quickly, it got screenshotted and it got shared a lot on WhatsApp before people like me really found out about it, and started saying well this is probably not true. 

     

    Kyle: Now what about with a natural infection if someone gets COVID-19? Any chance that that could reduce their fertility? 

     

    Dr. Male: Well, this is one of the things that we have been on the lookout for, because you can imagine that it might, but so far the evidence seems to suggest that people who have COVID-19 early in their pregnancies or people who have COVID-19 and then go on to become pregnant seem to have absolutely normal pregnancies, so COVID-19 early in pregnancy as far as we can tell is not a problem. Later in pregnancy, though, it can be. 

     

    Kyle: Okay, so what happens later in pregnancy? 

     

    Dr. Male: Well later in pregnancy we find that people who get COVID-19 are more likely to need to go into intensive care than women who are the same age, but who are not pregnant. And if you compare them to other pregnant women who don’t have COVID-19, they’re about three times more likely to give birth early, and their baby is about three times more likely to need to go into the neonatal care unit. So for this reason COVID-19 is definitely something, that’s worth your while trying to avoid when you’re further along in your pregnancy.

     

    Kyle: And from a fertility standpoint, just a woman’s ability to get pregnant and maintain that pregnancy full-term, are there any viruses, other viruses besides SARS-CoV-2 virus that causes COVID-19 that have impacted fertility negatively, that we can learn from?

     

    Dr. Male: Oh, I’m not sure if there are definitely viruses that impact fertility negatively, but they’re not very similar to SARS-CoV-2, so I don’t know how much we can learn from them. So an obvious example would be human papillomavirus, which causes cervical cancer. If you get cervical cancer, it can make your cervix a bit less competent or, at the extreme end, if you end up having to have a hysterectomy that is extremely bad for your fertility. Similarly we have things like rubella, which are, if we take a broad view of fertility, bad for your fertility, because if you get infected while you’re pregnant, then you can have congenital rubella and there are also other congenital viruses like that. The other one that’s worth thinking about, I suppose, is influenza, and the reason I’d like to think about that is not so much because it’s bad for your fertility, but because it’s dangerous during pregnancy, and this is one of the things that we actively vaccinate pregnant women against in order to protect them and their babies. 

     

    Kyle: Are pregnant women any more likely to get COVID-19 than the general population? 

     

    Dr. Male: So this is a really interesting question, actually, and I would say that what the evidence so far seems to say, and it’s difficult to tell because pregnant women in lots of places are being more careful than their non-pregnant counterparts, and you can understand why. But it seems to be the case that they’re not more likely to catch COVID-19, and kind of early in pregnancy actually they tend more often to not have things like fever or the kind of classical symptoms, and this might be because of that slight difference in the immune system that I mentioned in pregnancy. So in some ways actually early in pregnancy they may do better.

     

    Kyle: Why were pregnant women excluded from the initial vaccine trials for the COVID-19 vaccines, and do you agree with that decision to exclude them from the trials?

     

    Dr. Male: So, they were excluded from the trials, I would say, because that’s standard practice when you’re trying a new medicine, just because in case there’s something really surprising and unexpected for these vaccines, we have no reason to believe that they would harm pregnancy, but just in case there was something we were not expecting, it would be bad if we had included a lot of pregnant women and the impacts would be not just on them but also potentially on their babies. 

     

    So that’s why we usually don’t include pregnant people in trials. However, there is an argument for these trials, because we’re in a situation where we should have known that as soon as the vaccines were approved for use that we were going to have to give them to pregnant people, because so many healthcare staff are women of reproductive age who are having babies, because that’s what women of reproductive age often do. 

     

    So we should have known that we would need to quite quickly deal with this question of whether it would be safe to give pregnant women the vaccine, and I think actually that in the end, we have come to a reasonably good compromised position. Certainly in the United States, you have. Because what’s happened is the vaccine has been rolled out to pregnant people who are at high risk, so the risks for them are high, which means that — of COVID, rather, I should say — so the benefits of having the vaccine are high. 

     

    And then what the US is doing is they are really tracking these people. They are absolutely tracking these people all the way, and that means that really quickly we’ll know if there’s any kind of problem. And that data is put out, published, quite regularly, and I’ve been taking a look at it myself, and so far I’m going to say it raises no flag, “no red flags.” That’s not actually my words. That’s Anthony Fauci’s words, so obviously some of the people who have been vaccinated have had some problems, but they’ve been having problems at exactly the same rate as people who haven’t been vaccinated. 

     

    So, so far the profile — the safety profile — of the COVID vaccines looks good too, and it’s my hope that by the time we get to the point where we’re offering the vaccine to people who aren’t at high risk, where you know the benefits are less clear, we’ll have really, really good safety data, which will mean that we can offer the vaccine to these people with confidence. 

     

    Kyle: For pregnant women who get the COVID-19 vaccine, is there any evidence that their immunity is passed on to their developing fetus?

     

    Dr. Male: So we know that people who get actual COVID-19 will pass some of their antibodies onto their babies and we’ve seen one case report so far where a woman got the vaccine, the Moderna vaccine, three weeks before she gave birth, and when she had her baby, it was a happy and healthy baby girl, and the baby had antibodies that had come through from the mother. 

     

    Kyle: From the perspective of the immune system, just kind of in broad strokes, what happens during breastfeeding? How much immunity is passed on to a baby during breastfeeding?

     

    Dr. Male: Well, some immunity is passed on to a baby during breastfeeding, and we know that women who got COVID-19 naturally, actually, did pass on some immunity to their babies through breast milk. But it’s an interesting question of whether that will happen for the vaccine, because there are five kinds of antibodies, and the one that is mostly raised by the vaccine is called IgG. And that goes really well across the placenta, which is why we saw it in the baby who had antibodies from her mother getting vaccinated. But the other kind of antibody that is not so well raised by the vaccine is called IgA, and that mainly protects us at mucosal surfaces, and that’s the antibody that mostly goes through in the breast milk. 

     

    So we saw antibody going through in the breast milk of women who were naturally infected, because those women made a good IgA response to natural infection, but the vaccine mainly makes an IgG response and IgG doesn’t really go through in the breast milk. It goes through a tiny little bit, but not very much. So one thing that will be quite interesting to see is if antibody from vaccination goes through in the breast milk, and if it does, does that give any protection to the baby? We don’t have that data currently. As far as I know we don’t. I have a colleague who’s actually doing this kind of a study, but I haven’t seen that data yet. 

     

    Kyle: And how about T cells? I’ve learned a lot about T cells during this pandemic and their central role in immunity, and sometimes prior to the pandemic, I thought of immunity as just antibodies or just B cells that make antibodies. Are T cells transferred to through breast milk as well, sometimes?

     

    Dr. Male: T cells do get into the breast milk, and there’s some evidence that those can be transferred kind of across the lining of the gut. So I suppose another possibility is that there may be some anti-COVID T cells that could be transferred to the baby in a breastfeeding mother. And that’s also something that I know the people who are doing the breast milk studies will be looking at.

     

    Kyle: If someone is breastfeeding and they haven’t had the COVID-19 vaccine and they’re offered it, do you think they should get it?

     

    Dr. Male: If I were breastfeeding and I were offered the COVID-19 vaccine, I would absolutely get it.

     

    Kyle: What about women who are planning on getting pregnant in the near future? I know we talked about this a little bit already, but if they’re thinking, “all right the next three months or so really want to try for that,” do you recommend they get the vaccine? 

     

    Dr. Male: Again, I would say that for that group of people there’s no reason not to get the vaccine, and potentially there’s a good reason to get the vaccine, because if you are successful in getting pregnant, you’ll then find yourself in a position, you know, nine months down the line where you really want to avoid getting COVID-19 because of those extra risks that we talked about around having a pre-term baby or ending up in intensive care, and one of the best ways to avoid getting COVID-19 is to have been vaccinated. So again for those people, vaccination looks pretty attractive. 

     

    Kyle: For a lot of people that want to get vaccinated, it’s still going to be a number of months before they might have that opportunity. You mentioned that there’s some increased risks for pregnant women if they get COVID-19. From a public health standpoint, I guess it seems obvious that pregnant women should probably be even more vigilant with regard to physical distancing, hand washing, ventilation, these strategies. Would you agree with that, and do you think it even would get to the point where they should consider taking time off work until they get offered the vaccine?

     

    Dr. Male: That’s a very difficult question, because not everyone is in the position where they can take time off work, and for a lot of families that would be a very difficult decision, because you’d lose one income. What I would say, and I think pregnant women are really good at doing this anyway, is, you know, mask, hand wash, distance, and if you are able to and you feel more comfortable to take time off work, then it wouldn’t be a bad idea. But I think that most people can carry on working safely, if they take these precautions that we’re all being asked to take. 

     

    Kyle: So just to summarize a bit, if a friend or a family member came to you and said, “I’m pregnant” and let’s say they’re in their second trimester of pregnancy, “I’m offered the vaccine and should I take it?”

     

    Dr. Male: In that case I would absolutely say that from everything I’ve seen, taking it seems to be the better option. It’s protecting you against a real risk and, from everything we’ve seen so far, looks to be safe in pregnancy. So on the balance of risks and benefits, I think it’s a good idea. 

     

    Kyle: And if they were in their first trimester, do you think they should consider waiting until a later trimester to take the vaccine if offered one?

     

    Dr. Male: That’s a very good question, and again from what I’ve seen of the data, I would say that on the balance of risks and benefits, if you’re being offered it but you’re at this point you’re being offered it because you’re at high risk, you’re probably still better off taking it. But I know some people have said that it’s better to wait until after 20 weeks, and as far as I can work out, the logic for that is not so much that they think there’s any bigger risk before 20 weeks, 

    but just that often things go wrong before 20 weeks because that’s how pregnancies are ,and they feel that if something went wrong, a woman might blame herself for having had the vaccine. So that’s not really a risk and benefit decision. That’s a decision that you would have to take yourself knowing how you would feel. But from my point of view, having seen the safety data, so far I would still say that if you’re being offered it in your first trimester, probably it’s a good idea to have it. 

     

    Kyle: Taking a step back from the COVID-19 pandemic, since you are an immunologist that specializes in, specifically, reproductive immunology, for anyone watching this that’s planning on getting pregnant or maybe already is pregnant, what are just some general tips to consider to optimize immunity?

     

    Dr. Male: Okay, so when we talk about lifestyle things we can do to improve immunity they’re always really boring, because they’re the things that your mum probably always told you to do. So, you know, eat a healthy, balanced diet, get a good night’s sleep, get some exercise. All of these things that you need to just be healthy are also good for your immune system. So in terms of pregnancy, keep up that good work and if you know that’s not something you’ve been great at so far, well maybe this is your motivation to get better at it. Not really an immune thing, but very, very useful and important in pregnancy to take folic acid. 

     

    So people who are starting to think about that might even want to start taking folic acid while they’re trying to conceive and to continue taking it during their pregnancy. And then specifically speaking to your immune system during pregnancy, the main thing that I would say is important to do is you will be offered the flu vaccine. You will be offered the vaccine against whooping cough or whooping cough depending on where you are living — it’s the same disease, by the way, we just pronounce it differently — and I would recommend that you take those vaccines because they will protect you against flu, which can be bad for you as a pregnant person, and they will protect your baby against pertussis, which will be bad for your baby until he or she is able to get his or her first set of vaccinations. So those are probably the most important things to do. 

     

    Kyle: As you very eloquently said, there’s unknowns to these vaccines there. We would of course like to have more robust data on some things. But there’s also known risks to getting COVID-19, to getting influenza, to getting pertussis.

     

    Dr. Male: Yeah, exactly. But I think one of the things that people are finding quite difficult — I think people find it difficult in general — is balancing these kinds of risks, because we don’t have a very good instinctive feel for these kinds of things and particularly when we’re in a new situation — like you know for most people when they’re pregnant, it might be the first time and a lot of people will only have you know a couple of pregnancies in their life — so it’s not something you get super experienced at. 

     

    Like I can set off driving in my car and I know that I’m almost certainly not going to crash it, because I’ve never crashed it, whereas it’s harder to assess those risks in a situation that’s so new for you. And of course the pandemic’s new for  all of us, which makes it doubly difficult. But what I’m trying to do and what I hope people, doctors, and midwives will try to do with them is to have these kind of discussions about ” this is exactly the risk and this is exactly the benefit and this is what we don’t know.” And with all of that together, people I hope can make an informed choice, supported by the evidence and supported by their care team. And that’s what I really hope everyone will be able to do.

     

    Kyle: Well, amidst the challenge and the suffering of this pandemic, I think there’s been some silver linings, including more recognition of health care professionals, more recognition of scientists like yourself that are really

    contributing to our understanding of what happens with SARS-CoV-2 infection, with specific instances like SARS-CoV-2 and pregnancy. So, tell us a little bit about your pathway to becoming a scientist and your current position as a lecturer at the Imperial College in London. 

     

    Dr. Male: Well, I was always quite interested in the human body, because when I was very little girl, I used to get up early in the morning before my parents got up and I would watch a programme, which is called “Once Upon A Time… Life” where all the cells in the body had characters and they did stuff, and the immune system was pretty important, actually, because they’re like the army in that story, and that’s kind of what triggered my interest in the human body and probably even in the immune system.

     

    And then, you know, that ultimately led me to going to university to study biology, human biology, and I studied both pathology, which included immunology, and physiology, which included human pregnancy, and I had a really inspirational teacher there called Matt Mason, who basically asked me to go and look into the intersection between these two areas. And that really set me off on looking into this, and that took me into a PhD uh in Cambridge, which is with with my supervisor Ashley Moffat. And I was really interested in a subset of immune cells, called natural killer cells, which have a very important role in pregnancy, actually in helping the placenta to implant properly during pregnancy. 

     

    And then I went away for a little while — well I went away from Cambridge. I went to to London, and I wanted to do some work not in humans but in mice, because I thought it was important to have more than one way of looking at the immune system, and I was very interested in how NK cells develop in the bone marrow of mice. 

     

    And then I had my own baby, and because of how the funding system works, I actually ended up losing my job on the day before he was born, and that meant I was unemployed at home with a baby. And I spent a whole year basically applying to every possible job, because I was so keen to get back into science, and at some point I thought, “gosh, I’m never going to get back into science,” and it caused me to apply for things that I never thought I would ever have a chance of getting, including a fellowship that was funded by the Welcome Trust and the Royal Society, which allowed me to start my own lab. 

     

    So I went from not even working in someone else’s lab, pushing a baby around the park, to starting my own lab at UCL. And I was looking at cells, NK cells in the liver, and after I’ve been doing that for a couple of years, Imperial said, “well why don’t you, why don’t you come back, and why don’t you come back and look at these cells in the uterus, which is what you’ve always been very keen to do?” And so I thought that sounded like a great offer, so I moved back to Imperial just before this pandemic started. So I kind of only just found my feet there before we had to shut everything down, but we’re kind of getting started back up again, so that’s been my, yeah, my career story.

     

    Kyle: Excellent. Any current research that you and your team are working on?

     

    Dr. Male: Well, we’re very interested still in natural killer cells in the lining of the uterus, and one of the things that we want to know is: are they involved in good and bad outcomes to pregnancy? So there have been some immunogenetic approaches that look at this that basically say, if you’ve got certain genes on your NK cells, do you have a good and bad outcome to pregnancy? But what we’re trying to do is to look at the actual cells and to see if having them more or less activated is associated with having certain diseases. So I’ve got two PhD students who are working on that, and I have one PhD student who’s working on another kind of cell that’s related to NK cells, called ILC3s, and she’s also taking similar kind of approaches to see if they’re important for the outcome of pregnancy. Kyle: Where can people follow you on social media or learn more about your work? 

     

    Dr. Male: So probably if you want to know what I’m up to, Twitter is the best place, and a lot of what I’ve been talking about today is the kind of stuff that I tell people about on Twitter to act as a resource for spreading information about immunology, pregnancy, and these vaccines. So you can follow me @VikiLovesFACS. That’s FACS F-A-C-S, which stands for flow-assisted cell sorting, which is a technique and immunology that Ireally love.

     

    Kyle: Yeah, what is that? I’m curious. 

     

    Dr. Male: FACS! Oh, FACS is just the best. So FACS is, basically, if we get a single cell suspension and we put antibodies on it and we’ve attached the antibodies to all different coloured fluorescent things, so that basically each cell has the potential to shine a different color or a different set of colors, then we can suck the cells up one at a time past a series of lasers and the lasers will basically tell us what is on the cell. And if we know what’s on the cell, we can tell you all sorts of things about what kind of cell it is and what it’s doing. So we can use that to answer really pretty much any question in immunology, and your audience who’ve been following, you know, a lot of the studies that have been done about the immune response in COVID or the immune response to vaccines, a lot of those studies will have been done using flow cytometry.

     

    Kyle: Dr. Male, thank you so much for sharing your expertise with us today, and hope to chat with you again sometime.

     

    Dr. Male: Yeah, thank you for having me. It’s been a pleasure.

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