This one's for the kids

Dr. Carina Rodriguez has transported her skills from her home nation of Argentina to the US. While she has experience in a wide range of illnesses, as a pediatric infectious disease specialist her focus has been on the little ones.

From HIV to COVID-19, Carina has worked on prevention and treatment. Most recently she has been a lead investigator on the clinical trials for the COVID-19 vaccine in children under 5.

Whether dancing or diagnosing, join us to learn more about Carina, her work and experiences.

Thank you to NO!, the Argentina-based band who made their track “Arti” available through creative commons. Check out all their work on their bandcamp page.

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Episode transcript

[Background intro music playing is "Arti" by NO!]

Parmvir: Okay. So welcome friends to the launch of season nine of our 2Scientists podcast. I am Parmvir Bahia a neuroscientist at the University of South Florida, and your podcast host. With me is my partner in crime and producer David Basanta Gutierrez. Now this is going to be a particularly special episode as we're going to be releasing this recording in Spanish as well with David conquering his fears to step up as host.

And with this, we'll be launching our partner series, 2Científicos. Why Spanish, well you'll realize, as you learn more about today's guest, Dr. Carina Rodriguez.

How are you? Carina?

Carina: Oh, very good. Thank you. This is very exciting for me to be here with you all.

Parmvir: I'm glad you joined us today, particularly since it feels like, you know, people are starting to forget about COVID-19 or they don't want to think about it anymore. So it feels like, you know,

Carina: No that's true [nervous laughter].

Parmvir: It's probably good to remind people that this is still a thing, and maybe we should be trying to look after ourselves.

But before we get onto that, I mean, obviously you've had a varied career. You study many things. Can you start by telling us about your studies? What inspired you to go into like a scientific related field of work?

Carina: Sure, sure. So since really I was a teenager. I was fascinated with the field of pediatrics and, I had the privilege of training as a medical doctor at the University of Buenos Aires in Argentina. And then I did a residency in pediatrics at the Hospital de Niños Ricardo Gutierrez, which is actually the first hospital in Latin America to have a pediatric residency. So through medical school and my pediatric residency, I became interested in the study of infection in particular, in the setting of immunocompromised conditions.

Why? Maybe because I have most of the childhood infections. So I remember [laughs] mumps and chickenpox, Hepatitis A and all that. So it was not fun. Now I have to think back when, you know, actually I saw my last patient with some of these infections, so we have accomplished quite quite a bit, but getting back on track I completed several rotations working in different units that were focused on, infection complications in children with cancer, with HIV.

And you know, just to name a few, I worked with Dr. Lopez and Dr. Rivas and Dr. Lita Fallo and those have contributed a lot actually, to my early knowledge in infectious diseases. Then after that, I actually came to the, to the US and trained at St. Jude, which is also a pioneer in pediatric malignancies, and their complications. So at that time I became involved in bench studies in ID (Infectious Diseases) looking at pneumococci and Haemophilus influenzae and understanding how these bacteria maybe become tolerant to antibiotics and how viral infections actually may open the door and upregulate receptors in our respiratory tract making secondary bacterial infections more likely.

Parmvir: Yeah. All of those seem very, very topical right now. All of a sudden, right?

Carina: [Laughs] Yeah, that's true.

Parmvir: But just before we started recording, you told us that if you weren't a scientist. Or a researcher or physician rather there's another career you really would've liked to go into.

Carina: Yeah. So I love to listen to radio. So actually I'd loved to have done this professionally; interview people, but I know that I'm not good at it [laughs]. So that's why I went into medicine and and I also love to dance. So actually I do I used to do quite a bit of Spanish dances.

Parmvir: So do you do the typical Argentinian tango?

Carina: Not tango, actually. So my parents are from Spain, so I

Parmvir: Aaah!

Carina: I do more flamenco, I know that part, so I know how to play castanets and you know, so that part is long back though, in the days.

Parmvir: What a small world, what parts of Spain?

Carina: So they're from Northern Spain, from Galicia.

Parmvir: Oh, this is going to be very interesting for the Spanish version you'll find out.

But, okay. So going back to your actual medical career you became a physician in Argentina, but like so many immigrants you find when you move to another country, you have to retrain. So what was that experience like?

Carina: Ah, yes, this is certainly a long path. So I originally came to the US as part of my pediatric training from Argentina. So I had the privilege of rotating at the Children's Hospital of Philadelphia. And then I actually learned from some very astute ID physicians. I trained with the pioneer in rotavirus vaccine with Dr. Offit and also with Dr. Jeffrey Weiser, who is a leader in microbiology.

So following that experience, as I said to complete the US medical exams, so those are three not fun. And then I applied for a fellowship in pediatric infectious diseases at St. Jude once I actually completed my residency in Argentina. And after that I actually have also great mentors at St. Jude with Dr. Tuomanen and Dr. Flynn, and they guide me in lab and clinical research at St. Jude.

And then I, to complete all the board requirements then I have to do again a second residency in the state. So that's how I came to the University of South Florida, and I did an additional fellowship in HIV.

And after that, I was done with all the training. I was offered a position as faculty at USF and then I continued as division chief, which is currently what I am. So I guess for people that want to follow a pathway you know, abroad I think it's it's a lot of work. But certainly I think, you know, if you're passionate and hardworking, there are a lot of opportunities really here to follow your dream. So I think, you know, I was fortunate to learn from different health systems. I think that that's also gives you kind of a different perspective into, into medicine, but really at the end of the day, it's really, you know, touching the people that you encounter, through your medical career. So, you know, it may have a little bit of a different flavor, you know, in, in different countries and different health systems. But for those that would like to go into the adventure, what I would suggest is, you know, just make sure that you reach out to you try to understand, you know, what you're getting into.

Parmvir: Yeah, for sure.

Carina: And and then, you know, just ask for help because, usually you know, there is, a lot of help along the way you know, to get to the final line.

Parmvir: Yeah, absolutely. So, I mean, on top of your work as a physician, obviously you do research as well. And one of the things that you've mentioned so far is that you do studies on HIV. So can you just give us a kind of a brief recap of what HIV actually is and what your work involves.

Carina: Okay.

So really HIV has become an example of a disease that went from literally a death sentence to really a treatable disease with a similar life expectancy that a person not infected with HIV has. So HIV is a retrovirus that is transmitted through blood, sexually, or from mother to child. And fortunately one of the major advances has been really the improvement in in the prevention of mother to child transmission. So if we think, you know, back in the days when I actually started as a pediatric resident in Argentina, really, we have very, very limited medications for the mother and actually for the infant, if it was infected. So we went from approximately 25 or 40% of the pregnant women may actually transmit HIV to their infants to really have transmission that is actually less than 1%. And, you know, we, we want actually to get to zero transmission. So really there has been, you know, kind of a, a lot of improvement in in this.

I guess in particular what I have done so I have been involved in several pediatric HIV studies. So in the lab um, I have I studied the impact of immune reconstitution and immune activation in HIV Uh, using flow cytometry, so for those are less familiar. Uh, What we do is we look at immune cells stained with different monoclonals antibodies, and that can help us to understand the impact of the virus in the immune system. In a way HIV is an inflammatory disease, and many of the effects of the illness are linked to the, this persistent activation of the immune system. So the virus is tricky in that it evades, multiple steps of the immune response, and also targets the specific cells that actually help us to combat infection.

Parmvir: And that's what the name means, right? Human immunodeficiency virus.

Carina: Correct. So, so very early on what we were actually doing in the lab is we were actually looking at the effect of the thymus, which is a gland that is located in the neck and actually is very active uh, when you're young and then, you know, kind of involve with time. Uh, So we were wanting to understand why some children actually were able to reconstitute without necessarily having a good virological control. Now really the target of HIV treatment is really, you know, having a very strict viral control. So what we want to do is really suppress the virus as much as possible to decrease that immune activation and also you decrease the amount of virus or the reservoir of the virus in a, in the person. And then you also avoid potential resistance to HIV therapies as well as transmission to others.

So one of the hallmark advances have been that a person that, you know, that is infected with HIV, but has an optimal control of the virus, which is called viral suppression, does not transmit either to their partner or to the child in case of a pregnancy. And that is what is known as "U=U" so undetectable means untransmissable.

Parmvir: Ah, okay.

Carina: And then I have also participated in in trials in pediatrics to approve some of these drugs, so now we actually have some medications are similar to what is actually used in adults. So, you know, just a single pill, which was really unheard of at the time that I started in the HIV field. We had, you know, many, many suspensions. It was, you know, really crazy to really give all these medications to little babies and children. Now, we have some options, that are just, you know, either a one tablet or, you know granules that are dispersed. So, you know, really we have come, you know, kind of a long way.

And then I have also participated in some studies to prevent HIV. So there is a lot in what is called prep or pre-exposure prophylaxis. And there is really a lot of new developments in the field. Not just with oral medications, but with injectable medications, maybe in the future patches, a lot of things like they are coming in the pipeline and some actually maybe able to be used once every six months or so. So it's, it's really very exciting.

Parmvir: So I actually saw in the papers recently, there was a story hopefully I'm remembering this correctly, but there are some people who seem to be naturally resistant to the virus, right? So I think there was a stem cell treatment that somebody received and it actually cured them of the disease?

Carina: So there are there are actually three cases, so two with bone marrow transplantation. And the most recent one was a woman that actually used core blood, received core blood from recipients that are CCR5; have a deletion so there is kind of a receptor where the virus actually attaches. So if you have a deletion, the virus cannot go in.

So the very, very first case was actually in Berlin, so was called the Berlin patient and he actually had to undergo a bone marrow transplantation because of other issues and happened to be HIV. So they say, well, you know, maybe let's find a resistant bone marrow to transplant this person. And actually, you know, he was cured

Parmvir: Oh wow.

Carina: of HIV and this woman so far is also, you know, a negative, off medication. So, you know, some of the research is actually going that way, how we can make and you know, some of those that has been, you know, kind of pseudo observations that some people, even if they have a very high you know, risk or exposure risk, they did not become HIV positive. So that kind of spearheaded that, that line of investigation.

Parmvir: That's so exciting.

 Yes. So the reason why we brought you here today, and the reason why we found you actually, because of a completely different virus, with which we're all sadly very familiar. And we got in touch with you because you are leading a major clinical trial in the vaccine for children.

And so I think that the tests had already been done from 12 years and upwards. Right. And that's been approved. But you're looking at the younger children from five years to what's the lower end?

Carina: Six months.

Parmvir: Okay. So can you tell us about how you got involved in that study?

Carina: Yes actually it's interesting because a lot of HIV researchers were invited to participate in COVID vaccine trials just because the network and, you know, a lot of the research capacities actually were, you know, kind of set up through HIV. So I was originally invited to be a participant of the COVID vaccine prevention network that has been funded through the NIH, so I started with the first, for a phase three here at USF with the protein-based vaccine for adults. And then I was invited to participate in the mRNA vaccine from six months to to 12 years. So it really has been, you know, really a very exciting and exhilarating time for all of us on top of the COVID vaccine pandemic.

Parmvir: Yeah, absolutely. Can you tell us, or rather give us an overview of how a clinical trial is first set up, like, what do you need to do to get a clinical trial, to take place?

Carina: So, I mean, there are actually many, many, many steps, so it goes, you know, really from the design to selecting, you know, which are the trained investigators that are actually going to to do this study it goes through different, you know, institutional approvals and IRB approvals to make sure that, you know, the protocol has all the safety net, you know, kind of included within the trial and then to the execution. So it really takes usually quite a bit of time you know, from the start to to the, the initiation.

What has happened with, you know, some of the COVID vaccine trials is that a lot of things, instead of going, you know, one after the other, they kind of, they moved in parallel and that is, you know, what accelerated some of this that otherwise it takes years and years for a vaccine to become available.

Parmvir: Yeah. So actually there were lots of really interesting diagrams of what we would call Gantt charts of, you know, these timelines to say these are things that we did in parallel to save us so much time to develop these incredible vaccines.

Now, given that you're working with very young children, many people might be wary of signing up for such a study. So how do you ensure (a) the safety of participants and to get people to participate in the first place?

Carina: Yeah, so, I mean, COVID I think was you know, really a very unique situation, I think, you know because it did kind of encounter the unknown and you know, what could happen and we didn't have any therapeutics or anything like that at the very beginning.

So, kind of the quick development of, of, of things. But really you know, these trials, I mean, not necessarily just in, in pediatrics, but any clinical trial, they have you know, you, you have a lot of different things to make sure that their safety is first. So for example, from the clinical point of view, we meet with the patients. We see them at any kind of concerns that they have either in a medical visit or through telehealth, the patients, for example, for these studies, they complete what is called an e-diary, so they actually go on the phone, they download applications. And in this case, you know, their parents will be you know, taking the temperature of the of the child and, you know, saying, you know, the child has X, Y, or Z symptoms. We are kind of 24 365, you know, available for, for any, for any concerns. And then the studies have what is called kind of pause rules. So if let's say, you know, some reaction becomes apparent and, you know, it happens at different sites. So the sponsor gets all these notifications and of course, can actually put a hold on this study. So it puts a pause on this study. There is also the SMB (safety monitoring board), so there are monitoring boards are actually are completely independent of the pharmaceutical company that is sponsoring the trial that you know, monitor all the safety signals. So they meet regularly. Or if there is any adverse event, that may be serious and they have, you know, of course the authority to actually stop the trial and they also can stop the trial sometimes early on, just because of the results, because they see that there is a wonderful response in the patients that are receiving, let's say the treatment versus the one that are on the placebo.

So it kind of goes both ways. You know, you can be stopped because of bad things or stopped actually because of good things.

Parmvir: Yeah. And actually having said that, one of my colleagues was considering submitting her daughter for the trial, who's eight years old. And, you know, she wanted to make sure her daughter was comfortable. And within the space of the three days she was doing this, the age group was full. So clearly a lot of parents were very keen to get their kids involved.

So another question I wanted to ask you is about the fact that, in the past, there wasn't a lot of attention paid to ensuring that participants come from diverse backgrounds, and this is absolutely necessary to make sure that these treatments and vaccines work for as many people as possible. Right. So how do you address this problem now?

Carina: Yeah, so I think, you know usually, in, in our patient population, our catchment area I think USF is actually quite diverse. So we actually, we, you know, we usually have a good diverse population that we see for, you know, for clinical care. um, What, you know, we have done and, of course, you know, HIV has been also another area where, you know, kind of community outreach has been very important to reach out, you know, hard to reach population. So we have some, experience on that area. So for example, for these particular COVID vaccine trials really, there was a kind of an, allocation of the number of people actually that have of any particular race just to make sure that there was not, you know, 80% of people caucasians in the study and, you know, there was no Latinos. So so there was actually kind of a cap that we actually have to follow. So from our end, you know, as you said, we did receive actually, you know, it was, it was hard because I think we had to say no to many people. I mean, we have, you know I would say, you know, five to 10 times, you know, more part, you know, people actually wanting to participate that we could enroll. So and it was really, I think, very interesting with the patients and some patients actually, you know, made t-shirts. So, I mean, this study, we had families that made t-shirts and all wore t-shirts.

But so, you know, there was a lot of people that were very, very motivated to be, to be part of it. You know, sometimes it doesn't happen, you know, to that degree, but I would say a blessing and the kids are so smart, you know, they ask you questions, you know, they were actively coming prepared to have, you know, their swab in the nose and they knew they were going to get blood draws and stuff like that.

But it was really, you know, a great experience.

Parmvir: That's so cool. So obviously the, the thing that we would really like to know is that this study has been taking place for several months. Are you allowed to share with us what preliminary results are?

Carina: Or so I mean, I can share with you what is published. So the information for 12 and older is available and it has been, you know, a very efficacious vaccine. Right now actually there, we're almost to the completion of the earlier cohorts.

So the 6 to 12 years and then the other one is still enrolling. Um, So has been actually very, very safe. I know that, you know, there has been some concerns about the myocarditis and, you know, some additional provisions actually were done doing the trial to actually collect blood to make sure that, you know, those signals were not missed uh, in case that happened. And from what we have received from, from the company there hasn't really been, you know, any, any signal on that, on that end. So so far, again, it's very safe and they have excellent, you know, the, the adolescents have either a similar or a stronger immune response, which is not surprising than adults with this vaccine.

Parmvir: Yeah.

So I'm going to do the audience questions first. So understandably many parents have concerns and reservations about getting their young children vaccinated. And so we have some questions from them too. The first one I have is from my youngest sister Sukhy, who has two children, under the age of ten. And she'd like to know if it's safe to give the vaccine to a child who has food allergies. I know that we had particularly with Pfizer, I think it was some people had anaphylactic reactions.

Carina: Yeah. So those, I mean, they are reported are actually very unusual still. So food allergies is not a contraindication to get the vaccine. Um, just to, this specific vaccine products, which is actually pretty unusual. So what I would suggest is, you know, to just discuss with the pediatrician or with the primary care provider with their specific vaccines. So all these patients, for example, in the trial, they're monitored for 30 minutes after the injection, we have not had any, any issues, you know, locally, neither, you know, anything that has been brought to our attention through the, through the trial.

But again, they are very, very, very unusual.

Parmvir: Yeah. And as you said, I think they discovered that from the Pfizer one, it was actually like the fatty layer that went round the outside, not the actual component of the vaccine.

Carina: Correct.

Parmvir: So I also have a series of questions from my friend, Sam, who is really quite concerned, but she said, what are these vaccine risks?

So you've mentioned, and obviously this you're sharing this with the caveat that this is from children, 6 to 12, is that correct?

Carina: So what has been published is 12 to 18.

Parmvir: Aha, okay, yes. So can you tell us what has been described. Cause I think you're right in saying that it's myocarditis that people have heard, what is the actual incidence of these things?

Carina: So this is actually extremely rare. So you have a much higher risk of having myocarditis due to the COVID 19 virus than actually have to the vaccine. Um, It has been seen and there is a slightly more frequent as with myocarditis in general, in usually is in males and actually within the teenage year to young adults. So um, those are usually kind of the signals, but they're actually very, rare. And nothing actually has had, you know, kind of long-term effects on, on the heart.

So for the majority of the patients, you know, they feel better in a couple of days. Some of them are going to take some NSAIDS, like you know ibuprofen and stuff like that. And and it goes away. And again, you know, we have seen, you know, much more myocarditis because either of COVID-19 or there is another entity that can. Uh, I mean, these viruses is really fascinating. So in, in, in children, you know, we have actually seen not as much with Omicron likely, but with the initial ones something that has called MIS-C, or multi inflammatory syndrome in children.

So these patients actually have, you know, sometimes very mild COVID approximately two to six weeks after the COVID infection that sometimes it's not even recognized. They'll come to the hospital really. I mean, sometimes very very sick and, you know, sometimes actually they need ICU care uh, with like rashes, persistent fevers, it's kind of the immune system, you know, kind of going wild after the infections of this kind of inflammatory disorder, which is treated in a similar way to another entity that we are familiar as pediatricians that is called Kawasaki disease.

So the vaccine actually has also been effective in decreasing the amount of people actually have a MIS-C after, you know, after the vaccine is actually the, the frequency is actually much lower. .

Parmvir: So you've basically answered her next question, which is, which is more dangerous to health getting COVID as a five-year-old or the vaccine risks?

Carina: And, and, you know, and I think that the, the important part is that we just cannot predict.

Typically, you know, there are other co-morbidities, so people that are obese that have hypertension, they have, you know, other kind of immunocompromising conditions, they may be at a higher risk, but, you know, I have seen plenty of children that have no other risk factors and they end up, you know, having to come to the hospital because of complications of, COVID.

So, you know, I think it's again, it's milder in children, but it's not out of risk.

Parmvir: Yeah. Before I forget, can you define what myocarditis is?

Carina: So myocarditis is kind of an inflammation of the myocardium, which is part of the, of the heart. It's usually actually seen not, not just with COVID or not just with vaccination, but is actually very frequent with all infections and many times, you know, may be completely, you know, under recognized. So the majority of the times, you know, it just goes away with with time and nothing to do, you know, and you don't have to do really anything with it.

Parmvir: Okay. So I guess just hearing a clinical term like that might be making people more afraid than they necessarily should be.

Carina: Correct.

Parmvir: Okay. So long-term. What are likely side effects of the vaccine for children and is it possible that there would be long-term impacts we don't know about yet?

Carina: I mean the most common side effects are, you know, kind of the typical from vaccines, so pain at the injection site. And then there can be some redness at the injection site uh, headaches, nausea, vomiting there'll be uh, um, kind of muscle pain or feeling or feeling fatigued.

So those are kind of the most common ones, that are reported. And usually they go away, you know, in like 24 to 48 hours. Some people may have, you know, kind of a more persistent or delayed redness in the, at the injections site. And usually they most of the vaccine effects happen within you know, the very initial, time to usually not more than six months or so.

So that was why, you know, the trials and the start of the immunization they wanted to have, you know, at least the two months first. And then, you know, kind of going to the potential side effects, you know, later on. And this is why it's important to do randomized clinical trials, because some things can happen just because, and there can be a coincidence because a lot of people are actively getting the vaccine. So that's why, you know, you can tease out if it's vaccine related or really was, you know, at the same time, just because of chance. So I can say there is not going to be any kind of unknown effect, but it would be very, very unusual. I mean, right now we have had you know, millions and millions of people worldwide with these, with these vaccines. So if there would be, you know, other unknown signals you know, I, I think we should have seen it that this by this time.

Parmvir: Yeah, because the first people were getting the vaccine, how long ago now?

Carina: Oh, now I guess it's like almost two years.

Parmvir: Yeah. And do you know, off the top of your head, whether there's ever been a vaccine, which did cause serious side effects that were this far down the line?

Carina: The majority really have, you know, kind of uh, side effects either right away or within these, you know, two months, time is usually the case like Guillain-Barré you know, and some other autoimmune diseases that can come up here, usually it's within, you know, that early timeframe.

Parmvir: Okay. So before we wrap up, I was wondering if you could tell us, so you're still working on the clinical trial for the younger children, but what is going to be next for you once that's kind of done with? Do you already have something lined up in terms of a future project?

Carina: So I mean, I will, you know, continue to, to work on the COVID vaccine.

We will be following up with with HIV research and you know, not just for HIV treatment but also for HIV prevention. So, you know, those all, will be kind of the lines that will be, you know continuing.

Parmvir: Oh, very good. Um, I really appreciate your time today. I mean, this has been super interesting and I think this is going to be a valuable listening experience for a lot of people.

So thank you again.

Carina: Well, thank you for the opportunity to, you know to participate. This has been really great.

Parmvir: No, of course.

[musical interlude]

Carina: All right. So something embarrassing. Well I do remember my only time of of ID research being asked to actually go with another fellow I was actually studying pneumococci in St. Jude. So one of the one of the projects was actually looking at how, you know, these bacteria went into a mouse, into a rabbit model and actually, you know, how quickly the bacteria was killed or if it was actually, persistent on the CSF. So I remember going with a, you know, with another fellow I had not done, you know, animal studies in Argentina, so that was new to me.

And so. I say I cannot do that. So I just remember the little rabbit looking at me and it's like, I cannot. So I think that that was my, you know, like it gives my fear to the contribution of science. Luckily I love, you know, all the other stuff with bacteria, you know, Petri dishes flow cytometry, but no animal models for me.

[musical outro]