Can pregnant women’s COVID infection cause brain injury in newborns?
A Newswise Live Event
What:
A group of physicians and scientists are releasing an important study that will be published in the journal Pediatrics on Thursday, showing that COVID-19 can cross into the placenta of pregnant women and cause brain injury in newborns, as evidenced with 2 cases they treated here in Miami. One of the infants also died at about 13 months old. Further testing of the infant’s brain specimen showed that the virus was still present in the brain at the time of death—which was over a year after birth.
When:
April 6th, 2023, 10 AM - 11 AM EDT (Tentative)
Who:
TBD
Where:
Newswise Live Event Zoom Room (Link will be provided once you register)
MEDIA REGISTER HERE TO ATTEND AND/OR RECEIVE A TRANSCRIPT WITH VIDEO
TRANSCRIPT:
Jessica Johnson:
Welcome, everyone, to this NewsWise Live event with the University of Miami Health System and the Miller School of Medicine.
I would like to welcome everyone today and begin by introducing the researchers from the University of Miami Health System and the University of Miami Miller School of Medicine that have recently published research about findings that COVID infection breached the placenta and caused brain damage in newborns.
So to start, we're going to introduce the first author of the study, Dr. Merline Benny. She is the Assistant Professor, Division of Neonatology Department of Pediatrics at the University of Miami Miller School of Medicine.
Then we also have Dr. Shahnaz Duara, the Professor of Pediatrics at the University of Miami Miller School of Medicine, and the Medical Director at the NICU at Holtz Children's Hospital.
Then we have Dr. Michael Paidas, who is a Professor and Chair of the Department of Obstetrics, Gynecology, and Reproductive Sciences at the University of Miami Miller School of Medicine.
And then we have Dr. Ali Saad, who's a Professor of Clinical Pathology, Director of Pediatric Pathology at the University of Miami Miller School of Medicine. And Dr. Aru Mugham Jayakumar, who's the Research Assistant Professor at the University of Miami Miller School of Medicine and Neuroscientist and Molecular Biologist in the Department of Obstetrics, Gynecology and Reproductive Sciences. Thank you all for being here.
This is an important study that happened among many researchers that were collaborating together very well and I would like to introduce Dr. Benny, who will give a presentation, a summary of the paper.
Merline Benny:
Good morning, everyone. Thank you for coming to this meeting today.
So the task that has been assigned to me today is to summarize our study.
We all know that COVID has had a profound effect on the global health of people around the world and more so in pregnant women, and this is because COVID not only affects the mother herself but also puts the unborn baby vulnerable and puts the baby at risk. So in our experience since the start of the pandemic, we have had nearly 700 and more mother-infant pairs in the Jackson Hospital who were admitted. And all these mothers who were COVID-positive, majority of them were asymptomatic. And even the infants, majority of them were very healthy after delivery and left the hospital without any complications.
However, here we report in this study two babies who had a very unusual clinical picture. These infants were born to mothers who were COVID-positive, who became positive in the second trimester of their pregnancy and delivered a few weeks later. Neither of these babies, however, tested COVID positive. However, in their blood, we found that the COVID antibodies were present, which suggests that the COVID antibodies must have crossed from the mother through the placenta to the baby. The classical clinical picture that we saw in these two babies was seizures, seizures that developed from the first day of life, and they had profound low tone in their clinical exam, what we call hypotonia. As they grew, they further had a very small head circumference. The brain imaging on these two babies showed significant brain atrophy and on the neurodevelopmental exam, and they had a very delayed neurodevelopmental exam. One of these babies died at 13 months of age, and the other was in hospice at the time of our submission of this manuscript.
So as a neonatology team, we couldn't precisely identify what caused this unusual presentation. We discussed this with our multidisciplinary team of doctors who cared both for the mother and the baby, including the team of doctors that we see here, including the OB, neurology, neuroradiology, and our pathology colleagues, who were all very intrigued by this unusual presentation. So we decided to study this further.
The OB team and the pathology examined the placenta of these mothers, and they found some characteristic COVID changes in these placentas of these mothers. They also found the presence of COVID virus in the placenta. This was associated with increased markers of inflammation and oxidative stress in the placenta - and also a very critical hormone, which is important both for the placental health and for brain development, was very reduced in the placentas of these COVID moms.
This was very intriguing to us, so then we further examined the brain autopsy slide, and we found that in the brain autopsy slide of the infant who passed away, there was COVID virus in the brain, which raises the possibility that the SARS-CoV-2 infection of the brain directly could have contributed to this ongoing brain injury.
That was the gist of our study, and we are happy to take any questions. We have a multidisciplinary team of doctors here, happy to take any questions and take it from here.
Jessica Johnson:
Yes. And just for everyone, for journalists in the room, if you have questions, please feel free to chat with them. We can also turn on your mic and you can ask them yourselves. Maybe raise your hand or chat, feel free to do so.
Also, it would be helpful if you were able to identify your name and media outlet if you haven't already done so.
We have a question from WSVN - how many weeks were babies born?
Merline Benny:
So one of the babies was born at 32 weeks, a little preterm, and the other baby was born at term.
Jessica Johnson:
Okay. From Sarah Anwar from WPLG, a local 10 station, were the women vaccinated?
Michael Paidas:
Hi, this is Michael Paidas, I'll jump in here.
So these babies actually occurred early in the pandemic, so no, we didn't have vaccines at that point. And I wear a few hats here, I've been through on the front lines for the six rounds of Covid and so one of the patients, and I think it's probably helpful to point out - one patient was delivered at 32 weeks, as Dr. Benny said, that patient had a very severe COVID presentation and spent about a month in the ICU and through a multidisciplinary team, we decided to actually deliver the patient so that we can care for the mom. So in that instance, the mom was very sick and so it was delivered at 32 weeks.
In contrast, the other case was actually a healthy person who had essentially nearly asymptomatic infection and in the second trimester, around the same time, around 27 weeks or so, and then delivered full term close to her delivery date.
So really separate, diametrically opposed presentations with respect to the patient.
Jessica Johnson:
Great. There was a question from Rennie Lewis from NBC News.
When were the moms infected? What wave of the pandemic?
Shahnaz Duara:
I can say that this was the Delta Wave.
Jessica Johnson:
Okay, the Delta wave. What was the baby's age, what was the baby's age, I guess at the time of death?
Merline Benny:
So the baby who died was 13 months of age when the baby died.
Jessica Johnson:
Lorena from NBC 6 is asking how many total babies were involved in the study. What's your biggest message to pregnant women in light of this study? And I think that Dr. Duara, maybe you would like to answer that, that would be great.
Shahnaz Duara:
So this is really, we're following these mothers serially. These are women who deliver babies, who test positive and deliver babies, who may have some problems. It was just in the first few months of the pandemic that all babies were coming up to the cohort nursery. That was based on CDC guidelines at the time. But within three or four months, if the mother was healthy and asymptomatic and the babies were healthy and asymptomatic, they roomed together, the mother used precautions, and then the babies got discharged with the mom. So any baby who came to the cohort nursery adjacent to the NICU either had medical problems of their own or had a mother who was too sick to take care of the baby. That way, from April 1 of 2020 to March 31st of 2023, we have had 367 newborns. And of those 367 newborns, most of them had transient issues, many of them medically related to their own gestational age. Only a handful of babies tested positive. Several of these babies had minor symptoms that disappeared, but these were the things that kept bothering us, that these were atypical symptoms, and maybe this had something to do with the COVID in the mother. And then we got two of these babies, and these were strikingly different. We had absolutely no good explanation for the early seizures and the degree of brain injury we saw.
They were not infectious, there was no issue during labor, and we investigated every avenue and when we hit a blind end in every other way, except for the fact that they had these elevated antibodies directly to the COVID virus, the SARS-CoV-2, and indirectly lots of inflammatory markers. That's when we began to talk to our pathologists, we started talking to the neuroradiologists who did not see the signatures of other injuries, and we went back to our obstetricians. So it sort of was a little bit of a detective story.
Jessica Johnson:
Dr. Duara, can you also maybe address the kind of message for pregnant women overall?
Shahnaz Duara:
For sure. I think the message here is that most women who contract COVID go on to have healthy babies, okay. But there is a subpopulation of people who have babies who are sick. This is not to panic the population whose babies may have been exposed to COVID in pregnancy, but we do think that these are the extremes, and we do think if you've had COVID during pregnancy, it's something you should tell your pediatrician, and maybe those babies need a little closer follow-up because we know that things can be fairly subtle until seven or eight years of age until kids start going to school. And for some unfortunate reason, developmental follow-up in this country is not as widespread as it is in many other places. We send our kids to pediatricians, and we give them their baby shots, but developmental follow-up is available, but you have to ask for it.
Jessica Johnson:
Thank you so much, Dr. Duara. There's another question from Julie Steenhuysen from Reuters, and she asks, what variant were the mothers infected with?
Shahnaz Duara:
We believe they were Delta because it was during the spike of Delta in Miami.
Jessica Johnson:
And also for Dr. Paidas, this might be a good question for you from, again, Julie Steenhuysen. Why are we just learning about this now? Is this the first time we've seen microcephaly associated with maternal infection?
Michael Paidas:
Well, that's a great question. So, one is, we're also on a learning curve about the detection of the virus and the organs. You know, for a long time there's been debate about does the virus cross, etc. And so now, we've clearly shown that it does cross. And in terms of the microcephaly and just, these babies, this is over a year, you know, 12 months where we're seeing this after delivery. So, antenatally, we're not seeing, brain malformations in COVID-positive patients, unlike other viral conditions that we've had recently. So, we had to take the time to actually go through and document the presence of the virus in the organ. I mean, this is the first time that we've been able to demonstrate the virus in an organ - in a fetal organ, well, newborn like this with transplacental passage. So, that's why we think this is so important.
Shahnaz Duara:
And also to point out that the babies were not born with microcephaly, unlike Zika, where the babies are born with a tiny heads. These babies were born with normal proportions, but seizing, tremendously encephalopathic and seizing, not infectious that we could find in terms of bacteria, viruses, fungus, those sorts of standard things. And over time, the brain stopped growing. So, it was that they started out symmetric, and then over time, as Dr. Lopez, our pediatric neurologist followed them in the clinic, the body grew in terms of length and weight, but the head fell off and became microcephaly. We took time to document that - it wasn’t a birth finding.
Jessica Johnson:
And this is maybe a good time to, just to step away from the questions for one moment and introduce Dr. Saad, and who can maybe speak about that and how, what happened, how you addressed and found COVID in the brain, basically.
Ali Saad:
So, basically, let me start with the placenta first. The placenta showed some changes that we know based on the placentas I've seen during the pandemic, that are commonly seen in patients who are COVID-positive. To avoid the use of medical terminology, I'll just use one - all the changes fall under the umbrella of fetal vascular reperfusion, meaning the chorionic villi, which are the functional unit of the placenta are smaller, and the cells within these chorionic villi are undergoing apoptosis or necrosis.
Upon examining the brain, I was struck by the amount of loss of white matter. Remember, the white matter is very large in the brain, especially in the neonate, and also it contains all the wiring systems between the cerebral cortex and the rest of our body. So, the white matter mental was severely reduced in size and also the cerebral cortex contained neurons, which are also the functional unit of the gray matter or the cerebral cortex were on their way to die. So, they showed what we call hypoxic/ ischemic changes. This is what triggered the entire process of this investigation. So, I communicated with Dr. Duara, Dr. Paidas, Dr. J, and Dr. J did the stains on the placenta and the brain, and we found evidence that the virus indeed crossed the placenta and infected the brain.
Jessica Johnson:
Okay, and can you or anyone here - any of the researchers, would you be able to speak about why this is a very important finding, and has this been addressed before or seen before?
Shahnaz Duara:
No, this is why we think this is very important news because this is the first time that Dr. Paidas and Dr. J have helped to demonstrate that there is actually a virus in the brain. So, I will let them describe what they did, but this is a first, transplacental.
Michael Paidas:
There's a question in the chat, did we check for the RNA? So, just to explain, so we demonstrated the nucleocapsid protein and the spike protein co-localized, so that really has definitively shown that the virus is there in the organ, and so that should answer the question, and I think the really important part about this as well is the overwhelming inflammatory and COVID-related changes that we see in the placenta. You know, we don't know if it's the infection from COVID in the brain that's causing this issue, or a combination with the overwhelming other factors, the inflammation, the oxidative stress, you know, all the other things that we showed, also the decrease in the HCG, very important placental hormone in the syncytiotrophoblast, the outer placental layer. So, it could be a combination, or together, or two discrete pathways, and that's why we want to pursue it, and most of this, the reason for being able to also to identify this is that we're doing a lot of work in the laboratory on the animal side so that we can help understand the COVID pathology and also develop therapeutics for it.
Jessica Johnson:
Okay, thank you. Also, Marcia Freilich asks, have similar findings been reported elsewhere at other institutions?
Michael Paidas:
Not to our knowledge.
Jessica Johnson:
Yes, okay, great. I just wanted to address that directly, and Jacqueline Keeney from CBS4, is there a way to protect babies at this point? Is it vaccination? Is that a way to protect them, or another way to prevent them?
Shahnaz Duara:
Maternal vaccinations have been shown to be not harmful during pregnancy. I'd like Dr. Paidas to address that more, and pre-pregnancy if you're planning to get pregnant, that would be a way to protect yourself as well.
Merline Benny:
Yes, and breastfeeding, if the mothers are vaccinated and breastfeeding, that too can help the passage of antibodies to the infant, and protect that infant in that manner.
Jessica Johnson:
So, is it a matter of protecting the newborn against the antibodies?
Shahnaz Duara:
Against the infection.
Jessica Johnson:
So, next question is, Julie from Reuters says, because this happened early in the pandemic, do we know if this has happened since then, or with any other variant? Is this unique to the Delta variant? Has it happened in other countries? Are vaccines protective?
Shahnaz Duara:
We haven't read about transplacental passage or this presentation prior to this report, so we don't, we really have any knowledge of anybody else reporting it, and we haven't seen it subsequent to these two variants. So, when we have seen close to 700 mother-infant diets at this institution, because Miami's been one of our hot spots for COVID, and we've had babies with other problems, but these two were the only ones who had this very striking neurological presentation.
Jessica Johnson:
A question from Alicia Bigica. It's Neurology Live. Do we know if the timing of infection plays a role in the possible effect it has in-utero, early pregnancy versus mid or late?
Merline Benny:
There is not much known about, you know, the time of the infection and the outcomes on the baby, and I think that is something that really needs to be studied and followed. In our cases, we found that it was in the second trimester that the moms had those infections, but again, these are just two cases. I think it is very important to look into further the timing of the pregnancy and whether that changes the neurodevelopmental outcomes that we see in infants. A lot of research needs to happen in that area.
Jessica Johnson:
Okay. Also, Lorena asked, can you share a little bit more about the demographics of the women whose babies developed issues? Age, race, ethnicity?
Shahnaz Duara:
No, they were both primary gravidas, the early 20s, and Latin. Yeah. Local people, use our medical center as their medical home.
Jessica Johnson:
Judy George from MedPage, was the SARS-CoV-2 protein in the near brain areas that showed damage? Or I guess, or near brain areas?
Shahnaz Duara:
It was everywhere. I suppose, yeah. Everywhere. It was everywhere.
Jessica Johnson:
Ronnie Rabin - were both babies born in Miami? Same hospital?
I believe, yes.
Merline Benny:
Same hospital.
Jessica Johnson:
Yes, okay. Okay. And Veronica is asking if we can repeat the names of the doctors and the first and last names of the doctors. Also, all of them have within them, if you hover over them, you can see their names, hopefully. But we can also send you a list and we have a news release that we will send to everyone, as well as a video with a transcript of the event. So, everyone who registered, we will send you that. We should have the video ready within three hours, approximately.
And the pronunciation - yes. So maybe everyone could just go through and introduce themselves. Also, that would be helpful. Maybe we start, with Dr. Benny.
Merline Benny:
Yes, so I'm Merline Benny, a faculty in neonatology and pediatrics at the University of Miami.
Shahnaz Duara:
I am Shahnaz Duara. I am also a neonatologist and medical director of the NICU FACT.
Micheal Paidas:
Hi, I'm Michael Paidas. I'm chair of the Department of OB-GYN and Reproductive Sciences. I'm a maternal-fetal medicine specialist. I'm chief of service for Jackson Health System and University Health Tower.
R Mugham:
I'm R. Mugham R. Jayakumar, faculty in the Department of OB-GYN.
Ali Saad:
I'm Ali Saad. I'm a professor of pathology and pediatrics and I'm the director of the pediatric and perinatal service at the University of Miami.
Jessica Johnson:
Also, Kaia Hill, who's here, she is the communications officer and you can feel free to contact her. Her information will be also on the news release, but please feel free to reach out to her or even chat her now, if you would like follow-up questions.
Julie from Reuters says, is there anything unique about the pregnancies that could explain why the virus crossed the placenta in these two women?
Micheal Paidas:
So, you know, this is the striking part about this. You know, one patient, severely sick, had to be delivered from maternal indications to help her get through and survive, literally. And the other case, is completely asymptomatic. So they couldn't be farther from different.
Jessica Johnson:
Could we ask, I think there was a question early on about whether these two women were vaccinated.
Micheal Paidas:
Right, this was before all of that.
Jessica Johnson:
Okay, so any other questions? Is there anything that the researchers and participants would like to address or mention?
Shahnaz Duara:
It's just that, you know, this is something that we want to alert the medical community to more than the general lay public. We do not want the lay public to be panicked by this, but it is important for us to get the message out that it is not always benign. So, you know, a lot of young people who are in the reproductive age group treat COVID as a nuisance illness. And, it doesn't matter. I can go to a rock concert and expose myself, not take vaccines, and I'll be okay. You probably will be okay. But there is going to be a proportion of pregnant women who will expose themselves and may not have the consequences they anticipated.
Micheal Paidas:
And I would echo just two points. One is, you know, vaccines, they've been shown to be safe and they will afford some protection for pregnancy. So I would encourage that.
And secondly, the an urgent need to develop therapeutics for our vulnerable populations, for moms and newborns, and adolescents. So we need more research and we need more patient engagement in the clinical trial arena. And finally, we need a longer-term follow-up.
Jessica Johnson:
Yes. Also, I would like to ask Dr. Saad, if you could tell us about your team's role in the screening of infants a little bit more and how you get involved in this process.
Ali Saad:
Well, I'm the pediatric and perinatal pathologist in the system. And we examine the placentas of mothers who are COVID positive and also we did the autopsy on one of the patients. So this is how I got involved in the brain. And I happened to be a neuropathologist as well. So pediatric pathology and neuropathology - it's a perfect combination in this particular case.
Jessica Johnson:
Okay. And what did the scans of the infants reveal? You talked a little bit about that, but maybe you could say some more.
Shahnaz Duara:
The scans, I'm afraid we don't have our neuropathologist or radiologists here with us today, but it's as you will see in the manuscript, but initially, they did not look abnormal, but gradually over time, they began to show areas of atrophy, and injury that could mimic another disease called hypoxic-ischemic encephalopathy. You know, if a woman delivers abruptly because her placenta separates or something traumatic happens to the cord, babies can present similarly. Yes, sorry, just to mention that the hypoxic-ischemic encephalopathy, just to HIE refer to it sometimes. And it's also, it's mentioned in the news release.
Shahnaz Duara:
Yes, but you know, this was distinct from that, which is why we went down the path of investigation. Okay.
Micheal Paidas:
Just one point, there's a comment about vaccines being available. Just to point out the first case of severe ICU admission in all the sick patients, was July 2020. So, you know, that was well before, we had the vaccines.
Jessica Johnson:
So that answers that, And then another question, one more question from Judy George at MedPage today. What other confounding factors could account for the findings in these babies?
Shahnaz Duara:
Not really. I mean, that's why we took on this big investigation. We really didn't find anything that was plausible and convincing enough to let us stop them. There were other cases with minor things, which we could explain away, but these two just stuck out.
Ali Saad:
Yeah, I just want to reiterate the severity of the brain findings - the significant reduction of the white matter. I've seen literally thousands of brains at autopsies over the last 14 years since I started practicing. And this was the most dramatic case of leukoencephalopathy or loss of white matter in a patient with no significant reason. So again, that's what triggered the entire process of investigation.
Merline Berry:
So just to add onto that, when these babies got admitted to the NICU, right? When they had seizures from the day of life one and with significant hypotonia, there were, a lot of differentials that we looked for, and hypoxic-ischemic encephalopathy was the first one that could trigger something like that. But there weren't lab values or any maternal factor - the classical maternal factor to call it HIE that was evident in this case. So we clearly ruled that out.
Then the other things were, is this possible infection?
Is this something congenital infections?
Could that be causing something like that?
We did a whole panel of workup. Nothing came out. We did a lumbar puncture on the babies to look for the spinal fluid, to look for any evidence of infection in their brains. Nothing came out.
So there are so many of these. Then we look for - sometimes seizures, you can also have what we call metabolic errors in the newborn, which could present with hypotonia. We looked for that and that too couldn't. So nothing, it was like a puzzle. And no matter what we were trying to, slowly take off the picture, we couldn't really pinpoint. That is what prompted us to think that this might be something more than what the classical clinical picture shows. And that then the discussion came up, could this be something related to the mother, her inflammation, and whether that could have triggered that, the fetal inflammatory response Dr. Paidas mentioned about in the baby causing, the baby's brain is at a vulnerable point growing, right? Whether that caused it. So then we had to go back, and look into the placenta, which they did, and they were able to show the virus and these markers of inflammation, the hormone that was significantly reduced. And then the classical finding of the brain slide showing the virus as well, which makes - links the story to it being COVID and COVID-related brain injury.
Jessica Johnson:
Yes, thank you, Dr. Benny. There's another, from Judy George, another question. When were the brain MRIs done? Right after birth or a year later?
Shahnaz Duara:
No, no, they were sequential. They were done.
Merline Benny:
We did it, the first, I think we did it in the first week of life. Then we followed it up with, when you see like any changes in these hypoxic, this initially, that was our thought, is this something like that? We followed it up for three months and then outpatient follow-up was done. And then even at one year, so there was sequential follow-up multiple times on the brain MRI showing classical brain atrophy imaging.
Jessica Johnson:
Kia is also offering in the chat for everyone, a press release study photos, and B-roll. So please feel free to access that and also contact Kiah if you need any more assistance or have any further questions.
I have one question - do you have data, Dr. Paidas? Do you have data about the number or the percentage of women, pregnant women who are vaccinated currently?
Micheal Paidas:
So, The numbers, are you speaking about in the for what we're seeing here in Miami or –
Jessica Johnson:
Yeah, maybe for you personally or nationally.
Micheal Paidas:
Yes. So, I will say that one there has been a general slight more in uptick and getting the vaccination. There's a lot of vaccine hesitancy to begin with. And so I think it's probably around the 20% or so. It's not, honestly where I think we really need to have it. So, it's work in progress.
Jessica Johnson:
Yes, to summarize it – it appears that maternal inflammation from SARS-CoV-2 infection led to the baby's brain changes. Is that a correct assessment?
Shahnaz Duara:
Well, we have the information and that certainly can affect the brain, but we also have evidence of direct infection of the brain. We actually have shown that there's virus in the brain. So that's a whole different ballgame.
Micheal Paidas:
Yeah, and just more to the point, it's about the placenta. I think that's the message. It's not so much the maternal, it's on the placental side, on the fetal side, the fetal placental unit. And it's that complex, that inflammation there - Of course, we can see it on the mom's side as well, but it's the placenta in combination with the infection in the organs, right? So that's I think the issue.
Jessica Johnson:
Maria Fernandez Lopez is saying, can we have any Spanish explanations? And I believe that there can be from Dr. Lopez, is that correct? Or is there any Spanish speaking participant that can be a contact for media, Spanish-speaking media?
Shahnaz Duara:
I think Dr. Lopez will be the best person. He's unfortunately in clinic today, but he's very aware that this is going on and that he will be available, perhaps at the end of the day, for questions. So if you can get them in writing, and forward them to him, I'm sure he will be happy to.
Jessica Johnson:
I would say that for Maria Fernandez, maybe you could contact Kaia Hill, the media contact here. And also, Victoria McAllister has two questions. Were both babies born in Miami? I think yes. And when you say this is novel, do you mean the viral transplacental transfer or viral transplacental transfer leading to brain injury?
Second, neither of those has been seen before with other viruses, or do they mean this is just the first time it's been seen with SARS-CoV-2?
Micheal Paidas:
Yeah, so just to unravel that for a minute. So there was debate about whether or not the virus was actually getting across in the placenta. There have been some case reports, but one, we've definitively shown that, so one.
But the real issue is that not only does it go to the placenta, but now we have it in the organ and we've documented damage so you have the inflammation that's going on in the placenta with the virus, and then the brain - the organ finding. And that's what's novel about this study.
It's never been seen before with SARS.
Jessica Johnson:
Looks like we don't have any more at this time, so I would like to thank everyone for attending.
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