Considerations Related to Covid & PFIC

Considerations Related to COVID and PFIC Video

SPEAKERS

Dr. Ron Sokol, Emily Ventura

Emily Ventura  00:00

I’ll give just a few minutes to let people roll in. All right, let’s go ahead and get started. Well, good morning, everybody. Welcome back to the PFIC Virtual Family Conference. Thanks for joining us on day two. We’re really pleased to have you. We had a really great day yesterday, had a lot of interaction with the sessions, very positive feedback. Everyone asked some really great questions, so I hope that we keep that up today. We have a pretty great lineup, starting with Dr. Ron Sokol, here in just a few minutes. Just want to remind everybody that in between sessions, we do have the lounge area and the exhibit hall that has some booths with some great information. We have our educational brochure and a few other resources that are available for download. You can add them to your backpack so that you can just keep everything in one place. So please, in between sessions, take a look around. Feel free to explore or find somebody in the chat if there’s somebody that you want to meet. Find me, if you want to do a chat. We could have as a side Zoom conversation. But other than that, we’ll roll through with our webinars and we hope that everybody enjoys. So real quickly, if anybody is using our translation software today, just a reminder, in the top left hand corner of your screen, there should be a red Live button. You can click that and that’ll open up into a new window for the Wordly screen. Find your language in the drop down and it should bring up the closed captioning language software. Remember, it is software based, so it might not be perfect, but hopefully it’ll be helpful. A few disclaimers. These sessions are for education and information purpose only. So any advice that is specific to you or your child, please consult your doctors. Zoom is not a HIPAA compliant platform. So please keep that in mind when you’re asking questions. Please leave patient identifiers such as name and date of birth out of those questions. And this session is being recorded. It will be housed in this platform and later visible on our website for further viewing. Any questions please ask them in the chat or the Q & A today. And we’ll get to them at the end of the session or in the q&a later this afternoon. So I’m going to turn it over to Dr. Ron Sokol of Colorado Children’s Hospital, who’s going to walk us through what’s happening with COVID today in relation to PFIC and transplant patients. Thanks Dr. Sokol.

Dr. Ron Sokol  02:49

Well, thank you so much, Emily. Congratulations on this very successful and very important webinar for families and patients with PFIC diseases. And thank you for inviting me to present. I’m the chief pediatric GI, hepatology and nutrition at Children’s Hospital Colorado. I’ve been involved in the research, clinical care and education around cholestatic liver disease, including all of the PFIC diseases for many years, so I really look forward to this interaction with the families and communities around the world that are that are dialed in. I was asked to speak about a topic that all of us talk about, not just when you see your doctor, but I’m sure with your neighbors, with your families, with your children. And that has to do with COVID. So let me share my screen. That’s probably the most used… overused phrase in 2021: “Let me share my screen.” And one more adjustment, and we should be fine. Do you see the right view now? Is that right, Emily? 

Emily Ventura  04:11

We do. 

Dr. Ron Sokol  04:12

So I’m going to be speaking about considerations related to COVID and PFIC and liver transplantation in children.

And let me first say, let’s start right off that there is limited data in children regarding COVID in children with liver disease, with any liver disease. So some of the data I’m going to show you and I’m going to talk about is obtained in adults. It may or may not be pertinent to children and where we do have information, good information on children. I will be sure to show you that information. And I just wanted to quickly say I consult for several companies that have nothing to do with COVID, however, two of the companies are producing drugs that I’m sure you’re all aware of that are being tested in PFIC. That’s Mirum and Albireo. So COVID-19, let’s just level set and put some basic information out there. I think you all know this is the name of the disease, COVID-19, but it’s caused by the SARS-CoV-2 virus, which is a novel coronavirus. And coronaviruses have been around for a long time. They cause the common cold and mild disease, and they are spread through droplets and aerosols. And droplets are generally visible droplets of fluid when you sneeze or cough. Aerosols are droplets that are basically microscopic and float around in the air. But they are initiated by the same thing coughing, sneezing, speaking loudly, perhaps singing, breathing heavily. And that’s how these viruses are spread. Now, this is not the first Coronavirus that’s caused a serious illness. And SARS, which initially stands for Severe Acute Respiratory Syndrome happened about 15 years ago and then MERS Middle East Respiratory Syndrome happened later and they were both caused by a novel coronaviruses. However, they did not spread worldwide as the COVID 19 virus has. I think you all know that started in China in late 2019 and then literally spread to every country in the world over the next three to six months. And as in almost every country, our country has seen many waves of this infection, the technical term is “surges”. And we’ve had either three or four in the United States, depending on where you live and the timing also depends on that and one of my slides will illustrate these surges. Many of us are a bit concerned with the new variant, the Delta variant, that seems to be more infectious than the prior versions, that the Delta variant is spreading rapidly through the country. And in those areas where there’s poor vaccination rates, it’s very likely we’re going to see another surge. Unfortunately, it’s already started and we’re all hoping that doesn’t, doesn’t get to the level that we saw in January and February, but it may well happen again. And what has become known and little of this…none of this was known before last March, is that there’s many risk factors for people to develop severe disease. So if you develop the cold from this virus, you wouldn’t get very sick, but you could still spread it to other people. And those people who do get severe disease, it’s usually defined by needing hospitalization, and intensive care unit being put on a ventilator, or actual death rates. So what we really want to do is prevent severe disease. And again, what’s become known by studies all over the world, and many of these were first in China and in Italy, where the pandemic hit hardest first, is people who are older age, over 65 to 70, have a much higher risk for those severe course definitions that I just said, hospitalization, ICU, ventilator, et cetera, and also people in underserved communities. And these generally then mean people of certain ethnic and minority groups. Now, some of that may be because of the jobs that they hold, and in order to maintain their job, they were exposed more than other people. Some of it has to do with crowding in housing. Some of it has to do with poor access to medical care. But clearly people from underserved communities had more and worse disease. But other diseases that one had one may have, chronic diseases, do predispose to a more worse course and that includes diabetes, heart disease, hypertension, high blood pressure, virtually any kind of lung disease, which makes sense because this is a primarily lung infection. People with chronic kidney disease, children and adults with Down Syndrome have a very high risk for progression to hospitalization. People that are overweight, people that have cancer, and particularly may be on chemotherapy and then individuals with a weakened immune system, either because they were born with it, or they have an infection that weakens their immune system such as HIV, or they’re on medications that may weaken their immune system. And this is where we get into the immunosuppression that transplant patients are receiving. But what was remarkable about this pandemic, is that what is not a risk factor is being a child. And children were actually protected against severe disease, which was a surprise to everybody. Because with influenza, young children and infants can have very severe disease and other lung disease, that common flu, but COVID-19 really did not affect children nearly to the extent as adults. However, children could get infected, not get sick, and pass it on to adults. And this is one of the real risks that led to the recommendation that grandparents should not be around their grandchildren early on in this pandemic. Because even though the grandchildren may not be sick, they may carry the virus, infect the grandparent and if they were over 65, or 70, they would be at relatively high risk to get hospitalized.

Dr. Ron Sokol  11:45

So why don’t children get severe disease? Well, there’s several theories. But one is based on the fact that this virus enters the cells in your body through a receptor, it’s called, it’s a protein that the virus binds to on the cells and allows the virus to enter the cells and then infect the cells, and it’s called ACE 2. I think you’ve probably heard about the ACE 2 receptor. So one possible reason could be the children may have lower amounts of this ACE2 receptor on cells than adults and there’s several studies that suggest that this is the case. Whether this accounts for the protection of children, nobody knows for sure. Another hypothesis has been the children have frequent exposure to common cold viruses, other coronaviruses, and there’s about five or six of those and therefore, they may have built up immunity because they’re frequently infected with colds, to any coronavirus, and perhaps some of that immunity, some of the protection also protects against the COVID virus. And the truth is, we really don’t know why children don’t get severe disease. But these are two of the theories behind it. However, I do want to point out that children may get a specific complication of COVID that’s very rare in adults. And you’ve probably heard of this the multi system inflammatory syndrome due to COVID in childhood, so it’s called MISC, the C stands for childhood and this occurs rare in children. This is not common, but it does occur two to four weeks after infection with COVID. The belief is that certain children perhaps are predisposed to this if they get this infection, and their body develops a severe inflammatory reaction to the virus. So when they have MISC, they may not even have active virus in their body anymore, but this is their body’s response. And they get fevers, they get fatigued, they get achiness, they frequently get abdominal pain and diarrhea, they get a rash, and most importantly, they can get heart and lung involvement, kidney involvement and occasionally brain involvement. So it’s defined by this inflammatory condition and multiple organs that follows a COVID infection. Now, it’s uncertain why this happens in children and doesn’t seem to happen in adults. The good news is that there is treatment and almost all children recover with this treatment, which must be given in the hospital. So virtually every child with this condition gets hospitalized. And if you look at those children, almost half of them have elevated AST and ALT. Now I think you all know what AST and ALT are. These are chemicals that live inside your liver cells, normal chemicals in the liver cells that leak into your blood in a small amount normally. So there’s always some AST and ALT in your blood and there’s normal cut offs for how high it is in normal children. Elevated AST and ALT generally mean there’s something irritating or injuring the liver cells. So that the fact that it’s elevated and roughly half of children with MISC shows that there’s some inflammation in the liver like there is in all of these other organs that I mentioned. But the AST and ALT elevation is generally mild. It may be more elevated in children who really have a severe care case of MISC but what’s very important is that the liver recovers when the child recovers. And this alone does not seem to be a cause of chronic liver disease or liver failure. I just wanted to show you this chart. This is from the Centers for Disease Control on their website, anybody can grab this. And this is the daily number of cases of MISC, so the numbers on the left hand, y axis the left hand side, so you can see we’re talking about 5, 10, 15 cases per day, and it’s the dark line. But you can see how the reporting peaked in May of 2020 and then another peak in August and September and another peak in January and February and these cases now have fallen off as the vaccination rates have increased in the United States. The dotted line is the total cases of COVID reported and these are hundreds of thousands at any time point. These are national US data. But what’s interesting you could see is the peak here in COVID infection did not overlay the peak in MISC. As I told you, it occurs two to four weeks after the COVID infection. You can see this with every peak of MISC. It’s two to four weeks after the peak in COVID infection. So just want to mention this, as far as I know, liver disease and liver transplantation do not predispose to MISC. Matter of fact, I’m not aware of children that we have seen in our center with liver problems, PFIC included or with liver transplant who’ve developed MISC but it does occur. 

Dr. Ron Sokol  17:49

So what I wanted to focus on today is four questions that we get asked by families of any child with chronic liver disease, including our patients with PFIC and our patients who have undergone transplant and I wanted to try to address these for you and then leave time for you to ask me any additional questions. And the first question is, does this virus itself injure the liver? Does it cause liver disease? What happens to children with PFIC who got COVID infection? Is that something to worry about? Does a liver transplant put your child at risk for severe COVID infection? And finally, should your child and you and your friends get vaccinated for COVID? And what information do we have about how effective the vaccine is if you have liver disease, or if you’re on immunosuppression after a transplant? So let me try to cover these. 

Dr. Ron Sokol  18:53

First thing to mention is that the ACE2 receptor is present in your colon and to some extent in the liver. So it is possible for the virus to bind to the receptor and enter the cells in the colon and in the liver. Now in the liver, what generally happens again, is that AST and ALT get elevated, maybe bilirubin, but the liver generally recovers from this infection. And as I show on this slide, there’s mild elevation liver blood tests, very common in adults 50 to 75%, who are hospitalized may have elevated AST and ALT. And these are adults without underlying liver disease and again, the liver almost always recovers as the patient recovers. So what about children without liver disease? Do we have any information? There’s been a couple of studies that have reported AST and ALT in children. This study reported children who were hospitalized for COVID and as I told you, children generally don’t require hospitalization, so these children, 671, were actually in 27 hospitals from around the world, including some of the areas that were hardest hit with COVID. And you can see the over time, over the first two weeks of admission to the hospital, their ASTand ALT. ALT generally felt to be normal under 30 or so and AST under 40. And you can see that what we would call mild elevations of both of those, that is less than three to five times the upper limit of normal, so for ALT less than 150, for AST, excuse me for ALT less than, say 90 or 100. And for AST less than 100 to 120 and this shows the average in the dark line and the range in the shaded areas. What this doesn’t show is that after admission to the hospital, these enzymes recover in virtually every child. So this is to be expected if the child’s hospitalized, their AST ALT go up a little. Again, these children do not have underlying liver disease. Another study looked at 280 children. What they did was actually comb through published papers in the medical literature and pulled out the information. They found 280 children, not the ones reported that I just showed you, but 280 children in the other papers who have COVID infection, and they found ALT or AST elevated in about 29%, a little less than a third of children. All were mild, mild meaning again less than three times the upper limit of normal. If the child was less than three years of age, they it was more common to see again, mild elevations in ALT and AST, and this recovered in just about every child. So we expect these elevations and actually don’t change therapy or do anything different that the child has mild elevations and they have COVID. What’s more pertinent, I think, to all of you is what happens to kids with PFIC who get COVID? So first thing let’s talk about what happens to adults with liver disease. And there’s been numerous reports and lots of experience in this because adults who have advanced liver disease, meaning they have cirrhosis, which is severe scarring of the liver, and particularly those who have cirrhosis and decompensate and we define decompensation as things like having gastrointestinal bleeding, developing what’s called hepatic encephalopathy, confusion because the liver isn’t removing toxins from the blood, severe fluid in their abdomen, ascites, that requires aggressive treatment. Those adults clearly have poor survival, increased deaths from COVID and they generally have other problems besides the cirrhosis. But clearly if they have decompensated cirrhosis, they have a relatively high death rate from COVID. So, and chronic liver disease of any sort is a risk factor in adults, but it’s really those with advanced, almost end stage liver disease that are the ones that higher highest risk. What about children? Are there any data? And there are but there ain’t much. So let me show you what we know. Early in the pandemic, three different medical societies, professional societies of doctors, usually just hepatologists and gastroenterologists got together and put together an international registry, whereby they requested that any doctor who saw a child with liver disease or with a liver transplant, who got COVID to fill out a data form and submit it. So this is what we call a retrospective study, this is after they had the disease. These are data I’m going to show you that were collected during the peak, in the United States at least, of the first wave of COVID from April to September of 2020. And again, all this was voluntary data. So this data is biased in a certain sense, but It does give us information. It’s for children under 21 and what we had were data for 91 patients that were reported. This is from 28 different hospitals in six different countries. And these were the underlying liver diseases, the 44 patients who have what we call native liver disease. This means they have not had a liver transplant, and 47, who had a liver transplant, and I hope you can see these numbers. But the 44 with native liver disease, ten had biliary atresia, 8  autoimmune hepatitis, 4 acute liver failure, 10 fatty liver disease. If you scroll down, you will see that five of them were just labeled as “other cholestatic liver disease”. I can’t find information, whether any of them had PFIC, but perhaps they would behave like that. If you look at the group that had liver transplant, as in all of our liver transplant centers, about half of the children had biliary atresia, and only one of them had another cholestatic liver disease. But after a liver transplant, your underlying liver disease is no longer the key fact. There’s the fact that you’re immunosuppressed. So I think we could look at all the data for the children with liver transplantation and probably generalize that to children with PFIC that have a transplant.

Emily Ventura  26:29

Dr. Sokol, I’m very sorry to interrupt, but that last column, unfortunately was cut off. Could you just tell us what that far right column says? We see 47. Is that though, is that liver transplant on that bar column?

Dr. Ron Sokol  26:43

I’m gonna do something better. I’m gonna fix it so you can see because I think this is really important to see.

Emily Ventura  26:50

I apologize for the interruption, but thank you. 

Dr. Ron Sokol  26:52

Oh, no, I’m glad you pointed it out. I thought I had fixed that before. All right. Are you seeing this?

Emily Ventura  27:04

Reshare your screen please.

Dr. Ron Sokol  27:06

 Okay. Can you see it?

Emily Ventura  27:15

Yes. Okay. Yes, thank you so much.

Dr. Ron Sokol  27:25

So again, there’s the 47 children who had liver transplant and again, as you could see, there was only one child who had an other cholestatic disease, but biliary atresia is a cholestatic disease. Remember, again, after liver transplant, it’s the immunosuppression, that’s the main factor and not necessarily their underlying liver disease, which in almost all cases, is cured in their liver if you have a transplant. So again, this is just the breakdown of the patients. So I just wanted to show you in that red box, what happened to their ALT as a representative enzyme of representing ALT and AST, those liver enzymes. And you could see that the children that were reported, those who had diseases of a native liver, the second column, their average ALT was 145 and that’s their peak during their illness. It was 76 when they presented before their illness. So baseline means before they develop COVID. Peak is during COVID. And you can see it roughly doubled. Those who had a liver transplant though, their ALT rose much less, only to 51. Now, none of these levels are levels that would make us panic or worry that the liver isn’t going to recover. But it seems to indicate that those with diseases of their liver had more liver injury than the liver transplant patients. And more data are shown on this slide. So this is their outcomes. That is what happened to the patient after they recovered, or were they in the hospital. So let’s just go through this quickly. The dark bars are the children with liver disease. The gray bars are those who had a liver transplant and this represents the number of patients on the y axis on the left side. So as you can see, those that were hospitalized but did not go to an intensive care unit, roughly the same number of children in both groups, but those that required an intensive care unit, it was the children who had their native chronic liver disease that required an ICU and almost no children, just one or two children with a liver transplant required an ICU transfer. And then if you look at those that weren’t hospitalized at all, almost twice as many children who had a liver transplant were not even hospitalized compared to those who had chronic liver disease. And I want to point this out too, this MV is mechanical ventilation. So this means going into the intensive care unit, having a breathing tube put in and being on a machine to help you breathe. This means you have pretty severe lung disease. And no children who had a transplant, but a fair number who had their native liver disease. So the bottom line here is that children who seem to have chronic liver disease have a more severe course than those who had a liver transplant, which sounds a bit counter intuitive. You would have thought immunosuppressed patients may have done worse. So that study concluded again the children of chronic liver disease are at more risk for hospitalization. 

Dr. Ron Sokol  31:05

Well, how do we explain these data? First of all, this is a very biased, what we call sample of patients. This is a retrospective study. Doctors were more likely to fill out the forms and have all the data to fill out the forms on children who are hospitalized, rather than a child who may have been at home with COVID and the family called and said, “I just want to let you know, my child is COVID”. They may not even have gotten extra blood tests on their liver. So there’s a lot of bias and you have to take this really with a grain of salt. We really don’t know the frequency of infection or hospitalization, in children with chronic liver disease with PFIC or with liver transplant. And I think that’s the key number is really how often does this happen. So we really can’t assess the risk of chronic liver disease or the risk of a pediatric liver transplant, do you get severe disease. We only know what was reported. We don’t know what wasn’t reported. And another factor could be that if you’re on immunosuppression, and you had a liver transplant, perhaps your family is much more vigilant during the pandemic, about keeping you isolated from people with infection, the following mask and social distancing mandates and just being more careful because they knew that their child was on immunosuppression. So maybe that’s why children didn’t develop as many severe infections and there weren’t as many children, as you may have expected in the series, with liver transplant. But again, this is speculation. So the we have these data, but we need a whole lot more data to really understand the risk. 

Dr. Ron Sokol  33:05

So let’s talk a little bit more about liver transplants. What do we know in adults? And the American Association of the Study of Liver Diseases, AASLD,  has analyzed the published literature and there’s actually quite a bit published on adults who’ve had a liver transplant, and their exposure to COVID, what their outcomes were. I’m really happy to say that if you had an adult liver transplant and you got COVID, there was no higher risk of dying of COVID compared to people who did not have a liver transplant. And it was really the age of the liver transplant patient and any other medical conditions that were those risk factors that I showed you, but not the type or amount of immunosuppression that predicted a poor outcome meaning hospitalization, or a fatal outcome, which is quite interesting. You might wonder how could that possibly be? And the reason that that may be is, I mentioned earlier, that the virus initiates an inflammatory reaction that in adults may not turn into that MISC. However, hospitalized adults and those in the ICU will frequently have progressive disease in their body even after the virus is is gone and this is due to the body’s immune system reacting and causing this inflammatory reaction. So perhaps, if you’re on immune suppression, you’re suppressing this wave of inflammation. And although the immune suppression might make you more prone to the virus, it may actually protect, to some extent, against that secondary inflammatory wave. So that is what most experts believe is why immunosuppression does not necessarily cause worse outcomes. So question for all of you is does the liver transplant puts your child at risk? That’s data in adults. And again, unfortunately, we have limited data. There is a letter to the editor from Lombardi, Italy, which was one of the hardest hit areas of the pandemic and they did a survey of families of children who had pediatric liver transplant and who developed COVID infection. So they asked all of their pediatric liver recipients, whether they had COVID and 155 responded. 32% of them had respiratory symptoms, however, none of them needed oxygen, none of them were hospitalized, and none of them experienced severe respiratory disease from COVID. And this was an area of the world where their hospitals were overflowing with patients. They didn’t have enough ventilators in adults etc. So once again, this suggests that the children are behaving like the adults and those who have transplant don’t get severe disease. And I bring you back to the data I just showed you from that registry, that these gray bars show that there’s more nonhospitalized children with liver transplant who get COVID than those with chronic liver disease. There’s very few with transplant patients who end up in the ICU, no child ended up on mechanical ventilation, etc. So perhaps having a transplant does not put you at excessive risk. 

Dr. Ron Sokol  36:56

So let’s talk about vaccines. We’re pediatricians in our field, and we want to prevent disease rather than treat it. And vaccines have been probably one of the top two or three advances in the last century in helping to improve the health of children. So how do we prevent this disease? Well, vaccines are one way but there’s other ways and I think you’re all aware of avoiding infection risks: not taking your child to a crowded movie theater where people are coughing in the middle of the pandemic surge in a place where people are not vaccinated. A lot of more of the preventative measures were important in 2020, when we didn’t have the vaccine available. And by the way, we do not have an effective antiviral treatment for outpatients with this virus. I just wanted to make sure everybody understood that. So avoiding risks is really the way to avoid getting sick. Preventing transmission through wearing masks, hand washing, and using sanitizer and social distancing, those are also very important under various circumstances. Again, a lot of this was very common pre vaccination. And then vaccine. And it’s been said by many that really the only way out of this pandemic is through vaccinating 70 to 80% of any given population. So, as many of you know, currently there are no vaccines approved for children under the age of 12, 5-12 and under the age of five. So the best way to protect young children is to protect your family from getting the infection and your child catching it from a family member. That really means we all need to get vaccinated. Now, if and when the vaccine is available for five to 12 year olds, and currently it’s available for 12 to 17 and those about 18 and above. But if you have chronic liver disease or a liver transplant does the vaccine work? And this is very important. So first of all, there’s three vaccines available in the US: Pfizer, Moderna, Johnson and Johnson. All have high levels of protection two weeks after your final dose. Pfizer and Maderna are approved for 12 to 17 year olds now. And those that are less than 12 years of age, there’s an ongoing trial of both Pfizer and Moderna and five to 11 year olds, and we expect results to be available in the early fall and hopefully the FDA will give emergency use authorization and hopefully the vaccines will be available before the end of this year. But what do we know about the efficacy of the vaccines if you have chronic liver disease? Well in elderly adults who have liver fibrosis, they clearly have a lower response to the Pfizer vaccines. And in adults who have liver transplantation, it’s now very clear that immunosuppression does blunt the response to the immune system to vaccines. Which is not a great surprise because it’s the immune system that produces the antibodies that protect you after a vaccine. So because the immunosuppression blunts this response, a question has been raised, do additional doses of the vaccine give you benefit? And the data currently are very promising, but there’s no current recommendation to do this in adults in the US. Many papers have been published, such as this one, that state that there’s low immune reaction to the SARS vaccine among liver transplant patients. And here’s just some of their data from another paper showing that before the second dose of the Pfizer vaccine, after the first dose, only 4% of liver transplant adults had an antibody level after the after the second dose or before the third dose 40%. In a non liver disease patient that should be 90, 95%. But after the third dose, they were up to 70%. So in some countries, they are starting to give a third dose of vaccine to transplant patients. Again, that’s not the official recommendation in the United States. Once again, we recommend all 12 to 17 year olds and those above 18 get vaccinated with or without liver disease and with and without a transplant to provide protection. 

Dr. Ron Sokol  42:02

Now school always is comes up when we speak about COVID. And my recommendations for should your child go to school and not go to school, what protection in school is to really check with the local school officials for what their infection control measures are and their vaccine policy for everybody who works at the school as well. If it’s a high school for 12 to 17 year olds, you should really know what the infection rate is doing in your local area though, because where COVID is surging, everybody’s probably at increased risk. And your local health care provider, your doctor, your nurse, those are the people give you the most accurate information. But every state has a Department of Public Health, they have websites, they almost all post daily information about where there’s risk for infection, what the vaccination rates are, etc. And what we’ve all learned is that remote schooling, although not ideal, may be an option through internet connections until your child can be vaccinated. And then hopefully, they will return to school with all the other children. Now, as we all know, many schools have opened up completely for this fall. And we will have to see what happens over time whether it’s going to be safe for the children. Almost every school has required staff and teachers to get vaccinated to protect them. But whether the children are going to spread the virus to each other is still unknown. 

Dr. Ron Sokol  43:38

And last, I just want to mention that this depression has become a major health problem for children during the pandemic. And it’s no surprise that the isolation, social distancing, isolation from their grandparents, their friends, their fear of what’s going to happen, some are hopeless about the future, because it seems like this never ends. All of these factors can lead to depression. And it’s really important to know the symptoms in your child. There’s really no time to go over this in great detail, but you’ll have these slides to look at. And what can you do? You should always foster an environment in which your children feel comfortable sharing their thoughts. If they’re experiencing the feelings of sadness or depression, to take some time every day to talk about why they feel this way. Let them know that you hear them. You’re there for them, that we’re all going to get through this together and online through your physicians, through videos, you can get you can receive many different recommendations about precisely how to help your child deal with this. And finally, don’t hesitate to seek professional help if you’re really concerned about this. So I just wanted to mention there’s a lot of websites that have up-to-date, correct information, the CDC, the National Institutes of Health, Food and Drug Administration, AASLD has excellent handouts and information for patients, your local or state Department of Public Health. All have very accurate information. Your doctor’s office, also, and be very careful about what you hear from social media and various news outlets. Need I say more about the disinformation that’s interfering right now with why vaccination, for instance. So I really thank you for your attention. And I’d be happy to answer any questions that anybody may have. And I think Emily’s going to moderate this.

Emily Ventura  45:47

Thank you so much for that that was a wonderful presentation, and really helpful as we are obviously a community who falls into that high risk category. But also, you know, we just kind of we deal with chronic disease on the daily. So some of this is kind of practice that we have in place already. But then the question becomes, you know, how do we respond with society? So it’s really helpful to have you present all that information that’s specific to us. I do have a few questions, so I’ll go ahead and just roll through the chat. So does any of the research show if the level or the amount of immune suppression affects the efficacy of the vaccine or does higher immune suppression levels seem to blunt or just any or is there is or is it just related to any immune suppression period?

Dr. Ron Sokol  46:41

Oh, yeah, so the type of immune suppression, that seems to blunt the response the most are mycophenolate mofetil  and azathioprine. And part of that’s because they can act on the cells that produce antibodies. However, any immune suppression will have the tendency to blunt the response. Almost all children that have a transplant are on at least Tacrolimus, maybe that’s their only drug. They will likely have a blunted response, but that doesn’t mean they won’t respond. And when we say “blunted”, we look at the response to the vaccine by the titer, the amount of antibody in their blood to the virus. So they may not have quite as high an antibody level as somebody who’s not on Tacrolimus, but they may still have enough to be protected. So what we don’t have are any data in children related to immune suppression because it’s not approved for young children yet. In 12 to 17 year olds now, people are starting to collect data on children who may have a liver transplant and around immune suppression. There’s also other children who are on immune suppression for other diseases and data are being collected. They just haven’t been published yet.

Emily Ventura  48:11

Thank you. That’s very helpful. So another question can….this is specific to our PFIC population..do you know if COVID infection can affect a child who is on a drug trial for you know, one of IBAT or ASBT inhibitors? Does that… has has anything shown to affect, you know, the children who are in those trials?

Dr. Ron Sokol  48:42

So I’m not sure if the person is asking whether it will affect the outcome of the trial or whether being on those drugs put you at more risk. Right now, we don’t know of any reason why being on the IBAT inhibitors would pose a risk if you risk if you got COVID infection. But quite frankly, if one responded to those inhibitors and you had less itching and your bile acid levels were lower, you probably would do better with an infection than if you had severe itching to start with. And then like with any viral infection, children with PFIC can you know exacerbate their itching and feel much more sick. So I think if the IBAT inhibitor is working, perhaps they’d have less complications of COVID, but I don’t think it poses any particular risks to them.

Emily Ventura  49:40

Okay, good. That’s a great answer. That makes a lot of sense. Thank you. Related to the vaccine, I know that you know, the future of gene therapy in PFIC is you know, a potential, you know, opportunity for our community. Is there any information on if, you know, children receive a vaccine, would that affect their ability to receive gene therapy in the future, if it ever were to be an opportunity?

Dr. Ron Sokol  50:15

Well, it’s kind of an interesting question, because gene therapy is given by a virus generally. But these are viruses that have been engineered to not produce disease. They are adeno associated viruses, not coronaviruses. So those viruses are in a different family. If they were coronaviruses, one could wonder if you have immunity to COVID, does that mean you’re going to kill the virus before it can transmit the gene into your liver. But they are different viruses. So as far as I know, there’s no cross reactivity, either by having a COVID infection or a COVID vaccine that would prevent those viruses from delivering the gene. And I assume that’s what the question is about. I can tell you, I’m sure there’s no data available because right now, the number of patients who have had gene therapy for any disease are really handfuls of patients. I think some of the gene therapy may have been held off during the height of the pandemic, just to not complicate things, although the gene therapy trials are all up and back and running. But here’s an interesting question. I’ll…. that’s gonna prompt me to talk to some of the gene therapy people at my hospital to see if they know anything about that. But just from what I know, I don’t think it would interfere.

Emily Ventura  51:47

Okay, thank you. Yeah, it’s kind of it’s just a hot topic that’s, you know, it’s it’s on our mind when we’re weighing these decisions. And the questions just come up, so I appreciate you answering

Dr. Ron Sokol  51:57

Well, well let me state unequivocally the risk of getting COVID and, and having a bad outcome is so much higher than the potential risk of something that we don’t know even happens in the future. And if your child has chronic liver disease, as I showed you, they’re certainly at some risk to be hospitalized with COVID. So I would not hesitate to give them the COVID vaccine, given the fact that we have no clue whether that’s really going to have any effect on gene therapy. So we want them to be healthy until they can get the gene therapy, if that comes around. 

Emily Ventura  52:37

That’s very helpful insight. Thank you. One last question before we go. You had provided some data on hospitalization, but just not sure if you’re aware of any data concerning the prevalence of COVID in the immune suppressed adults and children versus non suppressed adults to children?

Dr. Ron Sokol  52:57

Yeah, so I am not aware of a prevalence data. And I think you’ll have to take it with a grain of salt because most of the data is based on hospitalized patients. And prevalence data really depends on exposure and I would think that most immune suppressed people take very strong extra precautions against exposure, probably beyond what the typical recommendations are. So as in anybody, if you follow the guidelines for when to wear a mask, when to social distance, who do avoid being with it being around vaccinated people, it’s probably just fine. If you follow those guidelines, immune suppressed people should have a low risk of getting infected.

Emily Ventura  53:53

Okay. And I guess there’s one more question, just before the hour is over. Related to vaccination, are there any specific vaccination that you would recommend for our population?

Dr. Ron Sokol  54:10

Well, you know, there’s three that are currently available if you’re 12 and up. And I would say whichever is available, is the one I would recommend. The Pfizer and Moderna probably give a little bit better protection than the Johnson and Johnson which is 75-80% rather than 90-95%. But I could tell you that all of the other childhood vaccines that we use, none of them are as effective as even the Johnson and Johnson. I mean, all of these have tremendous ability to prevent disease, so I don’t want to show preference to any one. But Johnson and Johnson is a single injection, which for many people and particularly children that might have phobia against needles may be better than the two injections that you need for the Pfizer and the Moderna. On the flip side, Pfizer and Moderna maybe give you a little bit better protection. 

Emily Ventura  55:14

Okay thanks. Well, thanks for that wonderful presentation and for going through the questions with us. And I just want to say I really appreciate you throwing in those slides with childhood depression. It’s something that’s extremely relevant to our community. And it’s helpful to know, you know, resources are out there and how to access those resources. Because, you know, related to COVID or not, there things that can affect, you know, our community in many ways. So I appreciate you throwing that in there. We’ll see you in the panel q&a discussion this afternoon. So if anybody has any lingering questions, you can bring them to that discussion and we can ask them then. But thanks again. Dr. Sokol. I appreciate it.

Dr. Ron Sokol  55:54

Thank you, everybody.

Emily Ventura  55:55

Alright, have a good one.