01:04:26
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[00:00:06] Dr. Christina Lampe: Welcome, everybody, to this online course about the multidisciplinary team approach to MPS patient care treatment and support. This first module will start with COVID- 19 and MPS, but they will follow five other modules about their personal perspective, understanding the MPS patient's needs. So from a parent and patient's perspective, we will have another module about the role of pediatricians managing MPS patients with everyday health issues. We will have another one about psychological care of MPS patients, then advances in treatments in MPS. And finally, the last and sixth module will be about transition. But today, and I'm very happy to have this webinar together with Maurizio Scarpa, Heather Lau, and Dafne Horovitz. So we are a very mixed team today, and we will have three presentations. First, I will make the short introduction and the housekeeping notes, then Maurizio Scarpa will talk about the COVID- 19 situation in general and the Italian situation. Then Heather Lau from New York, US, and Dafne Horovitz from Brazil will talk about their experience with COVID- 19 and MPS patients. And after that, we will have a discussion and hopefully a very fruitful discussion about how we can support our MPS patients in this realistic time. Just some housekeeping notes, please do not take any screenshots, do not reproduce these slides. The format will be 60 minutes with discussion at the end. So please use the chat and ask a lot of questions to make this webinar very active and interactive. Submit your questions in the question panel. Questions can be only submitted via text. We have quite a lot of participants today, so please ask your questions, and we hope to answer all the questions that you present. The recorded webinar will actually later be online on the link that you see on the screen. So now we will start.
[00:02:37] Dr. Christina Lampe: We have three learning things today that we want to review, the COVID-19 situation, comparing the current situation with examples from Europe, so Italy and Germany, Brazil and the US, and the practical advice how we can best support MPS patients at this time. And after this introduction, welcome again. I introduce Professor Maurizio Scarpa from the Rare Disease Center in Udine, but he will make a short introduction of himself now. So I hand over to you, Maurizio. Thank you very much, Christina. So let me just share my screen and tell me whether you see it, whenever it will be. Do you see my screen?
[00:03:29] Dr. Christina Lampe: Yes.
[00:03:30] Prof. Maurizio Scarpa: No? So now you see my screen? You do. Okay. So thank you very much for this invitation, and thank you to everybody who is participating. I'm very honored and pleased to be with Christina, with Heather, and with Daphne, to tell you a little bit what is the situation now about this strange moment. I put one of my favorite quotes from Winston Churchill, because this period is actually a crisis. And one thing that we should do is to learn as much as possible from this crisis in order that this crisis is not going to be wasted. And indeed, I think that the number of webinars that we are doing now are extremely important to share our experience and to find a way to indeed treat and protect our patients at the best as we can. So what is the COVID- 19? COVID- 19 is actually a disease caused by the severe acute respiratory syndrome coronavirus 2, which is the agent of this coronavirus disease. The coronavirus, the SARS- CoV- 2, is actually an RNA virus, and as all the coronaviruses, it has spikes with which he links to the receptors of the membrane and introducing the RNA inside the cell so that then there is the production of DNA and proteins. This virus has been said to be first originated in animals, like the bats, like the mannish pentadactyla, and then there has been a jump of species, and by direct contact or eating, it has infected the men, and exploiting the RC2 receptor, and through the operator, going from one man to the other, and to start the pandemic that we are going to have now. So as you can see here, the cycle of the virus is quite a very typical viral assembly and reproduction. The virus is linking to the AC2 receptor, entering the RNA virus, the RNA genome is actually retro-translated into DNA molecules, and the DNA molecules is then used, as usual, to create proteins, which is inhibiting the replication of the cell and taking all the machinery inside the cell for the reproduction of the virus, and then the exocytosis to release molecules of virus. So a very typical life cycle of a viral infection. Why this disease is so severe? First of all, because we have AC2 receptor everywhere, and for this reason, I mean, the virus can really be spread throughout the organ, but in particular, it is present in the lung cells, and for this reason, the virus is quite replicating very quickly in the lung. It's producing an incredible amount of inflammation, and the processes of restoring after inflammation of the tissues is actually fibrosis, and the inflammation process itself is creating a lot of edema, and for this reason, very quickly, the lungs of these patients are actually infiltrated by a lot of cytokines and a lot of molecules, inflammatory molecules, producing the typical interstitial pneumonia. You have, if it is not recognized, you can go to renal failure, you can go to myalgia, you can go to hemoptysis, you have a high fever, which is most of the time untreatable, and if the patient is not recognized at the end, the respiratory failure is the major cause of the disease, and you can have also at the end, also septic shock. It has been said that the virus was extremely aggressive for elderly, and especially people who are already weak because of other conditions like diabetes, hypertension, or already COPD, or something that is related to lung and heart problems. It was said that the children were less affected and with minor infection, but actually, and mostly with flu symptoms, but actually very recently, in the last month, there has been an increasing percentage of children affected by Kawasaki disease. The Kawasaki disease is a rare disease, an inflammatory disease, a vascular disease that is caused, indeed, and it is mostly as a reaction, an inflammatory sort of autoimmune reaction in the vascular system after bacterial or viral infection in patients, in children patients. More and more frequent are children reproducing this Kawasaki disease and having in particular problems with the coronary artery in the heart. So I mean, this is something that has been recently published, and it's an observation which is related to the inflammatory tsunami that the body is having after infection. COVID-19 is a pandemia. It start in China, and then it's spreading. This is the situation, let's say, at May 12, so last week. You can see that, I mean, now USA is the first country having infected people. In Italy, it was the first country after China being infected, and we have now much more than this. I mean, we have about 250,000 instead of 219 only. And in Italy, we had about 10% of them dying. It's a pandemic because, I mean, it is spreading all over. Now there are some countries here, like in Morocco, and also Libya, and also Central Africa, who are having this kind of infection. Of course, the control of this disease is also according to the national health system, and in poor countries, of course, this is a major problem, as it is also in other countries due to the severity of the disease. What is the risk for this disorder? I mean, to date, as we said, it seems that the children are affected beside the Kawasaki disease, are affected by less severe, but still need to be treated with care. Older patients with medical conditions as we said, the COPD and other renal or lung problems are at major risk for having the need of intensive care units. The patients with rare diseases involving the immune system are, of course, at greater risk to be infected by the coronavirus, too. And one important thing is that even if the patient affected by rare diseases is not challenged by the infection, there is, again, one major problem for this disorder, because, I mean, the hospitals have to change very severely the schedule of the control of these patients, and a lot of program controls were actually postponed due to the fact that the hospitals were invaded by a lot of sick people. And since there are no vaccine and there are no specific treatment, hospitals have been converted in COVID-19 hospitals, accepting only infected patients, and all the other patients were transferred to other hospital or postponing the controls. What we have done here in Italy was a study in March with our patients only affected by lysosomal disorder and treated with enzyme replacement therapy or other therapies, and we have studied 112 patients in order to understand what was the effect of this infection on their normal life. As you can see here, there have been 38% of patients which were receiving the treatment still in the hospital, because, I mean, they were able to have no COVID in the hospital, but a lot of other patients were changing quite a lot their treatment, and most of them were put in home treatment to change the management of the treatment itself. The patients were very scared about infection, and sometimes they did not want to come to the hospital just because they were feeling of infection. They were feeling unsafe, and the center itself had to reorganize the infusion center. So, I mean, this population of patients were very badly affected in their normal life. So, in conclusion, what we can say, that COVID-19 is indeed a new disease, and this new disease has taken the world totally unprepared worldwide in terms of health policy and medical structure. There was no country that was prepared for something like a pandemic. A lot of countries are prepared for nuclear wars, but it has been shown that, you know, a virus could not be handled in the same way. In the rare disease field, the COVID-19 was mostly controlled due to the vicinity of patients in the referral center. Indeed, we have done a survey, which has been finished now in Europe, in the metabolic field, exploiting the European reference network for metabolic disorder, and what we have seen is that the metabolic patients actually suffered minimally from the COVID-19. This is because the doctors were informing the patients quite before the regulation of the health system, and for this reason, we're preparing the patients to be ready for the infection. So, for this reason, the patients were at home, and they were not going around, and they were protected from the infection. The therapy and the urgent care were maintained. Most of the hospital were actually able to prepare different free pathways from COVID-19 and to accept the patient without being in contact with infected people. But physiotherapies and supportive treatment were severely affected. There are a lot of patients affected by rare disease of the skeleton and other disorders that are needed for physiotherapy that totally stopped the treatment. And this was creating quite a lot of problems. Of course, one major problem that we saw is that the patients affected by neurological and psychiatric problems, these patients are actually used to have a very, very usual and routine way of living. So these patients have a method in living their day. And if you change the rhythm of the day, they really have a lot of problems. We have indeed a lot of patients with psychiatric problems who are really affected by these alteration of the routine rhythm of life. And most of the centers have activated psychiatric help. We need to treasure the experience that we have done so far. There are a lot of studies now under publication in order to be ready for the continuation of this pandemic, because until we will have the vaccine, we will not be ready to forget about this virus. And for this reason, there is in our community quite a lot of exchange to share this experience. And I think that I stop here and I give to Daphne the floor. Thank you very much for listening this.
[00:16:56] Dr. Dafne Horovitz : Okay. Hello, everybody. I'm very happy to join and to be able to share my experience. And I would like to thank very much the Brazilian Society of Medical Genetics. They've been helping me with putting up all this data regarding our patients. So in Brazil, we have something around 1,000 MPS patients. And as you can see in this chart, many of them are treatable and those patients usually come in hospital for enzyme replacement therapy. They are scattered all around Brazil. Brazil is a very big country. We have 8 million square kilometers and population is about 209 million so far. And most of the MPS population is within the yellow region, the Southeast region, the Northeast region and the South, because this is where we have most of the population in Brazil. What's going on with COVID-19? This is actually data from last night. So, so far we've had 241,000 confirmed cases and it's very important to understand that testing here is still not widely available. So most of the less severe cases are basically not being tested. So for sure we have at least five times to 10 times this number. The death rate is more trustable. So it's so far 16,000 deaths, around 800 deaths a day. It has stabilized within the last few days, but we have to wait since yesterday was a weekend. We had 400 and something, but some data comes in during the beginning of the week. So we have to wait, but it might seem we're getting to the plateau and hopefully going down within the next few days or weeks. We've been in the pandemic beginning death around eight weeks already. So how are we looking after the rare in Brazil and especially MPS? Very rapidly right after the pandemic started that people went into quarantine, actually several days within the week, we had launched those guidelines for the COVID pandemic for rare diseases and patients and caregivers. And this was a joint effort of the Brazilian Society of Medical Genetics, the Ministry of Health and some other institutions. So in this booklet, and this is the second version was April 2nd. So the first version was about 10 days early, right when we started going into quarantine. So what does it say regarding the MPS treatment? Any modification in the ERT protocol during the pandemic, it should be individualized considering the status, the age, the multisystem involvement and the comorbidities associated. And this means the place of infusion. So most of our infusions are hospital-based and most hospitals are reference hospitals and some of them were really hit hard by the pandemic. There's a problem with displacement and transportation. Some of our patients live in very big cities, which are in quarantine, they're afraid to go out. On TV, everybody says, stay home, stay home, stay home, beware of the chronic diseases. So we have to individualize the risk-benefit evaluation. So it's a different evaluation if a patient has just started on enzyme replacement, if it's a severe MPS1 right before transplantation and it's very important to keep the infusions going. And compared to patients who have been on ERT for about 10 years, we've had several medicine shortages due to lack of the Ministry of Health giving the enzyme to the patient. So some of our patients have been without enzyme on and off for about two months, three months, six months. So we know what it means. And we also know at this time that it might be safer depending on the patient and depending on the city to keep them off medication for a while. And also we had to evaluate the possibility of home infusion. In the package insert, it's only for MPS II here in Brazil, but some of the companies have managed to offer a home infusion for the patients. So what is actually going on? We are a very big country and the health and the pandemic status is very different between states and regions. So the approach has to be individualized. And the pharmaceuticals finally are sponsoring some home infusions. So it's not through the Ministry of Health. The Ministry of Health provides the medicine, but now they are helping with the home infusion. But again, it depends on how the family and the patient feel because some of them do not even want to have home infusion. They are afraid from people coming in home. And we have many social differences. So some people live in high risk areas in slums and the home infusion will not go there. So there is a possibility also of changing the infusion location from a high risk to a lower risk and smaller hospital so they can go to a lower complexity unit. But again, it's not easy to start this during the pandemic. Some services have opted for a change in the administration regimen. For instance, there's a large group in Sao Paulo whose patients are coming every other week instead of weekly so they can get the infusions, half of them at least, and they can keep stable but not go through the risk of the transportation every week or leaving home every week. And some patients have interrupted the RT for a while and we're checking on them every week and if something comes up, we'll bring them into the hospital for the infusion. This is very interesting as well. Last Friday was the MPS day. So the Genetics for All and the MPS network just published this booklet for patients and it's called Beto, it's a character and the coronavirus. So, it has puzzles for kids getting back home from outside, Beto has to wash his hands and then there's a cute little puzzle. And then there are the questions, what is COVID-19, a cat, a flower, a virus, or a snake? Then the other question is very interesting is, should I keep on having my infusions? No, yes, depends on what my physicians tell me would be more important. So, it's very useful for the kids and for them to understand what is actually going on. That's the beautiful work from the group of Roberto Giugliani and Hospital das Clínicas de Porto Alegre. So, what is actually going on in our setting? We've had some confirmed COVID cases and fortunately no deaths so far. So, we've had two hospital admissions, one was an MPS , age 18. He was in hospital for only four days, probably because he started with the symptoms. We were hearing about chronic diseases. He was brought into the hospital, he was doing fine and he even had his infusion in the hospital and that was here in the northeast of Brazil. Two MPS II patients, ages 10 and 17, with other competing diseases. So, one of them had asthma and the other had diabetes. Both were in ICU, but they're out already. The others were treated at home. So, an MPS4, age 10, an MPS II, age 19, this one had absolutely no symptoms. We only knew he had COVID- 19 because the father had it and he was also tested, which is the same case of another two that I didn't even put in the statistics. I talked to the mom on Friday and she said, I've been on COVID- 19 for two weeks. I was in really bad shape. She has two MPS II boys, one in neurodegeneration process at 10 years old, the other is age 2. He was transplanted and they had absolutely nothing. So, I hope I can test them in the future and check if they had or not. And two other MPS VI and those were just suspected cases because they did have symptoms, but we couldn't test them. So, that's pretty much about it. I didn't change here. So, we have five confirmed cases and two suspected cases. So, I'd like to thank very much all my colleagues from the Brazilian Society of Medical Genetics and Genomics all over the country who contributed with the data. And Instituto Vidas Raras who helped with all the data regarding MPS in Brazil. And probably you've all seen on Facebook, people were publishing view from my window. So, this is from my window at sunset and I can see the tip of the True Brothers Mountain in Rio, in Leblon. And I think we really should aim higher. So, we escaped to the terrace, to the top of the building one day. And we really should look at things better and higher. So, that's about it. So, be well, stay safe. And let's keep on going here with the webinar. And let me see how I can send this to Heather Lau now.
[00:28:16] Dr. Heather Lau: Excellent.
[00:28:17] Dr. Dafne Horovitz : Okay. Now, I'm changing the presentation and send it off to her.
[00:28:25] Dr. Heather Lau: Thank you, Daphne. Thank you, everyone. Can you see my screen?
[00:28:31] Dr. Christina Lampe: Yes. Great.
[00:28:33] Dr. Heather Lau: So, I'm Heather Lau. I'm the Director of the NYU Lysosomal Storage Disorders Program in New York City. I'm the Associate Director of the Division of Neuroendocrinology. I'm a pediatric neurologist by training, actually. So, I'm going to focus on the impact of the COVID- 19 pandemic in New York City on our MPS patients. Here are my disclosures. So, when we had our first cases announced in the US in early March, my team and I decided to start looking at our lysosomal population. And we actually started to call all of our patients. I personally in NYU handle over 150 patients with a variety of lysosomal storage. And I looked at each disease state. This is before we had a lot of publications out there and knowledge. and to see how it potentially could affect our individual LSD patients. So for MPS, obviously, the respiratory aspects, we were quickly looking at it, and then we were calling our patients to guide them about sheltering in place and what's the potential impact. So we classified our MPS patients as high risk because of the underlying manifestations of MPS could then therefore exacerbate or synergistically work with COVID- 19. So obviously, our patients are already alerted in our hospital system as a difficult intubation and ventilation. And so that's flagged in our EMR. But if our patients who are scattered around the tri-state area needed help, they would go to ERs that may not know their underlying disease. And so it was important for us to alert our parents and our patients and then to provide letters or information about their disease state so that they understood that if they needed elevated care, how to manage them. In our ERs here, they quickly became overrun. And so there's not a lot of time to necessarily communicate with the team. And sometimes our adult patients were all by themselves. So there was no visitors or anyone there advocating. So we talked about looking at respiratory dysfunction, the abnormal pulmonary function at baseline, their obstructive sleep apnea. A particular interesting aspect is a lot of our patients are in CPAP or BiPAP. And so instead of needing ventilation, they potentially could use this non-invasive mechanical ventilation. But this could cause a super spreading event. And therefore, they were not recommended to use. So that could potentially lead to an earlier need for ventilation because of that. Cardiac dysfunction, obviously, we were starting to see not just the respiratory effects of COVID-19, but we did see a lot of cardiac death in our general population, sudden onset en route to the hospital. We also saw myocarditis and other issues with prolonged QT, maybe from the iatrogenic use of hydroxychloroquine. So our MPS patients at baseline could have a varying degree of cardiomyopathy, valvular disease, and they may not be candidate for their experimental trials, which were being offered in the major tertiary care centers. So we wanted to be able to have that information ready for them. Obviously, the liver and spleen is not as impacted in MPS, but in our triaging in the ER, they were used. LFTs and ferritin and other aspects of the liver function were considered parameters to decide if you had more severe course or not. And that could be confusing to our ER doctors. Kidney failure was seen in a lot of our COVID patients. Fortunately, most of our patients have normal kidney function. But again, this is a multisystemic disorder. This is not just a respiratory disorder. And so we had to look at the entire picture. Neurologically, as a neurologist and on service in the hospitals, we actually saw a lot of manifestations before they were reported, before there were just case reports coming out of Italy and Wuhan that helped inform us, we started to look for it here. And I saw seizures in children. We see a lot of stroke, actually. So not just the pulmonary aspect, but we're seeing stroke due to the hypercoagulable state from COVID- 19. We're seeing encephalopathy. We're seeing encephalitis. And we're even seeing Guillain-Barre. So in our MPS patients, both neuronopathic and non- neuronopathic, we were concerned that COVID- 19 could exacerbate an underlying seizure disorder or precipitate new onset seizures in our patients. Obviously, some of the signs and symptoms of COVID, which is vomiting and actually abdominal discomfort and diarrhea, but we still need to look for other signs and symptoms. Headaches are very common in a viral syndrome. And so that could make a mixed picture if our patient's presented. Is it from the MPS? Is it from COVID? And obviously, if our patients needed intubation, they are always at risk of hyperextension and difficulty during the intubation process. So they have to protect the C-spine. And our nonverbal, our neuronopathic patients, in general, can't communicate when they're in distress. And so obviously, our parents of these patients and their health care providers know to look for increased irritability and behavioral changes, but we may not know the etiology. Is it neurologic? Is it respiratory? So this was how we kind of approached all of our patients and tried to be there as a conduit, you know, a way to communicate between the patients and the families. And if needed, if they were referred to the hospital. So as the pandemic hit and as our cases increased, as of today, as Dr. Scarpa said, we have 1.52 million cases in the U.S. In the New York City alone, we have right now, 193,000 confirmed or suspected cases with 15,000 deaths. In New York State, we have 350,000 with 22,000. And these are probably underreported because we had lack of access to testing initially. And a lot of negatives after the fact. So we communicated to all our patients the current messaging from our government, which was to shelter in place. But we did it quite early, actually, before Cuomo came in. So we had them all shelter in place, limit contact. We quickly went to homeschooling. Now this is particularly difficult for our neuropathic MPS. One of my first phone calls from my patients was, you know, we don't have the routine anymore. We have the inability to have our one- to- one aid, and they're juggling working from home, other children in the home. And so that really impacted the behavior of our neuropathic MPS. My college- level MPS patients were able to convert to remote learning, and my adult MPS patients were able to work from home. And I actually, before they did do the shelter- in- place, I recommended to our patients with any type of lysosomal to preemptively start to do telecommuting and provided a letter, if needed, to their employer to understand why they're at increased risk of COVID complications. And as we saw from Dafne and from Maurizio, there's an impact on therapies in general. Our infusion centers and home infusions, I worked with our pharmaceutical companies to help message to the infusion centers and the home infusion agencies, and a lot of our patients actually have access to home infusion. However, we wanted to prevent mutual exposure, and initially there were not a lot of standard operating practices in place, so we would message to each of the agencies and go through what are their protocols to prevent exposure. So screening patients by phone and at the beginning of the appointment for symptoms and exposure, masking for all patients, and limiting the number of patients in an office setting, spacing the infusion chairs, preventing curtains. And then I know that a lot of us had a shortage of PPE early on, but as it became more available, our agencies are using full face shield masks and gloves for the staff, and they're self-monitoring. The other thing that happened in New York is that we started to have a shortage, not only of supplies, but of actual healthcare workers, and some of our dedicated nurses had to be redeployed to the COVID units. And so we, in certain cases, we had to find backup staff or backup nurses for our patients. Fortunately, at NYU, our on-site infusion centers were dedicated units and they were not redeployed, so they kept them from, the nurses kept them within the infusion center. So that provided an extra source of safety and reassurance to our patients. However, a lot of our patients still ended up deferring the infusions for at least the first few during the height of the pandemic until infusion centers were reorganized and proper SOPs were put in place. So as I said, there's a couple of different ways this was impacted. In our chronic care facilities, I have a 14- year- old MPS IIIA, and I got the call at night for a chronic care facility. They had their first COVID positive patients who were actually quite ill with pneumonia, and they were trying to decant the actual chronic care facility and send patients out and back to their home environment. However, my patient was unable to be cared for by her family, and so we worked together to figure out how to cohort the unit. By a couple of weeks ago, half of all the residents were COVID positive, but we were able to successfully quarantine and isolate her from the rest of the group. I have two MPS VII patients who are in a chronic care facility, and that facility successfully avoided COVID exposure to this date, and they were higher risk because they are ventilated on chronic ventilation and very vulnerable. Our infusions, here's two case reports of the 45- year- old. He decided to defer his home infusion until we verified the nursing procedures, and he was able to return and felt comfortable returning to home infusion with the various prescreening questions. We have a 10-year-old, though, who did have an exposure, not direct exposure, but there was a physician in an infusion center that had COVID positive, and so they were scared to return. We finally returned last week to infusions. We had an emergency hospitalization for non-COVID reason for a 17-year-old who was in respiratory failure, and so during the hospitalization there, we successfully avoided COVID exposure. She was discharged home, but because of progression of her underlying disease, she had to present to an ER, and that's where that communication was critical, so the ER called me. I was able to provide the background on this rare disease to ER physicians that were not familiar with it and provided an urgent transfer. The final case is just highlighting the behavioral issues that we're seeing when we have loss of structured environment for a neuronal pathic MPS patients and how it's really impacting their care and the family. All of our other patients were successfully sheltered in place and continued home infusions with extra precautions. So, as Dafne said, we are looking at each patient individually and deciding whether or not to continue an infusion depending on their individualized circumstances. They're very scared of exposure because they are afraid that their child or they themselves would be at increased risk of some of these severe complications due to their underlying MPS disease burden. Ideally, we have to continue these infusions during the pandemic because this is not going away. We are finally on the decline in New York City with a rapid drop in the number of new cases and the daily deaths have gone down substantially from up to a height of 1,000 per day to less than 200. So, how do we do this? So, again, it's an individualized approach with a discussion with their medical provider about your individual risk, thinking about disease progression, and risk of infusion associated reaction when you return to therapy and to reassess periodically. So, most of my MPS patients are returning to therapy, but my other lysosomal, which I have a larger cohort, we're doing this on a case- by- case and, again, we're assuming that we might have a second wave of infections in the fall and the flu season. So, it's best to start this now to figure out how to overcome the barriers to care. And in addition to the barriers of infusion therapy, our rehabilitative therapies were also impacted. And just as Maurizio said that, you know, our hospitals were converted to complete COVID units. Elective surgeries were put off. Our inpatient rehab was converted to COVID units. And our patients who need to have multidisciplinary care were impacted because we were not allowing on-site, in-person outpatient visits. So, we converted to telemedicine visits where we could. I'm conducting my clinics now. If needed, I can see patients in person, in full gear, and that's starting up now. Our rehab therapies, PT, OT, and speech, were halted for a few weeks, and now they've converted to telemedicine rehab, which has its limits, but at least there is access for our patients to see their speech therapist, their PT and OT, through video visits to guide the family on how to do their therapies. And then as we start to be able to resume home therapies or in our rehab centers, we are still going through the mitigating factors. Our chronic care facilities, again, cohorting patients and being very careful. So, again, we talk to our patients about what to do if they're exposed, to self-isolate, to self-monitor, and then when to go to the ER, which might be earlier than the general public. A lot of our patients were sent home and not hospitalized, but our MPS patients may need different criteria for admission. So, we discussed the preparation of a to-go bag, so our parents of our patients made sure they had an updated list of medications, of medical conditions, the advanced directives, primary contacts, and my phone number, so if they are sent to an ER that's outside of the NYU system, the ER physician or the ICU attending could reach out to me immediately. And finally, there was at one point here, which I'm sure happened in other places in Europe, where we actually were low or becoming short on chemical ventilators, and that was on the minds of myself and my colleagues about the access to care and just the scare that might be in the community, not just for our rare disease patients, but for any patient. And so, internally, we talked about the ethics of ventilator disbursement and that a diagnosis alone, a genetic diagnosis, should not automatically exclude a patient from mechanical ventilation. And so, each individual should be stratified by their own medical issues, their comorbidities, their age, and organ function, and that could be done in discussion with their MPS provider. So overall, you know, COVID-19, we saw, could exacerbate the baseline manifestations of MPS and put them at a higher risk for severe complications. And this diagnosis, this rare diagnosis, creates a particular barrier to care when we had professionals who were not familiar with MPS, because it is rare and it is complex. And so, our most, you know, our way to prevent this is prevent exposure so that our patients don't come down with COVID, but it's, you know, we have a long way ahead of us to continue to prevent this exposure as we're waiting for a vaccine or other mitigating factors. So, I just want to say thank you for the opportunity to present today and give you a little insight of how we managed COVID- 19 here in New York City. And I'm going to pass this off to Christina, Can you hear me now?
[00:45:48] Dr. Christina Lampe: So, first of all, thank you for your insights. Thank you, Maurizio, Dafne, and Heather for giving your experience with MPS and COVID because we had a lot of discussions also inside of Germany, how to manage our patients and how to deal with it. So, I think it was a great overview of what we can do and how we can change and also to have new ideas for the future. And actually, I want to come back to Maurizio's first slide and his sentence from Churchill, what we can learn out of the crisis without wasting that experience. And I would give this question to you three to give you a statement what we can learn out of the crisis and what we can do in future to what we can maintain for our patients. Who wants to start? Maurizio, you're the first.
[00:46:45] Prof. Maurizio Scarpa: Well, what we can try, what we can learn. First of all, I think that what we have learned is that, at least in the rare disease field, we have a very good community. And there has been the proof of a real vicinity, I don't know how to say in English. I mean, I have seen our center and other centers here in Europe, and I believe that this is really a community of rare diseases, which is very careful for the patients. Also Heather and Dafne, and I believe you, Christina, as well, have very little problems with patients. We don't have a casualty, so we don't have lost patients, while this was really very common and very sad in a community where old people were kept. So I think that we can be very proud in the rare disease community of managing our patients very carefully. And this, I think that what we have to do is actually, and what we have missed a little bit, is the awareness of rare diseases in our colleagues. So of people not involved in the rare disease field, we really need to work quite a lot in order to protect our patients, even if they don't go to the center of referral, but they find a sense of where they need to have some treatment. So what is important is that really, in my experience, I had a couple of cases where the patient did not have a sort of emergency chart. And for this reason, as all of us are doing, they had my number, they can call me, and we fixed it during the weekend. But I think that we need to be very careful in really having this kind of document to all the patients in order for them to be safe, even if they don't have, for any reason, a contact with the physician. And then I want to leave also to the three of you, so I will stop here.
[00:49:20] Dr. Heather Lau: I think that's, I agree with you, Maurizio, that I think because we're so attuned to our patients and their multidisciplinary care, that's probably why we successfully avoided exposure and death. Our patients know during the flu season to avoid the flu, and so they know when there's a risk, they mitigate that immediately, but it did highlight that difficulty with patients are sent to other facilities. So that was my first thing to address was, God forbid, they were sent to another institution. How do we communicate? As we're increasing our electronic medical record system, and it's communicating, we need to do better where we have charts that talk to each other. And we're starting there in the US, where we are sharing information across institutions, but it has to happen further. And it comes back to our patients, our advocates for themselves, our parents, because they've been on this diagnostic journey, where they didn't know their disease. They're already, they have been informing their doctors, their new doctors about the disease. So they know that they have to explain themselves. And so that's something that I think, you know, it helped in that situation as well. And I agree, we need to have more of a better communication and help our patients in that way. We're attuned to it, but I was there, my colleagues were asking what happens if our Fabry, our Gaucher, and all of these patients coming through, what is their disease? So I think we did well, and we could improve on it. Absolutely.
[00:50:59] Dr. Dafne Horovitz : I think the matter in Brazil is pretty much the same. I mean, the rare disease community is very particular and different from other communities. They communicate a lot among themselves. And they have been empowered over the last few years. As a medical geneticist, every time I confirm any rare disease diagnosis, I tell the parents, now you are going to be an expert in this particular disease. So it's very important that you know that we're working at the same level. Of course, I know a lot of more technical stuff than you do. But you are going to be an advocate for yourself and for your child. And I think they've been working quite well with this. And in Brazil, as we're very used to adversity in general, and I think most of my patients have missed several infusions due to medication shortage. So they're used to it. And they're actually not very afraid. They have our contact numbers, and they really feel protected with the guidelines and with everything that's coming from the rare disease community. They know they can reach out. They can reach out for us. And actually, I would say, comparing to the rest of the country, they are in a better position than most of the population. Thank you, Daphne.
[00:52:31] Dr. Heather Lau: There's a question from the audience. That is, should we stop the ERT in case of MPS and COVID? And if yes, for how many times?
[00:52:46] Dr. Dafne Horovitz : We really do have a lot of experience. And I'm going to be participating in the webinar later this week regarding ERT interruption in MPS. So, again, we have to see this individually. We were very afraid to miss infusions right in the beginning when we started out. And I started out treating patients in 2004 so we did struggle and vacation, holiday, everything. We had to have the infusions. And now we can see that they can deal quite well with missing infusions for a while. And we really start seeing some effects after maybe two to three months without infusion. So that's my impression. We've discussed this. We've published a paper this year about ERT interruption. But it depends on the patient. Some of them can go on for more months even. Last year, or 2018, we had a shortage for almost six months for some patients. Some did fine. Some came back with symptoms. So it depends. I think what we should do is monitor, tell them the disease is there and it's not going away. On the other hand, the disease is not going to come all back, all the symptoms. So, we have to check on them and reassure and every week a phone call will be good and if they see, no, I'm not well, I have a lot of upper airway secretion, he can come back, have an infusion and not necessarily, I mean, if it's too risky, maybe he can miss the next week and come every other week or it depends. So, it has to be monitored from patient to patient, but it's not the end of the world. I know, I mean, there are some things that we cannot get back, so if the cardiac issues get worse and if we have the valve getting worse, we cannot go back to the earlier stage, but upper airway secretion, abdominal volume, we know that this can be restored after he comes back to infusion. So, it's a one-on-one basis and the most important is to keep in contact with the primary or to the caring physician.
[00:55:32] Dr. Christina Lampe: Actually, it is an individual decision from patient to patient, his situation, his environment, his views at school, work and so on, I guess. And with the benefit, always. And this is actually what you all three said before, what I experienced as well. We have a really good and very close community in the MPS field, so we are in contact with other colleagues from other countries, but also inside of the country to understand what we can do best for our patients. There's another question, any guidelines for MPS parents working in hospitals? Any experience with that? Any recommendations?
[00:56:18] Dr. Dafne Horovitz : So, that's difficult.
[00:56:19] Dr. Heather Lau: I'll take that because anyone, right, so any of us physicians are working in hospitals and I have a family and we have to figure out how to do that. So, there's no absolute, there is a risk that you'll expose your family and so look at it general. So, the guidelines, this is not going to end in a finite period of time, so you cannot self-isolate from your family on a long term. I did it for five weeks and now we have to figure out how to do this. So, even, you know, you have to live with your family. So, what do we do is, you know, the guidelines are you're doing full PPE at work, make sure that you come home, stop at the door, strip down, shower, and then you see your children. There's only so much you can do, right? So, if you're obviously in a COVID ward for that period, you might want to self-isolate from your family and have a separate room and everything. But if you're doing your day-to-day job, which we all will be doing in the next year as this is still prevalent, those kind of mitigating effects, shoes outside the door, strip down, I change at work and then I change again at home, shower, and then go about my day. I self-monitor temperature every day and look for signs and symptoms. Obviously there's pre-symptomatic spread and as the access to testing becomes more prevalent, you can get checked every so often. Once we started having access, I would get tested and that would give me some reassurance. So, those are the things, you know, try to avoid, you know, when you first get home. And if there's periods of higher risk, for instance, if you are redeployed again, then you might want to have a separate room and a separate bathroom. But that's all you can do. It's really, you know, in the height of the pandemic, I would have isolated, but now we have to figure out how to live through this. And I would recommend that. Does anyone else have any?
[00:58:19] Prof. Maurizio Scarpa: I totally agree with you, Heather, regarding this. And here in Europe, for example, we have now quite a lot of testing with TAP and now with serological tests. So for example, in the hospital, we are all tested regularly just to see whether there is some asymptomatic physician or something that, you know, can actually be. So now I think that this kind of test will be more and more frequent on our category. And of course, it will be also important to understand exactly, you know, the asymptomatic carrier. And as you all have said, you know, the numbers that we know now is just the peak of the iceberg because we don't know how many undiagnosed these patients that are, especially in big countries like Brazil or in communities where there is not a variability of single diagnosis. So we just need to be careful, especially now where, for example, here in Europe, we are opening again from today, for example, in Italy, we have opened quite a lot of shops and whatever, but we are very, very stringent with our patients in keeping, you know, attention and keeping safety. Because I mean, even if, you know, you have more people on the street, it does not mean that indeed we are off. We are still inside and we will be for a long time.
[00:59:43] Dr. Christina Lampe: Yeah, so, but actually we are, Daphne, do you want to add something shortly?
[00:59:47] Dr. Dafne Horovitz : We are at the end of the webinar. I would have a recommendation regarding testing when it becomes more available. I think we all as physicians should be tested whether we did or not have symptoms. All of us for sure had, I had contact with so many colleagues who had COVID and I didn't have anything, but I don't know, I mean, it could have been asymptomatic. And I would say the same regarding patients. I think it's very important that in the future we are able to test our higher risk patients because they will feel more reassured on coming back for infusions if they know they've had it. They could have had it asymptomatically. I'm almost sure that my two MPS II also had the disease without any kind of symptoms because the mother is with them all the time and she did have the clear symptoms with amnesia and everything. So for sure they were infected. And also, I mean, we're seeing people getting tested and sometimes the whole family. So one had severe symptoms, the other had very mild, and usually the children, they have nothing and they have IgG, they are IgG positive as well. So I think it would be very important when we bring them in back, if we have testing available to have them tested because the virus is not going away just like this.
[01:01:14] Dr. Heather Lau: Yeah, we're starting to do antibody. I'll be doing a study of all my patients. We're doing home kits in the summertime for IgG. So to see truly what you're saying, Dafne, are they, have they been exposed and had asymptomatic disease? My gosh, they are like that. So it's really interesting because there are a cohort that are going to have severe, but some of our patients who you would think should have had a severe course did not. So that remains to, we have to, that's where we can improve, testing, absolutely.
[01:01:49] Dr. Christina Lampe: Maurizio, one last sentence before we close the meeting. Mute.
[01:01:59] Prof. Maurizio Scarpa: Sorry. So one last thing that we can learn from this is that everybody of us was speaking about telemedicine. I think that we should create actually a community inside the lysosomal or the metabolic or the rare disease field of telemedicine doctor. This will never substitute the contact with the physician for certain part. But if we actually develop some good platform where we can keep the contact with the patient very easily, that will be a major safety point for our patients and family. So I think that this is something, this is a program, this is a project that we should all work together in order also to collect some data from the family life that it is always very interesting and we can be used in order to improve the quality of life in such emergency situation because this will not be the last one. You know, for sure there will be others and we need to be more prepared. And thank you very much for this webinar which was extremely useful for me and I was very pleased to have these three wonderful women in as a company.
[01:03:14] Dr. Christina Lampe: Thank you so much. Thank you, Dafne, Heather and Maurizio to share your experience. There's one last question I just want to highlight is the mortality rate among MPS patients with COVID higher compared to general pediatric mortality? We cannot answer this question at the moment. All our patients are still alive. We have only a few affected patients. So stay healthy, everybody. Be safe. Contact your, be in contact with your patients or on the other side with your physician that knows you best and discuss your personal individual situation.
[01:03:52] Dr. Christina Lampe: And actually we will work on having more ideas when we are going a little bit in future and we know a little bit better what COVID is really doing and what we have to expect. So thank you very much and thank you. Bye bye and see you soon.
[01:04:14] Dr. Christina Lampe: Thank you.
[01:04:14] Dr. Heather Lau: Bye bye. Thank you. Bye.
[01:04:17] Prof. Maurizio Scarpa: Bye. Thank you very much.