So I want to welcome everybody for joining us in this timely manner to talk about an educational program that was developed by the Mobility Caucus, and also we are very thankful to the American Association of Neurological Surgeons to provide CM credit for this educational program on COVID-19 and rehabilitation. The genesis for all of this actually began about a year ago, I think some of us had family. Others had colleagues and friends that we started to see them suffering from the acute aspects of COVID-19. I think it was particularly painful for me to have a family member be one of the very first people to catch COVID-19, and then to watch them spend two months on a, nearly two months on a ventilator and then having to recover from it, it became clear by this time last year, that we were going to have a problem in the aftermath in meeting the challenges of these unique problems that these patients would suffer. With that, we looked at our organization and chose the top experts in terms of rehabilitation and the neurological manifestations, and the rehab that would be involved, and cornered them to join us in this offering today and cover really the overarching highlights of COVID-19, and this is merely a taste of what that aftermath is going to be in the post-pandemic area, but also just as important, we're covering aspects in terms of prevention when we talk about vaccines with our authors that I will introduce here shortly. There are going to possibly be questions and answers that will be posted and you can do that on the Q&A box, or as part of this seminar today. As you know, we are offering a CME accreditation, and let's go to the introductions here now. So the first thing I think we will have is our, I'm currently serving as chair elect of the Mobility Caucus, and I think I roped in the AANS to do the CME as their president elect this year. Peter Amadio is going to talk to you a little bit briefly about the Mobility Caucus, about what we're doing, and then after that we will be hearing from Carlo Malani when he talks about the neurological essentials of rehabilitation. So Peter, I'm going to have you take it from here. Thanks, Anne. So my name is Peter Amadio, I'm the chair of the Mobility Caucus. The Mobility Caucus is the first caucus of specialty societies within the AMA. The regional state societies have had caucuses for many years, but we're the first in the specialty society. It was started by Michael Suk back in 2018. Michael's now on the Board of Trustees, of course. So the mission of the Mobility Caucus is to work within the AMA, obviously, to improve care of patients with neurological and musculoskeletal conditions, to protect function, well-being, and quality of life, so hence the mobility term. Our thought is that a lot of the specialty societies in this field are relatively small with one delegate or maybe two, and so we can be stronger together and have a stronger advocacy effect by working together through the Mobility Caucus. We currently have 22 members, society members, and those societies in aggregate have about 40 delegates. So that's basically the size of the Mobility Caucus. We're very happy to sponsor this educational program and to be able to do things like this every year. So thanks, Anne. Thank you. So Carlo Milani, do you want to go ahead and get started on your topic? Will do. All right. Thanks so much. I'm Carlo Milani. I'm a physiatrist at the Hospital for Special Surgery in New York and an appointment at Weill Cornell Medical College. Today I'm just going to briefly review some of the essentials of rehabilitation as it pertains to post-COVID recovery. I have no disclosures. So some objectives here, we'll briefly review some background of COVID-19 that's relevant to post-COVID rehabilitation. We'll go over some general principles of rehabilitation. We'll discuss rehabilitation considerations after severe COVID and after mild to moderate COVID. And then we'll just think about a special consideration of rehabilitation of PASC. So some background here, of course, SARS-CoV-2 is a virus, or is the virus that causes severe acute respiratory syndrome associated with COVID-19. The infection leads primarily to respiratory illness associated with high levels of inflammation that result in pulmonary injury, but there's also many non-pulmonary manifestations, including central nervous system and peripheral nervous system manifestations, manifestations of the cardiovascular system and neuroendocrine systems, increased thrombotic risk and multi-organ comorbidity. One recent study from the UK and the British Medical Journal looked at data from national databases, including the National Health Service, and evaluated the burden of comorbidity through multi-organ dysfunction after discharge in patients hospitalized with COVID, compared to their general population. You can see here down in the bottom right that about 43,000 patients who did not require intensive care were included in the study and about 4,700 patients who did require intensive care were included. So the authors found that the patients who were hospitalized with COVID-19 had both increased prevalence and incidence of multi-organ dysfunction after discharge. You can see at the top that there was increased prevalence of those patients hospitalized with COVID who had diabetes, major cardiovascular events, chronic kidney disease, and chronic liver disease, which is in line with what we know about the risk factors of developing severe COVID. But what's also interesting is the noted increase in new onset of these conditions at discharge. So the authors concluded that individuals requiring hospitalization for COVID, the majority of whom didn't require intensive care, had increased rates of multi-organ dysfunction compared to the general population. And this is likely going to create an increased public health burden. And we know that this increased public health burden, especially related to COVID-19, is more broadly borne by disadvantaged communities. So this has the potential to exacerbate socioeconomic disparities. And in terms of rehabilitation for post-COVID, we need to take into account all these factors with an integrated approach among health care specialties and integrated pathways. So rehabilitation can feel like sort of a nebulous concept. A broad unifying definition of rehabilitation is a problem-solving process framed in the context of a biopsychosocial model of illness delivered in a patient-centered way. So this really gets at the heart of evidence-based medical management, along with a problem-solving process for patients and caregivers to facilitate functional recovery that's going to be most meaningful to patients. Ultimately, rehabilitation medicine is a team sport, and you can see here it takes a large team, especially in the acute inpatient side. In the outpatient setting for rehabilitation of post-COVID, it'll look slightly different, but it's probably going to require ongoing care from a variety of these specialists. Regarding the goals of rehabilitation, we want to prevent further deconditioning and promote gradual reconditioning. We want to help return individuals to their activities of daily living with the greatest amount of independence possible, help maintain individuals' mental and emotional health throughout their rehabilitative process. And we really want to cultivate resilience and problem-solving for patients and their caregivers, and to promote reintegration back into the patient's social roles. Principles we use to do this include graduated exercise, repeated practice of functional activities. We address psychosocial barriers to functional recovery. We provide education for patients and their caregivers, and we're constantly developing and refining specific rehabilitation assignments and plans to help patients achieve their functional goals. Regarding approaches for rehabilitation after severe COVID, while management and outcomes of post-COVID are not well-studied yet, individual symptoms commonly experienced by post-COVID patients, however, have been well-studied in other populations, and so we can apply what we already know. Some of these common symptoms include cardiopulmonary difficulties, fatigue, cognitive fog, psychological symptoms, and autonomic symptoms. Here we see some of the symptoms we just mentioned along with what we currently know about the timelines and duration of their development. From this very nice review article in Nature Medicine, which outlines many of these issues and the proposed pathophysiology, we know that broadly the potential mechanisms contributing to post-COVID syndromes include direct effects of viral infection on organ tissues, immunological aberrations and inflammatory damage in response to the acute infection, and the expected sequelae of post-critical illness, which include microvascular and ischemic injury, immobility, and metabolic alterations. This is just going to be a 35,000-foot view of management considerations for some of these more prominent post-COVID symptoms. I'm going to review them really briefly because I know some of the other speakers are going to go into more depth. Regarding cardiopulmonary symptoms, goals are to improve dyspnea, relieve anxiety, minimize disability, preserve function, and improve quality of life. Acute management of this may include addressing nutrition, airway management, postural strengthening, airway clearance techniques, oxygen supplementation, breathing exercises, and physical therapy. Chronic outpatient management may need to focus more on formal cardiac or pulmonary rehabilitation. One recent study looking at survivors of severe post-COVID found that about 35% had persistent fibrotic changes on CT at six months. These findings may be similar to other post-SARS or post-MERS sequelae, but characterization really of COVID survivors is still ongoing. Fatigue management, the goals here are to address both physical and cognitive fatigue, to improve exercise tolerance of activities of daily living, to decrease post-exertional malaise. Management includes evaluating sleep, mood, dietary and fluid intake, considering vitamin D levels, neuroendocrine screening such as thyroid and cortisol levels, and possibly evaluating for signs of ongoing inflammation or autoimmune processes. Regarding cognitive fog, we really need to address impairments in concentration, memory, multitasking, and executive functioning. Management may revolve around treating entirely subjective symptoms or findings that include mild cognitive impairment. A detailed cognitive assessment may be necessary, and a referral to speech therapy or neuropsychology could be considered. Supplements like omega-3 fatty acids and acetylcysteine might have a role, but there's really no strong recommendations or evidence for this, not yet. Regarding psychological symptoms, goals are to decrease anxiety, depression, or to address anxiety, depression, PTSD, and possibly adjustment disorder, which can be common in post-critical populations, but which seem to be a particular risk of our post-COVID population, especially during this global pandemic. Management should focus on development of coping skills for uncertainty, reducing a sense of isolation, which can be challenging with lockdowns and disruption of our social and support structures. Antidepressant or anti-anxiety medications may play a role, but exercise, sleep, and diet in certain instances are probably equally and importantly as effective. In terms of moving to an approach for rehabilitation after mild to moderate COVID, we know that most COVID cases are going to be mild to moderate and may involve more active populations. Goals for recovery in active populations may be just to return to active lifestyles and exercising to avoid morbidity and injury associated with post-COVID effects and deconditioning. In addition to the symptoms we just discussed, the one case you really don't want to miss in this population is myocarditis or myopericarditis, which can be associated with increased risk of fatal arrhythmia and sudden death in an exercising population. One recent study published in JAMA Cardiology noted that 26 competitive college athletes, none of whom required hospitalization for their COVID, 15% had cardiac MRI findings suggestive of myocarditis and 30% had findings suggestive of myocardial injury. Of those who had findings of myocarditis, half of them had shortness of breath while the others were asymptomatic. There were no additional findings on EKG, echo, or troponin levels. Expert consensus has recommended that those who have been diagnosed with COVID-19 shouldn't return to vigorous exercise in the presence of persistent fever, dyspnea, at rest, cough, chest pain, or palpitations. For those who had positive COVID diagnoses, there should be a two-week convalescent period without return to vigorous exercise or sport once they're asymptomatic. After that time, those who had mild or moderate symptoms could consider a high-sensitivity troponin screen, electrocardiogram, or echocardiogram. If any cardiac testing is positive, they should follow a myocarditis return to participation guidelines, which include a three- to six-month period of relative rest from vigorous exercise and sport and ongoing monitoring by a medical professional. After the relative rest period, if their cardiac testing is normalized, they can return to exercise. For those who don't require myocarditis guidelines, a 50-70-80-90 rule can be utilized, whereby an individual over the course of four weeks can start exercise by returning to 50% of their typical exercise load and progress 70% to 80% to 90% stepping up one week at a time over four weeks. After that time, they can return to their normal exercise. If needed, there's also more structured and extensive return to exercise protocols based on the Borg rating of perceived exertion scale, which uses a phased approach. Finally, in addition to the previous symptoms mentioned or discussed, special consideration for individuals experiencing past or long COVID symptoms includes signs and symptoms of autonomic dysfunction. Reports of increased incidence of autonomic dysfunction after COVID-19 are emerging, but in many cases, symptoms are mild. In some patients, however, more severe symptoms do persist and could be consistent with postural orthostatic tachycardia syndrome or POTS. This includes high heart rate variability and tachycardia even during minimal activity. These individuals may have persistence of shortness of breath, chest discomfort, and presynchronous symptoms. Management includes workup of orthostatic vitals, tilt table testing, cardiac workup, compression garments, and perhaps medications. I'll leave you with this slide pointing us towards the development of a post-COVID-19 clinical model to facilitate interdisciplinary management. This is something we're likely going to have to consider for patients who've experienced severe courses of COVID, but also those who have lingering effects of mild to moderate disease. That's great. I only see one comment in the chat box, and it's from me, and that's autonomic dysfunction. You were talking about that. I've been seeing a lot of patients with head injuries because of the autonomic dysfunction, although mild for some patients, is severe for others. Is that necessarily related to how difficult your recovery from COVID-19 is, or is it not really that selective? It doesn't appear to be so selective. I think maybe one of the other presenters is going to go into some of this as well, but it doesn't appear to be so selective. Patients who have had mild courses of disease or severe courses of disease seemingly can be susceptible to this. I think it's really ongoing, and it's evolving, whether or not this is something specific to COVID, and there's an increased incidence, or whether this mimics other similar severe courses of illness. Okay. Well, I'm encouraging others to put their questions in the Q&A section, but our next talk now is on COVID-19, looking at some of the overarching psychiatric and psychiatry highlights. Patrice Harris, I'm going to have Dr. Harris, our own immediate past president, is going to cover this very enlightening subject, and I'll have you then start next. Thank you. Thank you, Anne. I just want to do a check that you can hear me and see my screen. Absolutely. Very good. Thank you for the opportunity to be a part of this group, because it's so important that we have these conversations. As you so noted, it's just a short period of time, so just a taste, perhaps, of what folks should be thinking, and maybe a different lens as we look at neuropsychiatric and psychological symptoms of post-acute COVID. I think we start with some overarching principles. I was given an interview one day, and a reporter asked me about COVID and a lesson that I personally learned, and I said humility. Now, I think all of us practice with a great deal of humility every day so that we can make sure we are always willing to learn and continue to be curious. As I said, this SARS-CoV-2 virus is giving deserves rather an A plus on what viruses normally do, right? Replicate. I think that many of us would agree that every time we thought we were getting a little bit ahead of the virus, it changed course. I think we should, as we think about post-acute COVID, continue to make sure we keep that principle in mind. There is so much we know. We know a lot more now than we did even last month, but there is so much that we don't know, and it will change as we move forward. Of course, we're used to that period where we're always learning and growing as new data and new studies come along. The other issue is language, and I think that's particularly true when we think about neuropsychiatric and psychological symptoms, because we have not really had a lot of conversations. Of course, internally we have, and we can appreciate mental health more, but that's been gradually progressing over the last decade or so, and language is still very difficult. When the Lancet psychiatry study came out, and I received a request for an interview, and I always like to know the topic of the interview, they said, we're going to focus on the neuropsychiatric symptoms, and I said, okay, just want to make sure that you are talking about the neuropsychiatric symptoms and perhaps not necessarily the symptoms around emotional stress and psychological symptoms, and they said yes, but then all of the questions were about emotional distress and some of the psychological symptoms, and that was fine. I did a lot of education at that interview, had the opportunity to talk about the difference between a symptom, having a depressed mood, and of course, making sure that folks knew that having a depressed mood does not equal having clinical depression, so I think we are still on our journey. We were before COVID, and we still continue to need to be post-COVID regarding the language that we use, again, particularly around neuropsychiatric and psychological conditions associated with COVID, and the other good news and why I'm so excited to be a part of this talk today is we are thinking proactively about these issues. I recall when I was training, and this has been a while ago, and I had an inpatient consult liaison experience, and it seems like my colleagues would think of every other thing to do, and at the last resort, call in psychiatry. Now, again, it's been a while since I've trained, and more and more folks are bringing these issues and raising these issues at the beginning of the course of treatment rather than at the end, and so I think it's very important that as long-haul clinics are developed, there is screening at the very beginning regarding some of these symptoms and that there is a relationship with psychiatrists in your agency, in your academic institution, in your community to make sure that there's a proactive approach, and addressing these issues are not sort of an after-the-fact or an external to all the other work that has been doing, and I think Dr. Malani really talked about the importance of integration, and that's very heartening to hear, but certainly survey after survey, study after study demonstrated that if we just think about depression and anxiety and cognitive impairment, a wide range of symptoms I'll illustrate on a subsequent slide, they are increasing, and by the way, I'm talking about new onset symptoms, right, related to COVID, and so we have seen that from the very beginning, and that still holds true today. The numbers vary from time to time. The percentages vary, but still we are seeing an increase in these symptoms. Now, I don't subscribe to hyperbole, as many of you know, and so I've heard people talk about a tsunami and other hyperbolic terms, and so while I don't subscribe to that, we are a very resilient population. People are generally resilient. We do have to appreciate that there is going to be increased burden on our entire system, and remember, we come into this with a underfunded, fractured mental health and public health, by the way, infrastructure, and so I am really concerned about what we are going to continue to see as we get through the acute phase of COVID, and so there's an advocacy opportunity there that I'll talk to at the end, and of course, the Lancet psychiatry study, which got a lot of attention, I'm glad, and talked about the substantial neurological and psychiatric morbidity in the six months, again, following COVID, and of course, that continues to hold true, and so again, we've seen a wide range of symptoms. We've already heard Dr. Malani talk about cognitive impairment and brain fog. I don't know about you, but many of my patients talk about just feeling like they're in this morass, and they can't find their way through, and it's so difficult to concentrate, and they've lost memory and have difficulty finding the words they want to use. I think we all do that to some extent, but that's a real difficulty there. Anxiety, sustained depressed mood. I will just say again that we have to be sure that we are differentiating between normal human reactions and emotions to the stress that all of us have been under, and short-lived anxiety and depressed mood versus those that are sustained and continue beyond just a couple of weeks. Of course, people complain about difficulty sleeping, appetite changes, unfortunately, increase in alcohol or other substance misuse. Some folks, of course, talk about feeling hopeless and helpless, and we have seen some folks, some increase in folks endorsing suicidal ideation, some increase in suicidal attempts. I will say, going back to one of the principles and talking about language, we will have to make sure that we help our patients do what I call get beneath the headlines. I was very frustrated, I think, just in the last couple of days about some of the headlines around adolescent suicide, and a lot of folks did not bother to dig beneath those headlines and look at the data, so we really need to be careful about that. We know that our patients will come in perhaps having only read the headlines, and so there will be the opportunity, I would say the need and the responsibility for us to help our patients sort of dig beneath the headlines because it's scary. Actually, I'll just start with what you see, the last bullet point. This has been, and this is not in the DSM or ICD-10, just plain scary, whether you had the unfortunate experience of a very severe course of illness and you were in the ICU or whether you had a mild course. If you were fortunate enough, I would say, to experience a mild course, a lot of my patients said, but they were always on edge waiting for the shoe to drop because any day now they worried about whether or not they would have to go into the ICU, and so we don't know, right, the etiology, is it the disease, the infection, the actual inflammatory process, is it just what we've seen in other critical illnesses, is it our treatments, high-dose steroids we know cause mood changes, sometimes even psychosis, proning while being ventilated is very scary. I'll give credit to Dr. Ken Serta, who has experienced some of his patients talking about how scary that is. Is it a slower-resolving delirium? Is it, of course, being in the ICU, and of course, with the added burden that we have had, you know, the noises and all those are not unusual, but this time patients couldn't even see our faces, right? They couldn't even accept visitors, and so having that family member or friend come in and just hold their hand, they weren't able to do that. Some folks are having survivor's guilt. Of course, it's difficult with these near-death experiences back to it's been just plain scary whether or not you had a mild course or more severe course, and then those general psychosocial stresses you see on this slide, and all of us have experienced some of these missed milestones, of course, our disrupted lives. Unfortunately, we don't live in a vacuum, and we've had this context of divisive political discourse, a summer of racial injustices, and an assault on our democracy, financial stressors, job loss, and a lot of folks had disruption in their usual care and support services. Of course, we were able to make up some of that with telehealth, but not all of that, and so what is the principle? What do we do? Certainly, integration is critical. Just want to make that point. The AMA, of course, has great policy. We have a new project and a roadmap, the Behavioral Health Integration Collaborative. I urge you all to take advantage of the learnings there, but I also encourage all of you to connect on a local level with local psychiatrists, and again, as you are developing long-haul clinics, make sure that mental health professional psychiatrists are engaged and involved as we work together and learn more about these issues. Thanks, Anne, for the opportunity. Thank you, Dr. Harris. That was great. After Patrice, now we're going to go to Stuart Glassman, and Stuart, we'll let you get set up with your share screen. Stuart is one of our member-at-large here at the Mobility Caucus and moving up quickly in the leadership. Now, let's talk a little bit about the unique challenges of rehab. All right. Great, everyone. Glad to be part of this esteemed panel. Thank you, Anne. I'm Dr. Stuart Glassman. I am based in Concord, New Hampshire, and one of the AMA delegates for the American Academy of Physical Medicine Rehabilitation and a member-at-large for the Mobility Caucus. I'll be talking about some of the overviews of this whole issue of COVID-19 aftermath, unique challenges in rehabilitation and ongoing care. All right. Hold on. There we go. No financial disclosures or conflicts of interest. I want to thank the AAPMNR Academy, the Mobility Caucus, and, of course, the AMA as well. All right. Objectives, we want to try to improve understanding of some of the various terms of post-COVID-19 and definitions of signs and symptoms, look at the epidemiology and demographic data of this illness and aftermath, improve awareness of the challenges and importance of rehabilitation evaluation and management of post-COVID-19 recovery, some of which we've heard, and also review the AAPMNR's specific collaborative for long COVID and post-acute sequelae of SARS-CoV-19, COVID-2 quality improvement as well. All right. So I try to focus sometimes on some of the issues that maybe you haven't heard about before, some of the economic issues and some of the data issues as well. So total cases, this is as of Thursday night because we had to hand these in Friday, total cases of COVID-19, 33.5 million in the United States, 600,000 deaths, 27.9 million recovered cases, 5 million active cases. The new daily cases is around 20 to 21,000. The top county in the United States for cases is Los Angeles County. You can see the maps there of the spread as well. So what are we talking about? And I want to credit Dr. Alba Alzola, who's at the University of North Carolina, their post-acute COVID clinic. Long COVID is the syndrome presenting with the various physical, cognitive, and mental health signs and symptoms lasting weeks or months afterwards. And interestingly, during the interim meeting in November, when Dr. Fauci was one of our guests, he actually used the term post-COVID-19 syndrome. And at that time, Dr. Strunk and I were trying to actually get this topic in that meeting, but he actually coined the phrase, which at that time was the best you can come up with at that time. Long haulers are describing the patients who have these symptoms and signs. And post-acute sequelae of SARS-CoV-2 infection is PASC. That's the clinical condition that was announced in February, 2021 by the NIH. And they received the $1.15 billion grant for a four-year study of this. All right. The prevalence is felt to be between 10 and 30% of COVID-19 survivors. So that's between 3.4 and 10 million cases. So we're talking about a pretty sizable population around the United States. The prevalence appears to be highest in those patients that were hospitalized and needed ICU level of care and had coexisting medical comorbidities. However, realize many patients never even went to the hospital because at the time of the rampant infections, they were told, don't come to the emergency room. We can't take care of you. So they stayed home and they were never admitted to the hospital. They may have had milder symptoms, but they're developing PASC now as well. And there's a discussion about this on the JAMA network from a few months ago as well. So as talked about some presentations clinically, we've got fatigue, shortness of breath, dyspnea, chest tightness, orthostatic changes, myalgia. The issue of brain fog is almost presenting similar to mild TBI and post-concussion syndrome. And there's some question of, is there a correlation between patients with mild TBI pre-existing and the ongoing prevalence of PASC? The Veterans Administration is looking specifically at this issue with some upcoming research to be funded by the VA. Loss of taste and smell, we heard that with the acute infection, but it's persisting ongoing as well. Sleep disorders, fevers, GI symptoms, diarrhea, renal disease, trauma, embolism, and of course, depression, anxiety, PTSD, we've heard this in the other two speakers previously. So what are some of the theories of why this is even happening pathophysiologically? Virus particle remnants persisting in organs, autoimmune phenomenon with increased stimulation of immune cells from the original infection, especially in patients who've had pre-existing autoimmune disease, and inflammation, cytokine storm, we heard a lot about that early on with COVID-19 in the acute phase and has it caused ongoing endothelial excitement and autonomic nervous system irritation. So this is a medically complex and multi-system involvement as the slide from Dr. Malani showed at the end as well. So what about development of PASC recovery clinic? A lot of these began in June, 2020, as patients recovered and were being discharged to either acute care hospitals or rehabilitation units. And also Dr. Benjamin Abramoff, who's at the University of Pennsylvania, is one of the leaders in this from the PMNR perspective. Patients were noted to have significant decline in physical endurance, cognitive function, and quality of life. And these are often the focus and treatment areas for these clinics, especially if they're within the PMNR departments. But there are other clinics in pulmonology, internal medicine, rheumatology, and family medicine. So you're going to see a lot of crossover between different primary care and specialty clinics. But the patients, again, may have different needs and that may determine where they may end up going. We know there are at least 46 PASC PMNR clinics in the United States at this time, and they're often housed in academic medical centers. And here's some reports and publications on some of the clinics from the past couple of months as well. JAMA has a number of those publications as well. What about socioeconomic issues to consider in PASC? And I will tell you, we were on a national grand rounds earlier last week, Dr. Malani and I, and no one was really talking about the financial issues facing these survivors. So the average COVID-19 cost for Medicare patients was about $22,000 to the hospital. If you're on a ventilator, it went up to about $50,000. Medicare's deductible is about $1,400. So you think, well, that's not a big amount compared to the total cost. And yet, if you're on Medicare, that might be a lot for you. The costs were often higher in African-American, Hispanic, and Asian-American patients. They were more likely to be hospitalized and be on a ventilator or die of COVID-19. So this brings in certainly the question of health disparities and health inequities as well. If you are an uninsured patient, you're a young 20-something patient who said, I don't need health insurance, or you were in out-of-network care because your narrow network and your health insurance didn't cover where you had to go to emergently, well, then those costs went between $51,000 and $78,000 just for the hospitalization. And this is the article it came from. So imagine you came out of the hospital post-COVID-19 with all the physical effects, and you've got this crushing economic debt weighing on you. And now you're also out of a job, and you have no health insurance. If you're not talking about these economic and social issues for your patients, you're missing what may be one of the biggest concerns for them, is that they don't know how they're going to pay for this. How does that impact their depression, anxiety, chronic fatigue, and cognitive issues? You've got to be asking about housing and food insecurity, difficulty covering household expenses, and the issue of disability claims. I do a fair amount of disability assessments for the state of New Hampshire. A lot of them are put on hold for six months. We're not even seeing those claims yet due to COVID-19 sequelae. So it's coming. All right. Now, do I know you're from somewhere? So severe acute respiratory syndrome, the SARS virus from 2003-2004. There were publications about seven, eight years later, especially out of the Toronto area that looked at chronic widespread multi skeletal muscle skeletal pain fatiguing depression, distorted sleep in a post SARS population. So we have seen this before. And we saw 10 years ago. So it's important to look back and understand how it can impact our research going forward, because they were struggling with symptoms for years. And it's important to see the comparison similarities and understand what we have to look at as well. We're not really hearing a lot about this, you know, but it's important. About 263,000 veterans have been diagnosed with COVID it may be a little less than that because some of their data actually included employees at the Veterans Administration as well. But 95% of these numbers are actual veterans. 42,000 have been admitted to VHA facilities, about 249,000 are in convalescence. They've been 12,300 deaths from the veterans, or the employees who were counted within the veterans health affairs data. And they vaccinated about 3 million veterans so far, or the people that work here as well. And here's some of the links, where that data comes from. JAMA recently and the network open look at some of this. One of the interesting aspects was that in looking at 3000 veterans about 13% said that the PTSD symptoms went up and 8% contemplated suicides information Dr. Harris talked about earlier. But at the same time that same study showed that 43% of those respondents actually experienced positive psychological benefits during the pandemic. And they reported greater appreciation of life, closer interpersonal relationships and increased sense of personal strength. So it's almost like you have a yin yang, you know, sort of different to buy your bifurcation of how veterans. You know, saw this pandemic, and what they experienced psychologically. So, definitely something to be looked at that both in the same studies as well. Quickly, our academies long COVID PASC quality collaborative started in March 2021, focusing on three major areas, building necessary clinical infrastructure to address these needs, including the development of an ICD 10 code, U09.9, equitable access to care for all PASC patients, and focusing on funding for research to disseminate best practices to improve outcome. There have been ongoing discussions with the White House administration and Congress. I'm going to be part of a virtual Hill Day on Thursday, addressing these issues with congressional delegation as well. And we've had National Grand Rounds online education. The main focus areas and leaders for our collaborative have been at the University of Pennsylvania, Argonne Health and Science University and Mass General Hospital out of Boston as well. So thank you, Q&A to follow. Yes, thank you so much. Our next speaker now is Matt Gold. I gave him the challenge of trying to jam in as much neurology as he can, could you imagine that in a very short topic and so I think he's up to the challenge and Matt we really look forward to hear what what you think about this topic which I think is going to gain a lot of traction here in the next year or two. Well, of course, when I started to put this together it came out to be 2025 minutes so what I've squeezed out maybe some of the deep dives but I will give you some further reading at the end. I have no, I have no conflicts. So I don't even have a slide for that. So we're going to try to learn a little bit of the spectrum neurological symptoms there's going to be a little overlap and it may fill in some of the interstices of the other speakers, great minds work in the same way. I'm going to give an introduction to some of the mechanisms of harm implications, not necessarily of the details but implications of for rehabilitation. And as already been mentioned, there have been a number of terms, they've sort of evolved the one that people with the problem of chronic residual choose is long haulers so that's why you may have heard about that. The definition is varied. So basically after the onset of force for weeks maybe called sub acute but persisting more than 12 weeks might be termed chronic, and part of that is pathophysiologic, the virus cannot be identified after three or four weeks after the acute phase so that's it. I from personal experience I'll tell you that early on, the two issues that seem relevant to neurologist was the presenting an osmia, and the threat of thrombotic stroke. Fortunately, the latter was not that common but in osmia was fairly common and in fact became one of the prime things to test in the general population whether directly or by questionnaire, and I actually had a curious situation in late January of a true Italian young student lady who had just gone to see her boyfriend in Italy, came back here and complained of acro paresthesias. I was, unfortunately she was lost to follow up but I suspect something there. So the statistics obviously vary in varying studies and in fact the things that we have paid attention to and understand is connected has evolved over the last year. There's been evolution of the conceptual framework of studies. Over the last year, one source suggested 36% of patients with covert develop neurological symptoms. Which can include headaches disturbed consciousness seizures absence of smell and taste and paresthesias, even early on, more serious conditions include something called posterior reversible encephalopathy syndrome, which by itself can cause many of those symptoms as well as visual loss viral encephalitis directly brainstem edema partial neuronal degeneration clearly increased risk for acute cerebrovascular events was initially the most feared complication. There have been a few cases of Guillain-Barré syndrome, associated with covert 19 distinguishing features that it occurs earlier than in the common variety after the initial insult. We also know that the original SARS could cause polyneuropathy and persistent tachycardia in MERS almost one of five patients showed neurological symptoms including altered consciousness paralysis ischemic stroke, Guillain-Barré syndrome, infectious neuropathy or seizures. Most of those have in fact now occurred in covert 19 as well. An earlier study of post discharge persistent symptoms done in France yielded the following statistics. Okay. Well, you can take a look at this quickly. We'll come back to something like that. The following statistics. After a mean of 111 days, the most frequently reported persistent symptoms were fatigue, dyspnea, loss of memory, concentration, sleep disorders, and well hair loss. Got to watch out for that. So comparisons interesting we've done between ward patients and ICU patients and perhaps a disease severity scale, but there was no statistically significant difference regarding the symptoms, except possibly more residual pain in the ICU group. So they generated an interesting graphic I find this is well here's here's the expanded list you can see fatigue, muscle aches, weakness. I put chest pain and heart palpitations together because I'll throw in a little slide later that I'm wondering whether that's not half neurologic. Dizziness when you stand of course reflects autonomic dysfunction frequently as not headaches with a chronic daily feature became that way. Here's this interesting graph I've never seen it done this way there's a circle here you might not be able to see it. The blue is from the ICU group, and the red or the pink is from the ward group, and the worst symptoms radially go further out. So you can see that in the ICU group, there's more pain and discomfort in all of those groups there was mobility problems. And obviously the more severe people had problems with their activity even more. And I threw this in because when we have myocardial injury and myocarditis and cardiomyopathy and arrhythmias in a subacute fashion obviously could be immune but it could be part of the autonomic dysfunction, it could be a myositis. This suggests that neurological symptoms and manifestations resulting from COVID-19 can occur prior during or after respiratory involvement alteration and smell is usually early, the sensory neurons interestingly do not express the viral target of ACE2, so direct exposure is not seen but the olfactory epithelium does express ACE2 and is vulnerable to the virus. The European study showed 85% decrease in smell function, corresponding to an 88% alteration in taste, and interestingly, 25% of children had only olfactory symptoms and not the rest of the COVID clinical scenario. Perhaps 95% of patients do recover their sense of taste, perhaps 25% sooner in a few weeks, but leaving up to a year's worth of problems for the remaining 75%. Myalgias are present at a nearly 20% rate. The etiology is unclear but possibly related to the cytokine storm. Early presentation of headache is reported in the 6-20% range and interestingly evolves into a photophobic, quasi-meningeal headache in 7-10 days, possibly again provoked by cytokine storm. There are other migrainous qualities to those headaches, they can be persistent and disabling. A study also from England showed that acute confusion and delirium could be the primary manifestation of presenting COVID before respiratory symptoms, incidence as high as 9% in some studies. So aside from the pure neurological issues, as I mentioned, cardiac inflammation, palpitations, and tachycardia all overlap with neurological conditions of myositis and peripheral neuropathic ailments, including the autonomic dysfunction, and here comes the term postural orthostatic tachycardic syndrome. In terms of persistence of symptoms, in February 2001, a research letter in JAMA estimates approximately one-third of people with COVID-19 had persistent symptoms as long as nine months after infection. Statistics as to how many people actually have lingering effects of COVID vary widely. I've seen statistics between 10% and 60%. One study suggested those who have had more than five symptoms early in the disorder, perhaps in the first week, have a greater chance of experiencing long-term effects. A BMJ study suggested 70% of people with the low-risk COVID mortality later showed impairments in one or more organs four months after their initial symptoms. Further, though there are known risk factors associated with severe acute COVID-19, including high blood pressure, smoking, diabetes, obesity, and other conditions, there's really not a clear link between those risk factors and developing long-term problems, in case you were wondering. Data in this early phase of investigation is often gathered by either telephone or other subjective reporting, but self-help groups have a role to play and have contributed considerably to identifying valid complaints. One source, Healthline Online, suggests there may be a specific order for long-term COVID symptoms, starting with the obvious flu-like sequelae, fatigue, and headache, fever, and chills. I won't go into things. This is not an exhaustive list. But there is a tendency for waxing and waning symptoms, sometimes proportionate to the amount of physical or mental effort. A California study by Dr. Natalie Lambert suggests there may actually be regular intervals, such as seven to 10 days apart, in a cyclical way. But what appears clear, however, is not due to the persistence of the virus itself. And also, anecdotally, the waves do seem to get milder over time. So the most common lasting symptoms, somehow these things came out of order. I can't go back so easily. We'll catch up. The most common lasting symptoms are fatigue, shortness of breath, cough, joint pain, and chest pain, but also including cognitive problems, difficulty concentrating, depression, muscle pain, headaches, rapid heartbeat, and intermittent fevers and acroparasthesias. What has become increasingly evident is that there are neuropsychiatric consequences, a form of cognitive impairment colloquially called brain fog. Normally, for many, physicians can note psychiatric symptoms or maybe a post-ICU syndrome, possibly simply deconditioning from severe illness. But I'm convinced it is probably too simplistic and missing a direct effect on the central nervous system. I'm going to diverge with some history. You know, I'm an old neurologist. We had a lot of raconteur type of stuff. Here's one. Dr. Susan Kinsley-Kent is an arts and science professor of distinction in the Department of History at the University of Colorado Boulder. She wrote a book after the original SARS epidemic titled The Influenza Pandemic of 1918-1919, A Brief History with Documents. In an interview in April of last year, April of last year, at the beginning of the current pandemic, she noted that, and I quote, the flu left survivors with a variety of mental symptoms. British writer Carolyn Klain noted the plague of nervous character following the onslaught of influenza, pronounced fatigue, lassitude, depression, sleeplessness, hallucinations, emotional lability, and even dissociation accompanied the physical debilitation of the disease. Remember, we didn't have medicines, we didn't have ICUs then. Indeed, Dr. G. Holliday wrote in the British Medical Journal on August 17th, 1918, that mental symptoms were frequent in the cases he saw. Samuel West informed readers of the Lancet in February of 1919, quote, the depression which follows influenza is so constant that it ought to be regarded as part of the disease, close quote. The medical correspondent of the Times, having contracted the illness himself, advised readers that, quote, the most distressing symptom was a swift loss of mental capacity and then inability to think coherently, period, close quote. In fact, 2000, this is 1919, all forms of hysteria have been observed after influenza reported Thompson and Thompson in 1919, such as hysterical convulsions and the so-called hystereoepileptic attacks. Post-influenzal neurasthenia is very familiar, they noted. Post-influenzal psychosis, this is before workers' comp, for God's sakes, frequently observed and reported. They cited a study that asserted that influenza, of all the infectious diseases, is the most likely to be followed by mental disorder. The Lancet declared in December of 1918 that the higher centers, meaning of the nervous system, suffer chiefly. Marked depression is common, emotional instability is often seen, and suicide is by no means rare. So, what could cause that? Well, let's see. Dr. Gold, if we could get to your take-home points, because we still have to do the vaccine talk. Okay, sorry. Somehow there are a couple of things, and I'm sorry about that. But one of the interesting things is the blood-brain barrier, since the endothelium does have the ACE2 and is damaged, and some evidence suggests that microvascular insults have occurred on follow-up MRIs, which could also lead to more neurodegeneration because the pathology that that creates, or the opening for pathology, may overlap the inflammatory phase. Here's take-home point number one. Post-acute COVID-19 sequelae, they're real. They can be debilitating. We had a psychiatrist, young lady, who was debilitated for nine months, seeing patients while lying on her back, for God's sakes, because of POTS. The cure is preventing the disease in the first place, hence a good motivation to get vaccinated. The incidence of post-acute COVID-19 syndrome does not appear to be directly proportional to the severity of the original illness, although there is some tendency towards that. And however, you remain at risk, even if you have mild or even no symptoms initially. And the final take-home point, the severity, breadth of neurologic symptoms in conjunction with somatic symptoms may require serious and ongoing rehabilitative efforts. This, of course, has implications for mobility, which in and of itself can be affected by one of any number of ailments, respiratory, cardiovascular, endocrine, autonomic failure, and the so-called chronic fatigue syndrome. I am favored, in the last few months, there are two very good summaries and goes into the pathophysiology. Up to date is up to date by last May, May 15th or so. AMA has a good site and JAMA has a good site. Oh, thank you very much. So, Matt, I'm going to quote you now that the only known cure is to prevent a disease. And that's where Dr. Fryhofer, very nice of you to give us a segue why she gets her slides ready and talks about what our current status is and potentially what our future status might be. Dr. Fryhofer, when you're ready, start your screen sharing. I'm not hearing audio. Doctor, if you're on mute, can you unmute your microphone? I am not on mute, but let me double check. Okay, no, we can hear you now. We can hear you Sandra. And now it looks like you are muted, Dr. Fryhofer. Well, I'll tell you why she's getting organized here. Does anybody want to handle a question? There is one question in the chat about, excuse me, in the Q&A about cytokine storm. Does it exist or not in this disease? I sort of took it on faith. I had not heard any debunking of that, but certainly the idea of the worst of the pulmonary episodes are felt to be autoimmune. Yeah, and I think the Lancet looked at some of the outcomes for IL-1 and IL-6 treatments and seemed to show some improvement treating those. Thanks. Dr. Fryhofer, are you okay now? Can you hear me now? Yes. We can now. Okay. All right. So we now have three safe and highly effective COVID vaccines, and there's more great news about real world effectiveness. Okay, something. Are these slides? Okay. Sandra, we can hear you now. Okay. A study of healthcare professionals showed that the mRNA vaccines were 94% effective after two doses and 82% effective after just one dose. A bladed Mother's Day present from FDA expanded Pfizer's vaccine to children 12 to 15 and is sure to increase family social and geographic mobility. Vaccines for infants could arrive as early as this fall. Now two vaccine specific warnings most definitely affect movement. The first is TTS thrombosis with thrombocytopenia syndrome with Janssen's viral vector vaccines and recent reports of myocarditis with mRNA vaccines. Janssen is the pharmaceutical arm of Johnson & Johnson and Janssen's viral vector vaccine has been linked to rare types of blood clots in unusual places in combination with thrombocytopenia. Now this slide shows just how unusual those locations can be. At least 19 of 28 reported cases as of May 7 suffered CVST cerebral venous sinus thrombosis and of those 10 experienced intracerebral hemorrhage definitely a downer for mobility. Now these are not the usual types of blood clots and using heparin to treat them could be harmful. The clinical course is similar to HIT autoimmune heparin induced thrombocytopenia. FDA has amended Janssen's EUA emergency use authorization with the TTS warning and links to the ASH website for TTS treatment recommendations. Women under 50 need to be made aware of this risk and know that TTS has not been seen with mRNA vaccines. Some cases have been reported in men however by age group and gender the reporting rate for females under 50 is highest. And as of May 24 there have been a total of 32 confirmed TTS cases out of more than 10.2 million doses of Janssen vaccine administered. So the risk is there but it's rare and risk from COVID is much higher. Another alert and this is new, be on the lookout for myocarditis after mRNA vaccines. Reports have increased since April mostly in young males 16 and older several days after vaccination, most often after the second vaccine dose. CDC says to check an EKG troponin set rate and CRP if indicated. And here's a summary of the cases presented last week at FDA's advisory committee meeting. ACIP has called a special meeting to discuss this next Friday, June 18. And if you have a patient with anything unusual after COVID vaccination, please send a report to VAERS, CDC's vaccine adverse event reporting system. So how many of you are looking forward to traveling again now that we've been unmasked? Well, we'll come back to mass confusion in just a second. But this is the important question. What's really standing in the way of getting life in geographic movement back to normal? Vaccination, variants, and the need for boosters. When I think of variants, this chilling visual from Game of Thrones comes to mind. Variants are classified in three ways, of interest, those of concern, and those of high consequence. Now, fortunately, there are none of those yet. But right now, there are at least five VOCs, variants of concern, that CDC's watching closely. And these variants may, our concern may be more transmissible. They may cause more severe disease. They may be more resistant to vaccines. Their names are sort of like a bowl of alphabet soup. So I'm going to share how I remember them. The main variant circulating here in the U.S. is B.1.1.7, also called the UK variant. I think, 007, James Bond, British secret agent. Our vaccines work against this one. The next is B.1.3.5.1, the South Africa variant. I think safari and the big five. Both B.1.1.7 and B.1.3.5.1, the South Africa variant, are 50% more transmissible. The South Africa's variant is one of the most resistant to vaccine neutralization. So is the P.1 variant first detected in Japan and Brazil, I think Tokyo, Olympics, P.1 for first place. Now, have any of you ever heard of the B.52s? They're a new wave band formed in Athens, Georgia in 1976. But the B.1.42s are COVID variants first identified in California in February of 2021 and put on the VOC list in March. Variants are wildcards and vaccine researchers understand this. That's why Moderna is already working on a B.1.3.51 specific booster. A new study says Pfizer is 90% effective against the B.1.1.7, but only 75% effective against the B.1.3.5.1. So yes, we'll probably all need a booster. The question is of what and of course when. And boosters will also be discussed next week at ACIP's emergency meeting. WHO has just announced a name changer, a new variant naming system which uses the Greek alphabet, college, fraternity, sorority. The UK's B.1.1.7 is alpha, South Africa's B.1.3.51 is beta, P.1 is gamma, and India's B.1.617 has two letters. The 0.2 version is delta, the 0.1 version is kappa. Now the use of these names will depend on who the audience is. Scientists will likely continue using the numbers, physicians, we're going to have to know both and now you do. WHO is also concerned about the stigma of connecting these different variants with countries. Now as long as people keep getting infected, new variants will appear. It's sort of like the children's game telephone. Every time the message is repeated, it changes. I also worry about variants gone wild when unprotected people get COVID, especially if they have long-sustained viremia, which brings us to mask confusion. Fully vaccinated people no longer need to wear masks outdoors or indoors with some exception. Most unvaccinated people still do, but is the honor system reliable? It looks like Europe won't be trusting the honor code for those who wish to travel there, which brings us to vaccine mandates and digital vaccine credential systems, which some refer to as vaccination passports, Deja vu, BOT report 18, which brings us to herd immunity and barriers, including vaccine uncertainty and hesitancy. We still have much work to do to get everyone vaccinated. Some of the unvaccinated aren't necessarily opposed to vaccination. They might just need a nudge and creative incentives are being offered. Thailand's even giving away people, cows, to get people in the mood to vaccinate. Some people have questions about vaccination, and AMA's joined the COVID Collaborative, which has teamed up with the Ad Council on a new initiative called It's Up to You, and the goal is to answer those questions all in one place. And finally, remember this, physician recommendation is one of the most effective motivators for vaccination. The Band-Aid says it all. We must get vaccine into arms. That's the only way we can end this pandemic and return to a freely mobile society. I do apologize for the technical difficulties, but I'm glad I had a backup, and I have certainly enjoyed being a part of this conference and hearing about post-COVID, and I hope that's something I personally never experienced, and I'm looking forward to research that will help my patients who do have COVID recover. So thank you. Thank you so much, Sandra, and we had a bunch of questions that popped up, and I was going to ask our host, Shannon, would we have a few minutes to answer a few of those questions before we close this webinar? Absolutely. Great. Let's start with some questions, and you've been tracking them there, I believe, Peter. Do you have some that you think maybe we can all speak about? Yes, Anne, but I think most of them have been answered in the chat, actually. Dr. Milani did a great job of handling three or four of them, and Dr. Harris as well answered several. So I think we're good. I don't see any unanswered, except for maybe what useful blood tests to monitor progress in this post-COVID syndrome. Are there any blood tests that are worth doing? Anybody in the panel can answer. You may want to look into endocrinological variants, either adrenal, thyroid, new diabetes, actually. So those things may be in the end organs, but it may reflect pituitary dysfunction as well. Okay, great. I wanted to add one thing about, though, the cardiac rehab question. The young psychiatrist that we had heard talk to from a week ago said that she had gone through for the POTS thing, cardiac, I can't remember the eponym, that was supposed to take four months, and she's still, actually, she hasn't gotten more than four months through a nine-month program so far, because the exercise itself sets her back, number one. And number two is the limiting effects of POTS, despite getting mitogen and other things. So, you know, there's high variability between people, but you've got to use what you've got to use, and there's no magic bullet for this kind of problem. And to follow up on that, Matthew, so trying to stick these patients into an existing multi-disciplinary program that's not COVID-19 focused is probably not going to work. So if you have a big enough population, you really need to think about creating the new program to meet the needs of the patients, that's for sure. And just quickly, thanks, and just quickly, Resolution 410 is going to come up, obviously, I think on Monday or Tuesday, about resources for long COVID-19, so everyone on the presentation, just look at that resolution. It deals exactly what we're talking about today. Thanks. Great. All right. So, go ahead, Peter. I was going to say, there's just one other question, is if you get a booster shot, does it have to come from the same company that you got the initial vaccine from? Well, that's one of the questions that many people are asking, so the ACIP is meeting next Friday to discuss some of these issues, and that might be one that comes up, I hope so. If not then, certainly later. I know there are studies looking at that, and certainly that's what all of us want to know, who will need a booster, when, of what, what variants do we need to cover. Moderna is looking at a booster that contains a half dose of the original strain. They also have another booster that's half of the original strain and half of the B.1.351. They're also looking at a dedicated B.1.351 booster, so lots to learn, and so I don't know yet. One last question. Can I ask one more? Sure. One last question, then, also about vaccines. You talked about vaccines being a good way to prevent post-COVID syndrome by preventing you from getting the disease. What about as a treatment for post-COVID syndrome, there's a question, I've had some patients who experienced relief of symptoms after getting vaccination, so that the post-COVID syndrome got better after they were vaccinated, after having had the disease. I think we're still studying that. I'm not sure that's definitive, but I think we're still studying that. I've seen some information out there that it might help, but that's something we need to find out and maybe look at the timing, but what would be what's most wonderful is to try to prevent COVID in the first place so we don't have to deal with the post-COVID syndrome. Great. Thanks. Well, I want to thank everybody for participating. We actually had more than 100 registrants on this, so we had to turn some people down, so I wanted to make sure you all knew that we have recorded this, and so all of our talks and comments will go into perpetuity. I want to thank Shannon Gignac from the AANS who spent most of her Sunday with us, lucky lady, right? I also want to thank the Mobility Caucus for really seeing that education is a part of what we do at the AMA, and I'm hoping that this will continue to be a tradition for us. I also want to thank all our speakers. I understand you spent a lot of time not just creating the PowerPoints, but then calling them down so that we could get it into just such the essentials. I hope everybody has a great weekend, and that concludes our webinar. I might point out that the CDC is having a webinar this Thursday at, I'm not quite sure where, but it's one of the COCA calls, the Clinical Outreach and Communication Activity on the Subject of Evaluating and Caring for Patients with Post-COVID Conditions, so you might find that of interest as well. That's good. All right, so thank you very much.

educational program

COVID-19

neurological manifestations

rehabilitation considerations

post-COVID-19 syndrome

symptom screening

disadvantaged communities

mental health consequences

vaccine effectiveness

long-term complications

vaccine hesitancy