I want to welcome you. You are in a session that is on Long COVID, specifically called Blueprint to Frame, Follow, and Treat the Neuropsychiatric Aspects of Long COVID. We want to welcome you and thank you for coming. In my role, I am Anita Everett. I work as the director of the Center for Mental Health Services at a federal agency called SAMHSA, which is the lead federal agency in mental health and addiction-related or substance use disorder services. SAMHSA has sponsored this event, which, as you'll learn, is a continuation of some work that we've been doing together with the broader health and human services front on looking at and learning about Long COVID. We need to disclose that I am a past president of the American Psychiatric Association, but I'm not here in that capacity. I'm speaking strictly as a federal employee. So, setting a bit of a context, all of us have been affected by COVID in one way or another over the last three and a half years since it's been among us. Many of us are thinking about, you know, return to the office, not telemedicine, not reconnoitering or reconciling the things that have changed as a result of COVID. For some of us, it's overt. For some of us, it's more of a quiet kind of thing. A few of us, however, have been also have long-term effects that have to do with being post-COVID, a survivor of COVID, I guess you might say itself. So, we all are aware of the grim statistics that we are nearly at a million individuals who've died of COVID. A smaller portion of those than that, and we'll go over some of the details later, have a condition that's referred to as long-COVID, which has many psychiatric, psychological, and other related sequelae that we're learning about. So, we've brought a variety of different aspects of long-COVID to share with you today and hopefully have some opportunity for discussion. I'll go through our run of show, and I'm going to go ahead and introduce our speakers now and in the order in which they'll be speaking. So, first, we have Dr. Jacqueline Becker, who's a licensed clinical neuropsychologist and researcher at the Icahn School of Medicine at Mount Sinai's Division of General Internal Medicine. Her research focuses on the bi-directional impact of cognitive impairment in chronic medical diseases, particularly in underserved and minority populations. Currently, she's leading the effort to assess cognitive functioning through Mount Sinai's post-COVID-19 registry and is a co-investigator of various long-COVID projects, including an NIH component of the NIH-sponsored study or the NIH-supported set of studies called RECOVER, which includes a randomized controlled trial of cognitive rehabilitation, a really important thing that what we might do, in other words, after we've identified the features of long-COVID for patients with long-COVID. She's the co-chair of the International Neuropsychological Society's Neuro-COVID Task Force and is a member of the National Academies of Science, Medicine, and Engineering. And there, she serves on the Committee on Long-Term Health Effects Stemming from COVID-19 and Implications for the Social Security Administration. We first ran into her with the publication, a rather early publication on a cohort of long-COVID individuals that she had tracked and studied early in the game of thinking about long-COVID. Next, we have C.J. McKinney. He's one of our own staff. Dr. McKinney is a public health advisor within SAMHSA's Center for Mental Health Services. There, he provides programmatic support for the Mental Health Block Grant, a series of discretionary grants, and he is our lead on long-COVID behavioral health initiatives. He's a statistician that brings with him over 20 years of experience in the field of public health and cognitive behavioral research, having worked in academic, government, and community behavioral health in independent living settings. And C.J. is going to be discussing a little bit about the role that the federal government played or can play and is planning to play or is underway with regards to addressing long-COVID and, in particular, the neuropsychiatric effects of long-COVID. And then third, we have Dr. Alexander Yountz. She is an attending physician in the Division of Pediatric Infectious Diseases at Children's National Hospital. There, she's an assistant professor of pediatrics at the George Washington University School of Medicine and Health Sciences. She's the director of the Children's National Pediatric Post-COVID Program Clinic for Evaluation and Management of Long-COVID in Children and Adolescents and is active in multiple national collaborative efforts to promote awareness, advocacy, clinical guidance, and research on pediatric long-COVID. We really at SAMHSA, and hopefully all of us, we want to assure that children are not an afterthought in our planning for services. And so Dr. Yountz's experience with the clinic that she started very early after COVID is really gives some insightful information for us to think about with regards to the effect on children. So thank you. And with that, I'll turn over to Dr. Becker. Thank you so much, Dr. Everett. And welcome, everyone. Thank you for having me here. So as Dr. Everett mentioned, I'm Jackie Becker. I'm a clinical neuropsychologist and researcher at the Icahn School of Medicine at Mount Sinai in New York. I'm here to talk to you a little bit about the neuropsychiatric and cognitive sequelae that can persist after COVID-19. So as Dr. Everett mentioned, we all know that while most people do recover from COVID, it's approximated that many patients remain with long-term symptoms. And this condition does go by many names. We've been calling it long-COVID, and that's what we're going to call it for the purpose of the presentation. But just to sort of get on the same page about terminology, I wanted to give a brief understanding of sort of where the names have been coming from. So long-COVID was initially termed by patients, actually, back in 2020, who called themselves long-haulers. And this early recognition by the patient community and their efforts to sort of organize and name the condition is really what alerted the world to start studying it. Eventually, post-COVID conditions was designated the official term for the CDC and World Health Organization, and it covers sort of a wide range of health consequences that are all due to COVID, including the secondary and tertiary effects, as you can see from this nice figure that I added here. PASC later emerged, that stands for post-acute sequelae of SARS-CoV-2, and is sort of a parallel term and is emphasized mostly through the use of the term NIH, and it refers to the direct and indirect consequences of SARS-CoV-2 infection on human health in general. So again, but for the purpose of this presentation, we're just going to use the term long-COVID, which, you know, is more well accepted by patients. And the White House, by the way. So other than terminology, our understanding of long-COVID is actually rather limited, despite it being an ongoing condition for about three years now. And there are still many differences in terms of how it's classified, and that's been one of the reasons, probably, that we don't understand it very well yet. But we do know that long-COVID is a long-term And that's been one of the reasons, probably, that we don't understand it very well yet. So for example, the CDC defines it as a range of physical and mental health consequences that are present for four or more weeks after SARS-CoV-2, whereas the World Health Organization defines it as a continuation or development of new symptoms that last three months after the initial SARS-CoV-2 infection and last for at least two months, and with no other medical explanation, of course. So it's a highly heterogeneous condition with over 200 different symptoms being reported, and it covers multiple organ systems. Certainly, as we know, can impact patients at all levels of functioning and has significant implications for the physical, social, and psychological well-being of these patients. So with all these challenges in mind, across study, the prevalence of long-COVID has been estimated to be about 10 to 30 percent of COVID survivors. That doesn't seem like a lot, but given the scale of COVID, it actually translates to somewhere about between 7.7 to 23 million people in the U.S. alone. It's presumed most likely in middle-aged adults, and studies have found that it can occur in individuals who were previously healthy with no pre-existing conditions, regardless of COVID severity, though it may also be more pronounced in individuals with severe COVID. Individuals presumed infected with any and all variants are still susceptible. We are still seeing that individuals infected around the Omicron era are still ending up with long-COVID, and there's some data, mostly out of the U.K. so far, that vaccination may decrease the risk of long-COVID, but, you know, it's a little bit unclear why that is, and it may be because, you know, it prevents severe COVID from happening. And among the most commonly reported symptoms is the sort of gradient of cognitive and neuropsychiatric sequela, and brain fog is actually the term that has been described by patients, mostly to describe some of the cognitive symptoms that they experience post-COVID. So, anecdotally, brain fog is described by patients as problems with attention, concentration, some people say it's confusion, forgetting words for common objects, and general forgetfulness, but the data actually suggests that deficits tend to be most pronounced in executive functioning and is more frontal striatal in nature. Attention and processing speed is also impacted. Most patients report that they have good days and bad days, so these symptoms do tend to fluctuate, which is unlike some of the conditions, the other conditions that cause cognitive impairment, like neurodegenerative disorders, for example. Functioning also varies. Some patients are able to function but find it more effortful, whereas others, you know, have trouble doing even the most basic tasks. Various hypotheses exist to explain the underlying mechanisms, and they're still unclear as of yet, but among them is direct injury to the central nervous system through viral invasion or potentially hypoxia for those with severe COVID. Stroke is another potential direct mechanism, but indirect factors have also been hypothesized, like immune dysregulation, chronic inflammation, vascular dysfunction, and many others, but the truth is that it's likely multifactorial in some way, and it likely differs patient to patient, particularly depending on COVID severity. So just to give you a sense of what brain fog may look like, this is an email I received from a patient who was looking to participate in some of our studies at Sinai, and this is a very common sort of story that we hear. So he says, I'm a 44-year-old man, usually healthy. I'm a software developer in my occupation and recently was kicked off a job due to my degraded performance. My story starts something like nine to ten months ago when I got sick by COVID. I stayed home but was able to still work during the sickness, very similar to the flu I experienced in the past. After I recovered, my life was not the same any longer in terms of how well I was. My brain was like in the cloud, like always in some kind of denial. My thoughts were and are clouded, and I cannot change it in any way. I could not focus enough even to solve some of the simplest tasks, and sometimes it effectively changed my own ability to deal with missions and tasks at work. I was working with complex and sometimes less complex code parts at work, and it is impossible to deal with it now. Deep in my heart, I know and feel what happened to me. Please advise me if there's any way I can recover and get my mind back. So again, this is a story that we hear quite frequently, where it was someone who was previously functioning pretty well, had mild COVID, was middle-aged, and now, you know, is having significant difficulty with occupational functioning and other kinds of activities. So with respect to prevalence of cognitive impairment, studies have reported a very wide range, so about eight to eighty percent of patients who have had COVID having brain fog. So part of the reason for this wide range is other challenges with the research in general. Most studies have relied on suboptimal measurement of cognition, so for example, relying on dementia screeners, which have been shown to be inappropriate and insensitive to detect the impairment in this population. Other studies have used online tools, which are problematic for obvious reasons, and even characterizing cognitive functioning using subjective reports from patients, which is tricky because we know from COVID and other populations that the subjective impairment often does not align with our objective measures. Many studies have also had very small sample sizes, particularly the ones early on in the pandemic, and you know, some will lump patients regardless of COVID severity, while others separate them and then study them exclusively. So early on in the pandemic, we saw almost exclusive studies of just hospitalized patients. There's a little bit of a wider range now, but even how we characterize COVID severity has been challenging. Selection bias has also been a big issue, where data is collected specifically from patients seeking help for cognitive or psychiatric issues. And finally, several studies have neglected to include appropriate comparison group. It's a challenge at this point in the pandemic to understand what an appropriate control group would even be, because the majority of the population has had COVID at one point or another, but there needs to be some sort of consensus on what the most adequate comparison group would be. So using the data from the Mount Sinai post-COVID registry, my colleagues and I published on the frequency of cognitive impairment in a cohort of 740 post-COVID patients. The mean age of our sample was 49, and we found that even about eight months post-COVID diagnosis, about a quarter of our relatively young cohort had objective cognitive impairment in at least one cognitive domain, and we used validated neuropsychological measures, all of which were administered in person beginning April 2020. So here's a quick graph of our findings, which as you can see pretty clearly shows that those treated in inpatient settings, which are the darker turquoise color, had the greatest frequency of impairment in comparison to those treated in the ED or those treated in the outpatient setting. It's not particularly surprising that we found this, given that what we know from acute respiratory distress syndrome, for example, or even post-ICU syndrome, that patients who are treated in these intensive care settings have residual cognitive impairment. What was surprising, however, was that we found such a high frequency of impairment in such young patients and after so many months after having had COVID. And consistent with the literature, the pattern of impairment looked more like aspects of executive functioning and processing speed. Just to turn your attention here for a second to the memory retention, memory retention is clearly a very smaller proportion of the population from our cohort that was impaired in comparison to the immediate and delayed memory. So that suggests that it's not hippocampal functioning here that is impacted, but rather that frontal striatal pattern that I mentioned earlier. And now this is still in press, but I wanted to just quickly show some more recent findings of what we just published. So we looked at COVID patients in comparison to non-infected controls. We were fortunate enough to have gotten these controls very early on in the pandemic. And so, you know, what we found actually is that only executive functioning was significantly greater in patients post-COVID versus controls. And again, this is after controlling for, you know, depression, fatigue, and other potentially confounding factors. So, you know, that being said, it is still striking that even in patients with no history of COVID, we are seeing a higher than expected frequency of cognitive impairment. So you might ask why is this, right? Why are we seeing that only in executive functioning are COVID patients significantly worse? But why are, you know, patients who did not have COVID scoring so poorly on some of these measures? And so I think, you know, it's possible, there are a lot of possibilities, a lot of hypotheses, but I think, you know, one possibility is we did recruit from a lot of primary care clinics. So this might be a population with a lot more comorbidities in general, and that's what's impacting brain health. Another potential explanation though is that the pandemic itself has impacted brain health in some indirect way. And with this in mind, that's not entirely surprising either, right? Considering what we know about social determinants of health and how that can impact cognitive and mental health in general. And in the context of the global pandemic, with the implementation of widespread social restrictions also came a lot of loss for a lot of patients of important resources. People lost a lot of jobs, there was inadequate health care access, lack of companionship and low social support, which, you know, again, we all know has a tremendous impact and is actually a protective factor against cognitive decline. So in just the first years of the pandemic, the World Health Organization actually reported that there was a 25% increase in anxiety and depression in the general population. And most of this has actually persisted even with the reduction of these restrictions now. There are also, of course, several populations that have been disproportionately impacted by the social factors of the pandemic. We know that minoritized populations experienced higher rates of infection, hospitalization and casualties throughout the pandemic, which, you know, the pandemic itself has unveiled a lot of deep-seated inequities in health care in general and magnified a lot of the sociocultural and economic factors that contribute to poor health outcomes. And so, you know, because of the differential rates of vaccination, access to care, baseline comorbidities, socioeconomic status and even viral exposure, you know, some studies are beginning to show that minoritized populations may have different odds as well of developing long COVID. In addition to social determinants, we know that psychiatric disorders and cognitive impairment in general have complex and likely bi-directional relationships. We know that depression can contribute to cognitive impairment and that cognitive impairment is also considered a core symptom of depression. And likewise, impaired cognition can decrease one's ability to function and this can contribute to and exacerbate existing mental health conditions. So, in this context of the global pandemic, this relationship obviously became even more complicated with all of those other factors that I mentioned. A systematic review actually found that six months after COVID, about 56, so over half of the survivors, had cognitive impairment and at least one psychiatric disorder. Together, these factors may contribute to and have differential impact on individuals who are infected with SARS-CoV-2 and contribute to the overall long COVID picture. And so, in management of these conditions, we do need to occasionally consider one other possibility, which is that of somatic symptom disorder. I think we can expect to see it at least at the same rate that we've seen it in the general population and given the overall context of the pandemic, perhaps even a little bit higher. But the literature is still very mixed in this regard. And some samples have found that psychological symptoms were strong drivers of cognitive performance, while others have actually found no relationship between psychological factors and cognitive impairment. So of course, there are significant functional implications to everything I just mentioned here. Fortunately, long COVID is now considered a disability under the Americans with Disabilities Act. It's very important to consider accommodations and for individuals who are struggling to function who have long COVID. But it's also important for those of you who will be evaluating these cases to know what sort of the criteria is currently to assess, to evaluate a patient and submit a report for the Social Security Administration. So the Social Security Administration considers severe impairment, meaning it substantially limits one or more life activities and it has to occur for a continuous period of not less than 12 months. And the patient must be unable to do past work or any other work that exists in the national economy. So that means it's not just returning to your previous job, it means that the person is disabled to the degree where they cannot do any job in the national economy. One study out of China found that 12% of patients did not return to original work by 12 months, those who had long COVID. But given the scale of the pandemic, if you consider even 1% disability at one year, that has a tremendous, tremendous impact. So again, for those of you who will be completing social security disability applications, when the Social Security Administration evaluates a claim, there needs to be one, sufficient evidence of impairment. Two, you need to assess the degree of functional limitation that the impairment imposes, again, speaking to their ability to work. And three, and this is a tricky one, you have to be able to project the probable duration of the impairment. And some of you may wonder, well, how do I do that if COVID only exists for three years and we still don't really know what long COVID is? The short answer of that is that we need to extrapolate from other parallel conditions and consider the patient's pre-morbid functioning, meaning the way that they were functioning before having been diagnosed with long COVID, and sort of just give your best projection of how they will do in the next coming years. So with all this in mind, we have to turn our attention to how we can best support long COVID recovery. And I think that among the highest priority is addressing the stigma that patients with long COVID are facing. Certainly not knowing the etiology or mechanisms underlying long COVID perpetuates stigma, but I think it's also likely that because mental health disorders represent one aspect of the multifaceted nature of long COVID, it has been dismissed as a psychosomatic condition or psychological condition. I think everyone in this room, at least hopefully, can recognize that besides being contrary to scientific evidence, that this dismissal can be really harmful to patients with long COVID and can really impact their ability to seek care. That said, it's nonetheless important for clinicians to triage patients and attempt to rule out potentially other causes and treat other perhaps underlying conditions contributing to their cognitive and mental health issues. So before a referral to neuropsychology, for example, it's ideal for patients to have already started treatment for mental health disorders, to have treated sleep issues, like sleep apnea, for example, to do labs to rule out hypothyroidism and other issues so that we can make adequate treatment recommendations. One more thing to think about, which I already mentioned, is that of somatic symptom disorder. And while it's possible in general that some patients with long COVID will be found to have more somaticizing tendencies, I think we need to also consider what the baseline is now because since the beginning of the pandemic, people in general have become a little bit more preoccupied with their health and illness and interpretation of, for example, an elevated MMPI scale or performance validity measures. We need to think a little bit about what the new norm for that is. So to that end, managing the patients with long COVID will require a multidisciplinary effort. I have no doubt that primary care physicians will often be the gatekeepers in this regard, who they will be the ones referring to psychiatry and neurology and neuropsychology. But it's important that the communication continue through these multidisciplinary professionals so that patients don't get lost in the system. Given the potential chronicity of long COVID and the fact that we don't know yet if these patients will develop neurodegenerative diseases, for example, we need to make a plan and implement strategies for managing them long-term, not just at the clinician level, but at the system level. And finally, studies are underway to determine the best interventions for this population. Currently, as Dr. Everett mentioned, we have a few cognitive rehabilitation studies at Sinai that we're hoping will have some promise. But research is still trying to figure out the best options for treatment. So in terms of recommendations for research, we're just at the beginning stages of this, but researchers have finally started clustering patients with long COVID through phenotyping, rather than just lumping every patient into a single long COVID box. It's also important to consider COVID severity when thinking of the pathophysiology, since again, the causes of impairment in some people treated in higher levels of care will likely be very different from that of people with mild COVID. As always, rigorous assessment of cognitive and psychiatric symptoms is really critical, as is improving sample and minimizing bias. And finally, an important component of correcting systemic problems that contributes to the health inequities I alluded to earlier, is to ensure inclusivity in all aspects of the pursuit of science by not only conducting studies in health disparate populations, but also by identifying mechanisms that affect health outcomes in these populations, like social determinants of health. So with that, thank you so much for having me here today. So hi, I'm CJ McKinney. As I said, I'm a public health advisor with the Centers for Mental Health Services within SAMHSA. And what I'm here to chat with you about today is the federal response to long COVID-related behavioral health disorders. In our discussion of how the federal government is responding, we're looking at the impacts in two different ways. There's the actual impact from the infection themselves. Dr. Becker gave a great overview of a lot of the symptoms, brain fog, short-term memory impairment, and so forth, that go along with a COVID-19 infection. But we also do recognize that there are symptoms arising from just the quarantine themselves and the overall pandemic environment. And there's a lot of stressors that seem to be coming from this, such as social isolation, bereavement, contamination, fear, and survivor's guilt. What we've been seeing across the population is an increase in depression and anxiety, substance uses, and suicide rates. What we've also been finding is that these stressors are getting further exacerbated by other stressors that are coinciding with the pandemic, such as limited access to healthcare, domestic civil unrest, and even international unrest that is occurring, and affecting economic and other social factors. In the overall response, there were two reports that were requested underneath a presidential memorandum that was issued by President Biden on April 5th of 2022. So we're a year into, or a little over a year, into really studying and trying to tackle this problem. The two reports that were required at the time were a National Research Action Plan, and the services and supports for the longer-term impacts of COVID-19, and what we could provide. The National Research Action Plan, in and of itself, summarized key efforts that were currently underway, and made recommendations for future efforts. The focuses of the research that's being looked into was characterizing the full clinical spectrum of long COVID and diagnostic strategies, the underlying pathophysiology, epidemiology and surveillance, long COVID and overall well-being, therapeutics and other health interventions, along with human services supports and interventions. All of these research endeavors were placed underneath the Health and Human Services Office of Long COVID Research and Practice, which is led by our Assistant Secretary of Health, Admiral Rachel Levine. And they continue to coordinate care across multiple agencies within the federal government, looking at long COVID and COVID-19 in a variety of methods. The services and supports report summarized the known effects and what was currently happening with COVID and long COVID. At the time of the report, there were 86.6 million confirmed infections. Now it's a little over 104 million. There were over 1 million deaths related to COVID-19. And that is now over 1.1 million. What we've also found is that ethnic and racial minority populations have increased rates of deaths, severe illness and mental health disorders as related to these infections. Older adults have the strongest risk factors for death and severe illness. And that's becoming a very specialty topic in numerous work groups that I've seen. And then persons with disabilities also have a heightened risk for infection and severe illness and death related to COVID-19 infections. The areas of focus that were pointed out for these service provisions were really to decrease disparities in treatment and diagnosis, understand better the effects of bereavement in regards to our overall research, really provide more services in mental health and substance use and look at long COVID related disabilities. So like the social security administration have discussed has now defined long COVID as a disability as long as it meets certain criterias among other items that have been looked at. Across all of the federal services, we're really finding that there were 10 common areas of needs, rights, healthcare coverage and access, community service and supports, income and financial assistance, job assistance, housing, food and nutrition, pretty much all of our social determinants of health and environmental factors that really affect overall quality health outcomes. And because of this, there's been a heightened look at how we can increase federal funding and federal services towards all of these areas and where more assistance can be found. So before we move in, so what I'll talk about next, that's kind of the general overview of what we've been doing. And I'm gonna actually talk about what our centers for mental health services has been working on in our contributions specifically to these areas of getting more mental health services and appropriate mental health services out into the community. So one of the first things that we did in response to these overall efforts was to convene a panel of long COVID subject matter experts. They had a focus on primary care, neuropsychology, psych rehab, psychiatry and clinical psychology. The panel also included persons with lived experience and we will always continue to include as many persons with lived experience into our panels because it's important to really have that perspective. As part of this, we commissioned a report on the current state of long COVID related mental health symptoms, epidemiology and so forth that were called the impacts of long COVID on behavioral health overview. This was actually developed by our own Dr. Becker who has been coordinating and working with CMHS for pretty much since the presidential memorandum to move these forward and has continued her work. In fact, as usual, we just published this overview and it's already a year out of date. So we'll probably have to get a new overview set up here before too long. The discussions for this panel focused on COVID mental health symptoms, diagnosis and assessment, clinical recommendations and future areas of focus. Just to end up showing we had a variety of people, you should recognize a couple of our panelists, our board members of this subject matter expert panel. But we tried to get as wide variety as possible from numerous universities, practice settings and so forth. One of the key things, like I said, that came out of this was one, a literature review on the behavioral health disorders associated with long COVID. This is available in the SAMHSA publication store at this time and can actually be downloaded if you would like to review it. What overall we found from the panelists was long COVID has a very diffuse symptoms across all body symptoms. So this is very hard to just pin down and say, here are your definitive symptomologies. The evaluation is very complex and the shortest assessments that are neuropsych and psych rehabilitation experts could really come up with at least a 12 minute assessment. And this was not practical for the primary care physicians that were a part of our panel as that is just way too long. That means out of most of their appointments, they might get three minutes to talk about treatment options with regards to it after they've gotten through, and that's assuming they've gotten through the assessment that quickly. We also need more emphasis on underserved and disadvantaged populations. We're really talking about rural and urban minority, urban populations and minority populations across the United States. And we need more controlled research. And as you've seen from Dr. Becker's paper, I mean, presentations earlier, she emphasized, yes, that research has been started, but we still have much farther to go and really understanding specific symptoms and outcomes. And it could be a little while before we finally get that, you know, key identifier for that this is long COVID related behavioral health issues. One of the other things that CMH did is we actually had a intern. We have lots of interns. If you have people that like to do internships, I advise you to have them apply when they come on. But Ms. Johannes had done quite a great job of going across all of our professional societies, treatment clinics, and looking at what their overall treatment and diagnosis and related symptoms were. And from that, we had done some little magic with systematic analysis and created this nice little overview. And really what there seems to be is kind of a nesting. A lot of the focus has been on that intern nesting, which is behavioral health diagnosis and treatment, physical health diagnosis and treatment, case management, family and social. But one of the key things that was coming out is that, you know, it's being really emphasized that psychologists, physicians, psychiatrists have a shared responsibility for treatment of long COVID. This is a mixture of symptoms. And that really, no matter how you approach it, it should be taken with a trauma-informed approach. The pandemic was traumatic on people. It created overall stresses, traumas, and otherwise. And so the treatment of long COVID really should take on a trauma-informed services pattern. Outside of this, we see just the generalized treatment approaches. It should be a holistic approach, as we said, culturally competent services, anti-stigma and anti-discrimination based services, community-based is becoming more and more important to really get these services we need to be able to get out into the communities themselves. And expansion of peer support. We're finding peers can be just as effective with a lot of the therapeutic needs of our clients, of their clients, as case managers, other behavioral health specialists, and so forth. Outside of this is the general support systems. And honestly, this is where we need to go and explore a lot more in what we'll be doing within the Centers for Mental Health Services is how can state government, school systems, communities, and local governments, and federal agencies all work together to provide these supports for these treatment approaches and direct treatment methods. And so this moves into us moving forward. We need to continue to identify COVID-related needs and provide grants that support mental health, case management, crisis services. Our own mental health block grants have actually become part of this. Extra funding was put forth to address COVID-19 and even some of these long COVID efforts. There was, due to the COVID-19 pandemic and the sudden increase in need for mental health services, Congress also authorized these Centers for Mental Health, um, sorry, Community Mental Health Centers grant program. I'm getting myself all tongue-tied up here. I'm embarrassing my bosses, bosses, boss, so. Um, uh, so, um, but that put out a large sum of funding that allowed various agencies to get up to basically $2.5 million a year to support and expand their mental health services, and especially for those who didn't have other sources available. So we're continuing to try to promote and support these through the grants while also lobbying up the line to the President and to Congress to really put more funding towards this. You know, and so we'll continue to make those overall efforts. We need to provide education and resources to mental health providers. This is one of the things that we're trying to get more and more information that's out there. One of the publications that will be coming out, I'm hoping by the end of June, is from our Evidence-Based Resource Center, and they have a set of guidelines for overall treatment, various diagnostic techniques. It's kind of everything that's available at this point for very specific treatment, diagnosis, and testing for long COVID-related items, and that's currently being finished up in the overall review process. Identifying key gaps and expanding research, of course, should always continue to be one of the big projects. Doing this is the NIH Recover Project, and they are coordinating a lot of efforts, as pointed out, the NIMH and CDC and even like ACR, Administration for Community Living, is all being part of these research that's coming underneath NIH. And as I said, since we're more of a services-directed center within the federal government, we have been focusing on really our own long-term workgroups within SAMHSA to really address those service needs. We're also convening another SME panel to kind of help expand further on some of these things that were addressed, and to develop further guidelines and recommendations, specifically for rural and underserved populations. So we've been recruiting that panel together, it will be meeting in June, and we do hope to have a proceeding that comes out of that, that will hopefully elaborate more on services that are available, and how to best address and get this information out to these populations in need. Always like to end with obtaining help. There's a huge number of resources that are out there. If you know of people that need help, if you yourself can't provide it, there are numerous ways. And just to end up pointing out, the 988 services has been wonderful, I've been seeing a lot of reports on this lately. Really spread that around for people who are in imminent crisis, 988 can be a lifesaver. All right, well, thank you, and I will hand it over to Dr. Youngs. All right, I just first want to start off with thanking CJ and SAMHSA and all of my co-panelists for putting together this group, for inviting me as a pediatrician to the table as children are so often overlooked in a lot of these massive issues and in a pandemic. So if you forgive me a little bit, the beginning parts of my talk is going to be focused on, yes, COVID does exist in children. And then I'll move on to what we're starting to do about it in the clinical venue. As a quick disclosure, I am a principal investigator for the Pfizer mRNA COVID vaccine clinical trials, and my institution receives funding to support those trials. So as I mentioned, COVID and long COVID in pediatrics is a thing. In terms of the impact of this, so children under 18, there have been over 15 million cases of COVID-19 diagnosed, which makes up approximately 18% of the total cases. A little over 2,000 children have died from COVID-19. And there are other sequelae beyond long COVID. Many of you may have heard of multisystem inflammatory syndrome in children, which is sort of a mid-range post-COVID condition. And there have been almost 10,000 cases of this and almost 100 deaths as well. So while thankfully this is a small proportion of the population, it's certainly not nothing. And launching into long COVID, there have been numerous studies since the beginning of the pandemic, some of the earliest of which took place in Europe, doing survey studies of families of children with COVID. And more recently, there have been several more robust studies, including a meta-analysis published last year, and several comparative studies looking at children that were COVID-positive, presenting for symptoms at the emergency department compared to those that were COVID-negative, and as well as those COVID-positive in an EHR cohort compared to those that were negative. There's still a wide range, a point estimate for prevalence in this population, but it seems to be somewhere in between the range of 2% to 25% of those, depending on your definition of long COVID, as Dr. Becker mentioned earlier on. I think this is important to highlight because, as mentioned, there are numerous effects of the pandemic itself, and certain percentage of the population, including children, are affected. But there is a differential of 2% to 5% in this ED-based cohort and the EHR cohort that were noted of those with COVID history or positivity at the time of presentation. So those symptoms are more prevalent in this population, suggesting there is a true effect from COVID beyond the pandemic itself. And as I mentioned, even that lowest number of that estimate, that 2%, is still 300,000 children in the United States affected by long COVID. So I am a clinician. I am a pediatric infectious disease doctor, and I am the director of our post-COVID program clinic at Children's National. We've been open since May of 2021. We are a multidisciplinary clinic serving children and adolescents up to age 21 that have a positive COVID test in greater than 12 weeks since infection with some ongoing symptoms and prolonged inhibitions of function, I will say. As a brief sort of overview of what we've seen in our clinic, we've seen 194 new patients as of this Wednesday, and we are currently still booking new patients, even though COVID is over, into September of 2023. So the Omicron wave and subsequent infections have continued to happen, and we see more and more children presenting with these symptoms. Of our cohort, the average age is 13, but we've seen kids as young as 2 and as old as 20 presenting with symptoms following COVID. There's a slight female predominance, and while most of our patients are from the District Maryland Virginia, or DMV, area, we've seen patients from all over the country. There are maybe a dozen to two dozen, somewhere in that range, of pediatric-specific long COVID clinics in the country. So we get a lot of referrals. They all have long wait lists, so some shopping as well from patients all over the country. I really would like to touch on the demographic section of our clinic, only to say that the vast majority of the patients and families that present to our clinic are Caucasian, and this is disproportionate to the population in the D.C. area. We have a much higher population of Hispanic and Latinx ethnic population, as well as black And so we suspect that there is some disparity, lack of access, lack of medical literacy leading to this uneven presentation to our clinic. So another area of health care disparities that needs to be further researched and access that needs to be improved for our patients and their families. So how does long COVID present in children and adolescents? And this slide features several of our patients who have been brave enough to share their stories and their experiences with the media and various different venues, and also advocate in front of Senator Tim Kaine in his Best Practices for Long COVID Treatment Summit that's resulted in a large RFA for funding for clinical care of long COVID. So in our patient population, it's similar to what was described in previous talks. Fatigue is, by and large, the most common presenting symptom. 85% of our patients present with complaints of fatigue, followed by some other more nonspecific symptoms, headache, decreased appetite, post-exertional malaise or decreased exercise tolerance, which I'll touch on a little bit more later, brain fog or cognitive dysfunction, and abdominal pain. So this is all very similar to the adult population. Although I would like to highlight in pediatric patients, they have more frequent GI symptoms at presentation than the adults do, being comprised of decreased appetite, nausea, and abdominal pain, and rarely do they present with respiratory symptoms. And much of this is due to the general more mild case and lack of COVID pneumonia and other severe respiratory illness in children, which are thought to be some of the direct sequelae led to the pulmonary symptoms in long COVID. Briefly, I would like to highlight the WHO put out a large report in February of this year, doing a meta-analysis of studies to help inform a consensus definition of pediatric long COVID. From this report and looking at studies, they were able to identify a handful of symptoms that present above the rate of the control population and are strongly identified with long COVID or post-COVID conditions, as was defined in the report. And in this study, they identified altered smell or anosmia, anxiety, fatigue, and headache as the four sort of most common presenting symptoms, with lower percentages of other but also common presenting symptoms. This was looked at in the three-month window and two-month duration. So this is a little bit more heterogeneous group than have been described in past meta-analyses. So going forth from that, the sort of classic, what I call syndromic pediatric long COVID definition, based on what the WHO has reported, includes fatigue as a core presenting symptom, followed by anxiety and exercise intolerance or post-exertional malaise, plus a variety of other symptoms, but frequently chest pain, cognitive difficulties, dizziness, stomach ache, loss of appetite, and postural symptoms. Since this is a psychiatric conference, the rest of my talk will be focused on neuropsychiatric symptoms. Most of this is rehashing what's already been discussed, but I wanted to highlight a few things around the anxiety component of long COVID in children. A lot of this relates to anxiety about reinfection, about re-experiencing of symptoms, almost in a PTSD sort of presentation. And then neurocognitive symptoms really have fallen into a clear pattern for our patients anecdotally, with struggles with memory, struggles with word finding, and struggles with attention. And these are in patients both with pre-existing neurocognitive difficulties and who have previous neuro-normative or normal function. We have certainly seen a fair number of exacerbations of pre-existing neurocognitive conditions, a fair number of exacerbations of pre-existing mental health conditions. So many of the patients in our clinic have anxiety or depression at baseline, and this has gotten much worse since their COVID infection. And a significant impact from all of these factors, as well as the physical symptoms, on school, on peer relationships, and on extracurricular activities. And all of this is in the setting of these children being a part of a family, part of a school, part of a community. Are we looking at a child that's missing school, missing participation in religious organizations? We're seeing a parent who has to stay home with that child who is now missing work. We are seeing loss of those developmental and social building critical time frames for this population. So I think this is something that's undervalued because the children don't contribute to the workforce, but their parents do. So something that we need to look into a little bit more. This just rehashes, again, some of the research that's been done on neuropsychiatric presentations in children, emphasizing about 17% present with mood symptoms and a large amount of impact on functioning. So this German cohort looking at long COVID patients, I think it was important to highlight that a little over 50% of those were unable to attend school full time. And so that is a major impact on caregivers and on their educational status. At Children's in our clinic, and I'll speak on this a little bit further, we use the Promise screener to assess both parent assessment and self-report of children of appropriate ages of their functioning in several different domains. You can see generally parents and kids are pretty in sync, but there is about 50% of those reporting physical functioning, mobility impacts, anxiety, and luckily lower levels of reporting peer relationship dysfunction. So initial takeaways about pediatric long COVID. Some children present with pre-pandemic or pre-COVID psychosocial concerns, including ADHD, learning disorders, and anxiety, but many are amplified or present de novo. And a lot of that is disruptive. So evaluation. Don't worry, I'm not going to go through this table, but this is a snapshot from a review article that my colleagues and I published regarding treatment and evaluation of long COVID, and it really captures the multidisciplinary nature of this disease. So you can see there's about a dozen different subspecialties listed here with different evaluations and management strategies that need to be done to address the symptoms in these different areas for these patients. There is some guidance, and luckily over the past two years, we've been getting better and better guidance from large national institutions. Initially, the CDC came up with some very vague but useful guidance emphasizing the need for stepwise multidisciplinary workup involving shared decision making and goal setting with the families to return to function. But luckily since then, we've had quite a bit of development of guidance statements from the American Academy of Physical Medicine and Rehabilitation. They have sort of issue by issue been issuing statements. They now have a guidance document for cardiovascular symptoms, breathing discomfort, cognitive symptoms, pediatric management in general, and they just recently released a new document around neurologic symptoms. So these are very comprehensive, wonderful documents, and I encourage all to read at your leisure. And as mentioned, additional reviews being published in the pediatric literature talking about this issue. Our clinic, as I mentioned, is multidisciplinary. I wanted to give you a snapshot about what that means. So every single one of our patients is seen by the core physicians, which include infectious diseases, myself as sort of the quarterback for the visit, physical medicine and rehabilitation and psychology. And we've also added more recently hematology to that core for a potential pathophysiologic mechanism of microclots and endovascular dysfunction that's been reported in the literature. So testing in some of our more severely affected patients has become the norm. And then additional subspecialties are included in our clinic, such as gastroenterology or with a expedited referral process to neurology, pulmonology, cardiology, and pain medicine. I will skip through this, but this is our workflow, which is very stepwise and coordinated. So for our clinic, and I give a lot of credit to Dr. Linda Herbert, who's our clinic psychologist, as well as to the PM&R guidance document on pediatric evaluation. But when performing mental health and psychiatric assessment in our clinic, one of the most important things is not only to review all of the comorbidities, prior mental health symptoms, but really the timeline of development of new symptoms. So many of these kids are coming in with, you know, within a month or two of their COVID diagnosis, developing cognitive dysfunction or psychiatric symptoms and other physical symptoms. But we also see a fair number of kids who've had pre-existing problems that sort of have made it through our screening process, as there is a underserved population and those with chronic fatigue syndrome and myalgic encephalomyelitis that are looking for a place to go. That are looking for a place to be seen. So they often make our way into our long COVID clinic and end up getting sorted out as we see them. So really that timeframe is important. And we use, again, as I mentioned, the PROMIS pediatric item bank for children 5 to 17 and parent proxy to get at the domains and impact on functioning. For those of you that aren't as familiar with PROMIS, as I mentioned, for parents of children 5 to 17, they fill out their proxy form. And for children 8 and older, they are able to fill out their self-report score. This generates T-scores with clinical cut points and allowed to be interpreted compared to norms. This is something that we've started emailing to families ahead of time so that they can be discussed in real time in their multidisciplinary clinic visit. And then in the clinic, during the consultation interview, a lot of the focus with these children are their functioning both pre-pandemic and pre-COVID-19 diagnosis to now and how school was. How were their grades? How was their social functioning at school? How were their social relationships? What's sleep appetite like? And did they have any prior mental health diagnoses or treatment? And looking at that delta has really been the most powerful thing that we've experienced. So many kids that we've seen, especially in early times, were super high functioning, you know, straight A, honor roll, have an athletic scholarship to a Division I college who then got COVID and suddenly can't leave the house. So that those are kids that maybe won't be picked up on traditional cognitive functioning skill sets because they are still very high functioning, but the delta from where they used to be able to rattle off, you know, major math equations and things now to not being able to do that, but still function at a society norm is what we see, which is frustrating. We know these kids have the potential to do so well, but they're not being able to meet that potential. Other screeners that may be employed in clinic for anxiety, depression, PTSD, and cognitive dysfunction, in particular ADHD with use of the Vanderbilt scales are used as needed, depending on our evaluation and reviewed at follow-up. So management, I highlight this to say a couple of things. So there is no single treatment for long COVID currently. As has been mentioned in previous talks, there's still a lot of research evolving. There have been numerous very good studies looking at multiple pathophysiologic processes, including persistent viral reservoirs, autoimmune antibody development, microclots and endovascular dysfunction, but how these work together and in what combination in which patients is what remains to be seen. So a lot of what we do in our clinic focuses on managing symptoms as they come up with starting to dabble into treatment for some of these abnormalities identified in sort of novel lab testing. This is a picture of one of our patients who actually wrote a book about his experience with long COVID. And this was a very important way for him to help cope with what he was going through and to share his experience. And he is a very altruistic and enthusiastic young man. So his book is called The King of the Basement, referring to when he was quarantined to the basement during his initial COVID infection when his family got to stay upstairs. I won't go through this slide. This is a litany of our current management approaches in clinic, but I'd like to highlight the top, which is rest. So this is important for anyone dealing with a new COVID infection or a reinfection is that rest, both cognitive and physical, is a key step. The pushing to go back to work, the pushing to go back to school, the just work through it approach is detrimental. We've seen that time and time again. And now, you know, every single one of my patients, when they leave the clinic, I say, if you get reinfected, you need to sit out of school, you need to sit in a room, do nothing for a week. And this is very similar to sort of the recovery of concussion management strategies that have been used historically. And anecdotally, I've heard good reports from my patients about this helping prevent as severe of symptoms after infection, but many still have some worsening of their symptoms. I think this is important because there has long been a conversation, both in this population and the chronic fatigue, myalgic encephalomyelitis, and other post-viral syndromes about graded exercise therapy and physical therapy as a means to rebuild stamina. But for many of these patients, that's actually more harmful. Those that have post-exertional malaise or post-exertional symptom exacerbation, meaning one day they go to school and then the next two days they're unable to get out of bed, those are not candidates for pushing through with physical exercise therapy until they can get their underlying symptoms managed, which is something that a lot of community physical therapists and other, even counselors and therapists, are not really cognizant of. So you wanna make sure you're sending your patients to the right people that are sort of attuned to this problem. So touching on that, specific management strategies that we employ and emphasize with our patients for fatigue, we really talk about energy conservation. So, so many of our patients describe this push and crash cycle, which is really highlighting that post-exertional malaise symptomatology. And especially in kids, one of the greatest parts about being in pediatrics is that kids are resilient. And the second they're feeling a little better, wanna run around and play and do everything they do normally, well, this is somewhat counterproductive in this population. So they end up playing in their soccer game because they're feeling a little bit better and then not being able to go to school the next two days. So we really talk about avoiding that. So trying to minimize, maybe go sit on the sidelines at your soccer game and see how you do instead of jumping right in and playing a full 90 minutes. Prioritizing, so decide which activities need to be done. So one week you have a test, so you need to save your energy for school. The next week, perhaps you get to go play with your friends because you don't have a test coming up. Positioning, so modifying activities to make them easier to perform when possible. And then planning, which sort of goes along with the prioritizing. So if you have a particularly taxing event, maybe schedule it for a Friday so you have the weekend to recover. Similar strategies are applicable to cognitive dysfunction and return to cognitive activity. So scheduling rest periods, planning when you're gonna do homework versus when you're going to take tests in school and working with the school to develop these accommodations and strategies. 504 plans, which are medical accommodation plans in schools are pivotal for these children. Luckily, over the two years that our clinic has been in place, we've seen better involvement and better recognition by schools in getting these plans in place, but there's still some areas where there's resistance and challenges depending on the school environment and frankly, the parents and their ability to advocate. Some of the accommodations that we've recommended aside from scheduled rest periods are, in some cases, children have a hard time reading black and white on a page. So audio books may be helpful for them in this period of cognitive dysfunction. Being able to complete exams in a low light or a quiet room. And then as mentioned, sort of extended time on assignments or tests. Again, this is all sort of taken from concussion management strategies and seems to be very helpful for these patients. I will skip over the long COVID can be a disability just to say, think about it in children and we're still working on the best ways to get benefits for children and their parents in this setting. Again, to the fatigue and brain fog, our families fall into sort of one of two camps. Either we're trying to do everything like we did before or we don't wanna do anything. Both need some adjustment to their expectations, either that the four P's of pacing and prioritizing and avoiding that push and crash. Or how do we activate, how do we start doing some of the things that we did before to get out of a funk, to safely start to get back to life while we recover physically. So our psychologists in clinic really provides a lot of coping strategies and mechanisms to our patients and helps them get motivated to mobilize in a safe and non-harmful way. Also, she performs screening and referral to neuropsych for those that seem to be the most specifically impacted, although that has been a challenge given the severe limitations in access to neuropsychology. So I won't spend too much time on this again, but some of the techniques she actually uses and teaches our patients in clinic as a one-off visit are relaxation and grounding techniques, stop challenging, assertiveness training, little bits of cognitive behavioral therapy that can be taken, practiced at home, and sort of serve as a bridge until they can get into a long-term therapy program if that is what is necessary. Similarly, behavior activation is something that she works on. Every single patient that comes in, we say, what is your goal and what is one of your favorite things to do? So helping them identify something that motivates them, coming up with safe ways that they can get reengaged in activity and build that activation is really important. All right, I think we are moving right along. Briefly, I won't even talk about this other than to say there are, as mentioned, multiple different pathophysiologic mechanisms being explored and there is a upcoming clinical trial looking at use of low-dose naltrexone for post-COVID fatigue syndrome that I think is very exciting to many of our patients. This is something that's been used in other clinical settings, Crohn's disease, ME-CFS, rheumatoid arthritis, MS, for its purported anti-inflammatory effects. It does have some modulation of the toll-like receptor four and may impact glial cells as a type of immune cells in the brain that gets at some of these symptoms. There's been one pre-post study done looking at 38 long COVID patients who at eight-week follow-up did have improvements in six of the seven parameters that they evaluated, which included ADLs, energy, pain, sleep, concentration, and overall recovery. And important to note that only two patients discontinued this therapy because of diarrhea as a sort of minor side effect. So a safe and potentially very powerful therapy that's going to randomize controlled trial. So stay tuned for those effects. And I think I can skip this. I do have a case example, if anyone would like to go through this about how everything goes through our clinic, but I know that we are short on time. So I will go to my summary slide just to say, long COVID is a complex multi-system condition. Neuropsychiatric symptoms are often present and are worsened by the diagnosis of COVID in many patients and that management requires a multidisciplinary approach. There is definitely interplay between the body and physical symptoms, the brain functioning, and a cycle continues of all of these impacting each other. So we try to manage the physical symptoms as best we can, strengthen coping skills, and manage psychiatric sequelae. Really encourage avoiding the push and crash. So striking that balance of getting patients reactivated, but not going back to normal life right away, as that can be detrimental, and avoiding reinfection whenever possible, as this also sets patients back. And I think with that, I will end there. Thank you. So I believe we do have time for a few questions. If anybody has any questions they would like to ask of our panel, we'd be happy to take those. Question. So this is sort of a weird question, but you guys mentioned- Can you also identify yourself? Oh yeah. My name is Dr. Kelly Cook. I'm a private practice psychiatrist in Houston. When both of you guys were talking and you mentioned the pathophysiology of this, you mentioned maybe it's a viral reservoir, maybe it's this, maybe it's that, whatever. Last year, I went to a talk by Avindra Nath from the NIH and he said, oh, I got all these brains. I MRI-ed the crap out of them. There wasn't a speck of virus anywhere. So I was wondering what evidence there was, or why that's a point that's still unresolved, and kind of what your thoughts are on the pathophysiology. And then if this is a disabling condition that we're gonna have to be able to testify, like this person is disabled and I suspect the pathophysiology is gonna go in this trajectory, then how can we do that without knowing the pathophysiology? I mean, I think you've highlighted one of the core issues with this and other post-viral fatigue syndromes sort of historically, is that we know there's a timing, a connection with an infection, and then development of symptoms. But some patients will have abnormalities. So the sort of viral reservoir question comes in, those that have had continued evidence of spike protein in their bloodstream or in various parts of their body, not necessarily their brain, so it's not necessarily a direct effect with the symptoms, but maybe the source of ongoing inflammation and causing symptoms. But yes, that is a key issue, but one that we've been stuck on and has led to delays in management and therapeutics in this patient population for many years now, because it is such a complex question to resolve. And also to speak to that just a little bit in terms of the central nervous system, what's tricky is that in the beginning of the pandemic, a lot of those studies that sort of proposed viral invasion did find evidence of viral proteins in the brain, but from autopsy studies, right? So obviously there is a bias there because these are patients who did not survive. There was only a percentage of brains, and so we don't know also which of those patients would have had long COVID had they survived, right? There have been studies where they've been able to do it with living people, where they get samples of cerebral spinal fluid, and some have found evidence of the virus and others have not. And again, this is a very heterogeneous population, so I think that's part of the issue is, what does it mean when we find it in some people but not in others? There was a huge UK biobank study that had brains pre and post COVID, had scans, sorry, not brains, had scans, MRI scans of brains pre and post COVID and found actually that there were structural and functional brain changes in patients after having had COVID. And so, again, there are many hypotheses, but these are just facts of what we know is that it's very different, and I think like we both said in our talk, the path of physiology is likely different person to person. Thank you. Yes, sir. I'm Scott Guthrie, I'm a child psychiatrist. I actually love that stock was very centered around kids because that's my entire population. So I work in a really isolated, in terms of medical and psychiatric resources school system overseas, and the number of 504 and IEP requests have like quadrupled over the last pretty short amount of time. I'm wondering, there's so many confounders in my population that it would be difficult to tell. I'm wondering if you know of any studies, evidence, et cetera, pointing to log COVID as a potential source of the extra numbers of ADHD, the extra numbers of misbehavior in classrooms and outside, et cetera. Thank you. No, I think that would be a great study and would love to partner with someone in the school system to do that. Thank you. Yes. Hi, I'm John Campo from Johns Hopkins and Kennedy Krieger. Thank you for your presentation today. I share the conundrum, but we were all hearing the importance of rest, but as you point out, it's not just about rest. And I guess the question is, what do we know about how to balance rest and a rehabilitative approach, right? Because I think with many of these cases, as the gentleman just said, they are complex. So I recently saw a young person, he had been to the long COVID clinic. He was convinced he had Bartonella. He had been to the POTS clinic. He had gotten treatment for multiple moles. So this is gonna be coming in the door and it's you, the infectious disease doctor. Well, doctor, I really wanna go back to school, cure me and then I'll get better. Right, right. To be fair, we have seen that periodically over time with kids that come in with post-viral syndromes and one every couple of years. I think this is something that we definitely need more research and experience with. However, the one question that you can ask when evaluating these patients is, do they have this post-exercise fatigue, this exacerbation? So for every single one of these evaluation asks, after today's visit, will you expect to be more exhausted, have worse symptoms for the next day or two? If they don't have that or haven't identified that, it's acceptable to try a little bit more aggressive activation therapy and rehab, but then also checking in again with them sooner. So don't do that and send them on their way for six months and never check in again because they may have just not pushed themselves hard enough to unmask that yet. But really that PEM screening, I think, is a critical part of trying to find that balance. I'm sorry, how aggressively are you treating comorbid depression or anxiety when you go to let these kids see the doctor? So unfortunately in our clinic, we don't have a psychiatrist. So we sort of do screening and coping mechanisms and then get them referred into the community. So I would love to have one, and it's on my wishlist should we get funding. Thank you. Thank you. Yep. Yes. Hi. So I'm Rodrigo, I'm from Sao Paulo. And my question is kind of pretty straightforward. It's the question that the patient in Dr. Jacqueline presentation made to her, that is, is my brain going to get better? I mean, what do we know, even though we only have three years following patients with long COVID, what can we expect from the trajectories of recovery or not recovery from these patients? Because this is what almost every of my patients with cognitive dysfunction following COVID will ask me, and I'm kind of like, I hope it will, but what do we know today, even though it's not everything? It's a great question. And, you know, unfortunately, I also don't have the best answer for that. I think historically, even before COVID, when a patient presents with cognitive impairment, it's really hard to predict the prognosis. It's hard to predict, even with mild cognitive impairment, MCI, if it will turn into Alzheimer's disease or another dementia, right? Usually what we've used as indicators in the past, again, pre-COVID times, is we see how long it has taken for someone to decline. And we use that to sort of predict what the rest of the trajectory will look like. It's not really a perfect science, right? It's just a projection. Similarly for long COVID, it's the same sort of issue. We have seen a substantial proportion of our patients who do get better over time. Sometimes it's after that year mark. Sometimes it's a little bit before. Sometimes we have patients who continue to worsen over time. Those tend to be the older adults. And so it's possible that COVID has sort of incited a neurodegenerative process that just continues the cognitive decline over time. There are some patients that this may be their new normal. Patients that I see that have been experiencing this for the last three years, and it hasn't gotten better, but it hasn't gotten worse. And this is just their new baseline. So I think all of those trajectories are applicable. We know from other diseases, like from patients treated in the ICU or with acute respiratory distress, in other words, those with severe COVID, we know from those other diseases that even five years post having been treated in the ICU, they still have some remaining cognitive deficits. And so it's likely that that's a parallel population. For the ones with mild COVID, it's probably very variable. Okay. Thank you. The final question. Hi, my name is Lisa Grundahl. I work in Oslo, Norway. Had a couple of people come into our inpatient, where I work inpatient. Among others, a police officer was completely debilitated by long COVID. And my colleague also believed that there was a co-founding depression. And so she started ECT treatment. And after six ECT treatments, he was out running. And I just have, you know, someone who does work in the intersection between COVID, depression, ECT, because I did not think that was going to happen. And I was like, okay, go ahead and try. And literally he was out running after six, two weeks of three times. He did what? Sorry, I missed that last part. He was out running. So it looked like a miracle, but I don't know if you've heard anyone using ECT for long COVID, or if the thought is that it works on the long COVID, or it works on the depression, or. It's possible that, you know, by working on one aspect of it, right? So like rehabilitating the depression, the cognitive aspect also improves, right? Because we know that that happens in other populations as well. And in fact, in neuropsychology, when someone comes in with cognitive impairment and depression, we often say, well, let's treat the depression first, and then we'll send you to neurology. Because, you know, again, depression can really impact cognitive functioning and can look like objective cognitive impairment on our tests. So it's very possible that the depression treatment is what helped. It's also possible, you know, we have as part of the recover initiative, one of the components is the new intervention component, co-investigator of one of those that we're doing here through the NIH. And one of the arms is transcranial brain stimulation for the randomized controlled trial. So that's another potential avenue as well. So we're exploring that in comparison to a cognitive rehabilitation arm as well. So it remains to be seen, but great for your patient. Well, while you're in the realm of therapeutics or things that might help, and while we're waiting for your study to come out and get published, are there things that you've come across that an everyday practicing psychiatrist might be able to do in practice that might sort of get a little bit going with cognitive remediation like crossword puzzles or things that you would recommend even short of they're not being, you know, high level, high grade data? And, you know, I think those things certainly can't hurt. And I get asked even pre-COVID, I was asked a lot, you know, if some crossword puzzles and things like that can be helpful for cognition. They certainly don't hurt, but I think it's a question of near effects and transfer effects. And so, for example, doing a crossword puzzle might get you really good at doing crossword puzzles, but is that gonna translate to real world gains and, you know, actually improve cognitive domains? The studies show that it's not likely. Same with doing memory games or, you know, Lumosity or Brain HQ or, you know, some of those games that are publicly available. Again, they might get you really good at that game, but only some of them have sufficient evidence of transfer effects. It still can't hurt, but yeah, there's- But for your software engineer, maybe that's not- Right, exactly, exactly. Great. All right, I think we're at time. I wanna thank everybody for coming. Thank you for your interest and thanks to our panelists. Thank you.

Long COVID

neuropsychiatric aspects

cognitive impairments

trauma-informed approach

SAMHSA

Mount Sinai

pediatric Long COVID

mental health

multidisciplinary treatment

federal response

individualized care

pathophysiology