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Interagency ME/CFS Working Group – August 11, 2020
Dr. Walter Koroshetz: I'm Dr. Walter Koroshetz, and on behalf of Dr. Inger Damon at CDC, I want to welcome everyone to the first meeting of the group. Depending on the topics, we also have participants coming in from patient groups, patient advocacy groups and patients themselves.
We recognized the need for more coordination among the federal agencies, and also the need for a venue to hear from patients and their representatives about how to further the research and treatment and prevention of ME/CFS.
So working in partnership with the CDC, we brought together this working group of representatives across Government. The agencies represented here support research on ME/CFS or have interest in the issues that impact the lives of individuals with ME/CFS. We'll have different topics at different meetings and the participants may change meeting to meeting.
The goal is to increase communication and collaboration among the federal agencies and with stakeholders. The groups will meet to discuss issues of importance to ME/CFS research and the ME/CFS community and the agencies will provide brief updates on their related efforts and the remainder of the meeting will focus on specific topics of interest to ME/CFS stakeholders.
So please do send in your suggestions for topics for the working group. It's important that we hear from the community. We'll invite representatives from the advocacy organizations and other stakeholders to participate in the discussions that we have here at the working group.
And as I mentioned, the representatives may change depending on the topics to be discussed and the interest of the different groups. We also want to hear directly from individuals with ME/CFS and get input and feedback so time will be allotted during each of the meetings for us to respond to questions that come in from the community and at the end of today's meeting, we will have such a session for questions that have been sent in.
We've reached out to several federal agencies, some of them are able to participate today, some of them will participate in future meetings. It's a little bit wonky, I’m going to get into the weeds here, but as a working group, this is not an official advisory committee to any of the federal agencies. There's actually laws that govern who the government agencies can take actual advice from, that's under what's called the Federal Advisory Committee Act. So this group is not considered an advisory committee, it cannot make recommendations back to the agencies, but clearly the agencies are all looking to do better in this space and so what we discuss: the opportunities, the challenges, will have significant influence on what the different agencies do. And also it gives the working group -- identifies opportunities how we can increase our knowledge of ME/CFSs, how we can work together to find solutions that help individuals affected by this terrible disease. So, I wanted to just give that overview of the committee and give my great appreciation to the CDC for being pioneers in this space.
With that, I’d like to turn it over to Dr. Inger Damon from the CDC for some additional introductory remarks. Dr. Damon?
Dr. Inger Damon: I'm unmuting. Am I now audible?
Dr. Walter Koroshetz: Yes, we can hear you.
Dr. Inger Damon: Excellent. So I’m Dr. Inger Damon. I'm director of the Division of High Consequence Pathogens and Pathology at the Centers for Disease Control and Prevention. And so I’m the director of the division which is home of CDC’s ME/CFS program. I've been the director of the division since 2014, and a number of scientists from my division and office of the director have participated in various ME/CFS working groups, discussion groups and federal advisory committees in the past, so I think we're excited to now engage in this effort to really discuss what is going on across the interagency, and how we as Government scientists can help support the science moving forward to understand ME/CFS, how to diagnose it, how to treat it, and maybe even how to prevent it.
So, I’m happy to be the co-chair of this group, and I’d really like to thank Drs. Whittemore and Unger. I think over the course of a number of meetings, I think we'll probably get in a good rhythm and best use of the work group, so I hope people's expectations are appropriate coming into today's meeting and that this is really an opportunity to hear from each other and figure out the best way to use this work group.
Both CDC, NIH and other Government agencies have been working together through informal mechanisms. A few examples of some of the CDC work in terms of thinking about Common Data Elements for studies, participation of NIH with the multicenter study that CDC is focusing on, and CDC’s representation with NINDS and the working group for ME/CFS research.
And I think this work group will help to strengthen our collaborations and extend this to other agencies. So, I’d really like to thank those who are participating today and look forward to the discussions as they move forward. So, thank you very much.
Dr. Walter Koroshetz: Thanks very much, Dr. Damon. I think now would be a good time for folks to just introduce themselves. Following that, we'll go into kind of updates from the different groups who are on the call today.
So let's see, from the Zoom Meeting participants, let's see who we've got. From NINDS, we have Andrew Breeden and Vicky Whittemore. Joe Breen, Vicky Whittemore’s co-lead from NIAID. And the other NIH people, if they could introduce themselves now? Oh, I see Sophia from our office of the director here at NINDS. Other NIH people want to introduce themselves?
[I see] Nina is here and Lyn is here. Nina Schor, deputy director from NINDS, my partner in crime here, and Lyn Jakeman, director of Neuroscience here at NINDS. Avi Nath is here. Avi is the clinical director in the intramural program and you'll hear from him later. He runs the intramural protocol for ME/CFS here on the Bethesda campus. Brian is here as well. He's in the National Institute of Nursing Research. And he'll also talk to us later about not only the ME/CFS protocol but also post-COVID protocol that he's working on. Anybody else from NIH? Beth Unger, can I hand it over to you for CDC?
Dr. Beth Unger: Sure. Thank you. I'm Beth Unger in the chronic viral diseases branch. You met Dr. Inger Damon, and we also have invited Jennifer Giovanni, who is here representing the domestic COVID response program and will give a few remarks about CDC’s work.
Dr. Walter Koroshetz: Great. And then from the Department of Defense is Kristy Lidie and Patricia Modrow on?
Dr. Kristy Lidie: Yes, this is Kristy Lidie and my colleague, Patricia Modrow is also on the line.
Dr. Walter Koroshetz: Great. So you're from the CDMRP. Do you want to tell people what that is? You'll have a chance to go back and describe things in more detail but in case people don't know what it stands for.
Dr. Kristy Lidie: So we are a part of the Department of Defense, specifically the department of the army and CDMRP stands for the Congressionally Directed Medical Research Programs. And I’ll be telling you about our organization in a few minutes, during the agency updates.
Dr. Walter Koroshetz: Thank you very much, Kristy and Patricia. And from the VA, is Karen Block on?
Dr. Karen Block: Yes, I’m here, Dr. Koroshetz.
Dr. Walter Koroshetz: Great. And do you want to describe what program you direct at the VA?
Dr. Karen Block: Yes. I direct the Gulf War research program at the Office of Research and Development.
Dr. Walter Koroshetz: Carmen Sanchez from the Department of Education?
Carmen Sanchez: Yes, hi, this is Carmen Sanchez. I work for the Office of Special Education Programs in the Department of Education, and we're interested in some of the pediatric issues around ME.
Dr. Walter Koroshetz: Thank you very much. And Alania Ness, from Social Security disability office?
Alania Ness: Hi, yes, I’m here. I’m Alania Ness from the Social Security Administration. I am a technical expert in the office of disability policy focusing on medical policy issues.
Dr. Walter Koroshetz: Thanks a lot, Alania. And then from Open Medical Foundation? Linda Tannenbaum and Ron Tompkins. Want to introduce yourselves?
Linda Tannenbaum: Hi, thank you very much for inviting us. I'm the founder and CEO of Open Medicine Foundation.
Dr. Walter Koroshetz: Great.
Dr. Ronald Tomkins: I’m Ron Tompkins, surgeon at Mass General and involved with the Open Medicine Foundation.
Dr. Walter Koroshetz: Good to see you, Ron. And from Solve ME/CFS Initiative, Sadie Whittaker and Oved Amitay?
Dr. Sadie Whittaker: Hi everyone, I’m Sadie. I’m the Chief Scientific Officer at Solve and I’m joined today by our CEO, Oved.
Dr. Oved Amitay: Hi, thank you, I’m Oved Amitay, president and chief executive officer at Solve. Pleasure to meet all of you today.
Dr. Walter Koroshetz: Great, and Jamie Seltzer from MEAction?
Wilhelmina Jenkins: Jamie won't be joining us today. I'm Wilhelmina Jenkins, we have another representative as well.
Dr. Walter Koroshetz: Who's that?
Claudia Carrera: Hi, I’m Claudia Carrera, I’m a patient advocate with ME Action as well.
Dr. Walter Koroshetz: Thanks very much. I always forget somebody. Who did I forget this time? Let's see. Anybody else of the participants today that I missed? Okay. Very good. So as we mentioned, one of the major goals of the working group is to have the different agencies tell each other and also tell the public and people who are suffering from ME/CFS what is currently going on in their different agencies and institutes. So we'll ask each to give a brief update, maybe five minutes total, on what they think are the most important things that they want to get out on the table for the group today. And so first up is the CDC. And Beth or Inger want to talk about the multisite trial, the treatment guideline things?
Dr. Inger Damon: I think Beth fell off the call, so we're trying to get Beth back on to the call. So let me see where we are on that. So Tim, I don't know if you have any insights.
Tim: No, I’ve not heard anything. I have the slides up, but unfortunately I haven't heard anything about her trying to get back in.
Dr. Walter Koroshetz: So why don’t we move to NIH, then and when Beth comes back on, we can --
Dr. Inger Damon: Yeah, that sounds good.
Dr. Walter Koroshetz: Okay, great. So Vicky, would you want to start off in terms of the NIH update?
Dr. Vicky Whittemore: Sure. I'm happy to do that. So as everyone knows, we've been funding the collaborative research centers at Columbia, Cornell and Jackson Labs and they're nearing the end of their third year of funding. They will start their fourth year September 1st. And as is the case across the country, their research was completely shut down due to the pandemic, and most of the labs are just beginning to re-open, just beginning to be able to continue to recruit and finish the recruitment of participants for their clinical studies.
But what they have done in the interim when they were at home and unable to go into the lab or to continue their studies, was to begin to do some interim analysis of the data they have as well as to prepare manuscripts, so we know there's a lot in the works that they've been working on and publications that will be coming forward from the three different groups.
In addition, we have been working very closely with the data coordinating center, who has developed two very nifty tools, one that we call MapME/CFS, that will allow for the depositing and search of datasets from published studies that will be available to all investigators. Right now we're populating it with information from publications and from the funded collaborative centers, and I think that will provide just a fantastic tool to really help advance research. And I just wanted to ask Joe Breen if he wanted to make a comment, there was a recent publication that came out of the Columbia group, and Joe, could I ask you to give some brief comments about that recent publication?
Dr. Joe Breen: Sure, Vicky. Hi, my name is Joe Breen, I serve on the working group with Vicky as the NIAID representative and I’m the program official for the Lipkin center, one of the three that Vicky just described. Just in mid-July, there was a PLOS ONE paper published from the Lipkin lab that was actually a large team, titled Plasma Proteomic Profiling to Suggest an Association Between Antigen B-cell and ME/CFS. In this paper, they started with 50 cases and 50 controls that were historic actually, prior to the network, and they looked in the plasma to try and look for signatures that were different between cases and controls. And they did actually find significant differences between cases and controls, and were also able to differentiate those patients with self-reported inflammatory bowel syndrome, which this group had previously reported on.
The interesting thing here that I just want to note is that the markers that they found did show potential involvement of B cells in ME/CFS pathogenesis, which is -- it's really not clear what that means in detail, but the fact that this was found actually correlates nicely with some of the immune dysregulation that's been seen in prior reports, and also with some unpublished reports from Mark Davis’s lab, where he sees potential T cell involvement. So it looks like we may have an assay using plasma proteome that can be validated with a larger number, which is what needs to be done that might have clinical utility and a clue as to some of the biology of ME/CFS pathogenesis, which is really important and can help us pinpoint really what's driving the disease. So further studies will be doing that. So that's really the upshot. I wanted to make those two points from this new paper. And it's publicly available, so anybody can look in PLOS ONE down to the data level. Thanks.
Dr. Vicky Whittemore: Thanks very much, Joe. And just briefly, a couple of other comments. We released two program announcements with special review or what we call PARs, one for R21s and one for R01s. This last round, we just completed the review and those grants will be going to Council in September/October, and we're actually quite pleased because for the next cycle, we saw an uptick in the number of grants that came in on ME/CFS so we're very pleased about that.
Just a couple of other comments I'll make quickly is that as many of you will remember, as part of the report to the Working Group of Council, one of the recommendations was that we move into a strategic research planning phase, which we had planned to do and really seriously got sidetracked because of the COVID-19 pandemic, but it's not off the agenda and we're planning to pick that up and move that forward this fall in a strategic planning process to develop a research roadmap. So we will be announcing that and moving those plans forward in the near future. And I think the last thing I will say is that the Trans-NIH Working Group continues to meet and work together, both to be forward looking to think about what’s going to come after this first phase of the Collaborative Centers, as well as looking at the impact of COVID-19, both on the research that's ongoing currently on ME/CFS as well as how post COVID-19 is going to impact individuals who have the virus. And that's actually the topic of the second half of our meeting today.
So with that, I will thank you and turn it back over to Walter.
Dr. Walter Koroshetz: Thanks, Vicky. I just wondered if Avi or Brian wanted to say anything about the intramural protocol. I imagine that that's stuck in COVID as well, but anything to mention there in terms of where you are? Either Brian or Avi? Brian, I think -- oh, there you go.
Dr. Avi Nath: Yeah, happy to say – and I'll let Brian fill in all the details. So we've enrolled fairly well, certainly during the COVID pandemic it's been hard for us to bring in any patients because of all the restrictions at the Clinical Center as to who you can and cannot bring in to the hospital. Those restrictions are now being lifted so we will have an opportunity to re-recruit, but we also describe in detail what our plans really are. So we've taken the opportunity to look at the patients that have been enrolled and start analyzing the data that we've collected so far. So we have a huge amount of data, actually, and in a way this COVID was a blessing in disguise, because we looked at a huge amount of data we've collected, spinal fluid, blood, flow cytometry, there's all kinds of physiology, MRI and other things. So -- and data analysis takes a while. So we don't have concrete answers but we actually have very good leads and the, I think some of the stuff that Joe Breen just mentioned, information from other laboratories, are not exactly the same but quite similar and support those observations. But those observations mean that we need to now try and go deeper, trying to understand what the mechanisms are. So we have interesting leads and we're going to pursue them, so I'm very excited about what we've been able to accomplish so far, and the observations that we've made that could actually turn out to be very helpful for this population. At least provide important leads going forward. And I’ll let Brian Walitt give you further details on that.
Dr. Brian Walitt: What else is there to say? When COVID happened, we were a little more than halfway through the planned recruitment. So COVID has actually given us the opportunity, as Dr. Nath said, to analyze what we have and then recruit a second cohort that we can use as a comparator to confirm what we've seen. COVID is giving us a unique opportunity to study post-infectious ME/CFS right at the time it came into existence. So some of the changes or the directions that will be going will be to take advantage of the unique situation to really look at the onset of these symptoms soon after they really start in the population at large. A lot of the analysis is coming along. The first paper in the study has been approved for publication, which has to do with the focus groups to help us understand what post-exertional malaise is and to design experiments to look at post exertional malaise and that hopefully will be out there soon for people to look at. That's about it.
Dr. Avi Nath: Let me just add something to it. So Brian Walitt has done a fabulous job in trying to put this study together, study all these patients, and these focus groups that he mentioned was actually critical to our understanding of all the terminology that patients use, what it really means. A lot of the complaints are subjective, and unless one can really understand those complaints, trying to make sense of the rest of the disease becomes very hard. So he and -- from NINR took it upon themselves to try and understand what patients mean by words like post-exertional malaise, really not well-defined in the literature, but they did a fabulous job, trying to describe subcategories of what those things are, and that paper should be coming out very soon. And I think it will be a major advancement in the field.
Dr. Walter Koroshetz: Thank you very much, Avi. Let me move on now to Beth Unger from CDC for an update. Beth?
Dr. Beth Unger: Thank you. It really a pleasure to be part of this inaugural meeting of the interagency working group, and to present just a brief update on the work that's ongoing at CDC. We have been working with the National Association of School Nurses to develop a school-based approach to gather information about ME/CFS in school-aged children through monitoring of absenteeism and school withdrawal. So far the nurses have been educating their members about ME/CFS and working on developing an electronic platform to report the information. As a result of the pandemic, many schools will be online, so they're working on indicators other than absenteeism and withdrawal that could be used to identify the children that have chronic illness. Alternatives being considered are engagement in school and turning in assignments. We currently have three educational courses available in partnership with Medscape. The roundtable, Diagnosing ME/CFS: The Experts Weigh In, was renewed for another year.
We also have two new courses this year. The ME/CFS: Test your Strengths and Gaps in Knowledge is a test and teach module, and this was launched in January. Our newest course is the Case-Based Learning Module issued in April. Medscape has been directing all three courses to primary care providers and the uptake is comparable to their other courses.
Our next Stakeholder Engagement and Communication call will be September 23rd at 3:00 p.m. Eastern time. We are pleased that Dr. Maureen Hanson from Cornell University has agreed to present information about some of the exciting work her group has been working on in immune dysfunction in ME/CFS. She's the director of one of the three NIH-sponsored ME/CFS center grants, and this is another example of how we do try to support each other's formats. The call will follow the same as in previous calls starting with a brief CDC update and ending with questions from participants.
So next I’d like to tell you about a very new project that is just beginning in collaboration with CDC’s Emerging Infections Program, known as EIP. EIP is the network of 10 state health departments and their academic collaborators. It is a national resource for surveillance prevention in the control of emerging infectious diseases. EIP projects impact policy and public health practice, and as shown in the illustration, EIP has been quite fruitful in its contributions to surveillance, prevention and control in a variety of areas such as bacterial infections, influenza, food-borne illnesses and HPV. We're really excited to be collaborating with EIP as this is one of the premiere programs at CDC.
Our project is being initiated in the California EIP site and will be conducted in collaboration with Kaiser Permanente, Northern California. We had our first planning meeting in July. Project goals include developing and initiating methods for surveillance to identify new onset ME/CFS, identifying risk factors for progression from the prolonged fatigue to ME/CFS and characterizing ME/CFS subgroups.
We've also made arrangements to partner with the National Center for Health Statistics on the National Health Interview Survey, NHIS, a survey of households designed to represent the U.S. civilian, non-institutionalized population. Participant reported survey data has been used since 1957 to analyze health trends and track progress towards achieving national health objectives. The ME/CFS questions that we develop for the behavioral risk factor survey surveillance will be added to the 2021 survey, and this will provide national data on ME/CFS.
Finally, I would like to discuss plans for the ME/CFS guidelines. As you know, diagnosis of ME/CFS was strengthened by the 2015 Institute of Medicine report. However, the government has yet to issue guidelines on ME/CFS management and treatment.
The process of guideline development needs to be evidence-based, transparent and open. The most common pathway is to use a federal advisory committee, FACA, which Dr. Koroshetz introduced to you. But whether the pathway uses FACA or non-FACA, it involves reviewing data, gathering input, grading evidence, and then drafting guidelines for further input. Because ME/CFS has had so few clinical trials, gathering expert opinion from the clinical experience of ME/CFS clinicians is particularly important. So where we're at in this is that this systematic review report from Oregon Health and Sciences University was recently developed and delivered to CDC and we are preparing a process and timeline for receiving public comments on that document.
With the sunsetting of the CFS Advisory Committee, we could not identify a FACA pathway for ME/CFS guidelines. So we are currently looking towards a non-FACA pathway. This would require that Work Group members are federal employees. Because of that, or just in general, we really need interagency representation and input. We would appreciate the interagency input on discussion and consideration of how your Agency could participate.
The work group will direct the guidelines process, determine the number of meetings, need for initial information, determine the process to gather that additional information, and then finally develop the draft document. CDC is planning to provide administrative and logistical support. So given the additional topics to be discussed today, we don't expect responses or a full discussion today, however, we wanted to raise the issue so that everyone could begin considering how they would like to participate. Thank you.
Dr. Lyn Jakeman: Walter, you're muted.
Dr. Walter Koroshetz: Sorry. Thank you very much, Beth. That's great efforts there at the CDC. Certainly many of the people would be happy to help as you move forward with your group on the guidelines. Let me turn to Kristy and Patricia to talk about the DoD CDRMP Program. Kristy and Patricia, are you ready?
Dr. Kristy Lidie: Yes, we are. Thank you very much. I apologize for the video options for Pat and I. We are on DoD computers, so we have lots of restrictions that we have to adhere to. So good afternoon again, my name is Kristy Lidie, and I’m the program manager for the Congressionally Directed Medical Research Program or CDMRP. So my colleague, Patricia Modrow and I, are happy to be on the call today to tell you about ME/CFS funding at our organization. So I’m not quite sure if you are seeing my slides.
Dr. Walter Koroshetz: Not yet.
Dr. Kristy Lidie: Thank you. Okay, great. We can go to the next slide. So for those of you who are unfamiliar with CDMRP, I’m going to start with a very brief history because it really underscores the power of advocacy in disease research and also shows how it is unique in that disease-specific areas are defined for us by congress and are tied to very specific annual funding allocations. Starting at the top of the timeline, it the early 90s, grassroots efforts heightened political awareness of many health issues and in '93, one of these was the Breast Cancer Coalition, an organization of former cancer patients with local leaders in nearly every state, and within a matter of months, this group had hand-delivered letters to the President and Congress demanding more money for cancer research.
They put together a detailed request for $300 million increase in breast cancer studies. So these efforts were definitely noticed and in response, Congress appropriated $210 million to the fiscal year 1993 DoD budget specifically for a new breast cancer research program. So Medical Research and Development Command, which is an Army command, has a long history of biomedical research. Thy were directed to manage this new cancer program. However, this level of funding prompted the army to create a new office, and they also sought the advice of the National Academy of Medicine about ways to effectively manage the new appropriations. So the National Academy recommended a two-tier review strategy consisting of a scientific merit peer review followed by a second level program committee review. They also recommended a new model for cancer research, one that fully integrated patient advocates into program policy, investment strategy, and research focus. So these recommendations were quickly adopted and actually have been hallmarks of CDMRP ever since. So the success of that new breast cancer program and its new research model led to many additional programs and topics.
Today, CDMRP has continued to be annually directed in the Department of Defense Appropriations Act by sponsoring members of both the House and the Senate, and at the request of advocates. So this infrastructure and process has enabled CDMRP to manage more than 30 programs. New programs as well as support core efforts within the DoD, which leads to my next slide.
So while individual programs are unique in their focus, all programs share a common mission to responsibly manage collaborative research that discovers, develops, and delivers healthcare solutions for service members, veterans, and the American public. So currently we have management of over 4,000 active research awards, including over 500 clinical trials. So we have experience in all levels of research management from small proof-of-concept studies to large clinical trials. Most of our programs are open to any qualified investigator or research team and that includes international groups. So our active awards include both Congressional special interest programs and a smaller number of DoD programs focused on advancements primarily in military medicine. So our current director is Colonel Stephen Dalal, he’s an army colonel. [inaudible]. At the bottom of the slide, you can see FY20 CDRMP’s [inaudible]. There are 35 individual areas. It's important to note, again, CDMRP does not define the program areas we fund. Congressional special interest programs are specifically directed by members of Congress and specifically at the request of advocates. Of the currently funded programs, there are three that are relevant to the ME/CFS community.
The ones you see here [inaudible] explore the effect of deployment during the ‘90-‘91 Persian Gulf War. So as specifically defined by the Congressional language for this program, supported research must center around Gulf War Veterans and Gulf War Illness. However, chronic multi-symptom cohorts may be used as --[inaudible]. Fiscal year 20 funding opportunities had passed for this program, but we do anticipate continuation in the fiscal year 21 based on language that we've seen from the House.
The six funding mechanisms you see here are typically offered each year by the program and span basic research through clinical trials, as well as outreach strategies and opportunities for young investigators. So the Combat Readiness Medical Research Program, established just last year, supports research into life-threatening injuries and treatment for servicemembers in battlefield settings. Very specific focus areas under this program are directed by Congress. This year, ME/CFS was included as an area of interest. So a new funding opportunity was just announced by this program, and is currently accepting submissions through September 10th. The mechanism is the rapid development and translational research award to accelerate the movement of health care products, technologies, clinical practice guidelines, all these things to clinical application. So the last is the Peer Reviewed Medical Research Program, the longest running program of the three. It was established in '99 to support research across a full range of science and medicine. The program has an underlying goal of enhancing health and well-being of service members, veterans, retirees and their family members. The program, as you'll hear from Dr. Modrow, has many specific topic areas directed by Congress, including ME/CFS. So while the current funding opportunities for this program are also closed, it is of interest to this group that four COVID-focused mechanisms were offered. So Pat will talk about more about these opportunities later this afternoon.
To tell you a little more about the Gulf War Illness research program and how it's relevant to ME/CFS, so service members who deploy to the Gulf War were exposed to a combination of exposures you see here in the box to the right. Many were unique to the ‘90-‘91 conflict. 25 to 32% of veterans who served continue to experience symptoms associated with their deployment. Symptoms include widespread pain, muscle aches, headaches, fatigue, persistent problems with memory and thinking, and the other symptoms you see listed. Based on outward symptoms alone, Gulf War Illness looks very similar to ME/CFS, however, underneath these two illnesses do appear to be different. Gulf War Illness patients' immune systems exhibit a—is hyperconnected -- while ME/CFS patients' immune systems are characterized by depleted or overwhelmed immune networks. Despite these differences, many researchers in these two fields do think that a better understanding of one of these illnesses will greatly contribute to understanding of the other.
So what has been the approach to understanding Gulf War Illness? While the portfolio consists of many individual funded grants across the research spectrum, in 2012, the program took a bold step and developed a strategic multidisciplinary approach to design two clinical trials. It began with two separate preclinical multi-institute consortia to evaluate animal models, to perform large clinical sampling and also to use computational approaches to pull everything together and really gain insights into the pathobiology and treatment. So the knowledge gained from these two large efforts is now being combined under a new clinical trial consortium which is a single network of institutions and infrastructure to bring the early findings to Phase 1 and 2 clinical trials. So because the core processes underneath Gulf War Illness and ME/CFS are thought to be similar, similar approaches to treatment are anticipated.
So in addition to the large consortia efforts, there are independent studies looking at similarities by using ME/CFS as a comparator group, the two examples here are an extensive molecular profiling study and a study looking at brain activation following exercise challenge in both Gulf War Illness and ME/CFS patients.
The next program, the combat readiness medical research program, or CRRP, is the newest program area focused on medical threats and treatments for service members on the battlefield. In fiscal year '20, Congress specified very specific topic areas for this program. You see them listed here. Notably under the fifth focus area, which is solutions to enhance warfighter readiness in certain environments. You can see ME/CFS was specifically identified as an illness of interest for prevention and treatment strategies. The programmatic panel, or advisory body for the panel, went even further and added research to identify biomarkers to diagnose and test potential therapeutics for ME/CFS as a high area of encouragement under this new research area. So the brand new opportunity [inaudible] research is currently open as I mentioned to independent investigators at all academic levels. So there will be more to come for this community as applications are received, and are funded under this program.
I'm now going to turn it over to Dr. Modrow, who is the program manager for the peer-reviewed medical research program, to detail the ME/CFS research that she manages. Pat?
Dr. Patricia Modrow: Thank you, and thank you for inviting us. You can see for the fiscal year 20, Congress directed these 44 different topic areas, one of which is ME/CFS. And the funded research that makes up this program can only be in one of these topic areas. And as Kristy had mentioned a little earlier, the program supports research, it's considered to be high scientific merit across the spectrum, very basic research including clinical trials not only benefit military servicemembers, veterans, but also the beneficiaries, family members and the general public. Chronic fatigue syndrome was included as a topic area by Congress in fiscal year '11 and at that point, there were about 21 different topics, diseases, and conditions that Congress directed along with about $50 million, and for CFS, we actually supported one award that was looking at the pathogen infections to try to see if there's some correlation with specific genetic markers and immune responses to see if that determines any predisposition of an individual to not only fall ill with CFS but also to have it as a chronic condition. So for the first time, ME/CFS was included in the fiscal year 20 appropriation language. And what we've done for many years is included areas of encouragement under each of the topic areas.
These areas of encouragement really are the priorities that are important in each of those diseases and conditions. What we typically do is we have our programmatic panel, again, it's an advisory committee that has individuals from within the DoD as well as the VA and also academia, as well as we also get input from the different advocacy groups that go to the hill and lobby for these topic areas to be included in the program. So for FY20, we have four areas of encouragement that are specific to ME/CFS. They are not at all related to COVID-19 because these program announcements with these areas of encouragement were released prior to the pandemic.
But as you can see we have these four different research areas that we consider to be priorities. So if ME/CFS is a topic in FY21 for the Program, what we will do we'll reach out to the advocacies, particularly those that are involved in this Committee, for example, the Open Medicine Foundation and the Action ME and Solve ME, we'll reach out to ask them to help us better understand the needs not only of the patients but also of the community. And we'll use that information in developing areas of encouragement or the top research priorities for FY21. And that's all I have. So thank you very much.
Dr. Walter Koroshetz: Thank you very much for that. Now if we could turn to Karen Block from the VA.
Dr. Karen Block: Good afternoon. My name is Karen Block and I oversee the Gulf War Research Program at VA Office of Research and Development in Washington, DC. Many of you may be wondering why military research with emphasis on the Gulf War applies to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Servicemen and women deployed to the southwest Asia theater of operation during 1990-1991 Gulf War also known as Operation Desert Shield/Desert Storm were exposed to a variety of hazards including but not limited to multiple vaccinations, airborne hazards, chemical and biological weapons, prophylactic drugs, pesticides, oil well fires and burn pits. In total, approximately 700,000 servicemen and women were deployed. Upon returning home, approximately 40% exhibited startling and debilitating multi-symptoms of unknown etiology such as chronic fatigue syndrome, pain, fibromyalgia, cognitive dysfunction, functional gastrointestinal disorders, depression, headache, and insomnia. Cumulatively this is known as Gulf War Illness -- these symptoms parallel with ME/CFS. Our gulf veterans still suffer from diminished quality of life. Although the insults leading to Gulf War Syndrome and ME/CFS are different, there is an opportunity to research these similarities and differences in health outcomes to define novel treatments or biomarkers between the two disorders.
Here you see many peer-reviewed manuscripts with the literature focused on these two connections, similarities and differences. Here we see national funding targeted for Gulf War Illness research over the years. VA, DoD, and HHS have dedicated approximately $300 million toward the understanding of this illness. I would like to highlight a new effort we feel will provide novel insights into Gulf War Illness and define similarities with ME/CFS. Recently, we have secured a new partnership with the NIH National Institute of Neurological Disorders and Strokes, and National Institute for Nursing Research. This is a first of its kind collaboration of the VA with the intramural clinical component of the NIH. This project is known as project IN-DEPTH.
Here we see national funding targeted for Gulf War research illness -- sorry about that. This effort includes our VA study team, Dr. Matthew Reinhardt and Michelle Costanzo, from the War Related Illness and Study Center in Washington, DC., Dr. Nancy Klimas from the Miami VA in Florida, and the NIH study team, Dr. Brian Walitt, from the nursing research institute, and Dr. Avi Nath from NINDS. The project oversight is overseen by VA Office of Research and Development Gulf War Program Director.
So on the VA side, we have three specific aims. Basically the VA will be identifying 50 Gulf War veterans with Gulf War illness and 25 healthy controls. The goal of the research – is to recruit the Gulf War veterans to the NIH IN-DEPTH study using recruitment methods. The other aims of the VA include qualitative and quantitative research by the VA team for InDepth and collection of biospecimens for future research. We plan to enhance the Gulf War veteran experience and care throughout this project by incorporating a series of veteran checkpoints. Once our veterans are passed on to the NIH portion of the Project InDepth, the NIH will do a series of deep phenotyping studies on the Gulf War veterans and the healthy veteran controls using basal rest conditions and various peak exercise challenges. The goal of this project is to do a deep dive study that will generate lots of data and informatics and trying to identify new mechanistic pathways of Gulf War illness.
The secondary analysis of this project is to compare the Gulf War veterans and ME/CFS controls and patients that are ill. So the primary deep dive analytic objectives are to compare the effects of --exercise -- looking at neurocognition, brain function connectivity, immune system and inflammation, autonomic function, gene expression profiles and -- cerebral spinal fluid and mitochondrial function. Characterization of the microbiome will also be included and a characterization of physical and cognitive fatigue using functional magnetic resonance imaging and transcranial magnetic stimulation will be observed.
Coming up this week actually on the 18th and 19th, 2020, we have a VA/DoD Gulf War state of the science conference. This will highlight a veteran panel who will be telling stories about their health concerns and about how treatments are needed to define the illness and improve quality of life. There will be live presentations and virtual poster sessions. I included the information here in case you would like to participate in any of the conference. That's all I have for now. Thank you so much.
Dr. Walter Koroshetz: Thanks very much. So lots of activity going on in the ME/CFS space, and also in a related space, the Gulf War Illness issue. And so exciting programs coming out of the CDC, we heard about which for me were really new information about the CDMRP programs in ME/CFS, so that's a real testimony to the great work that the advocates have done to get ME/CFS as an encouraging area for these research grants in CDMRP. So with that, I wonder if anyone has any questions for the presenters?
Timothy Liden: Make sure you unmute yourself before you ask a question.
Dr. Walter Koroshetz: I think it was all pretty straightforward. Let me ask Beth in terms of the timeframe for the guidelines project, do you have a plan in terms of rolling this out and getting the group together and moving the guidelines along?
Dr. Beth Unger: We don't have -- we can't commit to definite time frames. COVID has really made everybody's time really short, but that's why we wanted to start making plans and I think the next two steps that we have are getting the systematic review in a position where we can get comment on it, and during that time of gathering comments will be when we'll be trying to assemble the work group, because the work group will need that systematic review, so we think the timing could be good there. So overall, it's not a fast process, but we think it's important to start and of course once the guidelines are there, and they need to be renewed, and so getting the first one started, I think is important.
Dr. Walter Koroshetz: Great. Thanks a lot for that, Beth. I would say NIH is fortunate in the sense that certain of our institutes have been hit heavily in bandwidth decrease for COVID, NINDS and many other institutes have been able to kind of just keep operating as they did in extramural side. The laboratories, of course, were closed until just recently they just started to open up again, but we'll get into that a little bit later. I guess for maybe Kristy and Patricia, I guess people might be interested in knowing when CDMRP has opportunities available for research projects to come in for review. How will people know about that? How do you kind of advertise those opportunities?
Dr. Patricia Modrow: Well, we advertise them several ways. This is Patricia Modrow. We advertise them on our website, we also have within the electronic biomedical research application portals, acronym, of course, the military always has acronyms, EBRAP, we have a subscription list where anyone can subscribe for any news, and any times we announce a preannouncement for and up and coming program as well as when funding opportunities are released, then we send an email blast to all of the subscribers. So if somebody really wants to know what funding opportunities are available and when they will be forecast to come out, they really should subscribe to the list of news on the EBRAP website, it's actually on the homepage, you don't need to register in EBRAP to do that, you can just subscribe.
Dr. Walter Koroshetz: Okay, great. I'm sure that NIH, maybe CDC and the other groups might be able to help too, so if there's any ME/CFS opportunities, let us know and we can try and use our social media levers to get the word out. So thank you for that.
Dr. Patricia Modrow: You're welcome. Thank you.
Dr. Walter Koroshetz: Are there other questions? People can always use the chat box with the Zoom if they want to ask questions. That was a very clear presentation, so thanks, everybody. Why don't we move on to the next section? We had planned a discussion about the federal and the non-profit responses to COVID-19, so clearly, you know, from generic points of view, COVID-19 has hit all of us from, you know, our family life to our professional life to the research, and so we have a panel with members from the ME/CFS disease advocacy groups, some of the federal agencies, and I think everybody is affected a little bit differently so we thought it would be a good idea to kind of share stories about particularly how COVID affected your plans, but also how different groups believe or think that COVID may actually affect ME/CFS patients or COVID actually causing ME/CFS in the future. Hypothetical, some of them hypothetical but we'd really be interested in hearing if folks have thoughts about this. So the federal folks have been kind of dominating the conversation right now, so I wondered maybe if we could turn to Linda and Ron from Open Medicine Foundation to kind of start us off in terms of how COVID has affected the Foundation and also how the Foundation is thinking about COVID and its relationship to ME/CFS. So Linda and Ron, would you be willing to kind of start off that discussion and then we'll turn to Sadie and Oved from the Solve Initiative.
Linda Tannenbaum: Sure, thank you very much. We really appreciate the time and that you’ve gathered everybody else around to hear what's going on -- hear the updates, so thank you very much. So as an organization focused on research, our obligation to the millions of suffering worldwide is to really provide data-driven information, and we're jumping on the opportunity to gather more information about ME/CFS by following people who are infected with the virus and are not getting well. So we'll go through a little bit on a PowerPoint in a minute that Dr. Tompkins will review of what we're doing right now to see that happen. So we recognize that this is a unique moment in history of ME/CFS showing the trigger and actually following what happens in the body of those who remain ill and those that get well, so the pandemic itself offers the opportunity to capture the onset, so we have just secured a million dollar grant from an interested party that's helping us begin to collect samples from all of our collaborative research centers. I'm going to share our slides with you on a screen share here you can see our slides there.
So we're going to begin collecting samples at hospitals that are associated with our collaborative research centers here. What is really needed, of course, is targeted and consistent investment in a disease that's really threatening to explode with patients that have COVID that may develop ME/CFS and we're gathering the samples as much as possible and grabbing this opportunity. So I wanted just to bring in our Chief Medical Officer, Dr. Tompkins, and he'll review an overview of what we plan for studying this right now. Dr. Tompkins?
Dr. Ronald Tompkins: Sure. We saw this as an opportunity with this pandemic to follow those patients that have been hospitalized to understand from a genomic and proteomic, metabolomic perspective how those we thought would be at a higher risk of ultimately having this persistent pathological fatigue. And so we divided it into three phases, and there is a phase of severity when hospitalized, including being in the intensive care unit, and then there is an opportunity in the first six months for those who have been discharged, we're discovering, as you can see from the social media, that this doesn't immediately go away and they're COVID long haulers who now we're getting out to six months for many of them in which this persistent, profound fatigue has continued. We do not yet know what fraction that will be of those who have had severe COVID-19 will have this persistent fatigue, but there is an expectation that this fatigue in some serious portion of these patients will ultimately have a persistent fatigue that would be consistent with ME/CFS.
So the three phases that we've chosen to look at is during the very acute complex phase, a second phase over six months in which some will recover, albeit early or late during that six-month period, but there will still be a group at six months who are continuing to suffer from a pathological fatigue and those are at high risk for the development of -- there are multiple different possibilities of a long term chronic fatigue, but ME/CFS is very high on that list. We're using an opportunity we had studied I think in research with NIGMS, the National Institute of General Medical Sciences, in a grant to understand after major injury the genomics and proteomics of individuals who have survived very severe stresses, and we have a very good understanding of how genomicly and proteomicly those individuals tend to recover over time, and we would like to use that as a benchmark to now understand how this very severe viral infection tracks in the same way over time for the development of this persistent fatigue. It gives us an opportunity to identify biomarkers and to understand and potentially identify drug targets or other potential prevention strategies. And this is just our phase one of the hospitalized individuals and looking -- using RNA seq, micro-RNA, metabolomics and proteomics, and this would be a very distinct opportunity for us to distinguish how this very severe viral disorder compares to other stress, which was injury, in which every gene that might have been responsive actually did respond. So that gives us some understanding of the human response. And then phase 2 during that first six months of follow-up, there are certainly patients who will recover between one and three months in a normal or healthy fashion but there's likely to be stragglers whose recovery will definitely last through the six-month timeframe, and then our intent [next slide] would be to follow those with persistent fatigue for up to two years.
And to understand which of those patients and what are their genomic, proteomic, metabolomic features which are correlated with this persistence of and even development of ME/CFS. So we have begun, as Linda mentioned, in our collaborative centers, with collections of these patients and samples and they're actually in the hundreds so far, and we look forward to filling this program out for hopefully some better understanding of the development of ME/CFS. Thank you.
Dr. Walter Koroshetz: Thanks a lot, Ron. That's a very important question to try to get our hands around and also potentially silver lining sometimes from these crises, you can learn something really important. NIH also really is interested in this space going forward. Let me see, I think I got a message from Beth Unger that she was -- that Jennifer Giovanni is here from the CDC to talk about their efforts in this COVID space, is that right?
Dr. Jennifer Giovanni: Yes, I’m right here.
Dr. Walter Koroshetz: Great. Oh, hi, Dr. Giovanni. Go ahead.
Dr. Jennifer Giovanni: Hi, Dr. Jennifer Giovanni, I am a member of the core clinical unit of our domestic COVID-19 response. So this is very interesting information, Dr. Tompkins, I appreciate hearing your approach and review of your three phases.
We are presently in the initial phases of designing studies to investigate reports of these long-haul symptoms, these longtail COVID patients that they've talked about in the media and so forth. So I can tell you, what we're doing is looking for ways that we can collaborate with academic medical institutions across the United States so that we gather data that represents the United States population in terms of racial, ethnic, and socioeconomic diversity. Now in these studies, first of all, we understand that COVID-19 impacts all systems of the body. And going forward as we're designing these studies, we are very determinedly looking at all symptoms, all of these long tail symptoms that are reported amongst persons recovering, in their post-infectious state of COVID-19. So our studies are not at this time designed to specifically address ME/CFS. However, certainly reports that we're getting are very much aligned with the symptoms of ME/CFS, but what we are doing is looking across the broad spectrum of this post infectious sequelae symptomatology. And we'll be designing studies that look at patients in a prospective fashion from hospital discharge forward, also looking at outpatients, and collaborating with providers to characterize these symptoms.
And I’ll be the first to say we're learning as we go. We do, however, have some institutional experience, as NIH does, with these post viral infectious long-tail symptoms, if you will, and so these will be looking across all body systems and certainly neuro aspects of this disease are a very important focus for us.
Dr. Ronald Tompkins: That's extremely important. We would love to be of assistance and work together to the extent that would be useful.
Dr. Jennifer Giovanni: Absolutely, Dr. Tompkins. I think that would be terrific. You know, I was on a call today and we have a neurologist on board with us right now, and then I was speaking with a cardiologist so as we get these studies designed and get all of the mechanisms in place, we will be looking for expertise and external guidance to make sure that we are capturing full spectrum.
Personally, I have been – you mentioned social media, and I think that's something that we often overlook, right, and there has been some very compelling publications in the grey literature and one that just came out in the peer reviewed literature that have mined social media and crowd sourcing to compile an extensive list among thousands of people of reports of post COVID sequelae.
Dr. Ronald Tompkins: Well, we'll be delighted to be of assistance.
Dr. Jennifer Giovanni: Thank you so much.
Dr. Walter Koroshetz: Thank you so much, Dr. Giovanni. Let me turn now to Drs. Whittaker and Amitay from Solve ME/CFS Initiative.
Dr. Sadie Whittaker: I'm excited to be here today, I'll start by making a plug for data harmonization as it relates to this post-COVID space. So I’m going to show you a few slides on what we're doing on the registry side of things. You guys let me know if you can see my screen in a second. So let me bring it -- can you guys see these slides? Okay. I think you guys know that towards the end of May, early June, we launched our registry and biobank for ME/CFS and healthy controls, and we've enrolled about 1,300 individuals into that system already, so we've been thrilled with the response. We have about 40% of those individuals who are using our symptom tracking app to track their symptoms on an ongoing basis. With that kind of as the backbone, we knew we had this infrastructure that we could use to both monitor those with ME/CFS and the impact that COVID has on them, as well as capture data on people who have long-term symptoms following a COVID infection.
So that's exactly what we've done. We introduced a COVID survey into the system for individuals who already have ME/CFS, we have data from about 300 individuals who've completed that survey. And then we also have information from some healthy controls who've indicated they believed they had a COVID infection as well. So, we're continuing to monitor the impact that COVID has on the ME/CFS patients. We'll be able to share some of that information in the coming weeks as that data matures.
On the other side of things, which is the post-COVID side of things, we've created a different entryway for post COVID. So though it seems like many individuals with these long term symptoms aren't likely to go on to develop ME/CFS, we're hesitant to give them that label out of the gate, so we've created a separate -- in the registry and the structure to come in and start entering many of the same surveys and many of the same data we have for ME/CFS patients, but all the labeling has gone away. We're not characterizing them as having this disease, we're just using an existing infrastructure to capture the data.
They will have the opportunity to start using symptom tracking, using -- on an ongoing basis using the app, and then we're recruiting patients, we're kind of taking the opposite approach to Ron and his team in that we're not following people to see what happens, we're recruiting people who are already in the long-term effects.
So we're going after the long hauler population, we're recruiting to the registry in several ways. One is through partnerships, with groups like Body Politic, in terms of gathering quick data and getting it out there, I know there's social media groups on Facebook, partnerships with health institutions, so I’m sure you guys are familiar with the work that David Putrino is doing at Mount Sinai where he's establishing a clinic there to study the effects and the Long COVID so we're in the early stages of a partnership with him. We're talking to some people at Kings College in London, they have a COVID registry they're getting up and running, so we're essentially -- we're looking to establish a network of partnerships across both essentially media groups and health centers to recruit patients to enter data into the registry.
And then our second approach is we are going to start using social media and have a targeted media buy behind that for people who believe they're suffering from long-term effects of COVID. All of that kind of recruitment funnel will come into the registry, people will fill out some surveys, and they'll begin to track – from individuals in the registry as a whole, both post-COVID, ME/CFS and healthy controls, and I think the beauty of the approach that we have with the registry. You know, this moment in time, it facilitates data collection at home, so nobody needs to leave their house, nobody needs to be in a clinical study.
The goal for us is to allow people to enter data at home, use the symptom tracking app to get longitudinal information, and then we're going to be mailing mailers to all the participants and collect that data so that as the labs start to re-open, suddenly we have this incredible body of information that can be used to probe further into research.
Dr. Walter Koroshetz: Great. That's going to be really important to have the good clinical data for sure, and the questions are, really important, what is COVID doing when it affects people who already have ME/CFS as well. So thank you for that.
Dr. Sadie Whittaker: And then on the advocacy side, if I can take one more minute, this is obviously something I’m less familiar with, Emily Taylor and I, their organization, they're working to educate members of Congress about the potential long-term effects of COVID and how it may end up being ME/CFS. We are sponsoring an educational briefing with the bipartisan women's caucus, women's chronic illness during a pandemic, so we'd be happy to share that. And Emily is continuing to work with Congress, don't give up funding for ME/CFS even though a lot of the money is going to COVID, and also COVID could potentially lead to ME/CFS so continuing that funding stream is more important than ever. So we have that one-two punch, we have our advocacy work as well as on the research side.
Dr. Walter Koroshetz: Great. Thanks very much. Can we turn to Wilhelmina and Claudia from MEAction now?
Wilhelmina Jackson: Certainly. Thank you. I'd like to begin by reading a statement from MEAction's Director of Scientific and Medical Outreach, Jamie Seltzer, who's not here today.
She says: “I would have liked to have been here today. Unfortunately, NIH let us know the evening before the meeting that we had to omit one of our attendees. I decided I would be the one to step away because it is essential that those who lead our national health efforts, all of you here today, hear the voices of our volunteers. We requested three slots because as an organization whose staff and volunteers, a majority of people living with ME, we knew that we would occasionally drop out by [inaudible] we made this reasoning clear from the start, when we asked for accommodations. Along with the inadequate time allotted for the responses and the wording of the questions, my impression is this is far from the only last second change NIH made, resulting in an event that is shambolic and [inaudible] I strongly suggest to leadership that they listen to their people with the most experience with our community. Real engagement and partnership with the community is the only way to avoid repeating mistakes of the past. Now in response to the particular question, there are limits to what a non-profit organization is able to do, given the deficits in clinical education, and the history of low research investment in ME/CFS. However, with the help of many people with me and their families, we are working to address the gaps. For instance, we have developed online resources, including a page of curated and created COVID-19 resources. Those certainly would be available to anyone who wants them. We have held community resilience calls and webinars and joined coalitions with Body Politic and COVID-19 Working Group New York, two advocacy groups fighting for people with Long COVID.
It is, however, necessary for Government agencies to exert their authorities in producing clinical education efforts to meet the broadest audience in the shortest amount of time. The scale of the need is so great that it can only be addressed fully by the federal Government and addressed with great urgency. Thank you.”
Dr. Walter Koroshetz: Sorry, I’m on mute. Claudia, did you want to add anything to that?
Claudia Carrera: Well, it looks like the other organizations have been talking about sort of one of the questions in the next section, the response to the COVID crisis in general and not just to people with me who develop ME/CFS. So, I think Wilhelmina was prepared to speak about that as well. Do you want to add on that, Wilhelmina?
Wilhelmina Jackson: The next question that you presented with, Dr. Koroshetz, were what gaps there are in our understanding of the impacts of SARS-CoV-2 virus on individuals with ME/CFS.
Claudia Carrera: Sorry, I was thinking about what MEAction has done in response to the post-COVID crisis. I can speak on that. So the world is [inaudible] and yet is ignoring the crisis occurring in the wake of acute infection. The tendency to treat every post-viral outbreak of ME as though it is entirely unique has left millions in the U.S. without care as they develop a similar disease with potentially similar useful interventions and management techniques.
MEAction has mobilized to help people with Long COVID by most recently hosting a seminar featuring people with ME and Dr. Bateman, an expert clinician, to provide them with technical expertise and advice for people with lived experience, and that's because they are receiving zero guidance from their own doctors, from the federal agencies that should be providing them with guidance. They are experiencing the same issues in the doctor's offices that people with ME do. They're not getting answers, not getting support from family and friends or employers, and so MEAction and these other orgs are stepping in to try to fill in a gap that can really only be addressed by federal action. We are also partnering with COVID advocacy groups including Body Politic and the COVID-19 Working Group New York to address shortcomings in the response to this crisis, both in New York and on the federal level, and specifically to focus also on the long hauler, on the development of the Long COVID crisis, which is not being adequately addressed at all on the scale it needs.
MEAction will also be doing a clinical seminar this month on August 29th at Meaction.net/seminar and that seminar will have three expert speakers, Dr. Bateman, Dr. Kathy Rows and Dr. Van Ness, and that will be targeted at clinicians who want to learn how to help their Long COVID patients since they have received no guidance yet from the CDC or from the NIH, despite the NIH having put out clinical guidance for acute COVID patients.
We're also recruiting clinicians who serve Black and Latinx populations as SARS-CoV-2 has disproportionately affected BIPOC communities. We know ME affects all races—Black, Indigenous, and people of color may be at even greater risk, but they often go undiagnosed. Government agencies have never, never made a concerted efforts to reach out to these marginalized communities and that has to be central to the response now.
So that sort of summarizes MEAction's response. There's been a lot of other stuff going on. We've been reaching out to the press, driving social media outreach to long haulers, trying to, again, fill in the enormous gaps left by the non-existent federal response to this long-term disability crisis.
Dr. Jennifer Giovanni: Hi. I just wanted to say, Claudia, thank you for your comments. And also Wilhelmina. You both -- and also, I’m sorry, I didn't get the first name of the one with Solve, the woman with Solve. I wanted to let you know, I'm glad you mentioned Body Politic. I actually had a lengthy conversation with four of the authors from that publication that came out from Body Politic. I don't recall exactly the name of the publication, but we spoke at length yesterday, and I do, I'm very sympathetic to what you're saying about the struggles that patients are saying, I assure you that CDC is paying a great deal of attention and things are in the works. I've been working on this very hard and it may seem like we're not, but there are over 2,000 people just here that are working very hard, and I assure you we care very much about this. So I appreciate it. I thought that Body Politic report was extremely informative.
Dr. Walter Koroshetz: So let me just kind of turn to the NIH side. So as was mentioned, that NIH has been really kind of focused heavily on the acute side, the prevention side, developing the vaccine, trying to figure out how to treat people in intensive care units, figuring out whether or not monoclonal antibodies or convalescent serum can be given to people to prevent their hospitalization or if they're in the hospital, prevent them from going on to dying, and also a lot of efforts have been put into trying to develop testing. As you can read in the literature that's really holding back kind of return-to-work things that are testing situations. We are just not up to the space where we can get really quick returns very frequently on people. So those are the kind of things that jumped out the door first. But as was said, this issue of the chronic effects are going to be with us for a long time and so I have been working and the other institutes working also in trying to think about how to attack this problem, and we'll talk to Joe Breen in a second from NIAID, which is Dr. Fauci's institute, in terms of how they're thinking about it. There are funding opportunities for people to come in with grants and some of this money is actually quickly distributed outside of our usual grant network through supplements to study the effects of COVID. We have a couple of projects we're going to announce shortly where people are focusing on the neurological and cognitive aspects of COVID-19, and so let me just turn to Joe now to talk about the NIAID institute, and their plans for follow-up studies.
Dr. Joe Breen: Can you hear me now? Perfect. Thank you, Dr. Koroshetz. So you referenced earlier about the changes at the other institutes and let me assure you that NIAID as culture was completely changed and we've been working extremely hard in many of the areas that you mentioned in terms of developing diagnostics, therapeutics and vaccines, some of well-known to the public, others are still ongoing. At the same time, there was a recognition of long-term effects of COVID-19 that was apparent as early as April, and several long-term longitudinal studies were started, and I just want to mention too, because I think they're emblematic of the work that is going on.
The first would be the IMPAC Study, which is an immunophenotyping assessment in a COVID-19 cohort. You'll hear me refer to it as IMPAC. There were press releases about this and the details of the IMPAC study are available on Clinicaltrials.gov, even though it's not a clinical trial, it's an observational study. This study is designed to look at up to originally a thousand, up to 2,000 hospitalized patients with COVID-19, adults, so it's similar to what Dr. Tompkins was talking about in terms of a population and actually much of the analysis in the acute phase would be centered on whole blood, looking at a variety of serum markers, antibody titers, as well as broad based proteomics, metabolomics, PDMCs, nasal swabs, even the endotracheal aspirant if unfortunately a patient is intubated – and then very advanced immunology analysis. And what I think is unique is that there is designed follow-up, so once a patient is discharged, they will be followed up at 3, 6, 9, and 12 months after discharge, and of course there's a lot of bioanalysis that we'll continue, but also symptomatology, patient-defined outcomes which include Promise measures which would include some of the things like fatigue and wellness that are really important here.
So I think that NIAID is supporting these studies which -- this is a cohort that's currently accrued to 300 or so. We're hoping to get to a thousand very quickly and could grow beyond, and that is – I mean, it's a terrible thing that we have COVID-19 but I think it is an opportunity to look in that population then for the emergence of sequelae but could include ME/CFS or could include many other things we need to know about, obviously.
The other study I wanted to mention was started by Michael Sneller at intramural at NIH which is also a longitudinal study. Mike is an intramural investigator at NIAID, and he is starting a longitudinal study of 900 patients where he is going to look at a variety of metabolomics aspects as well and also looking at overall health status to try and understand related post COVID-19 sequelae. And again, that study, Mike's study, is available on clinicaltrials.gov if you want more.
So there have been other studies launched and in process, and importantly we do recognize the unfairness of how this has hit disadvantaged communities, and we have recruited and started projects to try and address that, including populations of American Indians and others, Native Americans, that are really being disproportionately affected by COVID-19. So I think there is a recognition of some of what we heard on the call and we're trying to really make these studies as comprehensive as we can.
Now, the first study I mentioned, the IMPAC study is in hospitalized patients, and it does have limitations and hopefully we can broaden that. And I know there are plans for other studies that will include household contacts, for example, which we really need to know what's going on there too, which would include critical things like transmission. Something we haven't really talked about today is the effect on children, and there are a number of large studies that are being set up to look at children in coordination with NHLBI, NIAID, and other NIH institutes, because I think that's another important population that we haven't mentioned today but could have obviously long-term sequelae as well.
So those are two things I just wanted to bring to everyone's attention. I do recognize that things are in the process of being awarded and aren't yet known to the public, and we'll continue to make the public aware of these projects as soon as possible through social media and other aspects, and forums like this, frankly, where we can interact with other researchers and advocacy organizations and patients directly. Thanks.
Dr. Walter Koroshetz: I would add that NHLBI launched a study in June called the CORAL study that’s studying 3,000 people hospitalized with COVID and looking in follow-up. We're working with NHLBI as well as with a lot of other institutes to study patients who are actually previously enrolled in some large studies, so we have a huge study called REGARDS, for instance which enrolled 35,000 people, half African Americans, half in the southeast and then NHLBI has the Framingham study, Jackson Heart Study, MESA study, so the good thing about those is they have actually pre-COVID data on people so one could see what happens as COVID comes in.
Then lastly, Wilhelmina made a good point, Claudia as well, that this is really hitting hard at African American, Hispanic, and Native American populations, so NIH has a task force led by Gary Gibbons and Eliseo Perez-Stable to try to reach out to those communities to engage them in the COVID research. So I think everybody made really good points, and I think COVID has got lots of challenges and we just have to go after them one at a time, but I think the things we heard from the ME/CFS Groups, I think that's going to add a lot to the knowledge of how this interacts -- how this viral condition interacts with ME/CFS. I wanted to ask Brian Walitt if he wanted to just -- if he can unmute himself, is that possible to talk about the protocol that he's been working on in intramural?
Dr. Brian Walitt: For you, Walter, anything. So like everybody here, the idea of a giant viral pandemic led to thinking about history and all the other pandemics and all the other problems that happened after them, and it is no surprise that there are going to be major problems in the ME/CFS field after this. So we've been planning since the onset to how our -- approach is going to be.
And our approach is an inductive one. We don't want to predefine what the COVID -- post-COVID syndrome might look like before it shows itself, and we also have to understand that we're the Intramural part of NIH so we're in Washington and there's – we are under the rules of the Clinical Center and who we can bring in at this point in time and some of those sorts of constraints.
And so what we have done is we put together a multi-phased protocol to address post-COVID complications in convalescents. First is a screening protocol. We have developed some house-built web-based questionnaires, house-built telephone interview process and using some of the CDEs that come from the ME/CFS common data elements project, basically a project that we will take about a thousand calls from people who have positive COVID serologies or antibodies to understand how they were before they got sick, what the experience of being sick was like for them and the complications that happened afterwards and where they are now. So we'll be looking at about a thousand folks to get a sense of the different range of complaints that we're going to hear, and then we're going to use that in some ways as a referral network within the Intramural program.
We talked to all of our colleagues in all of the other institutes, the eye institute, there's going to be optic complications, pulmonary complications, gastrointestinal complications. We will be referring different issues throughout the campus. We've designed our protocol to be aligned with the neurologic institute, of course. There's a second protocol that will be studying the neurologic complications of COVID, people who come through our protocol will be directly referred there. For individuals who seem to have ME/CFS at the six-month marker, they will be referred into the NINDS ME/CFS protocol for deep phenotyping.
Once we collect this data, with he will look for patterns in the data to see if there are unique syndromes that are emerging from the pandemic and select groups of interest to bring in for deeper evaluation. We will start with a general evaluation for all these – for comparison and then move towards a deep phenotyping approach like we are applying to ME/CFS and to Gulf War Illness at NIH.
To look in a very detailed bench kind of way, part of the protocol will allow for longitudinal follow-up so all the individuals being screened will be allowed to participate every three months, and anybody that is involved in any other aspects of the protocol will be followed longitudinally. At the end of all of this, we will have a lot of data and if it looks like there is a unique illness that is peeking out or emerging, we will be set up to have basically a conference to create consensus criteria for a new entity if it's warranted. If it not warranted, we'll be able to talk about how this relates to other illnesses in space, including ME/CFS, fibromyalgia, and so on. So that's sort of an overview in terms of disparities, Dr. Nath, who just appeared on the screen, has been beating the bushes in the media space and setting up a bunch of collaborations throughout the country to ensure that we will have adequate representation from those who are generally underrepresented in scientific studies. Anything else you'd like to add, Avi?
Dr. Avi Nath: Oh, thanks, Brian, you did a fabulous job of describing all the things that we're doing. Let me just add a couple things. Number one is, it came to us as no surprise that ME/CFS-like symptoms were arising in this patient population, we had anticipated that would happen very early in the pandemic itself, so we are four steps ahead of the game, because we already had started planning as to how we're going to evaluate these patients, already discussing amongst ourselves, we already had a protocol in place for ME/CFS patients that we could enroll upon. We had a team of investigators attuned to studying these patients, we understand all the aspects of it, so unfortunate as it might be, we are in a very good place to be able to answer the questions that we wanted to answer for a very long time that but have been unable to do so. So more importantly, the thing is with the ME/CFS patients we've been seeing recently, oftentimes there's a huge gap between when the infectious process occurs and the symptoms develop, so it's very hard to go back and see what the offending agent is, what the early events may have been. Here is an early opportunity, we know what the offending agent is and we know what symptoms the patients are developing so we have an opportunity to actually capture data that could never have been done before. So we are taking advantage of that opportunity, and Brian has done a fabulous job, put in a huge amount of effort trying to put these protocols together. We've already put them to scientific review, they're currently sitting in IRB. You've had a lot of responses from patients who have approached us, we already got a list, so we're ready to roll as soon as we have approval to move forward.
Dr. Walter Koroshetz: Thanks, Avi. That's great, I think from the panel, you can just see how much activity there is, really stimulated by this crisis that we're in. We'll have a question-and-answer session now to end the meeting. We have -- why don't we start off if there are any questions that came in from the public that were not answered previously in the presentations, and then if the panel has questions for each other. Vicky, would you want to take it from here?
Dr. Vicky Whittemore: Yes, thank you, Walter. So as many of you heard, many of the comments were – questions have been answered and your questions really have influenced a lot of the comments, including diversity, making the distinction between post COVID-19 and ME, I think there's concern in the community about conflating the two and making sure that we do not do that, but do clearly study the post-COVID phases of disease.
So I would just like to go to a couple of questions that were not addressed in the discussion, and so for that, this question was directed to the CDC so I will start there, but anyone else who wants to address this, maybe any of the representatives from the non-profits, so is there -- this is a question that came in from Elizabeth Burlingame who was asking about the importance to launch widespread CME strategies, ME/CFS CME strategies, so that those that develop ME/CFS from COVID-19 are diagnosed and treated properly, so would you please address whether there is CME outreach and promotion, to help to educate those providers about the potential for ME/CFS in the post-COVID patients. So would someone from the CDC like to address that?
Dr. Beth Unger: Yeah, we have plans for new educational initiatives, and as Joe Breen mentioned, there's a lag between what you plan and what you can announce until things are awarded, and at the time when we developed the approach, we were not in the midst of COVID yet, but now that COVID is here, this will be an important topic to incorporate into our next CME initiatives. We hope -- the other aspect is that we're really looking for ways to reach more institutions that educate and train healthcare providers, but that, again, is still in the works. We recognize this is really important. Thanks.
Dr. Walter Koroshetz: It's really timely to see what we can do there. As was mentioned, lots and lots of hospitals are starting these post-COVID clinics. They're being run by pulmonary care people, and their experience with ME/CFS is probably limited if zero, so helping them would be good, but the bright side would be that there's an opportunity to educate a lot of people about ME/CFS.
Dr. Beth Unger: I think it is really striking that the long haulers have caught the attention of the media and people are all of a sudden paying attention when ME/CFS patients have been really living with this for years and years. So I do think the time is right to capitalize on the new knowledge and attention that we have in the public, as well as with healthcare providers.
Dr. Oved Amitay: I wanted to add specifically on the medical education question, we've been working very closely on the advocacy side to support the House Resolution 7057, which is very clearly named Understanding COVID-19 Subsets in ME/CFS Act and as part of the authorization process, it is included that there will be some funding specifically for medical education. So hopefully with the effort of the community, we can get this resolution passed with bipartisan support and hopefully this will ultimately allow for the appropriation of about $50 million a year to the NIH and for all of you to direct that money to where it needs to go. So hopefully we can get the Congress to do that as well.
Dr. Inger Damon: Yeah, and I think just in terms of to reinforce Dr. Koroshetz' comments and Beth's comments, if you look at the most recent CME modules that were posted on Medscape near the end of April of 2020, and as of June 30th, 2020, over 9,000 individuals had taken the course, almost 6,000 took the test and over 5,000 got certificates. So there clearly is a known uptick in hunger in the community so to leverage off of that will be important.
Claudia Carrera: And if I can say something as well, I just want to call out the situation here, that we're ending in two minutes, and that two hours has been given to discuss this crisis is ridiculous. We have not gotten through any of the agenda that was prepared for this discussion, we only got to the first question, and I need to take this time with access to the officers at federal agency to say that, you know, you're all going about this with the totally wrong response. We should not be discussing next steps as if incremental progress as usual is appropriate in this moment. And the agency efforts that you've all described, while welcome, are entirely inadequate. What we need is a massive coordinated federal response to take place across agencies at warp speed. This is a critical component of the COVID crisis, and the same level of urgency, resources, and commitment to outcomes characterizing the vaccine effort and research on acute COVID must be applied to addressing the critical needs of this moment.
And what we need within months, not years, is to identify biomedical treatments and develop testing, and that can be done rapidly as there are many that can go into clinical trials immediately already because they're in use. We need to educate clinicians nationwide on this disease and its management as well as the general public so they can recognize symptoms and we need an actual nationwide surveillance system. We need to deliver critical social services in an accessible way to the wave of people entering long term disability, and achieving these outcomes on the timeline required just necessitates a sea change in the response -- in the approach I’m hearing here. We need a top-down strategic effort focused on dealing with Long COVID and ME/CFS at the level of the federal administration, as well as within each agency, these efforts must be driven by task forces or special offices that have real resources, full time staff members, and authority to come up with the structurally creative approaches required to achieve these outcomes like we've seen with acute COVID, and they must include community stakeholder representation at every level, via FACA, Advisory Councils, and other means because a two hour call every four months does not cut it for community engagement.
Dr. Vicky Whittemore: Claudia, thank you very much for your comment and let me say, this is just the beginning of this conversation. And with the intense pressures on all of us, this was the time that people were available. But please know that this is just the beginning of the conversation. And we're unfortunately at the time that we need to wrap up, and I’ll ask Dr. Koroshetz and Dr. Damon if they would like to make any closing comments.
Dr. Walter Koroshetz: Well, I think Claudia said it right, I think we're in the middle of a crisis, and we really need to move quickly and see if we can turn the crisis in to something that's going to be a major health benefit. And so I think I agree with every point you make, Claudia, and we would like to push it hard here at NIH, exactly what you said, and I will continue doing that. And I’m sure Dr. Damon is doing the same thing at CDC. And we really -- I think we got a lot out of this meeting. I hope that other people also learned about things they didn't know about, which were new opportunities to advance ME/CFS research, and we're committed, you know, to kind of interact as frequently as people have the stomach to work with us. So with that, let me ask Dr. Inger Damon if she has any closing remarks.
Dr. Inger Damon: I’ll just say thank everybody for their participation, and I really appreciate -- although I may know some of what NIH clinical trials is doing from the clinicaltrials.gov website, it was quite interesting to hear a little bit more about some of the efforts and projects being run out of some of these foundations that are really pushing forward ME/CFS research needs.
And so I think we are interested to follow in terms of learning the tools that are being used and I’m sure that within the COVID-19 response of our [inaudible] and the clinical trials team, you know, they will continue to be efforts focused forward in terms of making sure the work that's initiated here is complementary and will support the work being done elsewhere, so this is a great opportunity to here. Thank you.
Dr. Vicky Whittemore: So I would just like to close by thanking everyone who is on the call today, including the 198 participants who are on via the NIH live webcast, and we will be following up with additional responses to the questions we received, and look forward to your feedback. Individuals who would like to send feedback should feel free to do that by sending an email to – I just lost the email address. I had it in front of me. Sorry. Here it is. So it's MECFSinteragencywg@ninds.nih.gov. So thank you for joining us today.
This page last reviewed on May 24, 2023