Dr Avindra Nath, NIH USA, views on ME/CFS and Long Covid

(almost one year ago today)

Neuro Frontiers, 7/11/23: "NIH Study Identifies Cause for Long COVID Neurological Symptoms"

Dr. Charles Tuck interviews Dr. Avindra Nath, Clinical Director of NINDS

Nath: “…long COVID could very well be a number of syndromes under one umbrella with multiple different pathophysiological mechanisms”

“..we screened over 170 individuals who were complaining of various kinds of symptoms having recovered from the acute phase of COVID…finally enrolled 12 people…100% of these individuals had fatigue, they had cognitive difficulties…”

“What we found was that, interestingly, these small subset of individuals had a lot of immune abnormalities. And one of the most striking observations was that almost all of them had B cell activation. So they had these B cells that we call antibody secreting B cells. They were increased in each of the individuals compared to healthy controls. Then they had some abnormalities in other cell types as well. So, for example, the T cells themselves were actually decreased. Those are cells that are important in very precise attack against the virus - so, suggesting that those cells were actually decreased while the antibody producing cells were actually increased.

"And we also found what is called checkpoints. So these are immune exhaustion markers, and they were increased in T cells as well as in monocytes - so suggesting that there's something wrong with the T cells, where they're unable to do their job, they're exhausted - but instead, what you're getting is the innate immune responses, which is the NK cells and the B cells that are activated. So I think that itself is telling you something very important about how the immune system is really dysregulated in these individuals”

"We also looked at their neurotransmitters…so, what we found was that in these patients there are some metabolites of dopamine that were actually increased in these individuals, as well as metabolites of norepinephrine, which is another neurotransmitter - and so that suggests to us that there is some abnormality occurring in the catecholamine pathway as well. And that correlates well with when we looked at their autonomic dysfunction….so that could explain the symptoms of dysautonomia that these patients were having."

“…one of the things that I feel quite strongly about is that it's important to understand pathophysiology, but you can do that in the context of clinical trial, because we have a lot of people who are suffering from this disease. It's true that we may not understand all the pathophysiology completely, but I think we know enough to be able to start thinking about ways of intervention, and yet in that process try to characterize the pathophysiology even further.”

"I'd urge the physicians and the researchers to try and think about designing clinical trials using immune-modulating drugs and the like so that we can quickly determine what can make a long-lasting effect to the lives of these patients.”

 

Sharing for sight

COVID On The Brain, 2/12/24: "Delving into Neurological Implications of Inflammation: COVID-19 and Viral Infections"

(35 minute interview with Dr. Nath)

Nath (on LC treatment): "..there are many different types of immunotherapies..it's a little bit hard to know...but that's the hope.”

Nath: “..we are doing a placebo-controlled study here at NIH that I am the principal investigator of. And that is to look at intravenous immunoglobulin to see if that impacts the neurological symptoms of COVID. There is another study being done by this entity called RECOVER which is a large, nationwide effort. And they are looking at intravenous immunoglobulin in patients who develop this POTS-like syndrome after COVID. And then there's a European study that's being done using an antibody to an endogenous retrovirus called HerbW. And that is in Spain, Italy, and Switzerland.”

Nath: “If TNF-alpha, IL6 are elevated, it would suggest that you have likely macrophage mediated processes, although some other cell types can produce those too. But that would be what I would be targeting and those kinds of individuals. There could be others in which autoanibodies are more important and those individuals, your targets will be somewhat different.”

“So I think you need to do what is called precision medicine. Each patient needs to be investigated with a panel. You identify what part of the immune system is abnormal and then target it.”

Host: “So with the spotlight now shifting from COVID-19, where is the majority of your research focus on these days? Will you be returning to your focus on myalgic encephalomyelitis and chronic fatigue syndrome?”

Nath: “So we did a lot of research on ME/CFS, and we have a paper that should soon be published out of that research. The thing is that there's so much overlap between that and long COVID, and the population affected by long COVID is so much larger, and the symptoms are so much more severe compared to ME/CFS, that we decided that what we should do is focus on long COVID. And all the experience that we gained from ME/CFS, we would apply to this population. The advantage of studying long COVID is that you know what the starting pathogen was. In ME/CFS, it's the same thing. People say, well, we had an infection of some sort, and now they develop these symptoms, but they have no way of going back to try and find out what infection they had, because you're seeing them several years after the initial event.

So I think whatever we learn from long COVID would be applicable to ME/CFS, but it will be a lot easier to sort it out here than in those other patients.”

Nath: “We hope that people will not be suffering for 40 years with long COVID. That would be miserable.”

 

(just sharing)

5/2/23, Smartest Doctor in the Room: “Clearing the Mist from COVID-19 Brain Fog”

(50 minute interview with Nath)

Nath: “I think executive functioning is really what stands out the most…there is persistent inflammation. The question is what is really driving it? And if there was persistent infection, there's no evidence of transmission of COVID from these patients...I mean, they're allowed to donate blood. There's no evidence that COVID will be spread through blood transfusions or through organ donation or anything like that.So if there was persistent virus, you'd start getting all these modes of transmission that don't really occur, right?"

So I don't think there's persistent virus. Is it possible that there's persistent antigen sitting around?”

“What really matters is what type of inflammation is taking place and then try to calm that down, you know, and you can help patients. So you're absolutely right. And so, you know, we and others have looked to see what parts of the immune system get activated. We've looked in brain, we've looked in spinal fluid, and it appears to us that one thing you do not see is T cell activation. We don't find T cell activation in the brain or in the spinal fluid. But what we do find is macrophage activation, and in some subset of individuals, we find antibody producing B cells.”

“And so when you look at that in long COVID, at least in small numbers of patients that have been published so far, it appears that there's increased activity in the brain. So when the glucose is low, the microglial cell activation is large. And that suggests to you that there's some kind of inflammation taking place in the brain and some kind of neural injury.”

"Where you see more white matter, you see less activity. And so you can compare that between a healthy individual and those with long COVID. And in general, you will see that there's decreased glucose activity or uptake within patients with long COVID. And there's certain areas of the brain, particularly at the base of the brain, where there tends to be less uptake in long COVID patients compared to controls. So that's with fluorodioxyglucose. Now you can take other kinds of radioactive ligands and do PET scan also.”

Nath: “So we have a paper coming out, and I just saw the proofs yesterday, and there we looked at the autonomic dysfunction in these patients with COVID. We find a lot of it...If you look carefully, you'll find a lot of it. And so there we showed that the neurotransmitters, and if you measure them in blood, you can find that they are abnormal. And so we think there's some central dysfunction, maybe some peripheral dysfunction, too.”

Host: “..as I mentioned, you know, for many years, and I tell you, it's the one thing I pray that comes good out of COVID, long-haul COVID, that all the research and the money that's going in to understand about these post-viral syndromes..”

 

Quote from Nath..

???!!!!

 

4/8/21 - Conversations with Scientists, “Long-COVID Part 2: A chat with Avi Nath”

(19 minute interview)

Nath: “So our motivation level collectively, it's extremely high…specifically about the long haul-COVID there is a huge interest...The average age is 40 for the long haul patients. And so they are in the most productive phases of their lives.”

“So let's start with the exercise in tolerance first. People call it fatigue, but it's not pretty..an example, I'll give you of a cardiologist..she got infected and she then recovered from it..she says that she developed this exercise intolerance. She couldn't even do telemedicine any longer."

“And there was one neurologist I talked to. She says that her disorder was so bad that she has to lie down all the time. And even while she's talking to me, she cannot sit up and talk because when she sits up, she can’t think any longer..I mean, these guys are living, but they're not really living now. They're just barely alive.”

(if vaccines would help in LC) “It's an interesting phenomenon. The thing is, this is known to occur in other diseases. Patients with ME/CFS or Chronic Fatigue Syndrome, they will also tell you they got the flu vaccine or something, they actually got better. But what they will also tell you, it doesn't last that long..”

“If you look at these syndromes, they are defining very particular areas within the brain. And so there are certain areas in the brain that are being affected in these individuals, and that's what is causing these kind of symptoms.”

“Now, the virus may be gone, but the music lingers on. But what is lingering: is it the immune system that is lingering or is it parts of the virus that are lingering?”

Host (Vivien): "Avi Nath has long studied viral diseases and persistent symptoms. In a number of instances he has encountered conditions that were thought to be post-viral syndromes or an immune system still in overdrive from an infection."

Nath: "I'm a virologist, so I look at viruses. I'm going to look at, very deeply, any evidence of restricted viral replication, remnants of the virus or any signature of it. And with the virus comes the immune system. So we're going to look at the immunology in great depth. So we're going to put the individual into a seven Tesla scanner and try to see if we can find these remnants of vascular pathology that we demonstrated at autopsy. Can we actually find it by imaging? So that's our goal."

 

(alright, last transcribe this time and thanks for following along and tracking with me)

5/13/21, SHEA Podcasts: "Post-Acute Sequelae of COVID-19"

Nath (18-min interview): "..Congress now has appropriated $1.5 billion just to study this phenomenon. Because they realize that this is a huge issue within the US and is going to be a problem worldwide..because these symptoms are occurring in the younger population..and these are individuals who are the most productive members of our society..so if this syndrome also has a strong immune component, then it's not all that surprising that people would see it in that demographic.”

“So these patients are very frustrated because once they've had all the other underlying diseases have been excluded...the physicians do all the testing that is available to them. They say, I can't find anything.”

“..the second study that we're doing is screening patients online who are complaining of post-COVID symptoms and trying to identify subset of individuals who have symptoms that overlap with chronic fatigue syndrome. Because you know that that's another dilemma. We have millions of people who complain of persistent symptoms after various kinds of viral infections.”

“And they also go from doctor to doctor and nobody knows what's wrong with them. And so we've been trying to study those patients. We collected a huge amount of data.

"The problem with chronic fatigue syndrome is oftentimes by the time we see them, we don't know what virus initiated their symptoms. With long COVID, we know what started it, right? We know what virus started it and we can capture them early on. So I think by studying them, it may shed light on the chronic fatigue syndrome, for which for years, we've had no idea what to do with these patients. And so this second study will bring in about 50 individuals who look like chronic fatigue syndrome and bring in another 50 individuals who had COVID but fully recovered. Now, these chronic fatigue syndrome patients are also multiple subtypes.”

“So we wanted to study the pathophysiology of these subgroups. And we think that we're going to find immune abnormalities. We will probably find that there is persistent activation of the innate immune system, like for example, macrophages. There's reasons to believe that we probably find decreased interferon responses and we may find T cell exhaustion. And so if these hypotheses hold true, then for each of these abnormalities, we already have existing modes of treatment. So that's the kind of clinical trials we would like to do so that we could give more targeted immunotherapies as opposed to putting people on prolonged corticosteroids or something like that, or immune suppressive agents that can suppress the entire immune system because you can't do that long-term to people."

"So that's the direction that we are moving in. Now there's $1.5 billion that's available now through Congress and part of that is going to be used for clinical trials. So there are going to be a lot of clinical trials popping up over the country.”

“...the healthcare system can't handle it. It's already breaking apart. So you have all these patients, they can't access care...we didn't have enough physicians in this country to handle a regular problem. Now you got millions of people with new set of problems that nobody knows how to diagnose or treat. So the healthcare system has already exceeded its capacity.”

 

Thanks for transcribing all this, Dakota15. Fascinating and frustrating.

 

6/27/22, Neurology Podcast: "COVID Brain Fog and Other Cognitive Syndromes"

(20 minute interview with Nath)

Nath: “I think there's a fair bit of excitement in the field because we're starting to understand some of the pathophysiological mechanisms. We still don't understand a lot, but at least we're starting to solve some of these things out. And there are some important observations that have been made now from autopsy studies as well as some of the new emerging animal models.”

“you have activation of glial cells within the brain. I think a lot of various kinds of things can do that don't really invade the brain, but yet can cause a systemic inflammation. And the brain also shows evidence of microglial activation at the same time. And I think the importance of that is that most people do not find virus within the brain. Or if they do, there's just very small amounts of virus within the brain.”

“So that alone cannot explain the symptoms or the pathology that we see in the brain. So you have to somehow explain it by some additional pathophysiological mechanism. What this paper found was that there was a lot of microglial activation within the brain, some macrophage infiltrates, and suggesting that this persistent glial cell activation is bad.”

“In the acute phase, if you have glial cell activation, it's good because it tries to repair whatever pathology there is. But if it persists for a long period of time, then it ends up causing bystander damage. So that's at least one of the mechanisms, but that may not be the only one”

“So we've looked at some autopsy cases ourselves, and what we found was that another component that is important is vascular damage. In a sizable number of individuals, you can find a fair bit of microvascular pathology. These blood vessels become leaky, and there are proteins that are coming out of the small blood vessels leaking into the brain.”

“You have perivascular macrophages there. What you do not find is T cells, very few T cells. If this was a viral encephalitis of some sort, you would find a lot of T cells. You actually don't find them at all. What we do find is that the endothelial cells themselves are not only damaged, they're also activated. So you will find platelets will aggregate there..and we think that in part that may be mediated because of antibody deposition on the endothelial cells itself.”

“So there may be an immune component and that is beyond just microglial cell activation, but that is mediating vascular damage and then causing a series of events leading to neural injury.”

“And yes, we don't have all the answers, but I think one of the things one can and what we will be doing is trying to sort out to see if you can find evidence of persistent immune activation in these patients..looking at cytokine levels, looking at the cell types within the blood and spinal fluid by sophisticated techniques, either single-cell sequencing, by flow cytometry, or something called cytotech, which allows you to look at a lot of the cells in a lot more detail.”

“You have such a large population that's been affected by it. How long, the patients are going to ask you and physicians too, how long do you want to wait to study the pathophysiology before you're going to do some kind of treatment trials? And the answer is you can't.”

“Even if you don't understand all the pathophysiology, you've got to do something for them. I and others will also agree that you can study a lot of pathophysiology in the context of a clinical trial. And we know enough already that we can start designing clinical trials. And let's assume we want to target the immune system, and that's what we're doing here within the intramural program at NIH. We have a placebo control study that we've just started in which one arm receives intravenous immunoglobulin, one receives intravenous corticosteroids, and the other receives placebo. And we'll study them before they get the stuff, we'll study them after they get it, and see what is changing in the immune system by that mechanism and their clinical symptomatology and other things that we study in these patients. Those are sledgehammer approaches. They are not really precise immune modulating agents, but it will give us a lot of information about these patients. And we will learn whether that does or does not alter the course of the illness.”

“Now, there are other things that people have shown that you can measure. If you are concerned about ongoing neural damage, one can measure neurofilament levels. There are people that are showing that you can see alteration in the amyloid beta peptide in tau levels.”

 

12/6/21, Neurology Podcast: "COVID Vaccines and Neurology Immunotherapy.."

Nath: “broadly, the neurological complications can be divided into three categories...you have a whole host of chronic symptoms that develop in patients. Most of them had mild disease early on, and then after several days or weeks, can present with a constellation of symptoms. And they can be broadly divided into four categories.”

“Collectively, they have been called long-haul COVID or long COVID. And some present with exercise intolerance. So they can get fatigued very easily with little amounts of exercise. And there's some that develop dysautonomia and will complain of tachycardia upon standing, or will even fulfill the criteria for POTS. And then there's another subset of individuals who complain of cognitive dysfunction...they have difficulty with concentration, gathering their thoughts, or remembering things. And then lastly, there are a variety of pain syndromes that can occur in this patient population as well. And they overlap with fibromyalgia"

“Most major centers are now developing these long haul clinics, which are multidisciplinary clinics. And so it would be good to take advantage of those opportunities. And there is also the ability to then study them more extensively to try and understand what the underlying pathophysiological mechanisms might be. And they're in the best place to even try empirical therapies for these patients. Our current thinking is that likely these are immune mediated syndromes. So if so, then some sort of empirical therapy could be tried.”

“there'll be a lot more to come on this topic”

 

3/27/20, Neurology Podcast: 'Dr. Avi Nath of NINDS Discusses What We Need to Know as Neurologists about the SARS-CoV-2 Pandemic'

Nath: "..a number of these patients can develop post-infectious syndromes..we've known with other coronaviruses..be on the lookout for that"

“So neurologists need to think about the possibility that some of these could be related directly to the virus. And then fatigue is a very important component of this. So it's quite possible that some of these patients may complain of prolonged malaise and fatigue for months on end...so we need to be able to be cognizant of it.”

“The other interesting thing about the coronavirus is that there are post-viral syndromes that can potentially occur, as I mentioned earlier. So, we need to look out for those things. The virus, when it enters the brain, and that's true of all viruses, once they enter the brain, they will adapt to that environment.”

 

8/14/20, Neurology Podcast: "Special Report: Looking Ahead at COVID in 2021 with Dr. Avi Nath, Part 2..."

Host: “...this brings me to another issue that's becoming more prominent, as it should, the increasing numbers of the long-haul Covid patients.”

Nath: “Stacey, you're absolutely right..the long-haulers are here for the long haul because we have millions of people infected. We have these kinds of symptoms, and they will still be around. And a lot of these symptoms are neurological in nature. So NIH is very eager, as you've seen, at least on the news, that Tony Fauci has asked this question repeatedly. And in Congress, he has testified many, many times. So NIH is going to do a whole workshop on post-COVID manifestations. And I'm going to be giving a talk on the neurological aspects and then their breakout groups. And they're looking at all organ systems and they will be one on the neurological manifestations as well.”

“So, yes, they're very eager. They've already pumped in a lot of money into establishing these cohorts. And we're hopeful that the bill that comes out, the stimulus package for COVID, will include funding for NIH. And if that's the case, then it will expedite our ability to fund these studies and to develop modes of studying the pathophysiology and new treatments for these patients.”

 

Is he fucking kidding? After all those years of studying it? I mean my expectations were low as possible post intramural study but Nath has broken through the floor. Despicable. Absolutely despicable.

My first impression of Nath was him telling Body Politic in an interview that it doesnt mean anything when pwLC talk about headache because almost everyone gets headaches. That impression was 100% accurate.

They need to put someone with actual post viral experience in his position ASAP. Not that they will that would make too much sense.

 

Nath went to Mars, without the precautions, and now he has the astronaut's version of ME/CFS/LC.

That is in his dreams he went and now he has to turn to Brian Walitt for help, who has music therapy and acupuncture on offer.

 

Yale Med: 'McAlpine Wins Grant to Investigate Causes of Post-COVID-19 Neurologic Condition'

'Lindsay McAlpine, MD, won the NINDS Mentored Patient-Oriented Research Career Development Award. This five-year K23 grant supports McAlpine’s ongoing study,“Magnetic Resonance Imaging Biomarkers of Post-COVID-19 Cerebral Microvascular Dysfunction.”

'The exact cause of neuro-PASC is unknown, but recent research in this area inspired McAlpine to investigate microvascular dysfunction as the potential culprit.'

'McAlpine helped found and directs the NeuroCOVID Clinic at Yale and is an expert on neurologic sequelae of COVID-19. She hopes that this grant will help advance her career goals in the field.'

 

Spite?

 

Yeah maybe. Like he's so angry that we dared criticise his dogshit study he's decided to leave us in the dust and tell everyone we're not even that sick on the way out.

Honestly they desperately need to replace him with someone like Mareen Hanson or Akiko Iwasaki.

EDIT: And kick Wallitt to the curb, obviously.

 

In relation to the LC is way more severe than ME point:

To me it sounds like he’s more interested in covering the NIH than anything. He was just trying to find a random argument to back the point that long covid got so much more research funding than ME. I’m unsure he actually believes what he said.

 

How the word "severity" is used in medicine is often more of a reflection of how seriously it is taken, than how seriously it affects the patients.

Kind of a "Gladiator" thumbs up or down. Thumbs up. Crowd cheers madly? Very severe. Low boos? Not severe. So says the crowd.