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

5/16/21, Body Politic: 'Dr. Nath Presents on the "Neurological Complications with COVID"

Nath: "This is a protein called fibrinogen and this protein is present only in the blood - it's never been in the brain, it's a big protein - it doesn't get through the blood vessel, the only way it can get through the blood vessel, the blood vessel has to be damaged. And so when we saw this in the olfactory bulb, okay that told us immediately these blood vessels, something is wrong with the blood vessels."

"...macrophages, so they're all these immune cells are getting in there too..the primary target of the virus are the endothelial cells in the blood vessel..."

"PEM..I'm very curious to figure out how on earth and why this really happens.."

"The thing is that what i'm excited about is that Congress appropriated $1.5 billion dollars just to study this Long COVID phenomenon - I mean that's the most money you would ever get or ever hope to - to study this phenomenon that has far-reaching consequences for all these other syndromes.."

“…I am told about 270 some grants were submitted from all around the country..the fact that so many groups of people are interested in studying this around the country, that's unprecedented..”

“What I’m excited about is once these studies get going, and the federal government is not the only one pumping money into it, we have other agencies looking at it as well - if we don't understand the pathophysiology now, we will never do it – so, I’m excited will be some answers now there's going to be a second phase to this thing and they're going to now invite proposals for clinical trials and my guess is you'll see the same kind of enthusiasm for clinical trials. So, we should not only understand the disease, we should find reasonable treatments for the disease too. And that is the most exciting thing I think that's happening at the moment.”

“…if you want to boost your T-cells there’s a number of things you can do, if you have exhaustion markers you can reverse them, they're called checkpoint inhibitors..”

"..you have a whole world full of scientists and physicians who have devoted their energies towards studying this thing...I'm very hopeful that we'll come up with something.."

 

10/4/22, AME: 'Neurologic Sequelae of Acute Viral Infections - Avindra Nath, MD'

Nath: "I think all the pathology is really in the blood vessels and viral-mediated stuff – and the parenchyma, it's all innate immune activation and there's leakiness in the blood vessels, you'll get fibrinogen and all kinds of blood products into the parenchyma and then the macrophages come in and they once they get in, they don’t leave. So you have persistent activated microphages in the brain."

 

8/8/22, GVN: Forefront of Virology COVID-19 Webinar Featuring Dr. Avindra Nath

Nath: "The reality is that ultimately the socioeconomic consequences long-term disability is almost all from neurological complications so I think understanding these things early on is absolutely critical.”

“My bias is we need to study pathophysiology in the context of clinical trials because we have millions of people affected and we can't be waiting too much longer or years before we do clinical trials - we need to start with clinical trials now and not wait”

 

Maybe the type of person who prioritises career ambition instead of truth. I mean it takes a lot of that type of thinking to get into such a prestigious position has his.

Maybe he didn’t want to stir up any drama within his field or within the NIH, to benefit his career , so he let Wallitt run free

 

yes I’ve found the latest stuff interesting for similar insight re Nath

Was that Walitts paper back then? I don’t know how things precisely work re the names of authors for all things but got the impression if you have deliver a paper by a certain date and one person has ended up in charge of doing that then it’s hard to have a strong opinion if they want include certain bits or angles because if that theoretical of academic literature of people can always just write their own paper if they disagree (although I think we know it doesn’t work like that in practice easily either)

 

10/20/20: “Neurological Complications of COVID-19 and NINDS Clinical Research by Dr. Avindra Nath”

Nath: "Post-viral syndromes..we think are largely immune-mediated..these COVID patients..it brings an opportunity for us to try & figure out underlying cause"

 

I don’t think so. I can recall the transcript of a conference he went too where there were nearly only psychsomatisers and he spent his whole speech and Q&A pushing back against them.

 

Nath complained vigorously about his own workload around the time the intramural was gearing up and I think said pretty directly that he didn't have time to do it. He seemed very grateful that Wallitt was willing to take it off his hands.
This complaint about not having time to do it was repeated when it was time to write it up. Nath and Wallitt wrote it up at weekends, with Nath complaining again about workload.
Goodness knows how he thought Wallitt would handle it. Jeanette Burmeister write her excoriating piece about Wallitt at that time so criticisms of Wallitt were rife.

It doesn't make sense does it?

 

12/18, Neurology Journal: “Reemerging Infectious Diseases and Neuroimmunologic Complications”

By Avindra Nath & Dennis L. Kolson

“We are ill-equipped to handle this crisis. We need targeted treatments based on our understanding of the current pathophysiology of the disease. While we have made substantial progress…we lack disease-modifying therapies and the medical personnel to provide long-term care.”

https://www.neurology.org/doi/10.1212/NXI.0000000000200356

 

9/1/22, Neurology Podcast: “September 2022 Neurology Recall: Cognitive Impairment From Less Common Causes”

(host) “What do you envision as the important contributors to this syndrome (Long COVID)? And this may be a good opportunity to draw some parallels, as this article does, between COVID brain fog and things like chemo brain or sequelae after other neuroinfectious diseases. What are your thoughts on that?”

Avindra Nath: “Yeah, so 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.

And I think this paper that you refer to, tries to draw parallels between patients who received chemotherapy, and really what they're talking about is that you have activation of glial cells within the brain. And I think a lot of various kinds of things can do that 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 cell 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. You will find platelets will aggregate there. You can find small thrombosis that can occur. Sometimes you can get micro hemorrhages also. We think that in part that may be mediated because of antibody deposition on the endothelial cells itself.

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

(Host): “I think the key take-home points here, what you've said about this, what we're looking at, what we think are the main contributors to post-COVID syndromes, are really indirect effects of viral infections…I'd like to know your views on whether the parallels that we're discussing today between long COVID and these other syndromes, does this open up the possibility that maybe some of these trials might include clinical trials using medications to try to improve symptoms in our patients or mediate these end effects?”

Nath: “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.

You know, 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.”

 

10/19/21: 'Long COVID and the Effects on the Brain'

Hosted by Oculogica

Panelists:
- Avindra Nath, NINDS
- Dr. Uzma Samadani, Neurosurgeon at Univ. of Minnesota
- Dr. Alice Perlowski, CMO of Blooming Magnolia

Nath: “So, what would you do to treat them? The possibilities are if you think there's persistent virus - then you need antivirals. If you think there's a dysregulation of the immune system - then you want to suppress the macrophage activation, but reverse the T-cell exhaustion - so these are potential modes of treatment that one could consider for clinical trials.”

Nath: "these symptoms, they overlap with what's called chronic fatigue syndrome, the same issue people don't believe their symptoms but it's quite likely that by these studies not only will we benefit patients with Long COVID, but you have all these other syndromes that have been around for awhile - we have not been able to develop good biomarkers or interventions - they will all benefit together."

 

8/27/21, PracticeUpdate: 'Neurological Complications Associated With COVID-19: Part 1'

Nath: “..suggesting that the virus itself does not invade the brain..it causes a breakdown of the blood-brain barrier and inflammation within the brain, one possibility is the viral proteins..'

 

8/28/21, PracticeUpdate: 'Neurological Complications Associated With COVID-19: Part 2'

Nath: "...in fact, I know one patient who attempted to take her own life..also there's also overlap between all these syndromes...can be quite devastating..."

"We think that it's largely immune-mediated phenomenon and although we don't understand all the aspects of immune dysfunction in the sub-acute phase, a number of groups have described presence of T-cell exhaustion, loss of interferon responses and increased macrophage responses in these patients and that's consistent with the pathology we saw in the brain, as well as what people have found in the spinal fluid of these patients. If that is the case, then the treatment would likely be reversal of T-cell exhaustion and inhibition of macrophage activation - so, clinical trials are now being designed in order to treat these patients of these kinds of symptoms.."

 

3/12/21, PracticeUpdate: 'An Overview of Neurological Manifestations of COVID-19'

Nath: ‘…the virus tends to invade the endothelial cells and by doing so it can disrupt the blood-brain barrier and blood will leak into the parenchyma that way and there are other long-term complications that the patient just started complaining about and those overlap with what we call Myalgic Encephalomyelitis or Chronic Fatigue Syndrome. And these patients - a number of them had minor symptoms with COVID - they did not necessarily get admitted to the hospital - they were able to manage things themselves and they felt that they recovered - however they continue to complain of difficulty sleeping at night, they have extreme exercise intolerance, difficulty concentrating as they term as mental fog, they have tachycardia upon standing or upon minimal exercise - a few palpitations they can have sorting abnormalities (not sure I heard right..) or powerful vasoconstriction so a lot of autonomic symptoms associated with this illness as well. And these patients have been calling themselves long-haul COVID and the pathophysiology of which is very poorly understood, so we are very eager to study these patients here at NIH.”


“..then with regards to the long-haul COVID or ME/CFS type symptoms that remains a challenge so I think once these patients come with long-term complications we need to make sure that there's no underlying explanation….it is also important for us to try and determine the underlying pathophysiology of the disease and so some of these patients should be enrolled into clinical trials that are ongoing or are being put together and that's an excellent opportunity to try and understand the basis and develop new treatments…”

 

9/17/20, Howard Hughes Medical Institute: 'Science of COVID-19: "Neurological Complications of Coronaviruses"

Nath: “…our biggest problem that i think going forward is going to be this long-haul COVID and that's the term that patients use to describe themselves but these are symptomatologies that overlap with another condition called chronic fatigue syndrome. The problem with this chronic fatigue syndrome is that people have seen these things happen after all kinds of viral infections but nobody knows what it really is..”

“What is most devastating is really exercise intolerance - so they, you know, very short amounts of exercise just climbing up a flight of stairs - is next to impossible for them. You know a lot of these people are very healthy active individuals - a lot of them are healthcare workers - who are taking care of these patients and now their lives are just totally devastated. They can't even practice medicine from home any longer - and they go from other one physician to another and because many of them are healthcare workers, they have managed to get themselves investigated very extensively - and most often, they don't find anything that's wrong with them. So, I think this requires a lot of work to try and see that this is somehow being mediated by persistent immune activation that hasn't really shut down yet but the answer to that still remains.”

 

Clearly if nath / NIH had bothered to fully believe in & investigate this "Chronic Fatigue syndrom e" In the decades before now, these new health care professionals he is capable of feeling empathy and urgency for wouldn't even be in the predicament they are now. If he thinks loosing physical functionality & independence is bad, consider when "CFS" turns that brain, I'm sure he treasures beyond all , to mush. I'm only 32 years waiting for assistance , some on a feeding tube.

 

4/19/21, VJNeurology: "Pathophysiology of acute and post-viral neurologic complications of COVID-19"

Nath: “..long-term cognitive complaints…these are individuals we've been calling them long-haul patients. Often times they have relatively mild disease early on and but then they recover from it and then a few weeks later they start complaining of a number of symptoms they can have…they can have word-finding difficulties, memory problems, some patients…describe a dissociation between time and object related memories - for example, the individual may remember what they ate for breakfast, but they can't remember whether it was today or yesterday or a week ago. They also may have exercise intolerance and so these individuals will complain that - let's say one flight of stairs they get so exhausted they have to lie down all the time”

“I remember talking to a cardiologist in New York and, she was doing telemedicine and her office was on the second floor in her own house and she says that once she climbed up the stairs, she couldn't even practice telemedicine for the rest of the day - others complain of autonomic disturbance….they have extensive examination of each other they can't find anything wrong with them..”

“We looked at the brains of individuals at autopsy and here this is a unique population and it's a subset of non-hospitalized individuals who died - some the brains were obtained from the medical examiner's office…we found a fair amount of pathology there.."

"..since there are millions and millions of anticipated individuals with these long-haul symptoms, understanding the pathology and the pathophysiology of that is absolutely critical. Importantly, what we found was that there was these blood vessels were compromised - so the small blood vessels were leaky and you could see blood products leaking out in some places they were frank RBC's you could see them leaking out around the blood vessel other places you saw the serum proteins like fibrinogen leaking out around the blood vessels. We also saw a fair amount of inflammation, largely macrophages and some T-cells there…so we think it's a largely macrophage-mediated disorder there's a lot of other evidence in the literature suggesting an important role for macrophages and so the immune-mediated phenomenon is critical in mediating neurological manifestations...we found no virus in the brain. Other people have reported viruses but only very, very small amounts and very few individuals so I think it's a rarity.

And so trying to understand how the virus mediates these things is it possible that viral products are formed and they are toxic and mediating it because you don't need the entire virus - you just need viral proteins. And we know that from studying other viruses we've done a lot of work on HIV for many, many years and shown that the that protein of HIV, for example, is extremely toxic and inflammatory and it's possible that these kinds of things are done by other viruses as well."

 

4/30/21, IAS-USA: 'Neurologic Complications of COVID-19'

Nath: "I think we can't wait to understand pathophysiology - as our understanding of pathophysiology improves, we should conduct intervention studies simultaneously.."

"..it's quite possible that's immune mediated phenomena in those patients.."