Multifaceted Long Covid is Like the Lernaean Hydra

A huge complication of Covid is that it affects so many different parts of the body. We can't kill it, but we can prevent it from getting in.  

On Wednesday, the journal Pediatrics put out an overview of Long Covid in kids, aka PASC (Post-acute Sequelae of SARS-CoV-2). Here's the gist of it in plain English with a mix of quotations and paraphrasing:

"Symptoms and conditions may reflect persistent symptoms from acute infection (eg, cough, headaches, fatigue, and loss of taste and smell), new symptoms like dizziness, or exacerbation of underlying conditions."

Children may also develop completely new conditions like POTS (heart rate out of control), ME/CFS (profound, perpetual exhaustion), autoimmune conditions (immune system attacks healthy cells), MIS (body parts become inflamed including internal organs), and type 1 diabetes. "These conditions may follow mild or even asymptomatic infection." Symptoms of difficulties in concentration, inability to stay awake, and depressed mood are "commonly triggered after physical and/or cognitive activities, which is referred to as postexertional malaise (PEM). . . . Common concurrent symptoms include musculoskeletal pain, cognitive difficulties, and persistent headaches."  

"Covid-19 disproportionately affects Black, Indigenous, and people of color communities, families living in rural communities, and/or communities facing economic hardships. . . . Given that ~20% of Covid cases in the United States are in children, and that current PASC prevalence estimates are 10-20%, PASC is estimated to affect up to 5.8 million children. . . . PASC symptoms resolved in the majority of children over the course of several months, with one-third of children having ongoing symptoms at 12 months. However, few studies have examined outcomes beyond 12 months."

"Numerous mental health conditions have been identified in children as a result of the Covid-19 pandemic, including anxiety, stress, depression, panic, irritability, impulsivity, sleep problems, emotional lability [rapid shifts in strong emotional expression], PTSD, eating disorders, and suicidal behaviour. However, mechanistic studies exploring the specific pathobiology and carefully conducted studies with adequate control subjects are required to explore effects from SARS-CoV-2 infection versus the situational context of the pandemic (such as . . . loss of loved ones)." 

Then they describe specifics about each type of symptom including a lack of smell and taste affecting eating behaviours, fatigue, respiratory issues, stomach issues, mental health conditions, skin rashes, muscular issues, heart issues, and exacerbation of other conditions like asthma and fibromyalgia, and postinfectious conditions like MIS, the most serious effect, diabetes, autoimmunity, and neurologic conditions. There are short and long term functionality concerns around "mental health, sensory functioning, communication, motor functioning, feeding ability, respiratory status . . . cognition, school performance, ability to perform daily routines, relationships, and sleep/mood status. Studies exploring the functional outcomes of children with PASC are lacking. A retrospective cohort study looking at outcomes of pediatric patients after MIC-C found that at six months, although few organ-specific sequelae were observed, physical reconditioning and mental health support needs persisted." Other studies found ongoing functional limitations. 

The upshot of it all is that allowing Covid to spread is causing significant harm to children. A big problem raised by Tern/Valeer Damen: "You'll only notice that your child has brain damage about 33 days after the (untested, asymptomatic) infection. And then you'll probably attribute it to smartphones or laziness or whatever."

There was also a recent interview with Dana Parish talking to a top Long Covid expert from Mount Sinai, Dr. David Putrino. He's launching a fifth center. "This one will focus on treating infections associated with complex chronic illnesses like chronic Lyme, ME/CFS, and Long Covid and also focus on pragmatic clinical trials and rapid integrations of some of these clinical trial outcomes in practice. . . . We're also putting a lot of effort into education for medical students and existing medical providers."

Dana asked, "I've talked to so many physicians and so many psychologists, and nobody knows anything about complex chronic illness, and it seems to just get a lot of people relegated to the psychiatric bucket, and there's something else going on here."

David's response: "All of our centers adopts this approach of being a hybrid clinic and research center because often a lot of the interventions that we adopt in our centers take a little bit more effort to get mainstream adoption. So in the meantime we say, well, we'll adopt 'em. 

He walked through the process of realizing something outside hospitals needed to be set up for all the people with persistent viral symptoms. Here are parts of the rest of the interview:

"There's no one size fits all treatment. . . . The reason that many of these complex chronic illnesses are easily psychologized by people who want to make a buck off of pushing people into that track is the fact that we've tried to say there has to be a single biomarker or thre has to be a single treatment. Well, no. Theses are complex chronic illnesses. What we see is that a pathogen has caused a lot of damage across multiple systems in your body. It appears to be related to your genetic predispositions or your past medicatl history, which systems are going to be affected and how severely. . . . We often see situations where individuals who, let's say, ran marathons previously, will experience more joint pain as a cluster of their symptoms than individuals who didn't. . . . They feel that more in the weak points where they already had some knee pain; now the knee pain is dialed up times five, times six. Someone who has had three or four concussions might experience more cognitive symptoms. . . . We are dealing very much in treatments right now, not cures. We are steering a lot of research toward curative interventions, but we don't have perfect, 100%, curative agents for a lot of viruses out there. . . . Dealing in treatments can give people their lives back. It can get them 70, 80, 90% better even if they're not feeling exactly as they were prior to getting Covid, and setting that expectation as a partnership. . . . 

I think people should care for a lot of different reasons. Something that I've said from very early in the pandemic is that death is not the only serious health outcome from Covid. An acute SARS-CoV-2 infection can absolutely rob you of your previous life as effectively as a severe infection that ends in death as anything else, understanding that we still do not have a clear cut understanding or list of who goes on to get Long Covid and who doesn't. . . . The median age in our clinic is 38; meaning that we have seen patients that range from six years of age all the way through to 93 years of age. . . . The overwhelming majority of people in our clinic were not hospitalized with acute Covid. . . . Most of them were just like, I've got Covid. It's no big deal. . . . Their acute Covid infection was not initially severe, and they've gone on to develop these symptoms. Also, the majority of patients that we see did not have a significant past medical history. So they weren't sick. They weren't old. They didn't have a bunch of comorbidities where healthy individuals out there in the world can say, 'Well, that's not going to be me.' . . . It does not appear to discriminate. . . . We have people coming in; they had their third Covid infection. They got over their first two no problems at all, and now they're unable to recover. . . . 

The only way to prevent Long Covid is to avoid getting Covid. That's it. That's the only thing we can do. Infection prevention measures related to masks, clean air, HEPA filtering, and just showing general caution around infection prevention is literally the only thing that we can do to avoid ourselves from getting Long Covid. . . . 

There is emerging evidence to suggest that things that protease inhibitors, Paxlovid, can reduce your risk of going on to develop Long Covid. Things like Metformin that boost metabolic function can reduce your risk. These are emerging evidence studies that exist. Also there is emerging evidence to suggest that resting while you have acute Covid can assist in preventing you going on to develop Long Covid. The way all three of those things are linked to my mind is that when you're infected with a virus, the virus will circulate around your body. It will enter cells and infect those cells. And as part of that infection, it taps into your mitochondria, the part of the cell that produces energy for the body, and it starts using those mitochondria to replicate. So it starts sapping energy from our body in order to replicate itself and circulate more widely in the body. When you get infected with this virus, all of a sudden your body actually goes into energy debt. You are producing far more energy than you were just a few days ago to that you can support this virus's brilliant tactic to use your own energy against you. So, what happens when you go into this energy debit is energy's not free. When your cells produce energy, they produce waste products, exhaust fumes called reactive oxygen species. And they're toxic. So if you produce too much of them, you start to go into oxidative stress, and your body starts to get clogged up with waste products as a result of your body always producing less energy than what your needs are. . . . which means that your immune function get muted and is less effective, and you start to produce a lot of damaging chemicals that cause organ damage. . . . Rest stops you from increasing your metabolic demands. . . . I'm a big proponent of early treatment. I also like Nattokinase and NAC and proline. . . . There's a lot of research out there on some of these supplements that are less well known in the public domain. . . . 

One of the things that has struck me as being so diabolical about this disease, among other things, is the cardiovascular effects, and seeing so many young people have strokes and cardiac arrest. I see it in my personal life, and then I read the headlines and all these tours are being cancelled. . . . We're definitely seeing people [in the clinic] who are showing signs and symptoms consistent with endothelial like inflammation of the blood vessels. As the blood vessels get more and more inflamed, you 're more likely to have hyperactivation of platelets, red blood cells clumping together because this protein called fibrin is being overproduced by damaged blood cells. The way that the virus enters the body is through ACE 2 receptors. The cells that make up blood vessels are the riches sources of ace receptors in the body. . . . We've seen publication after publication showing us that Long Covid is a vascular illness, not a respiratory one. . . . . 

One of our interventional neurologists at Mount Sinai, Tom Oxley, was among the first in the world to publish in The New England Journal, the correlation between acute Covid infection and stroke . . . and, my god, he received hate mail from people saying, 'What are you saying? This is such an irresponsible paper. You're going to create panic!' I think this is such a false narrative of don't panic the people. I think that an appropriate level of extreme concern if this virus is causing strokes is absolutely warranted. . . . .

We certainly do see people who absolutely are experiencing cognitive dysfunction that is measurable. In fact, in 2022, we published a paper about this, that one third of the people that presented to our clinic had cognitive impairment that was on par with a traumatic brain injury or a stroke. . . . We don't traditionally, speaking in the world of stroke, traumatic brain injury, Alzheimer's et cetera, we don't start treating cognitive impairment until you can't get through your day. That's not helpful from a performance standpoint for a 38 or 30-something year old individual who now can't multitask in their workday to be able to do the tasks that they used to be able to do pre-Covid. . . . . Currently you need to look at the blood under a microscope to see evidence of micro clots. It's not a challenging process. It's quite easy to do. . . . There is no question that inflammation of the blood vessels is a driver of Long Covid. . . .. I see a lot of reactivated Lyme and Bartonella from tons of patients who re-treat those, and their Long Covid symptoms calmed down. . . . 

In the majority of conditions, the most logical and evidence-based root cause for Long Covid is persistent pathogen. . . . 600 days after the acute infection that may not have been very severe, people still had this virus in their gut. People still had this virus all over the place, and what's that going to look like in ten years? What's that going to look like in five years? What's it going to look like when you're 80, if you get this ten times before you're 50? Pretty terrifying stuff. It's an important counter narrative; there were a lot of folks out there, card carrying virologists, that said these coronaviruses can't persist in the body. . . . That's not a narrative that is based on the science that is emerging. I find myself often in these odd arguments with folks who don't believe in viral persistence. . . . I was really passionate about this particular paper because you cannot in good faith tell me you don't believe in viral persistence. . . . We have multiple papers showing clear cut evidence of viral persistence in a way that you cannot argue about. Here is a viral reservoir; here is a partial virus that is still existing 600 days after an acute infection. Viral persistence is a fact. If you are coming to me and saying the science isn't complete yet, that makes you a fringe scientist or a fringe individual. . . . 

There's so much data on chronic Lyme, historic data, that shows the pathogen persists in spite of an extreme amount of antibiotic treatment. I mean, you can still find it. Now that narrative changed at some point around the Lyme vaccine . . . but now we're seeing this with Long Covid, and it's deja vu. Honestly 90 to 95% of the people I interact with, when I present them with this data and say this is evolving, like, you shouldn't feel bad that you didn't know this before. It wasn't taught to you, but now here is the new data, right? They say, wow, I was never educated about this. I was told that chronic Lyme or ME/CFS was psychosomatic. That was my training. Literally my training. I'm going to think about all this differently now. . . . 

Then there are these 5-10% of people that have built a career around treating conditions like FND [functional neurological disorder], and they are involved in lobbies, and they are involved in setting precedent for the way that Social Security administration or NHS or Medicare deals with theses patients, which is not kindly, by the way, at all. And they do have skin in the game; they do have a financial conflict of interest. . . . They haunt my Twitter mentions basically trying to drum up business for their clinic. . . . We should just clarify that in the DSM, they still, in brackets after functional neurological disorder, say 'conversion disorder'. And conversion disorder was the rebranding of hysteria. It is still a psychological diagnosis, which means, by the way, if you're diagnosed with it, as opposed to being diagnosed correctly with Long Covid, if you're diagnosed with FND and you are unable to work as a result of your FND, your Social Security Administration benefits lat for two years, and then that's it. You do not get long-term disability beyond two years with a psychological diagnosis, which is very shameful, and also points to an agenda. Why would we want to diagnose people with something psychological? Because we can cut their benefits off after two years. . . . We need to pause on diagnosing FDN for every single thing that a neurologist can't figure out. . . . For the last three, four decades that crowd of FND physicians has been living large saying everyone has FND using bogus testing. . . . The standard tests that help 95% of patients be diagnosed do not apply to these illnesses. So it's been so easy for the mainstream medical establishment to say, well, all of your tests are normal. . . . .We find better and stronger and more accurate ways of looking at things. People called MS a psychological illness until we had an MRI scanner. . . . The good news is that because of how quickly this technology is emerging and, because of how quickly the science is being communicated and now Long Covid all at once dumped 7% of the US population on the doorstep of the NIH. . . . 

Long Covid and infection associated complex chronic illness, they need solutions now. They need audacious clinical trails, not a mono therapeutic clinical trial. They need adaptive platform clinical trials that test six or seven interventions in combination all at once that use methodology that the NIH would say, whoa, way too risky. Yeah. We're not going to lear the incremental thing that we need to learn as NIH researchers, but ARPA H or DARPA will say, absolutely do it. It's crazy. I love it! . . . Congress should be giving money to groups like ARPA H. They should be giving money to DARPA. They should be giving money to industry to test crazy ideas. That's my approach. That's why for the last ten years, my lab has almost exclusively been funded by industry even prior to Covid. 

People should look up the history of Alzheimer's and what happened in the field of Alzheimer's, which was nothing. They were going down the wrong road for a couple of decades. And then they looked at finally, Rudy Tanzi and his former partner Rob Moore. It's a lot of infection driving dementia and Alzheimer's and neurodegenerative illnesses. And this was just not recognized forever. I think they wasted something like $2 billion on research that just wasn't helping anybody. It's devastating when you think about how many people could have been helped over the long haul by recognizing the infectious causes of neurodegneration, autoimmune disease, psychiatric disease. . . . 

We talked about the FND disgnosis, and this person is just crazy, or they're just anxious and depressed. . . . These infections cause psychiatric diseases too. So there is a reason that you feel anxious, depressed. Some people get suicidal; they get OCD; they get psychotic. This is long been documented with neurological Lyme infections, bartonella infections that can cause PANS. We're now seeing the same thing with Covid. And I really want patients to be empowered by that knowledge because it's very easy also for psychiatry to just say you're just depressed and I'll give you this medication, and they're still in physical pain. [Not unlike what happened to people with SARS-1.]

I do think that the future is bring here. I think that thanks to folks like Amy Pearls and the PolyBio Research Foundation who have been fighting since before Covid for people to recognize persistent pathogens as root cause drivers of illness. We are seeing a lot of attitudes shift, and we're starting to see pharmaceutical companies starting to understand that many of their drugs that they've either shelved or that they used in the past could be used and helpful here. Our team is working on methodology abd regulatory approval for three antiviral therapies in the next 12 to 24 months. . . . In addition, there are also existing medications that are rapidly being repurposed and tested for, for folks with Long Covid and other infection associated complex chronic illnesses. . . . . I think [popping a pill to prevent it like prep with HIV] is highly feasible. I think Paxlovid is not the perfect antiviral, not by a long shot. I don't even think Pfizer's out there saying that it's the perfect drug, even thouogh they keep increasing the price of it. . . . . Right now we need to balance the weight of hammering our body with a post-exposure protocol with the challenges that most of these drugs have pretty terrible side effects.