virology blog

By David Tuller, DrPH

David Putrino is a neuroscientist and physical therapist at Mt Sinai Hospital in New York. He runs a research lab and rehabilitation center that became a magnet for people grappling with what became known as long Covid–or what the US National Institutes of Health called post-acute sequelae of SARS-CoV-2 (PASC).

A native of Perth, Australia, he moved to the United States in 2009 to study computational neuroscience at Harvard Medical School and the Masachusetts Institute of Technology, and later New York University. We spoke a few months ago about how he began treating long Covid patients, the symptom of post-exertional malaise, why many doctors psychologize things they don’t understand, and related issues. I posted that video at the time.

Here’s an edited text version. In this case, “edited” means bits have been moved around, sentences tweaked, phrases rephrased, all for the sake of clarity. Luckily, Dr Putrino’s compassion and determination to do the best for his patients comes through as clearly in text as on video. He maintains an active Twitter feed, and has not been shy about calling out long Covid and ME/CFS skeptics and minimizers.

**********

What is long Covid?

Long Covid is a patient-led term. Depending on who you’re talking to, it can mean different things to different people. Many people with long Covid view it as an interchangeable term with post-acute sequelae of covid, or PASC, which is what the NIH and the CDC arrived upon. And they define it as any ongoing or returning symptoms that have occurred or worsened four weeks after an acute covid infection. Basically, that means it covers anyone who is still feeling diminished or unwell in some way, shape or form at that time.

Now, that’s a necessarily broad diagnosis. I like that. They’ve made the diagnostic criteria broad because it means that you can code someone for a long Covid diagnosis without too much difficulty if  people present as unwell. And I think that this was very much due to advocacy from groups like Body Politic and other long covid support groups. For individuals who didn’t have access to testing, that means your doctor could make a clinical diagnosis based on your symptoms. You don’t need to show evidence of a positive PCR test or antibody test, which is very important.

Why is that important?

Testing is imperfect, and one way it is imperfect is that it is not available equally to everyone. So from a health equity point standpoint, I think it’s important to acknowledge that if you’re living in a low socioeconomic status situation in the United States, you simply didn’t have access to testing and you were told to only show up to the hospital if you’re desperate, otherwise just stay at home. And that advice confounded long Covid care for many, many people because they did not get a formal diagnosis at the time of their illness. Now that was an issue for everyone at the start of the pandemic. But, as with all things related to health disparity, it was felt more by people with low socioeconomic status and members of groups historically excluded from various health care settings. So if you don’t handle this matter of definition correctly, it would have made those disparities even worse.

How did you and your center get involved with long Covid?

When the pandemic hit, we were remotely monitoring stroke patients with an app that we had developed in-house. And so we pretty quickly just re-jiggered the app so that rather than monitoring people for blood pressure disparities or issues with motor function, which we do in stroke patients, we started monitoring acute covid patients for evidence that they were experiencing signs associated with respiratory failure. We on-boarded our first acute covid patient in March 15th of 2020, and pretty shortly we had a few thousand patients that we were monitoring. By the end of April, a percentage of people on the app started to express that they were having persistent symptoms. Although only 5% were in hospital, roughly started complaining of fatigue and heart palpitations and issues with exertion and all of these things that are now classic long covid symptoms. They were testing normal, but they were very far from feeling normal and feeling the way that they felt prior to covid. 

While you were taking it seriously, did you run into the attitude that this was really a manifestation of anxiety or depression or post-traumatic stress disorder or something related to that?

Yes, absolutely. I think that many clinicians wanted to rapidly psychologize the concept of long Covid because it is easy to do so. Evaluate everyone for the superficial things, find that they’re within normal limits on those tests, and then say, ‘Well, I’m not seeing anything. It must be anxiety or depression or PTSD.’ I think that’s very lazy and harmful. We’ve seen this in the dysautonomia world before. In the United States, the average time to diagnosis of dysautonomia is seven years. Along that seven year period, over 75% of people with dysautonomia will get a diagnosis of anxiety or something related, despite the fact that anxiety occurs in this population in the same proportion as in the general population. So this is something that has existed for decades. It’s psychologizing a condition that the health care provider can’t explain.

What do you think is the impulse behind that, and the suggestion that the long Covid phenomenon is largely a form of mass hysteria triggered by news and social media attention?

I think that a lot of health care providers are either too burnt out or too blase to have scientific curiosity and to think, ‘Hm, this doesn’t seem to fit the mold. What else could it be?’ It takes much less cognitive effort to say, ‘Well, I’ve tested for all the obvious things, so I’m just gonna say that this is psychological.’ One of the things that struck me early in the pandemic was when we started seeing the signs and symptoms of long covid showing up on our app in April of 2020, the name “long Covid” didn’t exist. The phrase PASC certainly didn’t exist. And what was striking was how similar all of the descriptions were from this cluster of patients. They weren’t colluding with each other. They didn’t know each other. Covid was a brand new phenomenon. And this list of profound fatigue, inability to concentrate, the cognitive symptoms, the experience of post-exertional symptom exacerbation was consistent among so many people.

Besides PCR tests, are the antibody tests able to accurately identify who has and hasn’t had a prior covid infection?

This speaks to the imperfection of testing. There have been multiple studies at this point that identify a percentage of the population who actually don’t sero-convert—that is, people who don’t develop an antibody response that is detectable by these tests. That figure is somewhere in the neighborhood of 10% to 25%. So that’s a really big range of people who might test negative on an antibody test even after having had Covid-19. In addition to that, most of the tests have false negative rates of around 5% to 10%. So someone might get a negative result but actually have antibodies. And then, as we know from all the vaccination literature now, antibodies are a moving target. So if you got sick in March and didn’t get antibody-tested until after feeling persistent symptoms for three or four months, it is highly likely that your antibody levels had faded to a point where they were no longer detectable. And so all of those factors come into play when making sure that everyone who may have had the condition gets counted.

Obviously, any time you have a condition that’s defined solely by symptoms, some people who self-identify or who are identified clinically are perhaps having symptoms driven by anxiety or depression or related factors. Does that present a problem?

This is a relatively simple answer, actually. The baseline is that you believe everybody. You believe that everyone who says they’re feeling unwell is in fact unwell and you start going through the diagnostic process of running the appropriate tests and putting people through the appropriate evaluations and attempting the appropriate treatments based on this. Sure, a small percentage of the folks who are coming for care might be cases of psychological illness. The problem is that we’re ignoring the vast majority of people who are actively telling their physicians, ‘You know, something is physically wrong with me.’

I’ve worked clinically for almost 20 years now, and I’ve yet to find an individual who wanted to be unwell even in cases of depression and anxiety. It’s not like they’re saying, ‘Yes, I’ve got this great diagnosis and I can just stay home and never work.’ But the system is geared as though that is how people operate. The reality is no one wants their life taken away from them with any of the conditions that we’re dealing with. And so what they deserve is a health care provider who listens, who chases the symptoms that are being presented until we find the underlying cause and then address it.

So what is the situation with treatments at the moment? Is it mostly addressing symptoms?

Right now, we’re starting to pull together protocols to test for different types of things, like biomarkers of metabolic function, mitochondrial function, vascular dysfunction, cortisol production, the immune system. We’re starting to look at autonomic function and the autonomic nervous system–the part of your nervous system that controls your unconscious bodily functions. All of that research is pointing us toward targeted therapies that might help.

But in the short term, where we’re seeing signs of autonomic dysfunction, we’re treating those symptoms with rehabilitation approaches. Where we’re seeing extreme fatigue and activity intolerance and post-exertional symptoms, we’re having conversations with patients about energy conservation techniques like pacing. We’re also explaining that the definition of exertion in this context is not only ‘I got on the treadmill and I ran for a mile.’ It can be ‘I had a difficult and emotionally charged conversation,’ or ‘I had to spend a lot of time on Zoom today’ or ‘I had to digest food that is hard to digest because it’s high in fiber versus simple carbohydrates.’ These are all forms of exertion that can trigger relapses.

Are people aware of the concept or the symptom of post-exertional malaise, or is it something you need to explain to them?

I find it’s something that needs to be constantly explained both to healthcare providers as well as to people who are new to the field of long covid or who are having long covid symptoms themselves. I think in many cases, PEM, or post-exertional symptom exacerbation, can be very challenging to get your head around, especially if you’re the sort of person that is experiencing a significant delay between the exertion and subsequent crashes.

It’s easy to understand PEM if you engage in some exertion and then you’re crashed for the rest of the day. But in some people, it’s insidious—you do something, and then suddenly you crash a day-and-half later. It’s much harder for people to cognitively link something like that to the exertion they did a day and a half ago. And so having those conversations can be incredibly clarifying to a lot of patients who have just been baffled by it. You know, they say ‘I was able to exercise on Monday, why am I feeling so bad on Wednesday?

Some ongoing long Covid treatment trials are based on the theory that patients are mainly deconditioned rather than being physically ill and need an exercise program to get back into shape. What are your thoughts on those sorts of trials?

It’s incredibly discouraging and I think it’s scientifically lazy, and it’s dangerous. There appears to be, in some cases, almost a willful ignorance to not acknowledge the fact that PEM should at least be something that is screened for before you apply an exertion protocol to patient populations. One of the things that always strikes me about these trials that use graded aerobic exercise is that they often  seem to just gloss over the fact that lots of the people dropped out before completing the protocol. And then you only see a slight moving of the needle in symptoms of the sub-group of people who were able to actually complete the protocol. And that should be telling you big warning signs that a large population of individuals couldn’t stand the protocol.

And yet, because it’s there, because it’s published, people can cite it and say, ‘Hey, we want to do the same thing.’ And especially if they’re established researchers with a track record of getting funding, of course they immediately just get funded because these sorts of grant applications are all about being part of a club. It’s a dangerous thing that happens in science, where it perpetuates echo chambers. Again, it just demonstrates the lack of the intellectual curiosity that is needed to do good quality clinical research and actually help all patients.

Any last thoughts you want to you want to share?

I think that the thing that needs to be said over and over again is that long covid is complex. It is most likely many different things that we need to start to tease apart as we as understand the underlying physiology more and more. And so there’s no one silver bullet. We’re not going to see some miracle cure that does it for everybody. What we need to do is listen to our patients. We need to conduct thoughtful and rapid science to understand the different endotypes and then understand the different treatments that go along with each. And that’s how we’re going to solve this thing.

And some people remain sick, unfortunately.

For now, some people absolutely are not responding to available treatment options out there. And they should not be swept under the rug or ignored or labelled as difficult patients. These are individuals who just have a pathology process that we don’t know how to find yet. And they deserve care, attention and research as much as everybody else.

By David Tuller, DrPH

As in previous years, October is crowdfunding month at the University of California, Berkeley, and I am once again seeking funds to continue my work on ME, ME/CFS, “medically unexplained symptoms,” and now long Covid. (Link here.) These tax-deductible donations to Berkeley will support my academic position as senior fellow in public health and journalism at the Center for Global Health from January through June of 2023. The Center uses the funds to cover my salary and benefits (mostly health insurance).

**********

A short recap

Many or most of you reading this will likely be familiar with some of my work, but here’s a short recap. I launched the “Trial By Error” series with a 15,000-word investigation of the disastrous PACE trial, published on Virology Blog in October, 2015. The PACE trial tested graded exercise therapy and cognitive behavior therapy as treatments for ME/CFS. By now, I have written hundreds of blog posts about that piece of crap and other aspects of these issues not only in the UK but in the US, the Netherlands, Norway, Finland and many other countries. As part of this project, I also write commentaries for academic journals and stories for major news organizations.

Since my last crowdfunding in April, I have written dozens of post on a range of issues. Among other things, I have:

*Published a letter in the high-impact journal Brain to rebut a study arguing that POTS, a common symptom of both ME/CFS and long Covid, is “psychogenic.” Eight other academics and scientists co-signed the letter, which was posted in late September.

*Documented that experts in “functional neurological disorder,” or FND, repeatedly inflate prevalence rates by mis-citing data from a key study. They routinely declare that either 16% or even “up to a third” of all neurology consultations involve FND, when the actual rate based upon their own criteria for “rule-in” diagnosis is under 6%.

*Revealed that Professor Esther Crawley of Bristol University has not corrected seven of the eleven papers she was requested to correct by her own university and the UK’s Health Research Authority, the agency overseeing research ethics. The request that she correct her work arose out of my reporting on her ethical and methodological failures.

*Commented on the stupidity of new research from Professor Trudie Chalder, one of the most high-profile leaders of the CBT/GET ideological brigades.

*Posted interviews with David Putrino, a Mt Sinai neuroscientist, about links between ME/CFS and long Covid and the importance of trusting patients; physical therapist Todd Davenport on post-exertional malaise and the two-day CPET test; patient advocate Adam “Beyonce” Lowe, about developments after last year’s release of the new NICE guidelines; and journalist Ryan Prior about his upcoming book on long Covid.

Etc.

**********

Some more background

Last October, after a years-long struggle, the UK’s National Institute for Health and Care Excellence released its new ME/CFS guidelines. NICE found that the evidence for the psychotherapy and graded exercise approach was all of “very low” or merely “low” quallty–as patients have known all along and as I have relentlessly asserted and documented in my work. The new guidelines aren’t perfect but nonetheless represent an enormous improvement and a welcome reversal of the discredited psycho-behavioral approach championed by the so-called “experts” in the field. 

But the struggle continues! Publishing guidelines is one thing; implementing them effectively is another. Opponents have mounted fierce protests against the new guidelines continue to promote the same unproven therapies they always have. Now they are applying the same template to long Covid and post-viral illness in general. If successful, this effort will end up undermining the progress that has been in the ME field. 

Because of long Covid’s range of reported symptoms, many people with the illness have medical issues unrelated to ME and will not receive an ME diagnosis. But a great many will. So examining long Covid in the context of these scientific debates over the source and cause of the devastating symptoms is critical to sustain the momentum of change in the ME domain and affirming the advances in the ME field that have been made to date. 

Given the speed of events, it is hard to predict exactly what will be coming up in the next six months. I will certainly continue to smack down more bad research on psychobehavioral interventions for ME/CFS, “MUS,” and long Covid. My output for this project is a combination of posting on Virology Blog, writing articles for various news organizations, and working on academic papers for peer review. I also expect to be posting more video interviews with people involved in the field.  

One Final Note

Berkeley takes a 5% share as the university’s standard fee for gifts, plus 2.5% as a crowdfunding/credit card fee. Therefore, adding 7.5% to your donation will ensure that the full amount you intend is going toward the project itself. The donation is tax-deductible (for US taxpayers at least).

Thanks so much for your support. I really, really appreciate it, especially at this time of global trauma. 

**********

This is a link to my original Trial By Error series: https://www.virology.ws/2015/10/21/trial-by-error-i/

This is a link to all the posts I have written on Virology Blog: http://www.virology.ws/mecfs/