USA: The RECOVER Initiative - Long Covid research

[Utsikt]

The evidence is in the testimony of people who report massive rises in heart rate on standing, dizzyness, tacycardia etc etc after a covid infection that is disabling and chronic.

Yes maybe tilt tables and over 30bpm heart rate rise might not be the best way to diagnose, yes maybe a lot of these self appointed gurus are talking out of their arses, but there is just as much evidence that POTS is a thing as ME/CFS.

OI is definitely a thing. POTS as a concept is far more questionable.

 

[Jonathan Edwards]

The evidence is in the testimony of people who report massive rises in heart rate on standing, dizzyness, tacycardia etc etc after a covid infection that is disabling and chronic.

So what is the denominator for this observation? How do we know there are more than before?

 

[Jonathan Edwards]

Actually, I got dizziness and tachycardia on standing when I was ill after Covid but you expect that if you feeling really lousy for whatever reason.

 

[V.R.T.]

OI is definitely a thing. POTS as a concept is far more questionable.

My point is that there is very clearly a phenomenon of post infectious OI with tachycardia on standing, and maybe POTS isn't a good name for it, and maybe the research and practice around it can be dodgy but there is absolutely a real condition that people suffer from.

 

[V.R.T.]

Actually, I got dizziness and tachycardia on standing when I was ill after Covid but you expect that if you feeling really lousy for whatever reason.

So here is a sickness behaviour that resolved. And in some people it seems to get stuck on like ME does.

 

[Utsikt]

So here is a sickness behaviour that resolved. And in some people it seems to get stuck on like ME does.

I don’t think OI is uncommon in general when sick. It seems to be quite bad for some of the pwME/CFS, myself included, but I’m also very sick so it might just come with the territory.

I know one person with primarily OI, and nothing else for years post covid. But only OI seems to be very uncommon.

 

[Jonathan Edwards]

So here is a sickness behaviour that resolved. And in some people it seems to get stuck on like ME does.

Yes, I think that is probably as near as we get to a simple analysis.
The problem that I see is that the narrative around 'POTS' keeps shifting and the people I have come across with diagnosis definitely do not just have post-viral sickness behaviour. They have an ongoing problem and I wasn't't aware of it being linked to infection in the way ME/CFS has been.

 

[rvallee]

We are all after Covid. Where is the evidence that POTS is even a definable syndrome, let alone that there has been more of it since Covid? Social media? The diagnosis of 'POTS' is thrown around by physicians everywhere. It isn't free of charge but there is no restriction on who is allowed to have it as far as I can see.

I don't know what kind of evidence you would want. Because it's the same for ME/CFS, there is clear causal pathway here that can be observed by simply paying attention.

I've read tens of thousands of posts from people with LC and most of the research since, and there's a lot more that supports it, it basically put the whole thing into clear focus. It's very obvious that there is a direct line of evidence here. Medical evidence is simply useless here, unfortunately, so I don't know what could convince you, but it's as convincing as the evidence for ME/CFS, which also can only be observed by paying attention to the whole. I noticed PEM in the first few months, and this is why it was obvious to me that a lot of LC was ME/CFS, and I was one of the first to be insistent about it. It's the same with POTS. I just pay attention a lot.

Plus I've had POTS. And the descriptions from patients are unmistakable. I wouldn't value the opinion of 99% of clinicians on this, so wouldn't put much weight into it.

It probably makes more sense as OI + excessive tachycardia, but when you've felt your heart jump to 150 by simply walking 2m and trying to brush your teeth, it's about as plain as day. As far as I'm concerned, the facts of what POTS is are as clear as they are for ME/CFS, it will just take years, if not decades, for medicine to catch up to it. It still hasn't caught up to a quarter of what I knew by May of 2020 so I'm not holding my breath here.

 

[rvallee]

So here is a sickness behaviour that resolved. And in some people it seems to get stuck on like ME does.

POTS does seem to resolve by itself a lot more commonly than ME/CFS. I don't know of it lasting more than 2 years being a common thing.

It also seems to be caused by things like concussions and pregnancy, so clearly it's not strictly post-viral, but there is zero doubt that infections like COVID do lead to it.

In my case it wasn't after an infection either, as best I can tell it was straining a bit too hard stretching my legs when I started being able to move a bit more. But I've read far too many for whom it happened after a mild infection to make it obvious this is one trigger.

 

[Stuart79]

We are all after Covid. Where is the evidence that POTS is even a definable syndrome, let alone that there has been more of it since Covid? Social media? The diagnosis of 'POTS' is thrown around by physicians everywhere. It isn't free of charge but there is no restriction on who is allowed to have it as far as I can see.

While I agree that POTS may be a fuzzy concept, my personal experience is that extreme changes in heart rate and orthostatic intolerance are absolutely post viral for me.

I’ve experience multi-year ME/CFS like post viral illnesses three times in my life (ages 18/37/44). All began within a few weeks of recovery from a respiratory infection with the most recent having been caused by COVID.

All three illnesses triggered sudden rapid heart rate on standing (>120 bpm) and extreme difficulty being stationary while upright. After Covid, I essentially couldn’t stand without a dose of propranolol for a few months. In my case, it has always resolved over the course of several months. It’s usually one of the first symptoms to improve. Post-covid, it now returns with virtually any infection for a few weeks.

So, while I recognize one cannot generalize from their own symptoms, I am extremely confident it is a post-viral condition in my case.

 

[Dakota15]

4/30/25, "Physical Function Differences by COVID-19 Status: A Cross-Sectional Analysis from the RECOVER Adult Cohort"

'Physical function (main outcome) was assessed by number of repetitions on a 30-second sit-to-stand test (30STS)..from 11,578 participants...'

 

[Jonathan Edwards]

So, while I recognize one cannot generalize from their own symptoms, I am extremely confident it is a post-viral condition in my case.

Yes, but surely you have ME/CFS that includes POT, not POTSyndrome. For people with ME/CFS the problem will often be post-viral as we all agree. That cannot be used as evidence for the behaviour of some POTSyndrome that isn't ME/CFS, if there is such a thing. The discussion relates to the idea that there is another 'post-infective disease' called POTS. POTS is supposed to be some form of 'dysautonomia' but if it is just tachycardia and dizziness on standing as part of feeling terrible for whatever reason then that doesn't add up - the autonomic system is doing its usual job when you are feeling terrible.

OK I may seem to be labouring the point but my understanding is that the 'POTS' narrative that has been taken up by a large proportion of those taking a 'biomedical' line to ME/CFS is just as much a barrier to getting some decent science and answers as the BPS narrative. The narrative on Long Covid has been a dog's breakfast. If people had simply started from the fact that post-viral fatigue for many months that seems rather like ME/CFS has been a well-known phenomenon for at least half a century then maybe there might be less confusion.

 

[Dakota15]

11/30/21, NIHCM: 'Long COVID: New Research and Supporting Patients' with Walter Koroshetz

"At NINDS and NIH we've been working on another condition called myalgic encephalomyelitis / chronic fatigue syndrome and that has been very difficult to understand but the point to make here is that the overlap with the symptoms reported in people who have had COVID is extremely high..."

(on RECOVER) "we're hoping to get to answers quickly and then as soon as we have some ideas on what the trouble is we're hoping to bring in clinical trials to determine and test different treatments..."

 

[Stuart79]

The discussion relates to the idea that there is another 'post-infective disease' called POTS. POTS is supposed to be some form of 'dysautonomia' but if it is just tachycardia and dizziness on standing as part of feeling terrible for whatever reason then that doesn't add up - the autonomic system is doing its usual job when you are feeling terrible.

Ah, sorry. I missed that context. I very much agree with the above. I think there are at least two reasons nebulous concepts like POTS are thrown around so frequently.

The first happens at the researcher level, which you have illustrated well for us many times. The problem as I understand it happens when researchers speculate or make assumptions rather than plainly stating what the data shows.

The second, which doesn’t seem to be frequently discussed, happens at the patient level. At some point it occurred to me that we don’t really have words to neatly describes the physical sensations that accompany these illnesses and relatively few people have experienced them. Words like malaise, fatigue, tachycardia, etc. give the impression these sensations in ME/CFS are similar to how everyone feels when they get sick. I think for most of us, that’s not the case. So, patients fall into a similar trap of using ill-defined language to describe symptoms, or symptom clusters, because we don’t have more precise words to covey the associated sensations. It’s essentially short hand.

Generally speaking, as a lay person, I’ve found it’s very hard to avoid making unintended assumptions when it comes to science. I’m certainly guilty of doing it repeatedly despite my best efforts. I’m a lawyer, and my typical way of thinking about things does not work well when it comes to science. It’s difficult to unlearn that type of default way of looking at things.

 

[Dakota15]

Excerpts from most recent RECOVER webinar on Understanding Metformin Use and Long COVID and ME/CFS Following COVID-19 Infection.

Transcript here.

Dr. Susan Vernon: " So, RECOVER provided this incredible opportunity because of the infrastructure, the longitudinal follow-up in the study, and the large, diverse patient populations necessary to really begin to understand ME/CFS in a way that was previously not possible"

"So again, the opportunity to really study ME/CFS and understand that it is a postinfectious consequence of SARS-CoV-2 infection was great to really increase the awareness in general. So, this is just a very exciting opportunity all the way around. And of course, all the people that we work with in the RECOVER consortium—investigators, patients—I get goosebumps thinking about how important this paper is"

"The RECOVER cohort presents a unique opportunity to explore the biological mechanisms and the natural history of post-COVID ME/CFS, an opportunity that as tragic as the pandemic is, an opportunity that is really an unprecedented opportunity to understand and potentially solve ME/CFS. And it also gives us an incredible opportunity to develop objective biomarkers for diagnosis and severity"

"By understanding Long COVID, we will also gain a significant understanding of the pathophysiology as well as possible treatments for ME/CFS."

"Again, RECOVER has just provided an unprecedented opportunity to understand post-COVID ME/CFS. If you think back to that assessment table, included in that assessment table, all those dots across there all across time, was also the sampling framework that was used during the RECOVER observational study. And there are samples that were taken in the first tier—blood samples, fecal samples, saliva samples—that are ripe for testing and digging deeper into ME/CFS. Because now all the people that we have identified as ME/CFS in RECOVER, those samples are associated with those individuals. So that provides a crazy cool opportunity to dig deeper into biomarker discovery and pathogenesis. And then of course there are the tier 2 and the tier 3 assessments that are going on in RECOVER, which dig a little bit deeper in each tier into the various aspects of the pathophysiology. So, my hope is that now that we’ve identified this particular subset of post-COVID ME/CFS within RECOVER, and the data and the samples that have been collected and the additional assessments that are being done, will just really pull back the curtain on ME/CFS and show us a lot of what’s going on."

 

[Dakota15]

Pharmafocus Magazine: 'First official long COVID-19 treatment could emerge from the NIH’s RECOVER initiative'

'While this should lead to positive outcomes, the Long-COVID Alliance has expressed its concern that the NIH has not presented a solid timeline for the trial results, meaning it will be at least a year before any positive results come through.'

Dr Ziyad Al-Aly, from Washington University. US, commented: “It is a bit too late, but it’s certainly helping us move the ball forward… I wish they had the sense of urgency to get us to this stage two years ago.”

 

[Dakota15]

Bateman Horne Center: 'The Youngest Victims: A Mother’s Perspective on Long COVID Research and the ME/CFS Reality We’ve Lived'

'Part of the NIH-funded RECOVER initiative, followed over 1,000 children across 30 medical centers from March 2022 to July 2024.'

'This study represents a critical turning point. For too long, children with post-infectious illnesses like ME/CFS have been medical orphans—suffering without proper recognition, research, or treatment options. The fact that we now have robust data showing that even babies can develop chronic, debilitating symptoms after an infection should be a wake-up call to the entire medical community.'

 

[Dakota15]

June 2025, PLOS One: 'Severity of acute SARS-CoV-2 infection and risk of new-onset autoimmune disease: A RECOVER initiative study in nationwide U.S. cohorts'

 

[Dakota15]

University Hospitals: 'Igho Ofotokun, MD, MSc, FIDSA, Joins University Hospitals as Chair of the Department of Medicine and Physician-in-Chief'

'Drawing on his HIV experience, Dr. Ofotokun led the Atlanta hub of the NIH RECOVER initiative aimed at understanding long Covid. He also serves as the national Chair of the RECOVER Coordinating Committee that oversees the governance of the Adult Cohort – one of the largest of such cohorts in the world with 15 hubs and 83 sites across the U.S.'

 

[Dakota15]

4/24/25, UAB Pathology: '"The Path to Understanding Long COVID" By Nathan Erdmann, M.D., Ph.D.

Erdmann: "In the field, but particularly in the media, there's been a lot of trash talk about RECOVER lighting money on fire and not delivering the goods, which I get because you have thousands of patients that are miserable and frustrated and aren't getting treatments - and yet it is a prospective study for a very, very complicated disease and the way perspective studies work, is you put a lot of front end in it and then it starts manifesting later. I get why that is not warmly received, but it is kind of a function of the agreement that we had in the beginning. There are things coming out of this and again we have a really cool trajectory paper that New England Journal actually gave favorable reviews to but then squashed, but it's going to find a home very soon and we'll be able to tell you about what the trajectory looks like of long COVID symptoms in RECOVER. i'm writing and need to be submitting soon, a paper on what happens for people that do and don't have long COVID with their symptoms when they get reinfected.”