Eric Topol


Eric Topol, MD, cardiologist, scientist, author and innovator – has been a forceful advocate for long COVID and ME/CFS.

Decorated researcher, fierce critic, and innovator Eric Topol is not one to hide his light under a bushel. He speaks his mind. Whether he’s right or wrong, with the kind of bona fides Topol brings to the game (he founded the Scripps Research Translational Institute and received a $207 million dollar grant to co-lead the All of Us research program), he must be listened to.

Topol, thankfully, has taken the lead in promoting long-COVID and ME/CFS research, and in his free Ground Truths newsletter brings us up to date on what he considers key themes. A couple of recent blogs, “Ziyad Al-Aly: Illuminating Long Covid“, and “Long-Term Long Covid” have been doozies.

The Immensity of Long COVID

First, an analysis – “Postacute sequelae of COVID-19 at 2 years” – published in Nature charted what happened two years later to almost 140,000 veterans who came down with COVID-19 early in the pandemic. The results were so unexpected that the lead author, Ziyad Al-Aly, almost fell out his seat when he saw them.

Aly could not believe a respiratory virus could affect so many symptoms

Al-Aly could not believe a respiratory virus could increase the risk of a disease like diabetes.

First – hospitalization at the time of the infection – greatly, greatly increases the risk of many complications. Two years later, people who had been hospitalized early in the pandemic still displayed a significantly increased risk of having almost 2/3rds of the 80 sequelae (symptoms and conditions) that were followed in the study.

The range of sequelae the hospitalized patients were at risk of was remarkably wide – so wide – hitting every organ system – that the authors at first didn’t believe their results and redid them. The link to diabetes, for instance, complete shock – they had no idea how a respiratory virus could increase the risk of diabetes. That finding completely rearranged senior author Ziyad Al-Aly’s conception of what a virus could do. He told Topol:

“This is impossible…This is not how these things work. Again, from medical school, from all my education, we’re not trained to think that viruses, especially respiratory viruses, have these myriad effects on all these organ systems.

After they went back and redid the whole study, and even after they got the same results, he was still flabbergasted. He said:

I still was not believing it, and it was like, end, there is something wrong here. It’s weird. It’s strange…So I doubted it for the longest time, but the results came back exactly consistent every single time.

Al-Aly found that everything from cardiovascular conditions (angina, heart failure, arrhythmia, tachycardia, stroke, coagulopathy, pulmonary embolism) to gut conditions (IBS,  abdominal pain, gastritis, constipation, diarrhea, GERD, vomiting) to neurological disorders (Alzheimer’s, Bell’s Palsy, dysautonomia, migraine, paresthesias) to immune disorders (diabetes) to symptoms such as fatigue, headache, muscle pain, cognitive and sleep problems, hearing loss /tinnitus – an entire realm of diseases and conditions were increased in previously hospitalized patients. (Note that most autoimmune disorders were not assessed).

Notice how much bigger the world of post-infectious diseases just got! Respiratory viruses don’t just affect the lungs or the cardiovascular system – they also affect the brain, the gut, the nervous system, etc.

While things were considerably better in the non-hospitalized patients, they were not off the hook by any means. Two years later, non-hospitalized patients still had a significantly increased risk of having about a third of the 80 sequelae the authors assessed over time. Check how out closely the non-hospitalized patients resemble people with ME/CFS (see bolded text, below) and note the strong gut and autonomic nervous system theme.

The non-hospitalized patients were still at significantly increased risk of having acute coronary disease, anemia, bradycardia (slowed heartbeat), diabetes, acute gastritis, diarrhea, GERD, IBS, sleep problems, joint and muscle pain, fatigue, osteoarthritis, Bell’s Palsy (!), dizziness, dysautonomia, hearing loss/tinnitus, headache, stroke, migraine, paresthesias, cough and shortness of breath. (None of post-exertional malaise, fibromyalgia, nor ME/CFS were assessed).

This study did assess an older population, but it was predominantly done on men (veterans), and females are more prone to come down with long COVID. Plus, because some people who never had a verified COVID-19 infection – but who were still infected at some point – were likely included in the non-infected cohort, it’s possible the study may have underestimated the long-term impacts of a coronavirus infection.

Other large studies have found some dramatic increases in autoimmune diseases (rheumatoid arthritis, multiple sclerosis, Grave’s disease, spondyloarthritis, psoriasis and others) and diabetes over a two-year period.

Pathogens Taking Center Stage Again

rubiks cube diagnosis me/cfs

The complications COVID-19 is causing over time are causing researchers to rethink what viruses can do.

The takeaway from this and other studies is that we know incontrovertibly that infections can cause severe long-term consequences even after the immune system has “apparently” vanquished the virus.

Studies involving millions of people make it impossible to unwind this ball of string. In other words, pathogens – and not just the coronavirus – are back as an important study focus. The coronavirus may be nasty – and remarkably resilient and extremely contagious – but it’s not uniquely nasty.

The flu, after all, can kill, and produce inflammation of the heart (myocarditis), brain (encephalitis) or muscles (myositis, rhabdomyolysis), and multi-organ failure. It can trigger secondary bacterial infections, including pneumonia. One study found that about 6% of flu patients were still experiencing new symptoms long after they had “recovered” from the initial infection.

Both Topol and Al-Aly were very aware that other viruses are having similar impacts. Topol stated:

“The findings that SARS-CoV-2 leads to post-acute and long-term health effects should be framed within the larger context of infection-associated chronic illnesses—that infections (viral and nonviral) may lead to post-acute and chronic disease…”it’s not just this virus of SARS-CoV-2, the Myalgic Encephalomyelitis (ME/CFS) and many other viruses have led to a post-viral syndrome, which can be very debilitating.”

Al-Aly agreed, stating:

“…SARS-CoV-2 is not unique. There are a lot of viruses produce long-term conditions and they have different timing when they show up. And so we’re very, very interested in this and certainly are building our data systems here to look at five years and 10 years.”

The upshot is that after being mostly discarded for many years, pathogens are reportedly taking central stage in the research arena again – and that’s good news for people with ME/CFS.

The Vaccine Effect

Other studies are showing that if you can handle the vaccines, they can do a world of good. Vaccines have been shown to dramatically reduce the risk of hospitalization and death from the coronavirus and to provide some protection against long COVID, but a recent, very large study (@4 million people) concluded that they are also providing some protection against infection-triggered autoimmune diseases (Graves’ disease, anti-phospholipid antibody syndrome, immune-mediated thrombocytopenia, systemic lupus erythematosus and other autoimmune arthritis, pemphigoid). Topol reported that one study found vaccines produced a “quite substantial” impact on one’s risk of coming down with type II diabetes.

The RECOVER Initiative

Everyone has been counting on the RECOVER Initiative and it’s no wonder: the money provided to the NIH by Congress to study long COVID – $1.15 billion – was breathtaking. If any effort was going to lead long-COVID patients – and thus hopefully, ultimately people with ME/CFS – out of the darkness – it’s the RECOVER Initiative.

Two and a half years, repeated missed deadlines, an exercise study, and no really notable publications later – the enthusiasm regarding RECOVER has been muted, to say the least. David Putrino, the director of rehabilitation innovation at Mount Sinai and a clinician studying long COVID even went so far as to say, “This funding has been largely wasted.” Earlier this year, Topol told Stat News, “I don’t know that they’ve contributed anything except more confusion.

A Billion Dollars Later, STAT Asks What’s Up with the RECOVER Long COVID Initiative?

Even more upsetting was seeing ME/CFS expert Todd Davenport state that scientists on the RECOVER team “have parachuted into post-infectious illness and are now trying these things for the first time, to them. But it’s clear they haven’t done the reading.” Ouch!


  • Topol is a decorated researcher who has been plugging for long-COVID (and ME/CFS) research since early in the pandemic. A couple of recent blogs in his Ground Truths substack, “Ziyad Al-Aly: Illuminating Long Covid“, and “Long-Term Long Covid” have been doozies.
  • First – the coronavirus’s shadow is growing and growing. The results of a recent study of the effects of having a coronavirus infection 2 years later were so earthshaking and so at odds with perceived wisdom that the lead researcher had them redone again and again before he believed them.
  • It turned out that people who had been hospitalized were still at increased risk of diseases like diabetes and autoimmune diseases, as well as many cardiovascular and nervous system diseases and digestive conditions 2 years after having had a severe infection.
  • For the most part, people who had not been hospitalized during their infection looked – with their increased risk of fatigue, sleep, pain, cognitive, gut, and autonomic nervous system problems – like people with ME/CFS and/or fibromyalgia.
  • The point is that having an infection produces many more complications – including diseases one would not associate with it – than has been imagined. That fact should place pathogens and the effects they have on our health way up on the list of research priorities.
  • Recent research shows that vaccines – if you can tolerate them – are helping to reduce the risk of getting an infection-triggered autoimmune disease.
  • Recent data indicates that the mighty $1.15 billion RECOVER Initiative that so much hope has been placed in has blown through most of its money – the vast majority of which is going to “observational studies” of its projected 35,000-person strong cohort.
  • Topol and others believe much more money should have gone to treatment studies, and worry that RECOVER is simply reinventing the wheel with its immense but rather limited observational studies.
  • Time will tell, though, as RECOVER is still getting its feet on the ground. As the biological studies start pouring out of RECOVER over the next year or two, we should know much more about the impact the biggest long-COVID effort on the planet is going to have.
  • With data pouring out about the surprisingly diverse long-term effects the coronavirus is having, though, the field of post-infectious research should only grow and grow.

In August, Stat News reported that RECOVER has pretty much shot its $1.15 billion wad. Thanks to Representative Anna Eschoo – an ME/CFS supporter – RECOVER provided a budget breakdown which indicated that as of May of this year, it had spent $537 million to set up and study patient cohorts, $149 million for studying biological samples and health records, $122 million for following patients in the future, $225 million for “administrative coordination” which also includes “continuing pathobiology studies” ($68 million), $25 million for odds and ends. $171 million is going to treatment studies.

Both Topol and Al-Aly are frustrated with the RECOVER Initiative and the huge amount of money it’s poured into its observational studies. Al-Aly asserted that RECOVER is spending an extraordinary amount of money on things that we already know are happening in long COVID. Both he and Topol believe that much more money should be spent on treatment trials.

After 4 decades of waiting for a really good treatment for ME/CFS to show up, I’m wary – too wary perhaps – of the idea that something out there is going to make a huge difference for people with long COVID. I would actually rather RECOVER devote most of its money to research rather than spend money on interventions that may have limited effects.

For RECOVER to do that, though, it has to gather its data, generate and test hypotheses, and ultimately fund clinical trials. RECOVER seems to be spending most of its money, though, on that first step of a several-step process – gathering data via its “observational studies”, which include limited testing.

Is it possible that RECOVER spent much of its money on setting up its network, gathering preliminary, and not particularly illuminating data, and funding seven – mostly not very exciting – treatment studies? That seems inconceivable to me. There must be more to it than that.

Given that RECOVER has plowed roughly half its money into “observational studies”, though, we may at some point be asking why RECOVER chose to spend so much of its money following so many people (35,000) instead of doing more with a smaller cohort.

We were probably asking too much of RECOVER to quickly come up with the answer to long COVID, but should we expect RECOVER to be a leader that regularly is uncovering deep and novel insights into the disease? Yes, we should.

And we may still see that. At the recent Keystone long-COVID conference, Steven Deeks, a respected UCSF and RECOVER researcher, lauded the Initiative for getting off the ground so quickly and asserted that the RECOVER Initiative is doing just fine.

We should remember that RECOVER probably didn’t start enrolling patients in large numbers until early 2021. It takes time to get patients into its system, gather their data, analyze it, write it up, and submit its findings for publication. Perhaps it’s not surprising that we’ve seen no biological studies out of RECOVER yet.

The juicy biological stuff was always going to take more time, but should be coming down the pike soon – and hopefully in great volume. We won’t really know how successful RECOVER is until we see that – so let’s not write RECOVER off yet.

There’s no doubt, though, that RECOVER needs to make a splash to: a) justify its funding; and b) get more funding, and keep the long-COVID field alive. Its funding runs out in 2025 – just a year and a half from now – which means that unless the NIH picks up the slack – which it probably won’t – RECOVER probably will need to go back to Congress for funding. Unfortunately, no one seems to think that Congress is in the mood to give any more funding for anything COVID.




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