Six Years In. The Past, Present and Future of Long COVID

Part 1

With March 15th being the 4th international Long COVID Awareness Day, I felt as if a reflection is long-over due. If we are being honest, this topic is a big one, and there is too much valuable information to omit. Rather than writing one long article, I will be doing something special this month and splitting this up into a 3 part series.

Today, you are reading Part 1, which covers the past. Part 2 will discuss how the treatment gap is being bridged in the present day, and Part 3 will look to the future of Long COVID. Part 2 and 3 will be released March 15th and March 22nd respectively. Take your time with it. Pause when you need to. Come back to it over and over again.

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If back in early 2020 you had told me that I would become specialized in Long COVID rehabilitation, I would have looked at you with ten heads and asked, “what is Long COVID?” Honestly, we all would have. When the first wave happened, I was a physical therapist working in a hospital. Like the rest of the world, the hospital where I worked was learning in real time. I live 3 hours north of New York City, and as NYC became the epicenter of the pandemic we too were surging with cases hard and fast. To say that it was wild working in the hospital system at that time is an understatement. Everything was unprecedented and nothing was standard. COVID-19 was supposed to be a respiratory illness. You got sick. You recovered. You moved on…at least that was the narrative that was pushed.

And the truth (as we now know) is that many people didn’t move on.

In those first weeks and months, my colleagues and I were seeing things that didn’t add up. Again, everything about this virus should have been a severe flu or a severe pneumonia. Yes, it brutally attacked the lungs, but it did far more than that. The survivors we saw in the hospital looked like they had brain injuries. Some would have unexplained gout flares. Others would make tremendous progress in the hospital only to stop making progress once they got home.

None of it was adding up.

We didn’t have a name for it yet. We didn’t have a framework. What we had was a clinical reality that refused to fit the narrative we’d been handed, and like a moth drawn to a flame, I was determined to figure it out. As it should happen, 3 random pieces of fate helped me put the pieces together earlier than most.

1. I recently had a patient in late 2019 who had microvascular induced dysautonomia…I had never learned about it in school and became really fascinated with it. I was actively learning about dysautonomia at the time.

2. Early 2020 I worked with a patient who had POTS and hEDS, which again I never knew about. I started learning as much as I could to help them.

3. I grew up with Hannah Davis (one of the co-founders of the patient-led research collaborative), and I saw a Facebook post in May of 2020 about how she was on day 63 of being sick with COVID. Lightbulbs started going off in my head.

The combination of these rare events led me to see that we weren’t just dealing with a respiratory illness. We had a complex neuro-immune condition on our hands that was at the minimum triggering dysautonomia…and at the maximum…well we still didn’t know yet.

Six years later, that reality has a name, a definition, a growing body of research, and for the first time, drugs in clinical trials specifically designed to treat it. This is the story of how we got here, where the science stands right now, and what’s coming next.

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In the Beginning: Patients Named It First

Before any research institution had turned its attention to post-COVID illness, a group of individuals who were experiencing symptoms beyond the predicted 2 week quarantine and recovery timeline were already trying to figure this out themselves.

They gathered in online forums, comparing notes on symptoms that didn’t resolve, timelines that kept extending, and doctors who told them they were anxious or deconditioned. Out of that community came the Patient-Led Research Collaborative (PLRC), and out of the PLRC came the first-ever systematic research on what Long COVID actually looked like. This landmark study was conducted by the people actually living the reality, and it was done before the medical establishment had language for it, or quite frankly was even aware that this problem even existed. The PLRC were the ones to sound the alarm and say that expecting resolution of COVID after 14 or even 21 days was not the reality for everyone.

As I mentioned earlier, Hannah Davis, one of the PLRC’s co-founders, is someone I grew up with. Living on a small island, everyone knew everyone, but we also played drums together in middle school and high school. I had no idea, in those years of band practice, that she would one day help name and define a disease that I would spend my career treating. As it would happen, I also had the opportunity to meet another one of the co-founders, Lisa McCorkell, at the 2024 National Long COVID Rehabilitation Conference. In those moments, I felt a particular mix of admiration and inspiration that comes with understanding how much of this work began with people who were profoundly ill and decided that if the system wasn’t going to study them, they would study themselves….and that is exactly what the PLRC has done.

The PLRC’s early work wasn’t just data collection. It was an act of legitimization. They documented what patients were experiencing with the rigor and transparency that the medical establishment had failed to apply. They called for acknowledgment of Long COVID as a distinct illness, accurate prevalence estimates, basic symptom management, and aggressive research into pathophysiology. They asked to be taken seriously.

That ask took years to answer, and is still an ongoing battle.

Up until 2024, there wasn’t a uniform name for prolonged symptoms after COVID. Various names were used such as post-acute covid sequelae, long-term COVID, post-acute covid-19 syndrome, chronic covid, post-covid syndrome, and the list goes on. This was a major problem because health insurance didn’t have a single diagnosis to recognize and the research was scattered without uniform terms. The term “long hauler” and the name “Long COVID” came from patients, but it wasn’t until June 2024, four years into the pandemic, that there was finally a consensus name and definition. At that time, The National Academies of Sciences, Engineering, and Medicine (NASEM) formally enshrined “Long COVID” as an official clinical term, defining it as an infection-associated chronic condition present for at least three months, affecting one or more organ systems, that can be continuous, relapsing and remitting, or progressive.

This matters because naming is legitimizing. This matters because the NASEM definition was built not just from scientific literature and expert testimony, but explicitly from patients’ lived experiences. It matters because for years, people with Long COVID were told their suffering was psychological, and the definition made it clear that this illness transcends mental health, age, race, gender, geography and socioeconomic status. Long COVID does not discriminate against who it affects.

The patients were right all along. The science just had to catch up.

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The Past: Science Is Catching Up

In the past two years, the research on Long COVID has moved from “does this exist” to “here is what it’s doing to the body” and the findings are as validating as they are sobering. There are so many landmark studies that have happened along the way, and these are just a few of the ones that continue to advance the narrative.

The First of Many (2021 & 2023)
In 2021, Hannah Davis and Lisa McCorkell, along with their PLRC colleagues, published what would become one of the most important papers in the history of this illness. Surveying 3,762 people with Long COVID across 56 countries, they documented 205 symptoms spanning 10 organ systems, with participants experiencing an average of nearly 56 symptoms at a time. Ninety-six percent of respondents were still symptomatic beyond 90 days. Nearly half had reduced their work schedules. More than one in five had stopped working entirely. This paper put Long COVID on the map. It changed the narrative for what everyone thought COVID was or should be, and the truth was that it was far more than “just a cold”. I can remember when this paper was published and just pouring over it again and again and again. Truly groundbreaking for this field.

Two years later, Davis and McCorkell returned to the literature with a second landmark paper in Nature Reviews Microbiology, but this time synthesizing the mechanisms behind what they had first documented in patients’ own words. That paper catalogued more than 200 symptoms across organ systems, mapped the leading biological hypotheses for why Long COVID happens, identified the overlap with conditions like ME/CFS and POTS, and issued an explicit call for clinical trials, patient-inclusive research, and urgent investment in the field. What is remarkable is not only what these two papers accomplished at the time, but how thoroughly they have held up. In a field that has produced nearly 10,000 studies in five years, the symptom profiles, the organ system involvement, and the biological mechanisms the PLRC identified early on continue to be cited, validated, and built upon by researchers worldwide. They didn’t just document and put Long COVID on the map. They drew the map that the rest of the scientific community has been navigating ever since. Together, these papers are, in many ways, the reason the research landscape described in this article exists at all. It also was the first time I felt validated as a clinician in my thought process that COVID was triggering dysautonomia.

An Immune Fingerprint (2023)
In September 2023, a landmark study published in Nature by researchers at the Putrino Lab and Iwasaki Lab offered something the field had been waiting for: a measurable immune fingerprint. One of the most unfortunate and hardest parts about this condition is that there is no single biomarker for Long COVID. There isn’t a lab test that says, “Yes, you have Long COVID”. To be clear, this study didn’t find a biomarker, but it found a pattern. When those patterns were fed into a machine learning model, it could distinguish Long COVID from non-Long COVID patients with 96% accuracy. Part of the discovery was that people with Long COVID had marked differences in circulating immune cells in the blood versus people who knowingly don’t have Long COVID. They saw a distinct pattern of exaggerated antibody responses to SARS-CoV-2, and significant T-cell exhaustion. Essentially, they proved that the immune system had been fighting for so long that its soldiers were burning out, and they could measure it. Again, this pattern of recognition is not a biomarker. To date, there still isn’t a standalone blood test for Long COVID. The immune dysregulation was so consistent and distinct that a machine could detect it. That distinction matters, and it is not a small one. What this says is that Long COVID has a biological signature, it can be measured, and it is not in your head.

The Gut-Brain Axis (2023)
Also in 2023, researchers at the University of Pennsylvania published a study in Cell that added another piece to the puzzle. They found that Long COVID patients show significantly reduced serotonin levels, and not as a mood disorder, but as a direct consequence of viral inflammation disrupting the gut’s ability to absorb tryptophan, the precursor to serotonin. What’s the downstream effect of this finding? Less tryptophan in the gut means reduced vagus nerve activity, which connects to the part of the brain responsible for cognition and memory. In plain terms, the virus disrupts the communication line between the gut and the brain in ways that can help explain brain fog, fatigue, memory loss and cognitive symptoms that weren’t showing up on brain imaging. The finding has been subject to ongoing scientific debate, which is exactly how good science is supposed to work, but the broader point stands: there are identifiable, measurable mechanisms behind the cognitive change that otherwise doesn’t show up on brain imaging or anywhere else.

This is not Deconditioning (2024)
And then in 2024, a study came out that should end the deconditioning argument once and for all. Researchers biopsied skeletal muscle in Long COVID patients before and after a task designed to induce post-exertional malaise (PEM). They didn’t find evidence of deconditioning. In fact, what they found was severe exercise-induced myopathy, mitochondrial dysfunction, a shift toward less efficient glycolytic muscle fibers, immune infiltration in the muscle tissue itself, and (perhaps most striking) amyloid-containing deposits in skeletal muscle. Taken together, these findings point to microclots in the muscles when PEM is triggered, less efficient muscle fibers, along with metabolic and structural damage in the muscle causing tissue-level injury. All of it worsened measurably after exertion. THIS WAS HUGE!! We in this community already knew that post-exertional malaise was dangerous, but this study showed that when triggered it can cause physical damage to muscle tissue. This basically gave us a seat at the table to shut down the “push through, keep exercising” narrative.

Premature aging cells (2026)
Most recently, a 2026 clinical perspective published in Cell Death & Disease proposed a unifying framework for why Long COVID affects so many organ systems and refuses to resolve on its own: endothelial senescence. I recently covered this article in a previous substack. The theory holds that acute SARS-CoV-2 infection triggers dysfunction and premature aging in the cell lining of blood vessels located at the blood-brain barrier, in the GI tract, and in skeletal muscle. Normally, the immune system would clear these senescent cells. In Long COVID, immune abnormalities prevent that clearance, creating a chronic state of low-grade inflammation, microclot risk, and vascular constriction across multiple systems. In my opinion, it’s one of the most compelling and eye-opening explanations yet for why this illness is so pervasive and so persistent.

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Now, I don’t want you to walk away from this article feeling like the research is only exploring what is “wrong” with people. I know this landscape is complex, and can sometimes feel triggering. I know that navigating it isn’t easy. I also realize that there is a TON of mistrust from years of misinformation, gaslighting, and false promises because of the research timeline. There is a large gap between the development and testing of treatments and the rate at which it is happening. And it is true, there are systemic hurdles in place delaying treatments every step of the way (from funding for research all the way to insurance coverage of treatments). And in all fairness, in order to have successful treatments, we need to understand the mechanisms of the disease as much as possible. So, take a deep breath with me….in….and out…because amidst all the “doom and gloom”, I strongly feel that we have a FAR better understanding now, which sets us up well to bridge the gap. There are so many inspiring studies being done to help determine treatment pathways, and I’ll be highlighting them in Part 2 coming on March 15th.

I also know that you can’t sit idly waiting for the research, which is a big reason why I do what I do. There can be a lot of skepticism about what is the best next step in healing. This is why I have decided to tear down the walls and allow a 30-day free trial of my self-paced course for Long COVID to anyone looking to take control of their symptoms using food as medicine, pacing, intentional movement, and nervous system regulation as the foundation. I’m doing this in honor of Long COVID Awareness month. The opportunity will be available starting on Long COVID Awareness day (March 15th) and remain in effect for the rest of March.

To receive a reminder of the free trial you can receive reminders by joining the list here

We’re in this together, and don’t forget to stay tuned for Part 2 on March 15th!

With love,

Dr. Meg

P.S. Guided monthly breathwork is next week on March 18th at 5:15pm EST (available to paid subscribers).