Waves of Evidence: Long COVID Research Round-Up February 2026

Welcome to Waves of Evidence, a monthly research roundup where I highlight and break down key Long COVID studies through the lens of a physical therapist specializing in rehabilitation. Most features will focus on recent research, with occasional deep dives into foundational concepts. This is Rising Tides’ first edition of Waves of Evidence. I hope you find it as fascinating as I do.

Article Title: A digital platform with activity tracking for energy management support in long COVID: a randomised controlled trial

Publication Date: February 2, 2026

In Other Words: Can Activity Trackers Help Prevent Post-Exertional Malaise in Long COVID?

What You Need to Know:

• Researchers were testing if a wearable device and a pacing app could improve post-exertional malaise in people with Long COVID.

• Participants were randomized into one of two groups:

  • Control: Pace App only (no alerts)

  • Intervention: Pace App + fitbit that provided real-time pacing alerts at 50%, 75%, and 100% of their allowance

• Goal: prevent exceeding physiological limits associated with PEM (aka prevent overdoing it in real time)

• Findings: There were less people who met PEM criteria on the Depaul Symptom Questionnaire regardless of which group they were in.

  • There was no significant difference between the two groups, which means that the real-time alerts did not make a big difference in the outcome.

• Results: Structured pacing support helps reduce PEM risk regardless of whether an individual is receiving real-time alerts or not

Definitions:

• Post-exertional malaise: a severe, delayed worsening of symptoms, extreme exhaustion, brain fog, and pain that are out of proportion to the amount of effort (physical, cognitive, emotional) that caused them. It is often a hallmark sign of ME/CFS, but is not exclusive to ME/CFS.

• Depaul Symptom Questionnaire: A validated questionnaire that screens for post-exertional malaise

Main Takeaways: This study aimed to determine whether real-time alerts from a wearable device could help more people avoid post-exertional malaise by warning them as they approached their physiological limits. In the end, they did not prove that real-time alerts were more effective. It’s likely due to multiple factors, but there were many limitations to this study, which the authors acknowledged. The problem is that wearable devices aren’t the end all be all. The real winner is having structured pacing support. People did improve in either group, so this wasn’t a negative outcome. However, I have some insight as to why the researchers didn’t confirm their hypothesis and had to reject it. Pacing apps (to-date) do not help users with cognitive, behavioral or emotional regulation. Most pacing apps only account for physical demands, and therefore only address one piece of the equation. It is likely that users in the study may have been approaching cognitive thresholds or other thresholds of overexertion outside of physical activity and had no idea. Additionally, wearable devices are calibrated for users who do not have chronic illness. Therefore, step counts can be highly inaccurate when they are at a really low or slow pace, which often occurs in the Long COVID population. This also provides inadequate information to accurately base a pacing plan for everyone. Some people can use step, but others can’t and this was acknowledged by the researchers.

Here’s one limitation that the researchers did not comment on, which makes me wonder if they are even aware of it. The reason that they didn’t see as big of an effect as they thought they would was because the thresholds they set were inappropriate. Allow me to explain. Each individual person was set a personalized activity allowance. This allowance created a threshold to alert the individual if they were at 50%, 75% or 100% of their threshold. That threshold was defined as no more than 30 minutes of activity above 60% of their age-predicted heart rate maximum. For reference, the age-predicted maximum is roughly 220 minus a person’s age. For example, a 40 year old person’s maximum heart rate is 180. 60% of that is 108. This means that this particular individual would be allowed to have a heart rate above 108 for 30 minutes. The problem with using this threshold is that 60% of age-predicted maximum heart rate far exceeds the anaerobic threshold in people with ME/CFS and most individuals with Long COVID. Other research suggests that the anaerobic threshold is roughly between 40-55% of age predicted max heart rate. Therefore, the researchers set a threshold too high. The significance of the anaerobic threshold is that whenever someone exceeds their anaerobic threshold, they start pulling from less efficient energy stores and energy reserves. It sets someone up for an energy mismatch and is one of the main causes of PEM. This researchers did mention that if somebody experienced PEM they would lower the threshold until they didn’t but this constantly allowing someone to go into PEM can be dangerous, which is likely why some participants stayed the same or worsened during the study.

Overall, this research study is the first of its kind. It sets the stage for more research on structured pacing, and the researchers recognize this. As they said, “although our framework was not successful at reducing mean PEM values in people with LC in 2022 and 2023, it should be refined and further developed for deployment in different settings or populations, much like the model of drug repurposing.”

And so, I hope that they do refine this over time AND use a more appropriate threshold to improve the lives of so many affected by PEM.

Meg’s Wave Rating: I give this 3 waves. The study and the topic is very relevant to people with Long COVID. It is a hot topic, and it still needs a lot of research. This is absolutely something worth paying attention to. There is nothing black and white about pacing, and we would love more objective criteria to definitely guide people. Stay tuned for this month’s deep dive into pacing and anaerobic thresholds to understand this concept more in-depth.

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Article Title: Virus-induced endothelial senescence as a cause and driving factor for ME/CFS and long COVID: mediated by a dysfunctional immune system

Publication Date: January 9, 2026

In Other Words: Why Long COVID May Stick Around: The Body May Not Be Clearing Damaged Cells

What You Need to Know:

• This high level clinical perspective piece does an analysis of multiple research studies and clinical findings to discuss how Long COVID and ME/CFS may be driven by damage to the endothelium (blood-vessel lining).

• Main theory proposed in the paper: SARS-CoV-2 can infect endothelial cells directly and push them into a state called cellular senescence (they stop functioning normally, but don’t die off like they should).

  • Self-reinforcing loop: Immune system abnormalities from Sars-CoV-2 and Long COVID impair removal of senescent endothelial cells and senescent endothelium promotes immune exhaustion. This further reduces clearance and allows more senescence and malfunctioning of cells and sustains disease long-term.

• Sub-theories include:

  • Senescence (malfunctioning cells) disrupt mitochondrial ATP production resulting in impaired creation of energy

  • Senescence allows for lysosomal hypertrophy, which is the build-up of cellular material and byproduct thus creating a backlog to recycling and creating new energy

  • Malfunctioning endothelial cells can happen anywhere in the body, which explains random multi-systemic symptoms

    • Skeletal muscle = exercise intolerance, PEM, fibrosis (scarring)

    • Gastrointestinal tract = impaired barrier function, gut dysbiosis, microbial movement to other tissues

    • Carotid or vertebral arteries = impaired blood flow to brain, orthostatic intolerance, neurologic symptoms (brain fog, memory, etc)

    • Blood Brain Barrier = neurological symptoms

  • Endothelial malfunctioning contributes to vasoconstriction, sympathetic activity, and reduced oxygen exchange to local tissues

Definitions:

• Senescence: the process of deterioration in a cell where cells stop dividing and therefore stops growing, repairing damaged tissue, reproducing, or regenerating. This happens with normal aging, but can become problematic leading to things like chronic inflammation, tissue breakdown, cancer and alzheimer’s.

• Endothelial cell: the inner lining of all blood vessels and chambers of the heart

• Mitochondrial ATP: ATP stands for adenosine-triphosphate which is actual energy in the body, similar to a battery. It is produced by mitochondria, which are the powerhouses within each cell that makes energy (aka ATP).

• Lysosomal hypertrophy: A lysosome is part of a cell that contains enzymes responsible for breaking down cellular waste. Lysosomal hypertrophy is when this part of the cell starts to swell due to an accumulation of undigested substrates. Basically, leftovers of the energy making process build up, don’t get cleared out or recycled causing a backload and bottleneck to creating new energy.

• Blood brain barrier: thin barrier made up of endothelial cells and other cell tissues to protect anything toxic from entering the brain, while still allowing bloodflow, oxygen, nutrition, and other important molecules through.

Main Takeaways: Oh boy. This one was a big one to digest (even for me), but I had a lot of “aha” moments while reading this piece. The main focus of this entire paper is how Sars-Cov-2 has a unique way of impacting endothelial cells. It’s not just about damaging them, it’s how it has the potential to damage them. The natural life cycle of a cell includes cell death. Another normal process is senescence, which is the heart of this paper. Senescence is the normal aging process of cells. It’s part of why our skin changes as we age and many other things change in the body too. Even though senescence is normal in the body, it can be problematic since it can cause tissue dysfunction and more inflammation. The main argument of this paper is that when Sars-Cov-2 damages endothelial cells, it does it in a way that the body has significant difficulty repairing or replacing the damaged cell. It therefore leaves the body stuck in a cycle where the damaged cell won’t die off like it should and instead remains living and functioning poorly. Because endothelial cells line our blood vessels, and blood vessels are everywhere, this can cause problems in any part of the body….therefore explaining symptoms anywhere in the body. Beyond this, they do an excellent job of tying endothelial senescence to post-exertional malaise, micro clotting, gut dysbiosis, and neurological symptoms. This isn’t to say that everyone has endothelial damage. We still don’t know why some people end up with persistent symptoms and new conditions after COVID and some don’t. What this offers is the biology and one explanation as to why somebody may be seeing so many changes. Long COVID has many versions, so this doesn’t apply to anyone. In terms of finding if this is you, there still isn’t great testing outside of the research setting. Many of the tests they they referenced to confirm endothelial dysfunction in people involved genetic testing. There are some profiles that can be put together, but still no specific biomarker or anything definitive. This wasn’t the only thing the paper brought to light though.

The biggest realization for me was the connection between the immune system and the endothelium. Outside of this paper, there has been proposed theories and that some versions of Long COVID act very similar to HIV and AIDS in the sense that both conditions have T-cell exhaustion. For those who don’t know, the T-Cell is a type of white blood cell responsible for identifying and clearing out foreign agents in the body. The concept of T-cell exhaustion is when this particular cell is under prolonged overstimulation thus rendering it ineffective. This paper doesn’t go heavily into T-cell exhaustion, but it also doesn’t ignore it and helps us make the connection between endothelial senescence and immune exhaustion. Basically, the connected the dots between endothelial malfunction and immune system failures. Here’s what they had to say.

When the lining of blood vessels is malfunctioning, it draws more immune cells such as CD8+ T cells, natural killer cells, and neutrophils to remove the malfunctioning cell. The constant stimulation and draw of the immune system, can render these cells ineffective and essentially exhausted ....aka immune exhaustion. This paper makes the case that immune dysfunction and endothelial dysfunction directly influence each other in both directions. Endothelial malfunction can cause immune dysfunction and dysfunctional immune cells can enable long-term endothelial malfunction. In many ways it ends up being a vicious cycle in which the cells can’t clear out the dysfunction themselves and neither can the immune system, thus leaving someone stuck in persistent symptoms and issues following viral infection. I know that anytime damage is discussed in the body, it can sound dangerous or permanent, and I want you to know that the body is resilient. Nothing in this paper discusses permanence, and the body is always turning over new cells. The goal is to set your body up under the right conditions to support a healthier turnover of cells. There are so many more golden nuggets throughout this paper, but at the end of the day the main thing to take away is that nothing happens exclusively. Everything is related, and so there is no single root cause to Long COVID. It is multi-factorial. It has many layers and the way that Sars-CoV-2 goes after the body it knows how to touch every corner and every system.

Meg’s Wave Rating: I give this piece 5 waves. Even though this isn’t a randomized control trial or big study, this clinical perspective piece reviews and analyzes the relevance of 256 other studies. It makes a really solid case with evidence as to why this theory is valid in explaining Long COVID. It also acknowledges that this is not the only possible mechanism, which is important that it isn’t trying to position itself as an exclusive rationale. It relates biology and physiology to symptom presentation and even points towards where future research for therapeutics should go. There isn’t one specific action step from this article, but there are many takeaways that could lead to individual action steps. Not only that, it paints a science-informed picture of why symptoms can be unrelenting and persistent and hints at a root cause of many of the things seen in Long COVID.

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