Long COVID and ME/CFS: What Recent Research Has Actually Found

Anyone living with Long COVID or ME/CFS has often experienced not being taken seriously – partly because for a long time there was barely any robust research. That has changed noticeably in recent years. There is still no cure and no single causal test, but research has pieced together important parts of the puzzle. This article summarises what serious studies from recent years genuinely support – without promising anything that science can't (yet) deliver.

A clearer definition of Long COVID

One central problem for a long time was: what actually counts as Long COVID? The large-scale US RECOVER Initiative, run by the National Institutes of Health, analysed data from thousands of affected people to address this. The researchers collected symptom reports from around 8,600 people who had been infected with COVID-19 and around 1,100 uninfected people. The team found 37 symptoms that occurred significantly more often in people after a COVID-19 infection, of which 12 most clearly distinguished affected people from unaffected ones. These twelve core symptoms include, among others, post-exertional fatigue, marked tiredness, and "brain fog". This definition is not a diagnostic tool for everyday use, but it gives research a shared framework for the first time, making it possible to compare studies worldwide more effectively. Anyone wondering how the individual terms around Long COVID, ME/CFS and POTS actually differ can find background in the glossary on Long COVID, ME/CFS and POTS.

Biological traces: what happens in cells and blood

One major advance in recent years is that researchers are increasingly finding measurable biological abnormalities – even though this has not yet become a routine test for practical use. Several lines of research are currently being pursued intensively:

• Mitochondria and muscle cells: NIH researchers have shown that a protein called WASF3 is elevated in muscle cells in people with ME/CFS and disrupts mitochondrial energy production. Muscle biopsies from people with ME/CFS showed elevated WASF3 protein levels and disrupted activation of cell stress signals in the endoplasmic reticulum. This offers a possible explanation for why physical exertion is processed so differently in ME/CFS compared with healthy people.
• Skeletal muscle in general: A recent review summarises that disturbances in skeletal muscle appear to play a central role in Post-COVID and ME/CFS, evident among other things in reduced muscle strength measured in studies.
• Autoantibodies: The hypothesis that the immune system mistakenly attacks the body's own tissue after an infection is still being investigated. A systematic review arrives at a cautious conclusion: four studies found a possible but small association between autoantibodies and persistent Post-COVID symptoms, while one study found no association. The evidence is therefore real, but not yet conclusive.
• Microclots and blood vessels: Other work is examining whether tiny blood clots and activation of the inner walls of blood vessels contribute to persistent symptoms – a field of research that is also still in flux.

It's important to note: none of these markers currently form the basis of a standard diagnosis. But they do show that the once common assessment that the symptoms are "just psychological" is becoming increasingly difficult to sustain scientifically.

What is being researched in terms of possible treatment approaches

Something is also happening on the treatment front – though "being researched" here explicitly does not mean "proven to work". The RECOVER Initiative has launched several clinical trials, for example on autonomic symptoms such as dizziness, rapid heartbeat and shortness of breath, as well as on cognitive complaints such as concentration problems. One of these studies examined three non-drug approaches to cognitive symptoms; the focus was on complaints such as memory problems, difficulty concentrating and unclear thinking, colloquially known as brain fog. Some of these studies are still ongoing, while initial results are available for others – but the details of this belong in a conversation with a medical professional, not in general self-assessment.

What does this mean for everyday life with pacing?

As exciting as these advances are, little changes in everyday life in the short term. There is still no causal treatment that reliably prevents PEM (post-exertional malaise). This is precisely why pacing – the deliberate management of energy to avoid crashes – currently remains one of the most important tools for coping with Long COVID, ME/CFS and similar conditions. The biological findings on muscles and mitochondria even provide a plausible explanation for this: if energy production is disrupted at the cellular level, it makes sense that even small exertions can have major consequences. Anyone not yet familiar with the basic idea behind this can find a good introduction in the article Pacing basics: what pacing is and why it helps with PEM. And because the crash after exertion often comes with a delay, it's also worth taking a look at the article Recognising PEM: why the crash often only comes days later.

Research is moving forward – more slowly than many affected people would like, but in a direction that is making these conditions increasingly graspable in biological terms. Until this translates into approved therapies, carefully observed, individual energy management remains one of the few tools that can already help in everyday life today. For specific health questions or new symptoms, seeing a medical professional remains essential – mypacing can accompany this path, but not replace it.

Sources

• Development of a definition of postacute sequelae of SARS-CoV-2 infection
• Toward a deeper understanding of long COVID
• WASF3 disrupts mitochondrial respiration and may mediate exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome
• Autoantibodies in COVID-19 survivors with post-COVID symptoms: a systematic review
• RECOVER-NEURO clinical trial shares results of three non-drug treatments for cognitive symptoms of Long COVID
• Key Pathophysiological Role of Skeletal Muscle Disturbance in Post COVID and ME/CFS