Gregory Fretz is one of the leading Swiss experts on Long COVID (see the Infobox “Profile”). In a two-part interview, he comments on the current state of research: first on the causes of Long COVID, and then on the possible treatments. This first part is about the causes. Part two looks at the treatment options.
Gregory Fretz, what do we currently know about the causes of Long COVID?
Firstly, it’s important for me to make clear that there are probably different types of Long COVID that are currently being grouped under the same name, but have different causes. “Long COVID” is defined only by its duration – that is, if symptoms last longer than four weeks after the initial infection. However, it’s important that we don’t lump everyone together. This is the only way can we provide targeted treatment.
What types are there?
It’s probably more of a spectrum than clearly defined types. On one side of the spectrum, there are young, healthy patients who, after experiencing a mild case, suddenly show neurological symptoms such as fatigue, exhaustion after minimum exertion (PEM), sleep and concentration problems. On the other side of the spectrum, there are the older patients who had serious symptoms and had to go to the ICU. These two sides should be treated very differently.
Which theories about the causes are being discussed?
One theory states that it has something to do with a type of neuroinflammation, which means inflammation sites in the brain. It’s linked to a malfunction of the autonomic nervous system, whose control center is in the brain. The autonomic nervous system controls our autonomic bodily functions such as digestion, heart rhythm and breathing. It also makes sure that we feel ill if something isn’t right and we need to rest.
With Long COVID, the autonomic nervous system appears to set off this feeling of being ill even though the organs are actually healthy. The immune system then continues to react, although it doesn’t need to. Symptoms such as a sudden rapid pulse, digestion problems or sleep problems signal this kind of dysautonomia, a disruption of the automatic control of our bodily functions.
“It’s possible that the immune system turns on its own body.”
What else could be behind it?
Autoimmune phenomena are also being discussed. In laboratory research, autoantibodies have been found. These antibodies are produced by the immune system and turn against your own body. Some, but probably not all patients, appear to belong to this group. Medication for treating this is being discussed and has shown very good results in individual cases. And by the way, the theories of neuroinflammation and autoantibodies are not necessarily mutually exclusive.
What about the topic of circulation?
We have seen that circulation problems and a reduction in microcirculation – blood flow in the smallest vessels – can occur. It could be that the endothelium, the layer lining the blood vessels, is affected. This can be the result of a neuroinflammation or autoimmune disorder.
“It isn’t easy to keep an overview – but a lot is happening at the moment.”
And what about the theories on cell respiration and/or the mitochondria?
In some of those affected, energy production in the cells, i.e. cellular respiration in the mitochondria, doesn’t happen properly anymore. This can be measured to some extent, and would explain symptoms such as muscle pain. However, whether this is a primary cause of the complaints, or if it is actually a consequence of the disturbed balance in the immune system, is disputed.
It sounds like it’s hard to get a clear picture...
There are also other theories; for example, that some of the virus or the virus particles continue to trigger the immune system. This would explain why the vaccination has a therapeutic effect in some of those affected. It isn’t easy to keep an overview – but a lot is happening at the moment.
“Long COVID is a complex phenomenon that requires complex answers.”
How relevant are these findings to your daily work?
It’s probably not a case of one theory explaining everything. There could be a bit of truth in all of them, and they may also interact. Long COVID is a complex phenomenon that requires complex answers.
For us, a big part of it is understanding what is happening to each patient. This way, we can tailor the treatment to each individual situation. I know it would be nice if someone came and said: “I’ve solved the puzzle and cured Long COVID!” However, it’s not something I can see happening just yet. It’s more likely that those affected will receive a tailored treatment depending on what has happened and what their symptoms are.
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