Reply:
Post-COVID Syndrome and ME/CFS – Differentiation Is Essential
Response by Dr. Alexa A. Kupferschmitt & Prof. Dr. Volker Köllner to the letters from Sarah Born, Bettina Grande & Dr. Tilman Grande, Missing Doctors & Psychotherapists, and others.
We would like to thank you for the numerous letters and for the interest our article has generated. In several letters, we were criticized for devoting insufficient attention to “Post-Exertional Malaise (PEM)—the central symptom of ME/CFS” and thereby potentially putting patients at risk.
However, it was neither our assignment nor our intention to write about ME/CFS. The editors of the PTJ invited us to write an article on illness models in PCS—and that is precisely what we did. Almost half of the article is devoted to somatic explanatory models, followed by psychosocial aspects, and at the end we address therapeutic implications. The literature we cited likewise relates to PCS and explicitly not to ME/CFS. We also assumed that further contributions on this topic would follow in the PTJ—something we would very much welcome. Accordingly, we did not address differential diagnostic aspects (which would of course include severe ME/CFS) any more than we addressed psychotherapeutic strategies. And for PCS, there is evidence from controlled randomized trials supporting behavioral therapy and exercise therapy (including Zeraatkar et al., 2024).
We do not believe that people with ME/CFS are harmed by publishing these positive findings regarding PCS—just as we do not believe that people with bipolar disorder are harmed when positive study results concerning chronic depressive disorders are published.
We would like to make clear that we do not intend to ignore or minimize the suffering of people severely affected by ME/CFS—quite the contrary. This patient population is reached neither by standard guideline-based psychotherapy nor by conventional inpatient psychosomatic or somatic rehabilitation. What is needed are approaches adapted to the patients’ minimal exercise capacity, whether through online care, outreach-based services, or longer-term inpatient programs with intensive nursing support.
Regarding PEM: We consider the phenomenon of longer-term deterioration following exertion to be clinically relevant and took this into account at an early stage in our own clinical studies (Kupferschmitt et al., 2023), as well as highlighting its significance in a statement issued by our professional association (Köllner et al., 2024). Most of the exercise-therapy studies we cited recorded adverse events, even though they did not explicitly use the term PEM. In fact, the instruments used to assess PEM do not have the degree of discriminatory power that some of the statements responding to our article appear to suggest. For example, a large Danish cohort study (O’Regan et al., 2024) found a positive PEM score after 18 months in 25.1% of people who had been infected with COVID-19—but also in 20.6% of the seronegative control group. Here too, a more differentiated perspective and further research are required—particularly regarding the question of which subgroup actually warrants particular caution. Conversely, there is otherwise a risk of imposing unnecessary activity restriction on many people with PCS, thereby increasing anxiety and excessively limiting their scope for action and quality of life.
What perplexes us is the vehemence with which we are accused of psychologizing and even stigmatizing people with PCS. On page 110 of the article under discussion, we write: “This may lead to the assumption that somatic hypotheses regarding the development of PCS are a dead end and that the symptoms are ultimately predominantly psychologically caused. We expressly caution against this conclusion! On the one hand, the numerous and complex findings presented above clearly point overall to the presence of somatic pathology, even though this has not yet been fully elucidated…” It is difficult to distance oneself more clearly from a purely psychogenic view of PCS.
However, the fact that PCS has a primarily somatic cause does not mean that psychological and social factors cannot be involved in the development, persistence, and manifestation of PCS symptoms, or in influencing health-related quality of life. We cited several findings demonstrating such effects in our article, and further evidence has since emerged. There is also no reasonable reason to assume that PCS should be different from other chronic conditions in which the influence of psychosocial factors on disease course and/or quality of life is well established. It is difficult to imagine a hidden mechanism by which the COVID-19 virus would be capable of disabling otherwise applicable processes of illness coping and the influence of psychological comorbidity.
Even in disciplines with an unequivocally somatic orientation, such as orthopedics, the importance of, for example, depression for the successful outcome of hip replacement surgery is well established (reviewed in Schiltenwolf, 2025). In addition to PCS, our clinical and scientific focus is on psychocardiology. No one would think of characterizing a myocardial infarction or heart failure as a psychogenic condition. At the same time, however, the significance of psychological comorbidity (particularly depression and PTSD) and dysfunctional illness-coping strategies is well established and is taken into account in cardiology guidelines on diagnosis and treatment (reviewed in Kindermann et al., 2024). No one regards this as stigmatizing people with heart disease—including those affected themselves, whose patient advocacy organizations explicitly call for good psychosocial care in cardiology.
We are also puzzled by the accusation that we “blanketly accuse people with PCS of overexerting themselves.” First, one of our central concerns is to demonstrate that a differentiated assessment of dysfunctional persistence and avoidance patterns, together with differentiated therapeutic strategies, is necessary. Our empirical findings explicitly show that there are different patterns of illness coping that need to be considered in a differentiated manner (Kupferschmitt et al., 2025a).
The Avoidance/Endurance concept discussed here has, among other things, proved useful for treatment planning in psychological pain therapy, and there is increasing evidence that it is also relevant to the manifestation of symptoms in PCS (Burmehl et al., 2025). When, in psychotherapy, we identify indications of an unfavorable pattern of illness coping, we do not “accuse” the patient of having such a pattern—we try to explain it to them through psychoeducation and work toward changing it. Likewise, we do not “accuse” depressed patients of cognitive distortion; this is not about assigning blame, but about expanding therapeutic options—which is urgently needed in PCS.
We never claimed in our article that PCS could be cured. That would be presumptuous. As in pain medicine or psychocardiology, however, our aim is to support affected individuals in improving their quality of life and expanding their scope for action in small steps. The evidence to date indicates that this is possible with the help of psychotherapy and exercise therapy, with small to moderate effect sizes—no more, but also no less.
A study that did not recruit participants openly via the internet but instead surveyed 1,100 patients who had actually participated in PCS rehabilitation (Kupferschmitt et al., 2025b) likewise found high levels of satisfaction. If pharmacological or other somatic medical treatment options become available to affected individuals in the coming years, that would represent enormous progress—the goal here should be cooperation in the interests of those affected, not confrontation. Psychocardiology and pain medicine/pain psychotherapy demonstrate how this can be achieved.
Dr. Alexa Kupferschmitt & Prof. Dr. Volker Köllner
Teltow
