We thank van Rhijn-Brouwer and colleagues for responding to our Review (A. Fedorowski et al. Cardiovascular autonomic dysfunction in post-COVID-19 syndrome: a major health-care burden. Nat. Rev. Cardiol. https://doi.org/10.1038/s41569-023-00962-3 (2024))1 with their Correspondence (F.C.C.-C. van Rhijn-Brouwer et al. Graded exercise therapy should not be recommended for patients with post-exertional malaise. Nat. Rev. Cardiol. https://doi.org/10.1038/s41569-024-00992-5 (2024))2. They expressed concerns about our statement that the “[a]pplication of graded exercise therapy is especially important in the setting of coexistent ME/CFS [myalgic encephalomyelitis/chronic fatigue syndrome] to reduce the effects of the highly expected post-exertional malaise”. Although discussing the benefits of aerobic reconditioning in patients with postural orthostatic tachycardia syndrome (POTS) and other forms of cardiovascular autonomic dysfunction, we factually meant that a more cautious approach is required in patients who present with signs of ME/CFS. We did not advocate generic advice to ‘do exercise’, but were calling for a more nuanced, individualized and supervised approach to exercise in these patients, as recommended by the UK National Institute for Health and Care Excellence (NICE)3. In this spirit, we recommended a graded approach to exercise therapy. Although a graded approach can have many meanings, we see that some authors use the term ‘graded exercise therapy’ to advocate a more standardized and less individualized approach to physiotherapy. Our understanding is that, in some cases, a standard approach to physical exercise might potentially harm patients with a still poorly defined susceptibility to post-exercise energy depletion4. We apologize for our lack of clarity. Our intention was to raise awareness of this special subgroup of patients among those who have post-COVID-19 cardiovascular dysautonomia, rather than to promote the training programme in an indiscriminate way.

The issue of post-exertional malaise after different types of exercise is intriguing and hitherto not extensively studied4,5. Patients with post-exertional malaise undoubtedly feel substantially worse immediately, and in the short-term, after exercise. However, clinical observations demonstrate that, over time, exercise can be beneficial in many patients with POTS6,7, including those with post-COVID-19 syndrome8. Although post-exertional malaise was not formally assessed in these studies, some patients are likely to have had post-exertional malaise. We, the authors of the Review, see many patients with POTS in our clinical practices, and each of us has seen patients who had initial worsening at the onset of an individual training programme, but who improved during follow-up under careful supervision by professional staff. Importantly, this approach is supported by the NICE guidelines3. We undoubtedly agree with van Rhijn-Brouwer and colleagues that further research is needed to understand how best to care for patients with cardiovascular autonomic dysfunction in post-COVID-19 syndrome. New evidence based on well-designed trials will be crucial, as demonstrated by the list of ongoing projects in our Review1. Until then, the jury is still out; we should wait for the verdict and respect it when it comes.