Feb 16, 2023

Sustainable impact of the acute and subacute recovery-stress state on long COVID


The currently most widely used nomenclature differentiates between the acute phase and the post-acute phase of COVID-19 based on data concerning the virus shedding. Since generally no replication-competent virus can be identified beyond 3–4 weeks after the onset of the symptoms [1], it has been suggested to define all symptoms that persist or newly appear after that time as ‘post-acute COVID-19’ or ‘long COVID’ [1]. One of 8 people who have had COVID experience prolonged symptoms over many months [2]. The typical symptoms of long COVID include marked fatigue, exercise intolerance, post exertion malaise, difficulty breathing, brain fog, muscle pain and weakness, chest pain, headaches, and fast heart rate [1, 2]. The physiological response to exercise testing in long COVID is characterized by a reduced aerobic capacity, increased reliance on anaerobic metabolism, cardiocirculatory limitations, dysfunctional breathing patterns, and an impaired ability to extract and use oxygen [1]. The acute effects on exercise indicating a low cardiorespiratory fitness are often described as exercise intolerance and persist for months after infection in long COVID and likely provide a deconditioning effect. However, the findings from a recent review do not support deconditioning as the primary mechanism for low cardiorespiratory fitness in long COVID.

The main symptoms relevant for physical (in)activity and recovery-stress state are marked fatigue, exercise intolerance, and post exercise symptom exacerbation/post exertional malaise. They have similar profiles to post-acute infections syndromes and clinical features as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) [3]. The marked symptom profiles for ME/CFS following increased physical and cognitive activity and emotional demands are fatigue, exercise intolerance, and PEM. Indeed, an observational study of patients with fatigue and exercise intolerance for > 6 months after mild to moderate COVID-19 suggest that the extent of exercise intolerance (acute effects) and PEM (prolonged/chronic effects) are important stratifying factors for medical care, exercise prescriptions, as well as return to activity and return to sports guidelines [4]. In particular, exercise intolerance must be clarified immediately after the demand (acute stress-state) and possible PEM must be clarified in the hours and days that follow after an exercise or workload (acute recovery-state).

To maximize their effectiveness, exercise prescription and therapeutic strategies in long COVID should account for the acute and chronic recovery-stress state. Accordingly, to validate medical and non-medical therapeutic treatments and to identify possible long COVID phenotypes concerning recovery-stress state, it must be assessed before, immediately after (acute), and post exercise symptom exacerbation (subacute including overnight). Unfortunately, the assessments measuring PEM focus on longer time periods and are not suited to assess changes in recovery-stress state in long COVID over short time intervals. In particular, the assessment tools were not developed to assess temporal changes in acute and ongoing/chronic recovery-stress state or for repeated measurement designs, before, during, and after exercise. The recently established Acute Recovery and Stress Scale (ARSS, 5] – which assesses the recovery-stress state over short periods – appears to be suited to this purpose but this has yet to be empirically determined. Therefore, the aim of the present WUN-application is to develop and validate an international recovery-stress state inventory for the assessment of post-acute infections syndromes (RSI-PAIs) based on long COVID and the established ARSS.



[1] Haunhorst, S., Bloch, W., Wagner, H., Ellert, C., Krüger, K., Vilser., D.C., Finke, K., Reuken, P., Pletz, M.W., Stallmach, A., & Puta, C. (2022). Long COVID: a narrative review of the clinical aftermaths of COVID-19 with a focus on the putative pathophysiology and aspects of physical activity, Oxford Open Immunology, 3(1), iqac006, doi: 10.1093/oxfimm/iqac006.

[2] Ballering, A. V., Zon, S. K. R. van, Hartman, T. C. olde, Rosmalen, J. G. M., & Initiative, L. C. R. (2022). Persistence of somatic symptoms after COVID-19 in the Netherlands: an observational cohort study. Lancet, 400(10350), 452–461. https://doi.org/10.1016/S0140-6736(22)01214-4

[3] Marshall-Gradisnik, S., & Eaton-Fitch, N. (2022). Understanding myalgic encephalomyelitis. Science, 377, 1150–1151. https://doi.org/10.1126/science.abo1261

[4] Kedor, C., Freitag, H., Meyer-Arndt, L., Wittke, K., Hanitsch, L. G., Zoller, T., Steinbeis, F., Haffke, M., Rudolf, G., Heidecker, B., Bobbert, T., Spranger, J., Volk, H. D., Skurk, C., Konietschke, F., Paul, F., Behrends, U., Bellmann-Strobl, J., & Scheibenbogen, C. (2022). Author Correction: A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity. Nature Communications, 13(1), 6009. https://doi.org/10.1038/s41467-022-33784-x

[5] Kellmann, M. & Kölling, S. (2019). Recovery and stress in sport: A manual for testing and assessment. Abingdon: Routledge.

The WUN Global Challenge(s) addressed by this project

Developing therapeutic treatments for long COVID is a significant challenge. To achieve this, the evaluation of therapeutical approaches (which may result in effective treatments) needs to be based on validated assessment tools. With the development of the international recovery-stress state inventory for post-acute infections syndromes, this project provides important groundwork that can be used for long COVID interventions in both athletes and non-athletes. As the expertise of the team is primarily based in the sport context, the development and validation of the tool will start in this area and will be supported by sporting organizations. Indeed, long COVID is a significant problem in (elite) sport as athletic performance can be depressed for prolonged periods following infection. In Germany, the first cases of long COVID were described in athletes. However, the impact of long COVID extends well beyond sports. Besides the negative impact on infected individuals and their families, long COVID also affects the work force through reduced productivity and increased health care. Currently, the global consequences of long COVID are substantial and therefore there is clear necessity for developing therapeutical approaches that use both subjective and objective assessments. To address this, the research team will develop a validated subjective assessment and monitoring tool for use in athletic and non-athletic populations with the aim to support sustainable in therapeutic treatments.