Post-COVID-19 syndrome (PCS) is a condition that occurs following an acute infection with
the SARS-CoV-2 virus (COVID-19). PCS is characterized by symptom persistence for at least
12 weeks after the infection or the emergence of new symptoms during this period. Current
guidelines propose several criteria for diagnosing PCS, including persistent symptoms
from the acute COVID-19 phase, new symptoms leading to health limitations, symptoms
assumed to be related to COVID-19 after the acute phase, and worsening of pre-existing
underlying conditions. PCS is a complex and multisystemic disorder, with symptoms ranging
from chronic fatigue, decreased physical performance, muscular weakness, and pain to
cognitive impairment (often referred to as brain fog) and mental and psychological
distress resembling a post-traumatic stress reaction. The exact causes of PCS are not
fully understood but may involve processes such as endothelial dysfunction, cytokine
storm, and increased oxidative stress affecting various organs and structures in the
body. The incidence of PCS varies depending on the population studied and the severity of
symptoms considered, with estimates ranging from 7.5% to 41% among non-hospitalized
patients with acute infection.

Medical rehabilitation is essential for patients with persistent PCS, but there are
limited studies on its efficacy, especially in the context of aerobic endurance training.
Physical exercise, including aerobic training, has shown positive effects in various
diseases, and it is suggested that it may be beneficial for PCS as well. However, there
is limited evidence regarding the effectiveness of aerobic endurance training in reducing
the burden of decreased physical performance in PCS. Moreover, there is a lack of
guidelines for PCS patients related to exercise-based rehabilitation. Aerobic endurance
training has been proven to have positive effects on multiple physiological functions and
is recommended for chronic heart and pulmonary diseases. Studies have also suggested that
aerobic interval training may be advantageous for PCS patients, as it reduces ventilatory
demand and may alleviate dyspnea and breathing effort. This study aims to investigate the
efficacy of moderate-intensity aerobic endurance training performed as either continuous
training and interval training for the medical rehabilitation of PCS patients.

The study will include PCS patients referred for inpatient medical rehabilitation in
Germany with a history of (at least one) Covid-19 infection and ongoing or newly
expressed performance deficits lasting for at least 3 months prior to recruitment.
Performance deficits will be documented according to the recent consensus statement, with
the cluster of lead symptoms including fatigue/exercise intolerance, shortness of breath,
and cognitive dysfunction impairing activity of daily living and everyday functioning. A
detailed clinical workup will be performed, and the history of comorbidities and current
medication will be documented. After admission, patients will be randomized to a
continuous training (CT) or interval training (IT) group. Patients will receive
individual medical rehabilitation including a combination of strength, respiratory and
cognitive training, as well as physio-, psycho- and nutrition therapy, unaltered for both
groups. Data on medical rehabilitation including prescriptions of therapeutic actions and
participation will be recorded for all patients. Symptom-limited spiroergometry at
admission and after 4-6 weeks of inpatient rehabilitation (before discharge) will be
performed to analyze improvements in exercise capacity. Validated questionnaires will be
used to document patients' disease perception.