Potential Mechanisms of Long-term Muscle Weakness and Decreased Exercise Tolerance in Patients Infected by SARS-COV-2

Exercise intolerance and muscle weakness have important consequences on the quality of life of healed patients and significant clinical implications: increased risk of falls and bone fractures, physical deconditioning and increased risk of chronic lung impairment and other diseases. Physical deconditioning and muscle weakness are, in fact, among the recognized risks of chronic pathologies. The identification of any covid-19 myopathy and its pathogenesis it would be of great importance to define adequate measures to counter it, for example through the prescription of physical exercise, limit the clinical consequences, improve the quality of life for many patients and decrease the cost for the National Health System. The present study aims to assess the frequency of easy fatigue, weakness and muscle pain in the population at the time of the onset of SARS-CoV-2 infection and after 2-3 months after healing. Moreover, as secondary outcome, it will evaluate the presence of objective signs of muscle involvement of theSARS-CoV-2 infections 2-3 months after recovery, quantifying the presence of myopathic structural changes and the causes of any muscle damage.

The study is a pilot single center clinical study, with non-pharmacological intervention, aimed at improve of clinical practice as an integral part of non-purpose health care industrial companies in accordance with the D.M. 17-12-2004 (No-Profit Trial).

The screening of eligible patients will be carried out by consulting the records paper-based clinics of patients belonging to the SSD Cardiorespiratory Rehabilitation of the Hospital of SS Antonio and Biagio and Cesare Arrigo in Alessandria. To eligible patients will be then submitted the information and consent document to participate in the study during the routine outpatient visits planned for these subjects. If following the explanations of the Investigator regarding the experimentation and evaluation of the document informative the patient decides to join the study and proceed with the following phases.

In-vivo physiological evaluation will be performed in suitable premises of the Center Interdepartmental Research Department of Biology and Sports Medicine of the University of Pavia equipped with the necessary equipment for first aid and in the presence of a doctor specialist in cardiology or related disciplines, with constant monitoring of vital parameters (arterial saturation, blood pressure and heart rate) and signal 12-lead electrocardiography. It will consist of an incremental cycle ergometer test until exhaustion; exhaustion will be defined by the patient's inability to maintain an adequate pedaling frequency, from reaching an equal heart rate value at least 85% of the predicted maximum heart rate or from a perception level fatigue (Borg scale) greater than 17. Patients will be asked before the assessment to become familiar with the instrumentation and with the researchers involved, by making briefs evidence. In the event that the patient / control subject complains of symptoms of fatigue, headache, dizziness, precordialgia or increased blood pressure during the exercise, this will be immediately suspended. In the presence of cardiovascular diseases or internist or in any case of serious general conditions the patient / control subject will not be enrolled in the study. Incremental testing and physiological assessments are used by several years from the research group of Physiology both on healthy volunteers and on patients with different pathologies (patients with neuromuscular pathologies, patients with heart failure, heart transplant patients, bronchopneumopathic patients) with no evidence of events adverse (Lanfranconi et al., 2006; Grassi et al., 2009; Marzorati et al., 2012a; Marzorati et al., 2012b; Mezzani et al., 2012; Mezzani et al., 2013; Grassi et al., 2020).

During the physiological assessment tests the following measurements will be performed: