We performed a longitudinal crossover clinical study on survivors of COVID-19. We compared a standard rehabilitation protocol using elastic bands versus a novel eccentric cycling training protocol in individuals who have been discharged after being hospitalized due to COVID-19. We assessed the effects of these two rehabilitation modalities on physical performance, quality of life, and cognitive function parameters. We found that both protocols induced significant improvements in all variables. However, eccentric cycling induced such improvements involving less time per session. These findings could significantly impact strategies to treat COVID-19 survivors, which is a novel and impactful contribution to the body of knowledge.

Twenty patients (9 men, 11 women) between the ages of 30 and 60 years who had been hospitalized for COVID-19 in an ICU volunteered for this study. Participants were hospital-discharged at least 6 months before the start of the study and had not undergone rehabilitation after hospital discharge.

This study utilized a two-treatment crossover design. Each treatment was eight weeks in duration, with a two-week washout period. The order of treatments was randomized and counterbalanced. Twenty participants were recruited and completed this study. This sample was deemed sufficient as an a-priori power analysis (G*Power 3.1.9, Germany) estimated that 18 patients were required to test the anticipated effect, considering a statistical power of 0.8 and alpha <0.05. This effect was estimated based on the 18.7% increase in the 6-minute walking test observed after 12 weeks of eccentric training [10]. Considering a 10% dropout, we recruited 20 participants for this study.

Condition order was randomly arranged as either ECC then STD REHAB (n=10) or STD REHAB then ECC (n=10) to account for a potential order effect of treatments. Both interventions lasted eight weeks, and assessments were performed before and after the interventions. As shown in Fig. 1A, during the ECC participant performed eccentric cycling using an arm-and-leg motorized cycle ergometer (Model ABJ-107-2, Medical Technology Co LTD, China) while during the STD REHAB condition participants performed functional rehabilitation using strengthening exercises with elastic bands (Fig. 1B). During the 2-week wash-out period, the participants refrained from training in preparation for their second intervention.

2.3 Interventions The exercise intensity was matched between conditions throughout the intervention period using the 6-20 point rating of perceived exertion (RPE; Borg´s Scale) [10]. For both groups, RPE progressively increased during the first two weeks from 9 (very light) to 11 (fairly light), and then over the next five weeks from 13 (somewhat hard) to 15 (hard). Additionally, heart rate (HR) and blood pressure (Omron Serie 5/7156, USA), and oxygen saturation (Heal Force A3, CHOICEMMED, China) were measured immediately after all training sessions to quantify the cardiovascular demands of training, which were averaged between training sessions.

The training protocol for the ECC consisted of a 5-minute warm-up on a stationary ergometer (RS1 Go, Life fitness, USA) before completion of the prescribed workout. In the first two weeks, participants completed two sets of 10 minutes of eccentric cycling at an RPE between 9-11 with 2 minutes of inter-set rest. Then, during weeks 3-8, participants completed two sets of 15 min of eccentric cycling at an RPE between 13-15 with 2 min inter-set rest.

The training protocol for STD REHAB consisted of the same 5 min warm-up protocol used in ECC, followed by three sets of 8 repetitions of bicep curls, triceps extensions, shoulder abduction, bodyweight squats, deadlifts, and leg abductions with an elastic band with 2 min inter-set rest. The resistance of the elastic band tension was progressively increased according to the participant's tolerance based on RPE. ECC training was programmed for ~20-30 min, while STD REHAB lasted ~60 min per session.

Inclusion Criteria:

• Participants were hospital-discharged at least 6 months before the start of the study and had not undergone rehabilitation after hospital discharge.

Exclusion Criteria:

• Patients who did not pass the medical check-up before the study (patients with myocarditis and/or abnormal troponins or electrocardiograms from the last three months), oxygen-dependent patients, those with musculoskeletal injuries, bedridden patients, disoriented patients, or those with severe mental disabilities were excluded due to being unsafe to exercise.