Effectiveness of a telerehabilitation program for COVID-19 survivors (TERECO) on exercise capacity, pulmonary function, lower limb muscle strength, and quality of life: a randomized controlled trial

Objectives To investigate superiority of a telerehabilitation program for Covid-19 (TERECO) over no rehabilitation with regard to functional exercise capacity, lower-limb muscle strength (LMS), pulmonary function, health-related quality of life (HRQOL), and perceived dyspnoea. Design Parallel-group randomised controlled-trial with 1:1 block-randomisation. Setting Three major hospitals from Jiangsu and Hubei provinces, China. Participants 120 Covid-19 survivors with modified Medical Research Council (mMRC) dyspnoea score of 2-3 who had been discharged from hospital were randomised. 61 were allocated to the control group and 59 to the TERECO group. Intervention The control group received educational instructions. The TERECO group participated in a 6-week home-based, pulmonary rehabilitation program delivered via smartphone and monitored with chest-worn heart rate telemetry. Exercise types comprised breathing control and thoracic expansion, aerobic exercise, and LMS exercise. Outcomes Primary outcome was 6-minute walking distance (6MWD) in metres. Secondary outcomes were LMS measured as squat time in seconds; pulmonary function assessed by spirometry with parameters being forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, maximum voluntary ventilation (MVV), and peak expiratory flow; HRQOL measured with SF-12 physical component score (PCS) and mental component score (MCS); and mMRC dyspnoea, favourable outcome (no dyspnoea). Outcomes were assessed at 6 weeks (post-treatment) and 28 weeks (follow-up). Results 120 patients were randomised, 15 (12.5%) were lost to follow-up at study endpoint. No serious adverse events occurred. 38 participants in the TERECO group complied with the exercise protocol (64.41% of randomized). The adjusted between-group difference in change in 6MWD from baseline was 65.45 metres (95% CI 43.8-87.1, p<0.001) at post-treatment and 68.62 metres (95% CI 46.39-90.85, p<0.001) at follow-up. Treatment effects for LMS were 20.12 seconds (95% CI 12.34-27.9, p<0.001) post-treatment and 22.23 seconds (95% CI 14.24-30.21, p<0.001) at follow-up. No group differences were found for lung function apart from post-treatment MVV (10.57 litres/minute, 95% CI 0.26-17.88, p=0.005). Increase in SF-12 PCS was greater in the TERECO group with treatment effects estimated as 3.79 (95% CI 1.24-6.35, p=0.004) at post-treatment and 2.69 (95% CI 0.06-5.32, p=0.045) at follow-up. No significant between-group differences were found for improvements in SF-12 MCS. At post-treatment 90.4% endorsed a favourable outcome for mMRC dyspnoea in the TERECO group vs. 61.7% in control (adjusted RR 1.46, 1.17-1.82, p=0.001). Conclusions This trial demonstrated superiority of TERECO over no rehabilitation for 6MWD, LMS, and SF-12 PCS. We found no persistent effects on pulmonary function, SF-12 MCS, and perceived dyspnoea. Trial registration Chinese Clinical Trial Registry: ChiCTR2000031834, 11 Apr 2020, URL: What is already known Many Covid-19 survivors discharged from hospital have reduced exercise capacity, impaired pulmonary function, muscle weakness, and reduced quality of life, all of which might be addressed with pulmonary rehabilitation. However, evidence on effective pulmonary rehabilitation measures for this population is currently lacking. As delivery of conventional rehabilitation services is furthermore limited due to pandemic control measures, telerehabilitation programs represent a possible alternative. What the study adds We developed a telerehabilitation program for Covid-19 survivors (TERECO program) that is delivered via smartphone and can be carried out at home. Our study suggests that TERECO was safe and participants of the TERECO program had improved exercise capacity, lower-limb muscle strength, and physical quality of life. No relevant group differences were found for lung function, self-reported breathlessness, and mental quality of life. The TERECO program is inexpensive and could be implemented on a large scale to improve physical health of Covid-19 survivors after discharge from hospital. ### Competing Interest Statement Jian'an Li has received a research grant from Jiangsu CF PharmTech, Inc. Jan D. Reinhardt reports research grants from Xi'an Bureau of Technology, China, from the Fundamental Research Funds for the Central Universities, China, and from Sichuan Bureau of Science and Technology, China during the conduct of the study. No other relationships or activities exist that could appear to have influenced the submitted work. ### Clinical Trial ChiCTR2000031834 ### Clinical Protocols ### Funding Statement Funding This research was funded by Jiangsu CF PharmTech, Inc (to JL); Department of Science and Technology of Sichuan Province (21ZDYF1918, to JDR), the Fundamental Research Funds of Central Universities in China (20827041D4161, to JDR), Xi'an Science and Technology Bureau (XA2020-HWYZ-0043, to JDR). Details of the role of the study sponsors CF PharmTech, Inc provided technical and financial support for the conduct of the study. Department of Science and Technology of Sichuan Province, the Fundamental Research Funds of Central Universities in China, Xi'an Science and Technology Bureau provided financial support for the conduct of the study. Statement of independence of researchers from funders The funders did not have any influence on the design, conduct, analysis, data interpretation, and conclusions of his study. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was registered at the Chinese Clinical Trial Registry on 11 Apr 2020 (ChiCTR2000031834). Ethical approval was first received from the Institutional Review Board (IRB) of the First Affiliated Hospital of Nanjing Medical University/Jiangsu Province Hospital (2020-SR-171, 9 April 2020) and then subsequently from the IRBs of Hubei Province Hospital of Integrated Chinese and Western Medicine (2020016, 14 April 2020), and Huangshi Hospital of Chinese Medicine (HSZYPJ-2020-026-01, 20 April 2020). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Anonymised patient-level data on which the analysis, results, and conclusions reported in this paper are based will be shared on a public digital repository upon publication of the paper.