Effects of exercise rehabilitation in patients with long coronavirus disease 2019

Abstract

In the first phase of the coronavirus disease 2019 (COVID-19) pandemic early in 2020, the main scientific effort was devoted to find the best way to treat the acute phase of the disease. Subsequently, partially because of the availability of long-term follow-up data, there has been an increased attention to chronic consequences of COVID-19 infection. Since follow-up data up to more than 1 year are now available, long COVID-19 has been increasingly recognized, with symptoms lasting several months.1,2 According to a recent meta-analysis including 47 910 patients (age 17–87), more than 50 long-term effects of COVID-19 are recognized. The five most common symptoms of long COVID-19 were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnoea (24%).3 At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness (63%), sleep difficulties (26%), and anxiety or depression (23%).4 In our recent study, at 3 months after hospital discharge, half of the COVID-19 survivors showed a significant reduction in cardiorespiratory fitness, mainly explained by muscular impairment of the legs.5 Furthermore, patients who experienced persistent symptoms after COVID-19 demonstrated a significantly decreased distance at 6-min walking test 6 months after the onset of symptoms.6 The exact mechanisms underlying this exercise capacity reduction and functional limitation are not clear in long COVID-19 patients, but it seems that muscle impairment is an important determinant of this condition. Given the central role of physical fitness in patients with long COVID-19, rehabilitation could play a pivotal role in this new and poorly known scenario.7,8 Therefore, it is crucial to establish rehabilitation strategies that enable optimal recovery.7,8 In cardiac patients, exercise has been shown to be key component. Exercise-based rehabilitation reduces cardiac mortality, hospital readmission,9,10 anxiety,11 and is cost-effective for health care providers.12 Furthermore, both aerobic and resistance training exercise training modalities, especially when performed in the same session, have been shown to induce clinically relevant fitness improvements13,14 Therefore, we evaluated whether exercise rehabilitation programs could be applied to a cohort of patients with long COVID-19. In line with expert recommendations,7,8 we hypothesized that a combination of aerobic and resistance training performed in the same session for 8 weeks would be well tolerated and would effectively increase both cardiorespiratory and musculoskeletal fitness in long COVID-19 patients. We assessed consecutive patients undergoing post-COVID-19 evaluation three months after hospital discharge at the Outpatient Cardiac Rehabilitation Center of Genoa in Italy. For those patients who had a reduced exercise capacity (100 of 220 patients assessed), defined as the value below 85% of predicted peak aerobic capacity (VO2peak), a controlled exercise-based rehabilitation was implemented. Eventually, 50 volunteer patients (aged 55.8 ± 9.7 years, 15 women, body mass index 26.6 ± 5.2) were involved in this study. Detailed patient characteristics are defined in a previous publication5 (Table 1). The present study protocol follows the Declaration of Helsinki, and it was approved by the Ethics Committee of the Liguria Region (no. 430/2020CER). Baseline characteristics in the patients with the long COVID-19 syndrome (n = 50) Variables are expressed as n (percentage) or mean ± standard deviation (SD). CKD, chronic kidney disease; CPET, cardiopulmonary exercise testing; COPD, chronic obstructive pulmonary disease; MI, myocardial infarction; MV, mechanical ventilation; NIV, non-invasive ventilation. The patients started a laboratory-controlled 8 weeks exercise training program, which included three sessions per week. In each exercise session, aerobic exercise (starting 30 min and increasing to 60 min) was performed, including 5-min warm-up and 5-min cool-down. The intensity of aerobic exercise was defined according to VO2peak test results targeting the intensity (in Watts) reached at 80% of lactate threshold. Aerobic exercise was followed by nine major muscle group resistance exercises (for the lower extremity: leg extension/flexion, abduction/adduction, and leg press; for the upper extremity: push-up/pull-down; for the core muscles; abdomen, back). Resistance training load was determined for each muscle group according to the results of the maximal dynamic strength testing [one repetition maximum (1RM)]. The progression of resistance training was confirmed after 4 weeks by defining the new 1RM values to be used to continue training. Resistance training prescription load was defined as 40% of 1RM, 2 sets (3 sets for last 2 weeks), and 12 repetitions for each muscle group. The duration of a single training session was ∼90 min. Results for cardiorespiratory and musculoskeletal fitness are shown in Table 2 and expressed as means ± standard deviation (SD). Normal data distribution was verified by the Kolmogorov–Smirnov goodness-of-fit test. Changes in measured parameters were analysed by using paired-samples t-test. All analyses were performed with R environment 3.6.3 (R. Foundation for Statistical Computing, Vienna, Austria). A P-value of <0.05 was considered significant. The average number of exercise training sessions was 66.1 ± 34.0 and, during the 8 weeks intervention, none of the patients dropped out. VO2peak increased by 15% and peak ventilation by 9% (P < 0.001 for both). Eighteen patients (36.0%) had a post-training VO2peak above the 85% of predicted (indicating normality). Muscle strength markedly increased for all major muscle groups, ranging from a 16% to a 33% (P < 0.001–0.009). Effects of 8 weeks of exercise-based rehabilitation on cardiorespiratory and musculoskeletal fitness in the patients with the long COVID-19 syndrome (n = 50) Variables are expressed as mean ± standard deviation (SD). AT, anaerobic threshold; RER, respiratory exchange ratio; RM, repetition maximum; VCO2, carbon dioxide production; VE, minute ventilation; VO2peak, peak aerobic exercise capacity; VT, tidal volume; W, Watt. Several limitations are of note. Firstly, we did not have a control group, limiting insights regarding the effectiveness of exercise training itself, as well as regarding the comparison of same-session combined exercise training with aerobic or strength training performed alone. Secondly, all patients came from single Italian city with and represented a relatively small sample of long COVID-19 patients. Therefore, generalization of results could be misleading. In addition, the exercise capacity evaluation was conducted 3 months after hospital discharge, with the patients unsupervised in the meantime. However, all exercise sessions were controlled and realized with strict adherence to training prescription. In summary, the present study demonstrates that rehabilitation in which combined aerobic and resistance exercises are performed in the same session for 8 weeks is associated with markedly improved cardiorespiratory and musculoskeletal fitness. These results support the importance of exercise rehabilitation, to be added to the continuum of post-care of long COVID-19 patients. Conflict of interest: I.P. in the last 2 years has received consultant or speaker fees from Biotronik, ABIOMED, Terumo, Philips, Sanofi, Amgen, Daiichi-Sankyo, Astra Zeneca, and Bayer, not related to this work. V.D.M. has received speaker fees from Daiichi-Sankyo, Bristol-Myers Squibb, and Bayer not related to this work. Other authors have no conflict of interest to declare.

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