key: cord-1056121-ue67vnsz authors: Barbara, Cristina; Clavario, Piero; De Marzo, Vincenzo; Lotti, Roberta; Guglielmi, Giulia; Porcile, Annalisa; Russo, Carmelo; Griffo, Raffaele; Mäkikallio, Timo; Hautala, Arto Jorma; Porto, Italo title: Effects of exercise rehabilitation in patients with long COVID-19 date: 2022-01-25 journal: Eur J Prev Cardiol DOI: 10.1093/eurjpc/zwac019 sha: fa596f3e7c3cde780c511d7d266d136d9299da4d doc_id: 1056121 cord_uid: ue67vnsz nan In the first phase of COVID-19 pandemic early in 2020, the main scientific effort was devoted 1 to find a best way how to treat the acute phase of disease. Subsequently, partially because of the 2 availability of long-term follow-up data, there has been an increased attention to chronic consequences 3 of COVID-19 infection. Since follow-up data up to more than one year is available, long COVID-19 4 has been recognized with several months lasting symptoms 1, 2 . According to a recent meta-analysis including 47910 patients (age 17-87) more than 50 long-6 term effects of COVID-19 were recognized. The five most common symptoms for long COVID-19 7 were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%) 3 . 8 At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle 9 weakness (63%), sleep difficulties (26%), and anxiety or depression (23%) 4 . In our recent study, at 10 three months after hospital discharge, half of COVID-19 survivors showed a significant reduction in 11 cardiorespiratory fitness, mainly explained by muscular impairment of legs 5 . Furthermore, patients 12 who experienced persistent symptoms after COVID-19 still demonstrated a significantly decreased 13 distance at 6-minutes walking test six months after the onset of symptoms 6 . The exact mechanisms 14 underlying the exercise capacity reduction and functional limitations are not clear in long COVID-19 15 patients, but it seems that muscle impairment is an important determinant in this condition. Given the central role of appropriate level of physical fitness in patients with long COVID-19, 17 rehabilitation could play a pivotal role in this new and poor-known scenario 7, 8 . Therefore, it is crucial 18 to establish rehabilitation strategies, that enable optimal recovery of these patients 7, 8 . In cardiac 19 patients, exercise has been shown as a key component. Exercise-based rehabilitation reduces cardiac 20 mortality, hospital readmission 9, 10 , anxiety 11 , and has shown to be cost-effective for health care 21 providers 12 . Furthermore, both exercise training modalities, aerobic and resistance training, performed 22 in same session has shown to induce clinically relevant fitness improvements 13, 14 . Therefore, we 23 evaluated whether exercise rehabilitation program could be applied in a population of patients with 24 long COVID-19. In line with expert recommendations 7, 8 , we hypothesized that a combination of 25 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 aerobic and resistance training performed in the same session for eight weeks would be well tolerated 1 and would effectively increase both cardiorespiratory and musculoskeletal fitness in long COVID-19 2 patients. 3 We assessed consecutive patients undergoing post-COVID-19 evaluation after three months of 4 hospital discharge at the Outpatient Cardiac Rehabilitation Center of Genoa in Italy. For those patients 5 who had a reduced exercise capacity (100 of 220 patients assessed), defined as the value below 85% 6 of predicted peak aerobic capacity (VO2peak), a controlled exercise-based rehabilitation was proposed. (Table 1) , 9 the present study protocol follows the Declaration of Helsinki and it was approved by the Ethics 10 Committee of the Liguria Region (n° 430/2020CER). The patients started a laboratory controlled eight weeks exercise training program, which 12 included three exercise sessions a week. In each exercise session, aerobic exercise (starting 30 min and 13 increasing to 60 min) was performed, including 5 min warm-up and 5-min cool down. The intensity of 14 aerobic exercise was defined according to VO2peak test results targeting the watts reached at 80% of 15 lactate threshold. Aerobic exercise was followed by nine major muscle group resistance exercises (for 16 the lower extremity: leg extension/flexion, abduction/adduction and leg press; for the upper extremity: 17 push-up/pull-down; for the core muscles; abdomen, back). Resistance training load was determined for 18 each muscle groups according to the results of the maximal dynamic strength testing (1RM; one 19 repetition maximum). The progression of resistance training was confirmed after four weeks by 20 defining the new 1RM values to be used to continue training. Resistance training prescription load was 21 defined as 40% of 1RM, 2 sets (3 sets for last two weeks) and 12 repetitions for each muscle group. The duration of a single training session was approximately 90 min. 23 The results for cardiorespiratory and musculoskeletal fitness are shown in Table 2 and 24 expressed as means ± standard deviation (SD). The normal Gaussian data distribution was verified by 25 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 the Kolmogorov-Smirnov goodness-of-fit test. The changes in measured parameters were analyzed by 1 using paired-samples t-test. All analyses were performed with R environment 3.6.3 (R. Foundation for 2 Statistical Computing, Vienna, Austria). A p value of <0.05 was considered significant. The average 3 number of realized exercise training sessions was 66.1±34.0 and during the eight weeks intervention 4 none of patients dropped out from the study. VO2peak increased 15% and peak ventilation 9% (p<0.001 5 for both). Eighteen patients (36.0%) had a post-training predicted VO2peak above 85% (indicating 6 normality). Muscle strength increased markedly for all major muscle groups ranging from 16% to 33% 7 increase (p<0.001 -0.009). 8 Several limitations are of note. Firstly, we did not have a control group, remaining about the 9 considerable uncertainty remains regarding the effectiveness of same session combined exercise 10 training compared with aerobic or strength training performed alone or with control group included. Secondly, all patients came from a single area of the city of Genoa with a relatively small sample of 12 long COVID-19 patients, and therefore the generalization of results could be misleading. In addition, 13 the exercise capacity evaluation was conducted three months after hospital discharge, with the patients 14 unsupervised in the meantime and no data available, except for the anamnestic risk factors and 15 comorbidities (data not shown here). However, strength of this study was that all exercise sessions 16 were laboratory controlled and realized well according to training prescription. 17 In summary, the present study demonstrated that exercise rehabilitation in which combined 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 5 There was no specific funding received for this study. The author(s) declared no potential conflicts of interest with respect to the research, authorship 4 and/or publication of this article. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 Management of post-acute 2 covid-19 in primary care As Their Numbers Grow, COVID-19 "Long Haulers" Stump Experts More Than 50 Long-Term Effects of COVID-19: A Systematic Review COVID-19 in patients discharged from hospital: a cohort study Cardiopulmonary exercise testing in COVID-19 patients at 3 months follow-up The Impact of Post-COVID-19 Syndrome on Self-Reported Physical Activity 22 how to provide cardiovascular rehabilitation in the COVID-19 era Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) era: A Question and Answer session with the 5 experts Endorsed by the section of Sports Cardiology & Exercise of the European Association of 6 Preventive Cardiology (EAPC) Exercise-Based Cardiac Rehabilitation for Coronary Heart Disease: Cochrane Systematic Review 9 and Meta-Analysis The Journal of Cardiopulmonary Rehabilitation and Prevention at 40 Years and Its 12 Role in the Evolution of Cardiac Rehabilitation The effect of exercise therapy on depressive and anxious symptoms in patients with ischemic heart 15 disease: A systematic review Economic evaluation of exercise-based cardiac rehabilitation 18 in patients with a recent acute coronary syndrome The effects of same-session combined 20 exercise training on cardiorespiratory and functional fitness in older adults: a systematic review and 21 meta-analysis Resistance training and sarcopenia