Potential Application of Whole Body Vibration Exercise for Improving the Clinical Conditions of COVID-19 Infected Individuals: A Narrative Review from the World Association of Vibration Exercise Experts (WAVex) Panel

International Journal of Environmental Research and Public Health Review Potential Application of Whole Body Vibration Exercise for Improving the Clinical Conditions of COVID-19 Infected Individuals: A Narrative Review from the World Association of Vibration Exercise Experts (WAVex) Panel Borja Sañudo 1, Adérito Seixas 2,* , Rainer Gloeckl 3,4 , Jörn Rittweger 5,6, Rainer Rawer 7, Redha Taiar 8, Eddy A. van der Zee 9, Marieke J. G. van Heuvelen 10, Ana Cristina Lacerda 11 , Alessandro Sartorio 12 , Michael Bemben 13, Darryl Cochrane 14, Trentham Furness 15, Danúbia de Sá-Caputo 16,17 and Mario Bernardo-Filho 16 1Departamento de Educación Física y Deporte, Universidad de Sevilla, 41013 Seville, Spain; [email protected] 2Escola Superior de Saúde, Universidade Fernando Pessoa, 4200-253 Porto, Portugal 3Institute for Pulmonary Rehabilitation Research, Schoen Klinik Berchtesgadener Land, 83471 Schoenau am Koenigssee, Germany; rainer[email protected] 4Department of Pulmonary Rehabilitation, Philipps–University of Marburg, German Center for Lung Research (DZL), 35037 Marburg, Germany 5Institute of Aerospace Medicine, German Aerospace Center (DLR), 51147 Cologne, Germany; [email protected] 6Department of Pediatrics and Adolescent Medicine, University of Cologne, D50931 Cologne, Germany 7Head of Research & Development Department, Novotec Medical GmbH & Galileo Training, 75172 Pforzheim, Germany; r[email protected] 8Universitéde Reims Champagne Ardenne, 51100 Grand Est, France; [email protected] 9Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, 9747 AG Groningen, The Netherlands; [email protected] 10 Department of Human Movement Sciences, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands; [email protected] 11 Faculdade de Ciências Biológicas e da Saúde, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina 39100-000, MG, Brazil; [email protected] 12 Istituto Auxologico Italiano, IRCCS, Experimental Laboratory for Auxo-endocrinological Research & Division of Metabolic Diseases, 20145 Milan, Italy; [email protected] 13 Department of Health and Exercise Science, University of Oklahoma, Norman, OK 73019, USA; [email protected] 14 School of Sport, Exercise and Nutrition, Massey University, Private Bag 11 222, Palmerston North 4442, New Zealand; [email protected] 15 Faculty of Health Sciences, Australian Catholic University, Fitzroy, VIC 3065, Australia; Tr[email protected]g.au 16 Laboratório de Vibrações Mecânicas, Policlínica Piquet Carneiro, Instituto de Biología Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20950-003, Brazil; [email protected] (D.d.S.-C.); [email protected] (M.B.-F.) 17 Faculdade Bezerra de Araújo, Rio de Janeiro 23052-180, Brazil *Correspondence: [email protected] Received: 13 April 2020; Accepted: 13 May 2020; Published: 22 May 2020   Abstract: COVID-19 is a highly infectious respiratory disease which leads to several clinical conditions related to the dysfunction of the respiratory system along with other physical and psychological complaints. Severely affected patients are referred to intensive care units (ICUs), limiting their possibilities for physical exercise. Whole body vibration (WBV) exercise is a non-invasive, physical therapy, that has been suggested as part of the procedures involved with pulmonary Int. J. Environ. Res. Public Health 2020,17, 3650; doi:10.3390/ijerph17103650 www.mdpi.com/journal/ijerph Int. J. Environ. Res. Public Health 2020,17, 3650 2 of 23 rehabilitation, even in ICU settings. Therefore, in the current review, the World Association of Vibration Exercise Experts (WAVEX) reviewed the potential of WBV exercise as a useful and safe intervention for the management of infected individuals with COVID-19 by mitigating the inactivity-related declines in physical condition and reducing the time in ICU. Recommendations regarding the reduction of fatigue and the risk of dyspnea, the improvement of the inflammatory and redox status favoring cellular homeostasis and the overall improvement in the quality of life are provided. Finally, practical applications for the use of this paradigm leading to a better prognosis in bed bound and ICU-bound subjects is proposed. Keywords: COVID-19; SARS-CoV-2; coronavirus; whole body vibration exercise 1. Introduction COVID-19 is a benign condition in 80% of symptomatic forms with about another 15% considered severe, and 5% critical, requiring resuscitation [ 1 ]. The overall lethality of symptomatic forms is estimated at 2 to 5%, depending on the age distribution of patients, their co-morbidities, and the saturation of health care systems, however, the lethality of patients with critical forms of Covid-19 has been estimated at 61% in a series of patients hospitalized in Wuhan [2] with 20% under 60 years of age [1]. COVID-19 is caused by the virus SARS-CoV-2 and results in severe stresses to the various health care systems in most countries available to combat this disease. Most infected patients have mild symptoms including fever, fatigue and cough, but in severe cases, especially elderly patients with systemic inflammatory response syndrome (SIRS), cardiovascular diseases, rheumatoid arthritis, immunodepression, cancer or chronic obstructive pulmonary disease (COPD), the disease can progress quickly to acute respiratory distress syndrome, septic shock, metabolic acidosis and coagulopathy [ 3 ]. One reason for the potential rapid deterioration associated with the disease is based on the steady accumulation of detrimental cellular and molecular changes within tissues that reduces the body’s ability to respond to stress [ 4 ]. Consequently, in some cases, the virus can also negatively impact cellular homeostasis and immunity, with some studies reporting elevations in the expression of pro-inflammatory cytokines within skeletal muscle of patients with SARS-CoV-2 infection [4]. In a recent metanalysis, Sun et al. [ 5 ] also reported that several patients with SARS-CoV-2 infection have presented with muscle soreness or fatigue as well as acute respiratory distress syndrome (ARDS), whereas diarrhea, hemoptysis, headache, sore throat, shock, and other symptoms are rare [ 6 , 7 ]. Suspected and confirmed cases of SARS-CoV-2 need to be treated in designated hospitals with effective isolation and protective conditions with critical cases being admitted to ICU as soon as possible. Treatment involves different approaches and recommendations generally include bed rest, with the patient being monitored for vital signs (heart rate, pulse oxygen saturation, respiratory rate, blood pressure) and given supportive treatment to ensure sufficient energy intake and water, electrolytes, and acid-base homeostasis along with other internal environment factors [8]. Considering the clinical characteristics of COVID-19 and the necessity of resting in bed, individuals are not able to perform physical activity; despite recent reports highlighting the need for these patients in maintaining regular physical activity [ 9 ]. Several authors have reported that physical activity plays an important role in the maintenance of homeostasis for individuals [ 10 , 11 ] and that mild to moderate intensity physical activity aids in controlling the inflammatory responses in subjects with chronic low-grade inflammation [ 12 ]. Despite these benefits, patients infected by COVID-19 cannot actively engage in any type of exercise; therefore, passive strategies such as whole-body vibration (WBV) exercise could be recommended in patients suffering from a mild COVID-19 infection after careful clinical evaluation to ensure the safety of this type of rehabilitation. WBV exercise is a non-invasive physical therapy that has even been successfully included in ICU settings [ 13 ]. These authors assessed Int. J. Environ. Res. Public Health 2020,17, 3650 3 of 23 the safety and feasibility of WBV in mechanically ventilated ICU patients and concluded that this device was both safe and feasible. While there is evidence of the beneficial effects of WBV in numerous health outcomes in the general population [ 14 , 15 ], in the current review we aimed to examine the potential of WBV exercise as a useful and safe intervention for the management of infected individuals with COVID-19 in order to reduce time in ICU and/or to manage the disease sequels after recovery. This manuscript is a joint effort from members of the World Association of Vibration Exercise Experts (WAVEX), a world association of researchers interested in the potential of WBV for physical and mental health. 2. Effects of the WBV Exercises That Could Be Relevant to the Management of Individuals Infected with COVID-19 As reported in the previous paragraph, patients with COVID-19 typically have fever and cough and some will develop ARDS, possibly due to uncontrolled cytokine release [ 4 ]. The management of this condition in severe cases include prone positioning, lung-protective ventilation, and consideration of extracorporeal membrane oxygenation for refractory hypoxemia [ 16 ]. Therefore, in the following sections we will discuss the WBV benefits that could be relevant in the management of individuals infected with COVID-19 including: (a) the reduction of fatigue and the reduced risk of dyspnea, (b) improvements in inflammatory and redox status favoring cellular homeostasis and (c) an overall improvement in the quality of life, leading to a better prognosis in bed bound and ICU-bound subjects (Table 1). 3. Reduction of the Fatigue and the Risk of Dyspnea Fatigue and dyspnea are clinical characteristics as evidenced by COVID-19 patients [ 17 ]. The fatigue is present in about 22% of infected patients [ 18 ] and, although it is still early to evaluate it in this population, a recent study suggested that 70% of ARDS survivors reported clinically significant and persistent fatigue symptoms at 6 and 12 months [ 19 ] and these are also common in patients with COPD [ 20 ] or in intensive care survivors one year after discharge [ 21 ]. Moreover, as highlighted by Neufeld et al. [ 19 ], fatigue co-occurs with impaired physical function (33% out of 711 ARDS patients) and other clinically significant symptoms, such as anxiety or depression (27%). Consequently, fatigue, weakness and negative psychological symptoms seem to be common sequelae of these conditions and this connection should be considered when considering treatment options [ 19 ]. These authors have recently shown that small increases in physical functioning status were associated with less fatigue. Although this multidimensional construct is difficult to define and may vary across a range of conditions [ 22 ], previous studies have reported that WBV exercise can, not just enhance physical status, but also manage the fatigue in various populations such as those with fibromyalgia [ 23 ]; Parkinson disease [ 24 ] or multiple sclerosis [ 25 ]. Moreover, recent studies [ 26 ] evaluated the effects of WBV (frequency 20–27 Hz) on various physical and psychological capacities in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT) and reported that WBV might maintain maximum strength, functional performance, quality of life (Qol), and mitigate fatigue. In a similar fashion, Escudero-Uribe et al. [ 25 ] investigated the effects of regular exercise alone (aerobic, body weight, coordination, and balance exercises) and with the inclusion of WBV exercise (amplitude 3 mm, average frequency 4 Hz ± 1Hz/sec) on fatigue, gait pattern, mood, and quality of life in persons with relapsing-remitting multiple sclerosis (RRMS). Significant improvements in fatigue and mood were identified for both intervention groups, while gait parameters also improved significantly in the WBV group. It was concluded that combined training programs of regular exercise with WBV helps to reduce fatigue and improve mood in persons with mild to moderate RRMS. The effects of WBV exercise (amplitude 3 mm, frequency 30 Hz) was also tested in rheumatoid arthritis patients with similar improvements being reported [ 27 ]. Finally, Alentorn-Geli et al. [ 23 ] studied the effectiveness of a 6-week traditional exercise program with supplementary WBV exercise (amplitude 2 mm, frequency 30 Hz) on fibromyalgia patients (FM) and found that the WBV protocol resulted in reductions in pain and fatigue, whereas exercise alone failed to induce any improvements. Int. J. Environ. Res. Public Health 2020,17, 3650 4 of 23 Table 1. Intervention parameters in the included studies. Author Participants and Age (Years/Months/Weeks) ±SD or [SE] or (Min–Max) Condition Study Design Frequency (Hz) Amplitude or PPD (mm) Peak Acceleration (m/s2or g) Vibration Type/Device Position/Exercises Session Protocol Intervention Footwear Wollersheim 2017 [13] EG1: n =12 EG2: n =7 54 (52–59) years Immobilized ICU patients Clinical trial with longitudinal analysis (before, during, and after intervention) EG1: 26 EG2: 24 2–5 No information EG1: Synchronous vibration (Vibrosphere ® , Promedvi: Sweden) EG2: side alternating vibration (Galileo, home-ICU®. Novotec Medical GmbH, Pforzheim, Germany) Supine position with knees flexed at about 20◦ One session EG1: 9 ×1 min, 45 s rest EG2: 3 ×3 min Socks Chang 2018 [15] n=17 82.1 ±8.2 years Older people Quasi-experimental, single-group, pretest-posttest design 12 3 No information Vertical synchronous vibration (i-vib6050 model; Bodygreen, Changhua, Taiwan) Stand on position 3-Month period, 3 sessions/week 10 ×60 s, 30 s rest No information Alentorn-Geli 2008 [23] EG1: n =11, 55.2 [3.4] years EG2: n =12, 53.7 [2.7] years CG: n =10, 59.3 [2.3] years Fibromyalgia RCT (2-factor mixed experimental design) EG1: 30 EG1: 2 No information Synchronous vibration (PowerPlate®, Power Plate North America, Inc., Northbrook, IL) Static and dynamic lower extremities tasks (static and dynamic squat; ankle plantar-flexion with legs in extension; flexo-extension of the right leg or of the left leg; squat shifting the body weight from 1 leg to the other) 6-Week period, 2 sessions/week 3–6 ×4–18 min, 3 min rest No information Corbianco 2018 [24] EG1: n =10, 58.8 ± 3.9 years EG2: n =10 56.9 ±4.7 years Parkinson’s disease RCT EG1: 26 EG1: 4 EG1: 106.64 m/s2 Side alternating vibration (Galileo, Med L2000, Novotec Medical GmbH, Pforzheim, Germany) Isometric protocol in semi squat position with normalized workload (20–100% patient’s body weight, progressive increase of 5% body weight was added every week) 4-Week period, 4 sessions/week 20 ×1 min, 1 min rest No information Int. J. Environ. Res. Public Health 2020,17, 3650 5 of 23 Table 1. Cont. Author Participants and Age (Years/Months/Weeks) ±SD or [SE] or (Min–Max) Condition Study Design Frequency (Hz) Amplitude or PPD (mm) Peak Acceleration (m/s2or g) Vibration Type/Device Position/Exercises Session Protocol Intervention Footwear Pahl 2020 [26] EG: n =18, 55 (50–63) years CG: n =26, 56 (32–63) years Allogeneic hematopoietic cell transplantation RCT (subjects randomly allocated 1:1 to two parallel groups) EG: 20–27 EG: 0–3 No information Side alternating vibration (Galileo, Med L2000, Novotec Medical GmbH, Pforzheim, Germany) Standing position: five exercises from a repertoire of 16 exercises for lower limbs, especially the knee extensors and flexors 180-Day period, 5 sessions/week ~20 min/session Barefoot Prioreschi 2016 [27] EG: n =16 CG: n =15 EG: 51 ±10 yrs CG: 52 ±12 years Reumatoid Arthitis Female RCT 30 3 No information Vertical synchronous vibration ((DKN XG 5.0, DKN Technology, California, USA) Standing position holding on to the handlebars with knees slightly bent 12 weeks 2 sessions/week 15 min/session EG: WBV 10 ×60 s, 30 s rest CG: normal activities Barefoot Furness 2013 [28] n=17 69 ±8 years COPD Non-randomised, cross-over design to sham 25 2 24.7 m/s2 Side alternating vibration platform (Amazing Super Health, Melbourne, AUS) Static squatting position with knees flexed at about 20◦ One session 5 ×1 min, 1 min rest Flat soled shoes Gloeckl 2017 [29] n=10 62 ±8 years COPD RCT cross-over study 26 5 No information Side alternating vibration (Galileo, Novotec Medical, Pforzheim, Germany) Dynamic squatting position with knees and hips at about 90–100◦ One session 6×3 min, 10 repetitions per minute (to bend their knees 2 s concentric, 2 s eccentric, 2 s standing between each repetition) Flat soled shoes Furness 2014 [30] n=16 72 ±7 years COPD non-randomized, cross-over design to sham 25 2 ~24.7 m/s2 Side alternating vibration platform (Amazing Super Health, Melbourne, AUS) 53◦knee flexion 6-Week period, 2 sessions/week No information Flat soled shoes. Jawed 2020 [31] n=11 24 ±1 (6-Young) 55 ±3 (5-old) years Healthy male subjects Single site, within subjects, pre and post-test design, cross-over 35 4 No information Power Plate my3 (Power Plate North America, Northbrook, IL) EG1: standing platform vibration; EG2: repetitive leg squat exercise (no vibration); and EG3: EG1 plus EG2 (with vibration) 2 to 3-week period, one session EG1: 8 bouts (WBV) × 60 s ×120 (rest), knees slightly bent; EG2: 8 bouts (WBV) ×60 s × 120 (rest), 90◦knee flexion, 120 total repetitions of leg squats; EG3: same EG2 Barefoot Int. J. Environ. Res. Public Health 2020,17, 3650 6 of 23 Table 1. Cont. Author Participants and Age (Years/Months/Weeks) ±SD or [SE] or (Min–Max) Condition Study Design Frequency (Hz) Amplitude or PPD (mm) Peak Acceleration (m/s2or g) Vibration Type/Device Position/Exercises Session Protocol Intervention Footwear Neves 2018 [32] EG: n =10, 63.5 ±7.8 years CG: n =10, 63.8 ±8.1 years COPD Single-blind trial with a controlled parallel design EG: 30–40 EG: 2 EG: 1.45–2.25 g Synchronous vibration (Fitvibe Excel Pro C, Bilzen, Belgium) Static squatting position with knees flexed at about 30◦ 12-Week period, 3 sessions/week 6×30 s, 60 s rest Barefoot Ribeiro 2018 [33] EG: n =19, 52.1 [1.8] years CG: n =19, 51.0 [1.9] years Fibromyalgia CT 1:1 case-control paired study (variables assessed before and immediately after one session) EG: 40 EG: 4 No information Synchronous vibration (Fitvibe Excel Pro C, Bilzen, Belgium) Dynamic squatting position with knees flexed at about 10◦ to 60◦ One session 8×40 s, 40 s rest (to bend their knees to 60◦angle for 3 s and then to 10◦angle for 3 s, over the 40 s of each series) Barefoot Simão 2012 [34] EG1: n =10, 75 ±7.4 years EG2: n =10, 69 ±3.7 years CG: n =11, 71 ±5.3 years Knee osteoarthritis Clinical, prospective, randomized, single-blinded study EG1: 35–40 EG1: 4 EG1: 2.00-2.61 g Synchronous vibration (Fitvibe Excel Pro C, Bilzen, Belgium) Dynamic squatting position with knees flexed at about 10◦ to 60◦ 12-Week period, 3 sessions/week 6–8 ×20–40 s, 20–40 s rest (to bend their knees to 60◦angle for 3 s and then to 10◦angle for 3 s, over each series) Barefoot Song 2019 [35] EG1: n =11 (hum), 22–27 years EG2: n =10(mice), 6 wks EG1: healthy individuals EG2: old C57BL/6 mice Non-randomized study EG1: 21 EG2: 13 e 17 No information No information Vertical vibration (Weibutexun, Jinan, China) EG1: standing body vibration and seated for 10min in each position; EG2: no information 4-week period, 7 sessions/week EG1: 10 min (WBV); EG2: 30 min (WBV) No information Blanks 2020 [36] EG1: n =11, 33 ±4 years EG2: n =10, 28 ±8 years EG1: normal weight EG2: obese Non-randomized study 14 2.5 20.19 m/s2 Side alternating whole body vibration platform (RS3000, Rock Solid Wholesale, Atlantic Beach, FL, USA) Static squat position, knee flexion (~60◦) with a stable non-flexed trunk. One session 10 bouts ×60s (WBV) × 30 s (rest) Barefoot Tossige-Gomes 2012 [37] EG1: n =8, 75 ±7 years EG2: n =10, 71 ±4 years CG: n =8, 72 ± 6 years Knee osteoarthritis Randomized controlled trial (variables assessed before and after training) EG1: 35–40 EG1: 4 EG1: 2.78–3.26 g Synchronous vibration (Fitvibe Excel Pro C, Bilzen, Belgium) Dynamic squatting position with knees flexed at about 10◦ to 60◦ 12-Week period, 3 sessions/week 6–8 ×20–40 s, 20–40 s rest (to bend their knees to 60◦angle for 3 s and then to 10◦angle for 3 s, over each serie) Barefoot Int. J. Environ. Res. Public Health 2020,17, 3650 7 of 23 Table 1. Cont. Author Participants and Age (Years/Months/Weeks) ±SD or [SE] or (Min–Max) Condition Study Design Frequency (Hz) Amplitude or PPD (mm) Peak Acceleration (m/s2or g) Vibration Type/Device Position/Exercises Session Protocol Intervention Footwear Rittweger 2010 [38] CG: n =10, 33.4 ±6.6 years EG: n =10, 32.6 ±4.8 years Healthy male Randomized controlled trial 19–30 No information No information Side alternating vibration (Galileo Space, Novotec Medical, Pforzheim, Germany) EG: squating exercise, heel raises, toe raises and kicks 8-week, twice daily (except for Wednesday afternoons and Sundays) Exercises were performed rhythmically at a repetition rate of 1 in 6 s, and kicks (explosive squats with 10 s rest insertion) No information Greulich 2014 [39] CG: n =20, 70.4 ±10.1 years EG: n =20, 66.4 ±9.93 years COPD Clinical trial 12–26 1.5; 2; and 3 No information Side alternating vibration Galileo®, Novotec Medical, Pforzheim, Germany) CG: physiotherapy program, EG: physiotherapy program plus WBV (bended knees on the Platform) No information 3 ×2 min/day No information Stark 2016 [40] EG1: n =12, 8.6 ±3.2 months EG2: n =12, 19.4 ± 3.2 months Cerebral palsy Prospective, evaluator-blinded, monocenter, randomized waiting-control design with follow-up 12 or 22 2.5 0.72 g or 2.43 g Side alternating vibration Galileo®system combined with a tilt table (Novotec Medical GmbH, Pforzheim, Germany) Standing still or alternately squatting and standing up (using tilt table); sitting on the platform; four-point position 14-week, twice daily (10 times per week) Ten 9-minute (3 × 3) min Feet or hands were placed at equal distance from the center of the platform If possible the children trained without shoes, but with socks Gloeckl 2017 [41] CG: n =37, 63 ±9 years EG: n=37, 65 ±8 years COPD Randomized controlled trial 24–26 5 PPD No information Side-alternating vibration platform Galileo®(Novotec Medical GmbH, Pforzheim, Germany) Dynamic squat training, 90◦and 120◦Knee and hip flexion during each squat movement without holding on to anything 3-week, 3 times a week (non-consecutive days) 4 bouts ×120 s (WBV) Flat soled shoes Rittweger 2001 [42] n=12, 25.2 years Healthy individuals Non-randomized study 26 6 No information Side alterning vibration Galileo, 2000 (Novotec Medical GmbH, Pforzheim, Germany) Standing, squatting, and squatting with a load One session Exercises performed in randomized sequence for 3 min each No information Hazell 2008 [43] EG1: n =8, 25 ±3.4 years EG2: n =8, 25 ±2.6 years Healthy RA men Non-randomized study 45 2 No information Vertical vibration WAVE platform (Whole-body Advanced Vibration Exercise, Windsor, Canada) EG1: seated next to the WBV device (passive, unloaded), 90º knee flexion EG2: semi-squat (static, loaded), 120◦ knee flexion One session EG1 and EG2: 15 repetitions of 1 min (WBV) ×1 min (rest) and 10 min of recovery (40 min of total time) Barefoot Int. J. Environ. Res. Public Health 2020,17, 3650 8 of 23 Table 1. Cont. Author Participants and Age (Years/Months/Weeks) ±SD or [SE] or (Min–Max) Condition Study Design Frequency (Hz) Amplitude or PPD (mm) Peak Acceleration (m/s2or g) Vibration Type/Device Position/Exercises Session Protocol Intervention Footwear Boeselt 2016 [44] EG1: n =12, 41.8 ± 19.7 years EG2: n =12, 31.3 ± 6.6 years EG1: ICU patients EG2: healthy individuals Non-randomized study 24 No information No information Side alternating vibration Galileo®(Novotec Medical, Pforzheim, Germany) EG1 and EG2: WBV alone and WBV with a dumbbell One session EG1 and EG2: 3 min (WBV) ×1 min (rest) ×3 min (WBV + dumbbell) Barefoot Kim 2015 [45] Males: n =9, 29 ±3.9 years Females: n =9, 25.6 ±3.5 years Healthy individuals Single-group, repeated-measure, cross-study 0, 10, 20 No information No information Side alternating vibration Galileo®(Novotec Medical, Pforzheim, Germany) Three pelvic positions (neutral, anterior tilt, posterior tilt) One session 3×10 s (WBV) ×10 s (rest) in each position No information Ritzmann 2013 [46] EG1 and EG2: n =18, 25 ±4 years Healthy individuals Single-group, repeated measures, crossed-study EG1 and EG2: 5, 10, 15, 20, 25, 30 EG 1: 2 and 4 EG2: 2 No information EG1: Novotec Medical (Pforzheim, Germany); EG2: Power Plate. (Germany, Frankfurt am Main, Germany) One session EG1: side alternating vibration and EG2: synchronous vibration: 10 s (WBV) ×30 s (rest) Barefoot Eckhardt 2011 [47] n=14 26.0 ±4.5 years Physically active men Randomizedcross-over 22 Mean 4 (feet at shoulder width) No information Side-alternating Galileo 900 (Novotec, Pforzheim, Germany) Squat exercise knee bending angle 80◦ and additional load 10RM applied by barbell One session EG: WBV 5 sets of 10 squats within 30s per set. 3 min rest between sets CC: same procedure on floor Shoes Albercromby 2007 [48] n=9 male 32.7±7.0 years n=7 female 32.7 ±8.3 years Healthy adults Single-group repeated measures 30 2 No information Vertical: Powerplate Power Plate North America, Inc., Northbrook, IL) and side-alternating: Galileo 2000 (Novotec Medical, Pforzheim, Germany) Slow dynamic squatting movement from 5◦to 40◦knee flexion for several One session Two trials for in max 15 s per condition. 60 s rest between trials, 5 min rest between vibration directions Sport socks Int. J. Environ. Res. Public Health 2020,17, 3650 9 of 23 Table 1. Cont. Author Participants and Age (Years/Months/Weeks) ±SD or [SE] or (Min–Max) Condition Study Design Frequency (Hz) Amplitude or PPD (mm) Peak Acceleration (m/s2or g) Vibration Type/Device Position/Exercises Session Protocol Intervention Footwear Rohlmann 2014 [49] n=3, 62,63,66 years Patients fractured lumbar vertebral body, male Repeated measures 5–25 1, 2, 4 No information Vertical: Powerplate Pro 5. (Power Plate North America, Inc., Northbrook, IL). Side-alternating: Galileo advanced (Novotec Medical, Pforzheim, Germany) 4 postures: knees straight, knees slightly bent, knees bent at 60◦and on the forefeet One session 8 WBV trials on each plate, 12–15 s per trial, One trial 60 s. Breaks between trials 10–30 s, break 5 min when changing device No information Pollock 2010 [50] EG1: n =12 31.3 ±12.4 years EG2: n =15 36 ±12.1 years Healthy adults Single group repeated measures Randomized order 5–30 5.5 and 2.5 0.2–9 g Side-alternating Galileo 2000 (Novotec Medical GmBH, Pforzheim, Germany) Standing straight legs, without locking knees, resulting in 15.1 ±4.8◦knee flexion One session EC: WBV 7s for each condition (6 frequencies x 2 amplitudes) Rest 30s Barefoot Braz Júnior 2015 [51] EG +CG: n =11 62.91 ±8.82 COPD, 72.7% male Cross-over RCT 35 2 or 4 (wk1–4: 2 wk2–12: 4) No information Vibrating platform (MY3; Power Plate, London, UK) Static work of the lower limbs, semi squatting position at an angle of 120◦–130◦with the upper limbs lightly flexed in support 12 weeks 3 sessions/week Wk 1–4: 10 min/session Wk 5–8: 15 min/session Wk 9–12: 20 min/session EG: 1–4 wks (10 min; 30 s WBV ×60 s rest); 5-8 wks (15 min); 9-12 wks (20 min; 60 s WBV × 30 s rest) CG: no intervention No information Gloeckl 2012 [52] EG: n =42 CG: n =40 EG: 64 ±11 years CG: 65 ±7 years COPD, 51% female RCT 24–26 3 No information Side-alternating Galileo®(Novotec Medical GmbH, Pforzheim, Germany) Squat exercises 3 weeks 3 sessions per week 3×3 min/session EG: WBV 3 ×3min CG: same exercises on floor No information Boerema 2018 [53] EG +CG: n =20 15 weeks C57BI/6 mice, males RCT 30 0.0537 0.098 g Synchronous, 3D LEVELL R.C. Oscillator (Levell Electronics Ltd, Barnet, GB) with Shaker power amplifier Free choice 5 weeks 5 session/week 10 minutes/session EG: WBV CG: same procedures but without WBV No information Int. J. Environ. Res. Public Health 2020,17, 3650 16 of 23 a blanket will to a certain degree prevent the body from sliding down towards the vibration plate and therefor decreases effective loading and training intensity. The transmitted vibration can help to compensate at least a part of this effect since the transmitted movements will cause an effect similar to a vibration conveyor-system as used in industry and therefore will help to move the body towards the plate increasing the effective load. From observations a significant part of this decreased loading caused by friction can be compensated within the first 30 s of vibration application, which is one of the reasons to prefer application durations of 60 s or more. In addition, based on exercise science principles, the time under tension (TUT) of a muscle (the total active contraction time of the muscle during a set of a given exercises) for traditional exercises should be 90 to 120 s [ 72 ], which gives another rationale why a training time of 60 s is proposed as a starting point. Table 4. Parameters to alter training intensity for side-alternating and vertical whole-body vibration training devices [13,44,73]. Parameter Value 1 to 2 Times per day Standard ICU bed (severe cases): 0◦tilt +20◦knee angle 30◦tilt +bent knees Tilt Angle Special Tilt-Table (less severe cases): 30◦to 90◦ Standing device (further increase of intensity): 90◦(standing) Frequency Side-alternating WBV: 20 to 27 Hz Vertical WBV: 25 to 35 Hz Duration 1 to 3 min Number of sets 1 to 4 Amplitude (peak-to peak) Side-alternating WBV: 1–2.5 mm (2–5 mm) Vertical WBV: 1 mm (2 mm) Further increase of intensity by additional exercise tasks Squatting (hip & thigh muscles) Heel-raises (calf muscles) Toe-raises (shin-muscles) Pelvis lifting (thigh muscles & trunk) Negative effects of transmitted vibration could potentially be caused in the case of significant transmission of vibration to measurement sensors, infusion needles, drainage tubes and such, or to intubated patients and the Endotracheal tube. While studies examining the safety of using WBV showed no significant risk for disturbing tubes and sensors [ 13 , 44 ] and studies in COPD patients showed the safety and effectiveness of vibration training even when using an oxygen mask [ 41 ]. Currently, data is available concerning the use of vibration exercise in intubated patients under ICU conditions. As a consequence, the proposed guidelines aim to create high muscle activation to maximize training effects while mechanical transmissions are aimed to be as low as possible to minimize potential risks. It should be noted that research to date has shown a very low transmission of vibration from the feet to the head with 2 to 5% (side-alternating) and 6 to 14% of the amplitude created by the device under 100% loading conditions (free standing at different knee angles) [ 48 ], so transmission of the vibration stimulus to the Endotracheal tube would also be expected to be minimal. Transmission of vibration within the human body (transmission factor) significantly depends on the type of vibration used, as well as the vibration parameters of frequency and amplitude. Side-alternating devices only transmit about half the vibration to the torso and head compared to vertical vibration devices [ 48 ]. Similarly, in-vivo measured joint forces have been shown to be 30% to 60% lower [ 49 ] in side-alternating systems. Despite the lower vibration transmissions and the lower resulting joint forces, muscle activation for the identical parameters of frequency and amplitude have Int. J. Environ. Res. Public Health 2020,17, 3650 17 of 23 been shown to be more than double in side-alternating devices compared to vertical devices [ 46 ]. Based on these data, the use of side-alternating systems to maximize muscle activation and minimize vibration transmission, especially in ICU’s, would be the preferred form of vibration. Mechanical loading of the joints (joint-internal forces measured by artificial joint replacements with built-in force sensors) has been shown to be mainly influenced by the amplitude of the vibration. Doubling the frequency from 12.5 to 25 Hz, would in theory, result in a 4-fold increase in acceleration and consequently a 4-fold increase in joint forces, however, increases in hip-forces rose by only 10–15% and even decreased by 10% at the knee [ 45 ]. Additionally, the same study demonstrated that doubling the amplitude from 2 to 4 mm also increased hip-forces by only 10–15% but increased knee-forces by 20–25%. Along these same lines, several studies have shown that muscle activation, as measured by EMG, is significantly increased by oscillation frequency [45,46,50] with activation amplification of up to a factor of 5.5 compared to quiet standing and by about 80–100% when increasing oscillation frequency from 15 Hz to 30 Hz (Table 4). As a consequence of the combination of the observations above, to increase training intensity it is preferable to follow a certain parameter sequence to maximize effects and minimize potential risks. The proposed sequence to increase training intensity therefore consists of: Initial parameters: 30 to 60 s, if possible, twice a day. Then increase parameters in the following order e.g.,: Duration to 60 s (60 s to help to compensate effects of friction and to allow a TUT of 60 s per set), then tilt-angle (up to 30 ◦ ) (increase proportion of body weight as high as possible using a typical ICU bed), then frequency (high effect on muscle activation but lower effect on vibration transmission), then duration above 60 s (adding cardio-vascular aspects due to longer training duration), then amplitude (adding additional vibration transmission but also additional muscle activation) and lastly, the additional exercise tasks (could also be added earlier but are unfeasible for most ICU patients). 8. Effects of WBV on Quality of Life It was pointed out that COVID-19 leads to dysfunction at different levels (e.g., respiratory, physical, and psychological outcomes), with patients experiencing a serious decrement in the QoL. The effects of WBV on QoL have also been investigated and several authors reported that WBV exercise can improve the QoL of individuals with COPD [51,52,74]. 9. Effects of WBV on Mental Conditions in COVID-19 Patients Besides the aforementioned clinical aspects of the effect of WBV on various physiological systems, it should be mentioned that WBV also stimulates the brain, which could potentially contribute to improving cognitive function and the mental health of COVID-19 patients [ 53 , 75 ]. Although these aspects can be considered as secondary to the pulmonary dysfunction and pneumonia-like conditions, mental health is still important for these patients. This seems most critical during the recovery phase but keeping the brain more active during the acute phase of the disease may also accelerate subsequent full recovery. Pneumonia is known to affect the brain, including cognitive performance [76,77] . Declines in cognition after pneumonia can be caused by hypoxia [ 78 , 79 ], inflammation, and other mechanisms of organ dysfunction attributable to pneumonia [76]. Additionally, Davydow et al. [77] argued that immobility and lack of active exercise in patients hospitalized for pneumonia could exacerbate age-related muscle atrophy [ 80 ], and may worsen direct inflammatory, apoptotic, and hypoperfusion-mediated muscle fiber and neuronal degradation [ 81 – 83 ]. Also, proinflammatory cytokines are elevated in pneumonia-patients as well as in depressed patients [ 84 , 85 ], and prolonged neuroinflammation has been hypothesized to lead to late-life neurodegeneration [85]. Given that WBV activates the brain, and stimulates cognition [ 54 , 55 ], it could be of benefit for COVID-19 patients. Preclinical research showed that WBV induces enhanced neurotransmission [ 56 ], generates region-specific neuronal activity and stimulates hippocampal neurogenesis critical for cognition [75 and unpublished observations]. Moreover, results from previous studies suggest that Int. J. Environ. Res. Public Health 2020,17, 3650 18 of 23 WBV stimulates the cholinergic system, as well as the dopaminergic [ 57 ] and serotonergic systems enhancing mood (especially in case of mild depression). This is further corroborated by the finding that WBV, at least in preclinical studies, has the potential to reduce anxiety [53]. Taken together WBV, when used as an exercise modality, seems to affect the brain in a positive manner. This should perhaps not come as a surprise given that WBV as a form of passive exercise and reflects what is known of the positive impacts of active exercise on the brain [ 86 ]. Hence the use of WBV in seriously affected individuals with COVID-19 should also be considered in the light of cognition and mental health. Although the effect-size of the mental impact of WBV is small and its clinical relevance still debatable due to the lack of sufficient research, we consider it a bonus if WBV interventions are being performed on COVID-19 patients not (yet) capable of performing active exercise. 10. Limitations This is a narrative review based on the best available knowledge of the effects of WBV in several contexts that might be extrapolated to patients with mild COVID-19 infection, but it is a theoretical approach and lacks validation in the context of COVID-19. The potential prescription and employment of WBV in selected COVID-19 infected subjects will require careful evaluation by multidisciplinary teams, asked to carefully evaluate the risk-benefit ratios, monitor the efficacy of WBV exercise, and tailor the protocols to the single subject’s clinical conditions during convalescence. 11. Practical Applications Practical recommendations on how to perform WBV exercise in the hospital or on the ICU are presented in Table 4. Moreover, it is possible to suggest some specific practical applications of WBV exercise (i) for inpatients with COVID-19, that would relieve the symptoms of dyspnea, anxiety, and depression; eventually improve physical function and the QoL, reducing the time in ICU, (ii) for isolated patients, that could be conducted through educational videos, instructional manuals or remote consultation and (iii) for the improvement of post COVI-19 recovery and QoL. 12. Conclusions It is expected that these findings could aid the authorities to plan a simple action like WBV exercise that could help infected individuals to attenuate the decline in physical function, improve post COVID-19 recovery and perhaps reduce time in ICU and allowing for more individuals to be treated. Moreover, these considerations could stimulate investigations involving the use of WBV exercise in in the COVID-19 patients. Author Contributions: M.B.-F. and D.d.S.-C. have conceptualized the manuscript, B.S., A.S. (Ad é irto Seixas), R.G., J.R., R.R., E.A.v.d.Z., M.J.G.v.H., A.C.L., D.d.S.-C. and M.B.-F. have participated in the writing of the original draft, B.S., A.S. (Ad é irto Seixas), R.G., J.R., R.R., E.A.v.d.Z., M.J.G.v.H., A.C.L., R.T., A.S. (Alessandro Sartorio), M.B., D.C., T.F., D.d.S.-C. and M.B.-F. have reviewed and edited the final draft and A.S. (Ad é irto Seixas) and B.S. have prepared the draft for submission. 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