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 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.
COVID-19 is a benign condition in 80% of symptomatic forms with about another 15% considered severe, and 5% critical, requiring resuscitation. 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 with 20% under 60 years of age.
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. 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. 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.
In a recent metanalysis, Sun et al. 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. 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.
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. Several authors have reported that physical activity plays an important role in the maintenance of homeostasis for individuals and that mild to moderate intensity physical activity aids in controlling the inflammatory responses in subjects with chronic low-grade inflammation. 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. These authors assessed 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, 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. The management of this condition in severe cases include prone positioning, lung-protective ventilation, and consideration of extracorporeal membrane oxygenation for refractory hypoxemia. 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
3. Reduction of the Fatigue and the Risk of Dyspnea
Fatigue and dyspnea are clinical characteristics as evidenced by COVID-19 patients. The fatigue is present in about 22% of infected patients 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 and these are also common in patients with COPD or in intensive care survivors one year after discharge. Moreover, as highlighted by Neufeld et al., 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 . 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, 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; Parkinson disease or multiple sclerosis. Moreover, recent studies 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. 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.
WBV exercise has also been investigated in individuals with chronic obstructive pulmonary disease (COPD). Due to lung emphysema and chronic bronchitis COPD patients suffer from severe dyspnea especially during exercise. On the other hand, research has indicated that WBV exercise does not induce dyspnea while standing on a vibration platform with knees slightly bent even though the involuntary muscle contractions that occur due to the vibrations have been shown to improve functional exercise performance as measured by the 6-min walk test in COPD patients [28]. Even dynamic activities on the vibration platform, like squat exercises, produce similar levels of dyspnea as compared to squat exercises on the floor, but with significantly greater improvements in exercise performance [29]. The current evidence suggests that WBV exercise does not induce dyspnea during training could infer that this exercise modality could be tolerated by COVID-19 patients.
In patients with stable COPD, it has been shown that WBV does not alter oxygen saturation [28,30]. In two studies reported by Furness et al. that either utilized a single session of WBV exercise consisting of five one-minute bouts of vibration (~25 Hz, ~2 mm, ~2.5 g) interspersed with five one-minute passive rest periods [24], or two sessions per week for six weeks (~25 Hz, 2 mm, ~2.5 g for WBV) [26] that neither protocol had a negative influence on oxygen saturation, an important finding when considering the use of WBV in COVID-19 patients.
4. Anti-Inflammatory Biomarkers Responses to WBV
In the lungs, inflammation results predominantly from tissue exposure to bacterial and viral pathogens, and/ or environmental pollutants. Excessive acute inflammation and subsequent lung injury can cause pulmonary fibrosis and impair gas exchange. Unresolved lung injury and chronic inflammation are frequently observed in acute respiratory distress syndrome, cystic fibrosis, COPD, and asthma [58,59,60]. Mitochondria are negatively affected by systemic low-grade inflammation in individuals infected with COVID-19 [4], leading to their inability to adapt to higher levels of oxidative stress and ultimately contributing to the systemic loss of muscle mass and function. Understanding the molecular basis of how systemic inflammation and exercise (e.g., WBV) influence muscle mitochondria in this patient group could provide invaluable insight into the development of exercise protocols that could maximize the beneficial adaptations of exercise.
Jawed et al. [31] explored the effects of WBV exercise (amplitude 4 mm, frequency 35 Hz) on circulating stem/progenitor cell (CPC) and cytokine levels. These authors assessed the participants (a) standing on the WBV platform, (b) performing repetitive leg squats without vibration, and (c) repetitive leg squat exercise on a vibrating platform, and reported that CPC levels increased significantly with exercise alone (i.e., repetitive leg squats) and with WBV alone in younger participants. Angiogenic CPCs increased during combined activity in younger and non-angiogenic CPCs increased with WBV alone in younger, and with exercise alone in older participants. With WBV alone, anti-inflammatory cytokine interleukin-10 increased significantly as did tumor necrosis factor-alpha and vascular endothelial growth factor, while inflammatory interleukin-6 decreased. These results suggested that WBV may have positive vascular and anti-inflammatory effects. In clinical populations, such as in COPD, Neves et al. [32] reported that WBV (amplitude 2 mm, frequency 30–40 Hz) can induce changes in inflammatory-oxidative parameters. After WBV, along with improved functional changes (e.g., 6-min walking distance, peak oxygen uptake or handgrip strength), the authors also reported improvements in inflammatory-oxidative biomarkers and white cell count. Ribeiro et al. [33] assessed the effects of a single session of WBV exercise (amplitude 4 mm, frequency 40 Hz) on inflammatory responses in a group of women diagnosed with fibromyalgia. Based on changes in levels of adipokines, soluble tumor necrosis factor receptors (sTNFr1, sTNFr2), and brain-derived neurotrophic factor (BDNF), as well as changes in oxygen consumption, heart rate, and perceived exertion (RPE), it was concluded that a single session of WBV can acutely improve the inflammatory status in patients with fibromyalgia. A similar response was observed in elderly individuals with knee osteoarthritis [34]. Plasma concentration of inflammatory markers and functional performance were assessed after squat exercises combined with WBV (amplitude 4 mm, frequency 35–40 Hz) and resulted in significantly reduced plasma concentrations of the inflammatory markers sTNFR1 and sTNFR2 accompanied by a reduction in self-reported pain.
5. Immune and Myokine Responses to WBV
Given the complex situation generated by the COVID-19 virus, it could be speculated that WBV is able to influence the patients’ immune system. Repeated bouts of acute exercise have been shown to enhance production of anti-inflammatory cytokines (i.e., IL-10) and myokines [61], contributing to reduced inflammation [62] as well as a reduced pro-inflammatory cytokine production [63] and an increased anti-inflammatory cytokine production [64], all of which might have an important protective role in this virus. A recent study by Song et al. [35] aimed at assessing the possible effects of WBV on immune cell differentiation and inflammatory markers reported significant increases in lymphocyte and Treg cells normally associated with improvements in the inflammation barrier function. Blanks et al. [36] also assessed the impact of WBV on the immune system in healthy participants (ages 18–45 y) (14 Hz, 2.5 mm, ~2.1 g) with 10 sets of 1 min vibration periods followed by 30 s of standing rest. The authors observed a significant increase in neutrophil percentage and increases in IL-6, a well-known myokine. This response to WBV was attributed to increased neutrophil infiltration into the muscle [65] and a resultant pro-inflammatory cytokine response [66] that would help mitigate the exercise-induced inflammatory response.
Based on the aforementioned evidence, it seems that IL-6 in response to muscle activation (i.e., WBV) has a number of anti-inflammatory benefits including increased anti-inflammatory cytokine production which could contribute to an attenuation of basal inflammation [62,67]. Blanks et al. [36] even suggested that WBV enhanced tissue IL-6 sensitivity and hypothesized, based on previous results after acute exercise [64], that this exercise paradigm would increase anti-inflammatory cytokine production (IL-10). This is consistent with a recent pilot study aimed at assessing the efficacy of WBV on inflammatory markers in individuals with chronic obstructive pulmonary disease. Participants performed WBV training (35 Hz, 2 mm, 6 × 30 s) and showed increased plasma concentrations of IL-10.
Increases in the percentage of lymphocytes in response to WBV exercise have also been observed [36,37]. Authors showed that squat exercise training with superimposed WBV might modulate T-cell-mediated immunity [37], considered a key aspect in the management of COVID-19 [4].
6. WBV Exercise in Bed-Bound and ICU-Bound Subjects
Ample evidence demonstrates the benefits of early rehabilitation in ICU-bound patients [68]. In fact, given the profound homeostatic and neuro-inflammatory processes involved during (bed-ridden) immobilization [69], one can conclude that musculoskeletal depletion is a highly detrimental side-effect of critical illness, not only with respect to successful rehabilitation after critical illness, but also for the clinical management during the active disease state. We therefore propose that ICU-bound patients are in greater need of adequate medical exercise therapy compared to ambulatory patients. However, it is obvious that traditional forms of exercise and active physiotherapy are difficult to provide in ICU patients. In the context of developing countermeasures for spaceflight that prevent physical de-conditioning, resistive WBV has been found to be a potent mode of exercise [38,70]. Given its partly passive nature, WBV is particularly useful in situations where the ability of patients to co-operate and to exercise is limited, such as in geriatrics or COPD patients hospitalized due to an acute exacerbation. However, considering that traditional squat exercise training might be inappropriate for most COVID-19 patients, when combined with tilt-table technology, WBV can also be applied in well selected patients who are yet unable to stand by themselves, as has been powerfully demonstrated in pediatric rehabilitation [40]. Notably, the approach is also feasible in intensive care units. Technically, patients start to practice WBV in a supine position with a very small inclination, and the tilt table is then iteratively verticalized over several rehab sessions until the patients can stand freely. This approach targets all main muscle groups involved in standing and walking, and it relieves caregivers and physiotherapists from their physical labor during the period where patients are particularly unstable. Furthermore, the approach also relieves the necessity of close contacts with the patient, thus potentially reducing the spread of infectious diseases.
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