The Effect of Post-ICU Physiotherapy on Respiratory and Physical Functioning Status in Patients with COVID-19: A Pilot Study †

: Background and Objectives: According to recent physiotherapy recommendations (WHO, WCPT, 2020) for patients with COVID-19, after discharge from an ICU, they are expected to experience respiratory, physical, cognitive, and psychological problems due to the duration and nature of the immobilization and sedation, ventilation duration, and underlying morbidity. Moreover, only patients with a limitation in physical capacity and/or physical activity have an indication for physiotherapy. However, little is known about the effect of physiotherapy treatment on the functional capacity of patients with COVID-19. Purpose: The aim of the present study was to provide information for the effectiveness of physiotherapy intervention on the respiratory and physical functional status of patients with COVID-19, since there will be a great demand for physiotherapy


Introduction
Recent physiotherapy recommendations for patients with COVID-19 after discharge from an ICU declare that they are expected to experience respiratory, physical, cognitive, and psychological problems due to the duration and nature of the immobilization and sedation, ventilation duration, and underlying morbidity [1][2][3][4].Additionally, some patients with COVID-19, after discharge from an ICU, might be at risk of long-term impairment and disability of an unknown extent [5].
A holistic rehabilitation approach is needed in every stage of COVID-19 [4].Physiotherapists are frontline healthcare professionals and potentially involved in the management of patients with COVID-19, as members of the multidisciplinary rehabilitation team [5].They are engaged with the transition from the acute phase to the post-acute phase of COVID-19.After discharge from an ICU, among the patients with COVID-19, those with an indication for physiotherapy includes only those with a limitation in physical capacity and/or physical activity [3,4].Physiotherapy is suggested for the assessment and management of ongoing respiratory and mobility impairments [5].As recommended, physiotherapists should evaluate mobility (physical activity, balance), symptoms (dyspnea, impact of dyspnea), peripheral muscle strength, fatigue, quality of life, and oxygen saturation levels.In addition, physiotherapy should be tailored to the individual patients' needs, and goals including breathing exercises, early mobilization, and self-management for daily living were performed once a day, for five days a week, as tolerated [3][4][5].Nonetheless, the effect of physiotherapy treatment on the respiratory and functional capacity of patients with COVID-19 remains unproven as well as the benefits of early physical rehabilitation following ICU discharge on quality of life and mortality being unclear [6].

Participants
This pilot clinical study was conducted from March to June 2020.The sample consisted of 11 patients with COVID-19, discharged from an ICU and hospitalized in the COVID-19 clinic of AHEPA University Hospital.All participants had an indication for physiotherapy, according to the recommendations, and a medical referral as well.The duration of their hospitalization ranged from two to six weeks.Among participants, there were seven males and four females, aged from 44-75 yrs, five smokers and six nonsmokers, four obese and seven nonobese, seven participants had drop-foot, and all of them had dysfunctional breathing.SpO 2 ranged from 88-93% and patients suffered from severe and above-normal dyspnea, according to the Borg scale.

Respiratory Measures
Pulse oximeter (SpO 2 ) , respiratory rate (RR), the Borg scale (intensity of dyspnea), Medical Research Council scale for disability (MRCd), and clinical evaluation of dysfunctional breathing (DB) were used.
Borg scale: The Borg scale measures the intensity of dyspnea (maximal intensity is 10).Subjects are asked to score breathlessness by selecting a number or words that most appropriately described their sensation of breathlessness [7].
Medical Research Council scale for disability (MRCd): The MRCd measures the extent to which their breathlessness affects their mobility (maximal intensity is 5) [8].
Clinical evaluation of dysfunctional breathing (DB): A physiotherapist in the research team assessed this outcome.Criteria for the DB evaluation were upper chest dominant breathing, and thoraco-abdominal asynchrony [9].

Physical Function Measures
The Medical Research Council scale for muscle strength (MRCms), the Berg Balance Scale, 30 s Sit to Stand test (30CST), Time Up and Go test (TUG), 1 min walk test (1MWDT), and the Barthel Index (BI) were used.
Medical Research Council scale for muscle strength (MRCms): The MRCms is a commonly used scale for assessing muscle strength from grade 5 (normal) to grade 0 (no visible contraction).Six muscle groups are examined bilaterally (shoulder abductors, elbow flexors, wrist extensors, hip flexors, knee extensors, and foot dorsiflexors).An MRCms total score below 48/60 refers to significant weakness [10].
Berg balance scale: This scale measures a patient's ability to balance during a series of predetermined tasks of 14 items.A cutoff score of 56 indicates functional balance, and a cutoff score of <45 indicates a greater risk of falling [11].
30 s Sit to Stand test (30CST): The 30CST measures leg strength and endurance by counting the number of times a patient can stand to a fully erect position from a seated position with arms folded across their chest in 30 s time (floor effect five to ten repetitions) [12].
Time Up and Go test (TUG): The TUG measures general mobility (balance, sit to stand, and walking) and determines fall risk.The patient starts from a seated position, walks three meters, turns around, walks back to the chair, and sits down.The time stops when the patient is seated.Cut-off scores indicating risk of falls for the community dwelling adults is 13.5 s [13].
1 min walk test (1MWDT): The 1MWDT obtained during the first minute of a 6MWD is a valid measure for assessing functional ability and has shown a strong correlation to the total 6MWDT [14].
Barthel Index (BI): The Barthel Index (BI) measures the patient's level of dependency through its capacity to perform 10 basic activities of daily living, divided into self-care and mobility components.The score ranges from 0 (totally dependent) to 100 (totally independent).BI classifies patients as having minimal or no disability (BI score, >90), moderate disability (BI score, 55-90), or severe disability (BI score, <55) [15].
For the purposes of the study, measurements were conducted at two time points: at admission and at discharge from the COVID-19 clinic.

Intervention
Although consensus on the type of physiotherapy intervention and timing is still missing, we followed the current recommendations and developed and applied a program tailored to the patients' priorities, needs, and goals.Individualized breathing exercises, early mobilization, and self-management for daily living were performed one to one, once a day, for five days a week, as tolerated for intensity, duration, and frequency.
Individualized breathing exercises comprised airway clearance methods for patients with secretions (usually active cycle of the breathing technique), breathing retraining to reduce dysfunctional breathing, diaphragmatic breathing, pursed-lip breathing for dyspnea relief, rib cage mobilization, slow and deep breathing, use of incentive spirometer, and alveoli recruitment for lung segments expansion, patient's oxygenation, and prevention of atelectasis [5].
Early mobilization (Figure 1) was an individualized program that consisted of passiveactive exercises, actively moving or rolling in bed, sitting on the edge of the bed, stretching, progressive strength training, balance exercises, mobility training, and gait retraining.
reduce dysfunctional breathing, diaphragmatic breathing, pursed-lip breathing for dyspnea relief, rib cage mobilization, slow and deep breathing, use of incentive spirometer, and alveoli recruitment for lung segments expansion, patient's oxygenation, and prevention of atelectasis [5].
Early mobilization (Figure 1) was an individualized program that consisted of passiveactive exercises, actively moving or rolling in bed, sitting on the edge of the bed, stretching, progressive strength training, balance exercises, mobility training, and gait retraining.Self-management for daily living involved individualized education on breathlessness and fatigue management, energy conservation to promote independence with activities of daily living, participation in physical activity, when to stop exercising, and how to advise using the Borg scale (up to 4) and pulse oximeter (>90%).

Statistical Analysis
The distribution of all variables was checked using the Shapiro-Wilk test.According to the normality of distribution of each variable, the appropriate dependent sample tests were performed, to test for differences between ICU discharge and hospital discharge timepoints for all the respiratory and physical function measures.The significance level was set at p = 0.05.The Statistical Package for Social Sciences (SPSS, version 26.0) was used for all data analyses.

Results
All variables examined were normally distributed, as analyzed with the Shapiro-Wilk test (p > 0.05), apart from those physical function parameters (30 CST, TUG, 1MWDT, BI) that could not be performed by patients immediately post ICU discharge.Therefore, data were expressed in mean (SD) descriptive statistics (Tables 1 and 2).Dependent sample ttests showed a significant effect (p < 0.001) for the recommended physiotherapy treatment on respiratory variables (SpO2, respiratory rate, Borg scale score) (Table 1) and physical functioning (Berg balance scale, MRCms score, Sit to Stand test, TUG efforts, 1MWDT, BI) (Table 2).All patients displayed DB at post-ICU discharge, while nine of them adopted a diaphragmatic breathing pattern at post hospital discharge.At post ICU discharge, all patients were at level five disability (MRCd), whereas at post hospital discharge 10 patients improved (three at level four, four at level three and three at level two).Self-management for daily living involved individualized education on breathlessness and fatigue management, energy conservation to promote independence with activities of daily living, participation in physical activity, when to stop exercising, and how to advise using the Borg scale (up to 4) and pulse oximeter (>90%).

Statistical Analysis
The distribution of all variables was checked using the Shapiro-Wilk test.According to the normality of distribution of each variable, the appropriate dependent sample tests were performed, to test for differences between ICU discharge and hospital discharge timepoints for all the respiratory and physical function measures.The significance level was set at p = 0.05.The Statistical Package for Social Sciences (SPSS, version 26.0) was used for all data analyses.

Results
All variables examined were normally distributed, as analyzed with the Shapiro-Wilk test (p > 0.05), apart from those physical function parameters (30 CST, TUG, 1MWDT, BI) that could not be performed by patients immediately post ICU discharge.Therefore, data were expressed in mean (SD) descriptive statistics (Tables 1 and 2).Dependent sample t-tests showed a significant effect (p < 0.001) for the recommended physiotherapy treatment on respiratory variables (SpO 2 , respiratory rate, Borg scale score) (Table 1) and physical functioning (Berg balance scale, MRCms score, Sit to Stand test, TUG efforts, 1MWDT, BI) (Table 2).All patients displayed DB at post-ICU discharge, while nine of them adopted a diaphragmatic breathing pattern at post hospital discharge.At post ICU discharge, all patients were at level five disability (MRCd), whereas at post hospital discharge 10 patients improved (three at level four, four at level three and three at level two).

Discussion
The present study was an attempt to provide evidence for the respiratory and physical functional impact of a physiotherapy intervention in a specific sample of patients with COVID-19.This is the first survey to demonstrate respiratory and physical functioning benefits through a physiotherapy program tailored to the COVID-19 patients' priorities, needs, and goals after discharge from an ICU and hospitalization in a COVID-19 clinic.
This pilot study showed significant improvements on all respiratory outcome measures, with normative values achieved for the oxygen saturation (SpO 2 ) and respiratory rate.The intensity of dyspnea (Borg Scale score), dysfunctional breathing, and of disability (MRCd) were also significantly reduced for the specific sample of patients with COVID-19.This might be due to (a) the airway clearance methods that cleared secretions and promoted re-expansion of the atelectatic lung [16]; (b) the diaphragmatic breathing that reduced respiratory rate, improved chest wall motion, and distribution of ventilation, decreased dyspnea and energy cost of breathing and improved exercise performance [17]; (c) the pursed-lips breathing that increased lung volumes and reduced breathing frequency [17,18], improved oxygen saturation and reduced arterial partial pressure of carbon dioxide (PCO2) [17]; (d) the deep breathing exercises that reversed atelectasis, increased oxygenation, alveolar recruitment, functional residual capacity, and tidal volumes and potentially removed secretions [19]; (e) the incentive spirometry that increased lung volumes and re-recruits atelectatic or collapsed areas of the lung [19]; and (f) the breathing retraining that reduced dysfunctional breathing which resulted in dyspnea [9,20].
Additionally, a significant improvement in the muscular strength and endurance, balance, general mobility, functional ability, and level of dependency was achieved for the specific sample of patients with COVID-19.This could have been due to early mobilization that increased joint mobility and reduced skeletal muscle atrophy, via provocation of physiological effects such as blood flow increase in patients' limbs and internal organs of the body [21].Furthermore, mobilization limited the myosin loss and muscle wasting [22], while performing progressive resistance exercises led to muscle strength increases and higher mobility status of ICU survivors [23].Early mobilization improved functional capacity [24,25], muscle strength [26], walking distance [25], patients' independency after ICU discharge, and discharge to home rate [24].Balance training and gait training increased the distance the patient was able to walk unassisted at hospital discharge [24].Finally, self-management for daily living education as a part of the applied program in the present study was aimed at the facilitation of performance of activities of daily living (ADL) for the patients with COVID-19.The results showed significant improvement for the participant's level of dependency (the Barthel index), ranging from 'totally dependent' to 'moderate disability'.The importance of this specific outcome lies on the association of Barthel Index with ICU readmission [27].
A limitation of the study was the absence of a control group, due to the small sample and its inhomogeneity.The length of duration of ICU hospitalization or additional pathologies (i.e., pneumonia), as factors negatively influencing patient outcome, are suggested as areas for further investigation in subsequent studies with a larger sample size.Further research is needed to demonstrate that physiotherapists are vital to the rehabilitation effort for the patients with COVID-19.

Table 2 .
Mean (SD) values of physical function parameters after ICU discharge vs. hospital discharge (n = 11).