Effectiveness of Respiratory Rehabilitation in COVID-19’s Post-Acute Phase: A Systematic Review

Background: The COVID-19 pandemic, caused by the new grave and acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), generated an unprecedented danger to public health. This condition may impact survivors’ quality of life and includes extensive pulmonary and respiratory outcomes. Respiratory rehabilitation is known for its effects in improving dyspnea, alleviating anxiety and depression, reducing complications, preventing and ameliorating dysfunctions, reducing morbidity, preserving functions and improving subjects’ quality of life. For this reason, respiratory rehabilitation may be recommended for this category of patients. Objective: Our objective was to evaluate the effectiveness and benefits produced by the adoption of pulmonary rehabilitation (PR) programs in COVID-19’s post-acute phase. Material and Methods: A search of relevant publications was conducted using the following electronic databases: PubMed, Scopus, PEDro, and Cochrane Library. A single reviser selected pertinent articles that studied the effects of pulmonary rehabilitation during COVID-19’s post-acute phase in improving the respiratory function, physical performance, autonomy and quality of life (QoL). Results: After an initial selection, 18 studies were included in this systematic review, of which 14 concern respiratory rehabilitation delivered in conventional form and 4 concern respiratory rehabilitation provided in telehealth. Conclusions: Pulmonary rehabilitation combining different types of training—breathing, aerobic, fitness and strength—and not bypassing the neuropsychological aspects revealed itself to be capable of improving pulmonary and muscular functions, general health and quality of life in post-acute COVID-19 patients, besides increasing workout capacity and muscle strength, improving fatigue states and reducing anxiety and depression.


Introduction
The COVID-19 pandemic, caused by the new grave and acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), identified for the first time in December 2019, generated an unprecedented danger to public health and still represents an extraordinarily impactful event that continues to negatively affect people's health across the globe. Since the beginning of the pandemic, 640,395,651 confirmed cases worldwide have been registered and 6,618,579 deaths have been recorded so far [1], even though the number of new infections has significantly decreased in the past few months thanks to the ample vaccine campaign conducted by all countries globally. The infection's clinical spectrum is wide and varied, ranging from asymptomatic infection to a slight sickness of the higher respiratory tract, a moderate illness to a critical one, which can be described as a serious viral pneumonia with respiratory distress, septic shock and/or multiple organ failure [2]. A total of 41.8% of infected subjects developed ARDS and 52.4% of these died [3]. The American-European Consensus Conference on ARDS defined the acute respiratory distress syndrome (ARDS) as a process of nonhydrostatic pulmonary edema and hypoxemia associated with a variety of etiologies and carries a high morbidity and mortality (10 to 90%) [4].
A considerable pulmonary concern has characterized this condition; indeed, only 25.8% of patients had lesions affecting a single lung, whereas 75.7% of patients had lesions affecting both lungs bilaterally [5]. Respiratory damage plays a crucial role within patients who have passed COVID-19, since the removal of the cause of lung damage does not hinder the development of fibrotic and progressive interstitial lung disease. Pulmonary fibrosis is indeed known to be consequence of ARDS [6]. Not surprisingly, reduced diffusion capacity, restrictive pulmonary physiology, ground glass opacity and fibrotic imaging changes were found at the follow-up of COVID-19 survivors [7].
The issue for the survivors of COVID-19 does not terminate with the end of the pulmonary inflammation, since a significant number of patients continue signaling persistent symptoms way beyond the acute phase of the sickness. According to the Office for National Statistics, one person out of five found positive to COVID-19 shows symptoms for a period of 5 weeks or more, while one person out of ten develops symptoms lasting 12 weeks or longer [8].
These medium-and long-term effects-known as post-COVID-19 syndrome, signs and symptoms that continue for more than 12 weeks, or "Long COVID", including both ongoing symptomatic COVID-19 (from 4 to 12 weeks) and post-COVID-19 syndrome (12 weeks or more)-are extremely varied and extensive [9].
Data from the UK National Statistical Office suggest that Post-COVID-19 or "Long COVID" syndrome has an incidence rate of 13.7% [11]. This makes rehabilitation measures for the promotion of physical recovery a crucial necessity. Rehabilitation programs play a crucial role in combating the pandemic, in addition to the use of vaccines [12], as they are an effective means of containing the adverse effects of COVID-19 on public health [13].
The National Institute for Health and Care Excellence (NICE) recommends that gradual rehabilitation programs be used within the first 30 days (post-acute phase) to have a maximum impact on recovery [14]. In the literature, there is no unique and officially recognized definition of the post-acute phase; some authors use this expression to indicate the immediate phase after the acute one (after 4 weeks) with persistent symptoms [15].
It thus seems necessary to prepare a multidiscipline and holistic rehabilitation program that considers respiratory rehabilitation tailored on the needs of the single individual to favor complete recovery. Although respiratory rehabilitation was primarily planned for treating chronic lung diseases, numerous reports, guidelines and expert opinions focus on the recommendation of pulmonary rehabilitation in patients recovering from SARS-CoV-2 infection [16,17].
Respiratory rehabilitation aims to ameliorate dyspnea, alleviate anxiety and depression, reduce complications, prevent and ameliorate dysfunctions, reduce morbidity, preserve functions and improve subjects' quality of life as much as possible [16].
The objective of this study is to conduct a systematic review of the scientific literature to assess the efficacy and benefits of pulmonary rehabilitation (PR) programs in the postacute phase of COVID-19, which is useful in promoting an improvement in the respiratory functions, autonomy and quality of life (QoL) of people affected by COVID-19 and reduce the incidence and severity of lung complications.

Research
This systematic review was conducted following the international guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).
A search of relevant publications was conducted with the use of the following electronic databases: Medline (via PubMed), Scopus, PEDro and the Cochrane Library and was carried out between December 2020 and September 2022.
The literature presented has been vetted through the formulation of a search string common to the following databases: Medline, Scopus, PEDro and Cochrane Library containing keywords and Boolean operators AND/OR in combination as follows: (Pulmonary rehabilitation OR post-acute) AND COVID-19.
The search terms are shown in Table A1 in the Appendix A.

Eligibility Criteria
In alignment with the PRISMA guidelines, inclusion and exclusion criteria were laid out through the definition of the PICO strategy (population, intervention, comparison and outcome), as reported below:  Table 1 shows the PICO strategy used.

Selection of the Studies
After the deletion of duplicates using the EndNOTE software 20, an editor evaluated the studies taken from the databases based on the title and later the studies' abstract. After this initial selection, we moved on to analyzing the studies' full texts to determine whether they met the required criteria of inclusion/exclusion. Following the full-text analysis, a decision was made as to which articles must be included in the final review. For those articles over which there were some doubts, the decision was taken after another proofreading of the full text.

Data Collection Process
After inclusion, the studies' characteristics, aims and results were extracted and summarized using an extraction table. More specifically, the following data were gathered: name of the first author, publishing date, title of the article, study's design, size and characteristics of the sample (sex, average age of patients), rehabilitation protocol, frequency of intervention, primary and secondary outcome measures, evaluation time and obtained results.

Evaluation of Methodologic Quality
The randomized controlled trials (RCT) included were evaluated using the Physiotherapy Evidence-Based Database (PEDro) scale, considered a reliable instrument allowing critical evaluation of methodologic quality in experimental studies on physical therapy. The final score of the PEDro scale varies from 0 to 10 with each satisfied element contributing 1 point. No score is assigned if one criterion is not described or is unclear.
The Newcastle-Ottawa quality assessment scale evaluated the cohort and observational studies. The NOS scale allows the evaluation of the quality of non-randomized studies (cohort studies and case-control studies) with its design, content and ease of usage allowing for the incorporation of quality evaluation in the interpretation of meta-analytic results. A "star system" was developed in which a study is evaluated based on three outlooks: the quality of the selected cohort, the comparability of cohorts and the obtained results, thus assigning up to a maximum of nine stars.
The Newcastle-Ottawa Scale quality instrument is scored by awarding a point for each answer that is marked with a star symbol . Possible total points are 4 points for Selection, 2 points for Comparability, and 3 points for Outcomes with a maximum of 9 points.
The practical guidelines and declaration of consent were included, as they are relevant for the revision, but not methodologically evaluated.

Selection of Studies
The total number of articles identified through multimedia database research was 3542, of which 692 articles were duplicates and thus excluded. A total of 2423 articles were also excluded based on their title since it did not fit the required inclusion criteria; subsequently, 320 articles were excluded after their abstract was read and another 87 articles were eliminated after their full text was examined. In the end, 18 articles were deemed useful and relevant: 4 randomized controlled trials (RCT), 7 cohort studies, 5 observational studies, 1 practical guideline and 1 declaration of consent.
The diagram in Figure 1 shows the scheme that was followed to select the articles.

Evaluation of the Methodologic Quality
The evaluation of the randomized controlled trials was carried out with the aid of the PEDro scale. Following the PEDro criteria, the studies' quality can be sorted in low quality (0-3 points), medium quality (4-7 points) and high quality (8-10 points), with 10 being the highest score. A study with a score of at least 6-10 points is of medium-high quality. The final score obtained in the evaluation of the randomized controlled trials included varies from 5 to 7; with an average of 6.3, the included RCTs are of medium-high quality [18][19][20], and only one RCT is of medium quality [21]. The evaluation of the randomized controlled trials is shown in Table 2.

Evaluation of the Methodologic Quality
The evaluation of the randomized controlled trials was carried out with the aid PEDro scale. Following the PEDro criteria, the studies' quality can be sorted in low (0-3 points), medium quality (4-7 points) and high quality (8-10 points), with 1 the highest score. A study with a score of at least 6-10 points is of medium-high q The final score obtained in the evaluation of the randomized controlled trials in varies from 5 to 7; with an average of 6.3, the included RCTs are of medium-high [18][19][20], and only one RCT is of medium quality [21]. The evaluation of the rando controlled trials is shown in Table 2.
The cohort and observational studies were evaluated using the Newcastlescale. The final score obtained in the evaluation of said studies varies from a minim 3 to a maximum of 7 points, with an average of 5.1. The 12 evaluated studies [22-3 of heterogeneous quality with generally low scores. A total of five cohort studies 32] and two observational studies [24,33] obtained less than 6 points on the NOS sc were categorized as being of low methodological quality. In this case, the results o studies should be considered as questionable compared to the others. This signific ference is attributable to certain issues such as the absence of control groups, the a tion of a rehabilitation protocol on a small cohort made up of a low number of p and, lastly, a lack of adequate follow-up, which is necessary to better understand th term benefits of the variables under scrutiny. The evaluation of the cohort and o tional studies is shown in Tables 3 and 4 The cohort and observational studies were evaluated using the Newcastle-Ottawa scale. The final score obtained in the evaluation of said studies varies from a minimum of 3 to a maximum of 7 points, with an average of 5.1. The 12 evaluated studies [22][23][24][25][26][27][28][29][30][31][32][33] were of heterogeneous quality with generally low scores. A total of five cohort studies [25,[29][30][31][32] and two observational studies [24,33] obtained less than 6 points on the NOS scale and were categorized as being of low methodological quality. In this case, the results of these studies should be considered as questionable compared to the others. This significant difference is attributable to certain issues such as the absence of control groups, the application of a rehabilitation protocol on a small cohort made up of a low number of patients and, lastly, a lack of adequate follow-up, which is necessary to better understand the long-term benefits of the variables under scrutiny. The evaluation of the cohort and observational studies is shown in Tables 3 and 4.

Features of Studies
The characteristics of the studies included are given below in the way the data were extracted.

Population
The analyzed studies included an overall population of 1592 subjects affected by COVID-19 in the post-acute phase. The number of patients for studies varies from 23 [19] to 518 [32]. The average age of patients varied from 49.17 [21] to 72.15 years [25]. The average age of the overall population was 58.12 years. Most patients were male. The data related to the overall population included in the analyzed studies are shown in Table 5. At baseline, 6 weeks after baseline and 12 weeks after baseline (week 12).
The informed multi-component and biobehavioral telerehabilitation program for COVID-19 survivors is safe and feasible. Participants in both groups functionally improved from baseline to 6 weeks and 12 weeks after intervention.     Significant improvement in EG (TelerGr) in terms of mMRC (p = 0.035), 30STS (p = 0.005), 5 sitting to standing time, which is one of the subtests of SPPB (p = 0.039) and SGRQ scores. A significant improvement was observed only in the pain score in the CG (p = 0.039). Statistically significant difference between groups in SGRQ (p = 0.035) and total (p = 0.042) scores.
In addition, a more symptomatic improvement was found in TeleGr.

Intervention
The different approaches used within the selected studies include respiratory rehabilitation delivered through different protocols and with a varying number of sessions and methods of intervention. The approaches were different for all studies and w described for each one.
Four studies adopted a respiratory physiotherapy program comprising deep breathing, inhaling muscle training and bronchial hygiene techniques [19,23,29,33]. One study kept to the European Respiratory Society and American Thoracic Society's recommendations (ATS/ERS) for that concerning breathing exercises [22].
Another study provided a program of respiratory rehabilitation based on thoracic clapping and vibrations, breathing control and thorax-abdominal coordination exercises, breathing exercises using a pep bottle, forced inhaling/exhaling and the use of incentive spirometers [24]. Three studies envisioned the teaching of breathing control (breathing with pursed lips, secretion mobilization and diaphragmatic breathing) and controlled coughing exercises [20,30,32]. One study combined muscular training with active cycle breathing training (ACBT) [26,31]. Instead, two studies gave a less detailed definition of the respiratory rehabilitation program [25,27].
Four studies envisioned a telerehabilitation program that provided for a virtual and supervised respiratory and muscular rehabilitation program, deployed through a telemedicine platform [18,21,28,31]. Two of these studies (Hameed et al. and Pehlivan et al.) describe a rehabilitation program delivered on a telerehabilitation platform. In Hameed et al. [28], diaphragmatic breathing exercises, spirometry incentive, sit-to-stand, standing gear, shoulder scaption, standing heel lifts, sidestepping and wall flexion are proposed. In Pehlivan et al. [20], patient education, rhythm run/autonomous walk in the corridor, breathing exercises and an active cycle of breathing techniques is proposed, in addition to range of motion exercises and standing squats. Instead, in two of these studies, telerehabilitation program is proposed through a smartphone app. In Capin et al. [18], the program includes breathing and compensation techniques, high-intensity strength training, aerobic and cardiovascular exercises, exercise balance, functional activities, stretching, and lifestyle coaching and motivational talk. In addition, this application is used for facilitating selfdirected intervention outside supervised sessions. In Li et al. [19], the use of an application for smartphones called "RehabApp" is described, and this study includes chest breathing and expansion and aerobic exercise in a three-level exercise plan with the difficulty and intensity programmed to increase over time.
All of the studies adopted a rehabilitation protocol in which respiratory physiotherapy is deployed with strength and resistance training of both the upper and lower limbs, balance and coordination exercises, aerobic exercise based on walking/treadmill and cycling and muscular relaxation techniques. Five studies implemented educational sessions, in conjunction with the rehabilitation protocol, which concerned dyspnea, cough, fatigue, fear and anxiety, memory and concentration, self-management of ordinary activities and back-to-office activities [25,27,29,30,32]. Only four studies included psychosocial support with lifestyle and motivational coaching, nutritional consultation and occupational therapy as part and parcel of the rehabilitation protocol [18,19,23,29].
Concerning the length of the interventions, treatment length varies from study to study, from a minimum of one session [28] to a maximum of five-six sessions per week [32], distributed on a time interval spanning a minimum of 3 weeks [27] to a maximum of 12 weeks of treatment [26]. The intensity of the rehabilitation action is also quite heterogeneous and comprises between 20 [32] and 60 min per session [28] (Table 5).

Comparison
Not all the studies included had a control group. One of the studies compares three experimentation groups, each undergoing virtual physical therapy by means of a telemedicine platform, home-delivered physical therapy, an autonomous physical exercise program and one control group that receives no treatment [28].
Three of the included studies made a comparison between cohorts undergoing the same rehabilitation program, which differ in the type of COVID-19 they show: mild/moderate and severe/critical COVID-19 [27], acute/grave/serious/mild COVID-19 [29] and patients on ventilation or not [30].
Three studies compare two cohorts undergoing the same rehabilitation program but draw a distinction between: COVID-19 and non-COVID-19 patients [22], COVID-19 patients and patients with other kinds of pneumonia [23], COVID-19 patients and patients with other types of lung disease [32].
Three studies included a control group which received educational sessions [18,21,31]. Instead, two studies included a control group that received no treatment [20,26].

Outcome
The analyzed studies show the main results related to two macro-areas: lung function and functional capacity (exercise), which were evaluated in almost all of the studies using different scales and other tools.
The test which was most used to evaluate functional capacity was the six minute walking test (6MWT) [19,[21][22][23][24]26,[29][30][31][32][33]; one study used the shortened version of the test, namely, the two minute walking test [28]; one study used a different test, namely, the incremental shuttle walking test and the endurance shuttle walking test (ISWT and ESWT) [25]; and one study used both the six minute walking test (6MWT) and the endurance shuttle walking test (ESWT) [27]. Apart from the six minute walking test (6MWT), two studies also used as a stress test the 30 s sit-to-stand test [26,28], while two studies evaluated the functioning of lower limbs using the short physical performance battery (SPPB) [28,31].
The patients' physical functional, psychological and social state was mainly evaluated using the functional independence measure (FIM) [20,23,30,32]. Only three studies evaluated autonomy in the activities of daily life (ADL) through the Barthel index (BI) [19,24,33].
Only two of the studies considered did not use the six minute walking test as their functional capacity assessment (6MWT), but rather used the time up and go test (TUG) to evaluate patients' mobility [18,19].
Within the outcomes that were considered, we also have those related to the quality of life in correlation to health (QoL), which was analyzed in nine studies and evaluated through different scales: St George questionnaire [22,31], chronic respiratory questionnaire [30,32], short form 36 [20,27], short form 12 [21] and Euroquol 5D [25,29].

Summary of Results
The analysis of the obtained results highlights that, in the post-acute phase of COVID-19, a complete rehabilitation program, which is most frequently adopted, provides for respiratory physiotherapy deployed together with aerobic exercise and both strength and resistance exercise, carried out both in person and remotely through telemedicine platforms.
Indeed, out of the 18 studies considered in this systematic review, 12 provided for a pulmonary rehabilitation program deployed in hospital or outpatient settings, while 4 present a remotely deployed rehabilitation program through telemedicine platforms. To this, a practical guideline and a declaration of consent added, which gives suggestions for the planning of rehabilitation programs for COVID-19 patients in different phases.
Specifically for the post-acute phase, the following actions are suggested: disability recovery, peripheral muscle strengthening, thoracic physiotherapy with respiratory muscle training, dry nonproductive cough management and bronchial clearance techniques with appropriate preventive measures. To this, we must add aerobic exercise < 3.0 MET with progressive intensity increase in patients with no or slight disability (SPPB > 10; Barthel index > 70); a complete pulmonary rehabilitation program is necessary in patients with moderate-to-severe disability (SPPB < 10; Barthel index < 70). During exercise training, the continuous monitoring of essential parameters such as blood pressure, SpO2, dyspnea and perceived effort (Borg scale) is recommended. The use of continuous or temporary positive expiratory pressure devices with or without oscillation (PEP, TPEP and OPEP) is suggested for patients with hypersecretion, either alone or in combination with lung expansion strategies to increase lung volume, better control exhalation and facilitate peripheral and proximal mucus movement [34,35]. Based on the protocols suggested by the studies, we hereby summarize the results obtained for the main outcomes that were examined: In evaluating functional capacity, which is the primary outcome for almost all included studies, we detected improvements in all groups that underwent a complete rehabilitation program; in more detail, three of the studies taken into account detected significant improvements in all groups, which differed for the type of COVID-19 they exhibited: light/moderate COVID-19 and severe/critical COVID-19 undergoing the same rehabilitation program showed a slight difference in favor of the patients with severe/critical COVID-19 [27,29,30].
Three studies noted significantly better improvements in COVID-19 group patients compared to the control group, which received the same rehabilitation program but composed of patients suffering from common pneumonia or other lung diseases [22,23,32].
Four studies analyzed a single cohort of COVID-19 patients without a control group and have noted a significant improvement in functional capacity in terms of an increase in the 6MWT, the ISWT, the ESWT and the SPPB, as well as an improvement in autonomy in daily life activities (ADL), assessed through the Barthel index. [19,24,25,33]. The four studies that comprised a rehabilitation program deployed through telemedicine registered significant improvements not only regarding functional capacity but also in symptoms and quality of life, in favor of the group that received the complete rehabilitation program remotely through a telemedicine platform compared to the control group that received no therapy or brief educational instructions [18,21,28,31].
Lastly, two studies highlighted a considerable improvement in functional capacity including quality of life in favor of the group that received the complete lung rehabilitation program with respect to the control group that received no treatment [20,26].
In evaluating the pulmonary function, another outcome analyzed by most studies considered, the same instruments were used; however, heterogeneous results were obtained. Two of the studies noted statistically significant improvements in pulmonary function in favor of the group that received the complete rehabilitation program concerning the control group which received no therapy [20,21].
Two other studies, which compared two groups constituted by COVID-19 patients and patients affected by other pulmonary disease or respiratory failure, found a sizeable improvement in the lung function of the COVID-19-patient group.
Another study analyzed a single cohort of COVID-19 patients without a control group and registered a considerable improvement in lung function, which is still compromised even after the rehabilitation program [19]. One of the studies traced significant improvements in all groups considered, which underwent the same rehabilitation program. The patients differed for the type of COVID-19 they presented: grave/severe/moderate. The results also show a slightly more favorable outcome for those with grave/severe COVID-19, concerning lung function and quality of life and fatigue [29].
Lastly, only one study did not exhibit any significant differences in pulmonary function between the two groups that underwent the same rehabilitation program but were distinguished between ventilated and unventilated [30].
In the analyzed studies, it was observed that COVID-19 patients underwent a complete respiratory rehabilitation program with breathing, aerobic, strength and endurance exercises, carried out both in hospital and remote with telemedicine, recording a gradual recovery of functional capacity, the operating capacity that translates into an initial increase in the distance traveled to 6MWT. This results in a gradual increase in autonomy and improvement of the quality of life. Some studies have shown that the same rehabilitation program focused on respiratory function could improve functional capacity even in patients with different stages of COVID-19 (Table 5).

Discussion
Our systematic review was carried out to analyze the role of a multidimensional respiratory rehabilitation program in improving the functional impairments detected in post-acute COVID-19 patients to evaluate the effectiveness and the benefits derived and identify specific protocols that may be included within tailored rehabilitation programs.
The results suggest that a complete rehabilitation protocol comprised of respiratory physiotherapy, aerobic training and strength and resistance training is beneficial to ameliorate the typical fallouts in COVID-19 patients. However, the low number of high-quality studies in the literature does not allow the recognition of an elective protocol. Stemming from the suggestion given in the guidelines, recommendations and declarations of consent [34][35][36] that have followed one another in these two years of the pandemic, we can see that an aspect in common for almost all of the studies is the centrality of physical exercise, which represents the key aspect in treating pulmonary illnesses. This is because it allows for a progressive improvement of peak absorption of lung oxygen, functional capacity, muscular strength and size, systematic oxidative stress and health-correlated quality of life [37].
Therefore, the studies we analyzed in this review show results related to two macro-areas: lung function and exercise capacity, evaluated by the six minute walking test (6MWT).
The element that distinguishes the rehabilitation protocols is the type of exercise they suggest: some protocols consider deep breathing, training of inspiratory muscles and bronchial hygiene techniques with a positive finding in the functional tests used, significant results and performance improvement in 6MWT, Barthel index, functional independence measure and lung function tests such as FEV1, CV, TLC, TLCO [23,29,31,33]. Only one study proposes thoracic clapping and vibration, breathing control exercises and thoracoabdominal coordination exercises, breathing exercises with the pep bottle, forced inhalation/exhalation and the use of an incentive spirometer with a significant improvement in the main functional test used: 6MWT, Barthel index and perceived effort with the Borg scale [24]. Others planned the teaching of breathing control: breathing with wrinkled lips, mobilization of secretions, diaphragmatic breathing and controlled coughing exercises with a significant improvement in functional abilities and therefore positive results in 6MWT, functional independence measure and positive results on lung function test. This results in a general improvement in the quality of life [21,30,32].
Respiratory physiotherapy is associated with strength and endurance training of the upper and lower limbs, aerobic exercise, muscle relaxation techniques and, in one case, balance and coordination exercises [24] to achieve progressive functional improvement and a reduction in the level of disability. These rehabilitation programs have allowed the achievement of a gradual recovery of exercise capacity and extensive improvements in muscle strength, balance, reduction in dyspnea and its impact on daily life activities [22][23][24]29,30,32,33].
However, it must be recognized that respiratory rehabilitation does not limit itself to breathing muscle training, but it is indeed, as stated by the American Thoracic Society (ATS) and The European Respiratory Society (ERS), a global approach based on a deep evaluation of the patient eligible for tailored therapy. This therapy must include, but is not limited to, the re-education of physical effort, educational activities aiming at a change in lifestyle and bad behavioral habits and improving lifestyle [38].
To this end, certain studies envisioned coupling the rehabilitation protocol with educational sessions aided by handouts that included: dyspnea, cough, fatigue, fear and anxiety, memory and concentration, self-handling of daily activities and back-to-office activities [25,27,29,30,32].
Only in a few cases was psychosocial support included as part and parcel of the rehabilitation protocol, together with lifestyle coaching and motivational interview [18,23,29,31], to favor the improvement of physical and psychological health, promote therapeutic adherence and ameliorate health in general in patients affected by respiratory disease. In these cases, there was a progressive improvement in the quality of life and a reduction in the symptoms of anxiety and depression, although with minimal dimensions.
Both the educational and the psychosocial components hold key roles in the rehabilitation program; they indeed amount to an important factor that can influence one's perception of the functional condition and one's health status in general. This rehabilitation program can also improve patient compliance and better outcomes in terms of limitations and functionality, as well as rapid return to work and social activities.
A comprehensive and multidimensional respiratory rehabilitation program showed positive outcomes in all examined COVID-19 patients. However, most of the studies in the literature focused more on evaluating the effectiveness of rehabilitation in patients who survived intensive care, and little is known about non-ICU-COVID-19 patients. Some studies report how a comprehensive respiratory rehabilitation program can significantly improve functional outcome measures in patients with severe-critical COVID-19 [27,29]. Only one study reports no significant differences in the functional outcomes analyzed at discharge among patients [23].
The novelty suggested in this review of scientific literature is its focus on remote rehabilitation programs. The studies showed that a remote rehabilitation program deployed through telemedicine and under supervision is safe, feasible and effective. The data obtained reveal how a good efficacy and foremost significant improvements from the functional point of view in patients involved, as shown by the increase in distance walked in the six minute walking test (6MWT), to which we can add the increase in lung function and health correlated quality of life [18,21,28,31].
During the pandemic, there was a high percentage of patients with damage and limitations of physical and lung function, and remote rehabilitation has proved to be a viable alternative that could become a new frontier in rehabilitation, to ensure greater continuity in patient care. Since we have seen the issues healthcare systems experienced in the current pandemic, we consider it more important to assure equity in access to therapy in remote areas, continuity in assistance and support for the management of chronic situations.
Hence, we can state that even though we have the presence in the scientific literature, concerning COVID-19's post-acute phase and heterogeneous pulmonary rehabilitation protocols in terms of suggested exercises, we can still see that a rehabilitation protocol that combines respiratory physiotherapy, aerobic training and strength, without neglecting the neuropsychological aspect, produces a positive effect on exercise capacity, lung function, dyspnea, fatigue, reduction in anxiety and depression and improvement of quality of life (QoL). This goes to show the fundamental importance of starting complete and tailored rehabilitation protocols in the post-acute phase, especially in those patients that exhibited a grave/critical form of pneumonia, to ensure the obtainment of the highest level of physical, functional, social autonomy possible and improve quality of life in COVID-19 survivors, as well as reducing the incidence of serious lung and functional complications, thus producing benefits from the economic-health point of view.
In carrying out this systematic review, we encountered several issues, the largest of which was the selection of the studies, since the pandemic has hit the world with dramatic effects leaving few possibilities to carry out high-quality clinical studies on a wide range of patients. Hence, most of the current protocols are based on preliminary results, observational studies, cohort studies, experts' opinions, consent of professionals and previous experiences derived from the acute respiratory distress virus pandemic (SARS). This aspect has determined the vast array of suggested designs proposed by the studies we considered and their different methodologies and respective quality.
Another relevant limit is the absence, for the most part, of a control group, which did not allow the obtaining of absolute proof regarding the efficacy of the rehabilitation protocol proposed for the treatment of COVID-19 derived functional impairments.
Indeed, most of the studies accounted for that suggested the application of a rehabilitation program on a small cohort comprised of a limited number of patients, which further limits the extensibility of the acquired results over the global population. In addition, many studies did not carry out any adequate follow-up, thus needing further verification to better understand the long-term benefits of the suggested protocols for respiratory rehabilitation in the post-acute COVID-19 phase. Finally, a significant limitation is represented by the lack of a unique definition of post-acute phase in the literature, which creates differences between the different studies that have analyzed this phase.
Despite the limitations found, the quality of the studies included is such that it allows the definition of adequate results to the aim of the research for which they were intended.

Conclusions
To conclude, the consequences stemming from the COVID-19 pandemic caused a sizeable impact on the entire population's health, producing long-term effects that impair the physical performance and quality of life of COVID-19 survivors. In such a context, pulmonary rehabilitation, in its many facets, holds a primary role by allowing a gradual recovery of lung elasticity and optimal breathing flux, obtaining better alveolar ventilation and increasing oxygenation.
Combining exercises such as aerobic, respiratory, fitness and strength exercises without foregoing the neuropsychological aspect has proven to be apt for ameliorating health status, well-being and quality of life in post-acute COVID-19 patients. It has also increased exercise capacity, improved fatigue levels and inhalator muscle strength and diminished anxiety and depression conditions, which are very frequent aspects that can greatly influence patients' compliance, the latter being key in successfully implementing of a rehabilitation program.
Therefore, it is advisable to increase the implementation of comprehensive and customized rehabilitation protocols for COVID-19 patients, in which a large part is devoted to respiratory rehabilitation to recover overall function and improve in the quality of life.