Pulmonary Rehabilitation For Patients Post Severe COVID-19: Review Article

INTRODUCTION:

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic with the first outbreak in China, the relevant literature has focused on the disease’s epidemiology, diagnostic testing, and treatment modalities as well as the cardiopulmonary complications of patients with COVID-19, particularly those admitted to hospital 1–3. With the ongoing pandemic, the overall understanding of the clinical outcomes and prognostic factors among patients discharged from hospital following the acute phase of COVID-19 is still limited 4,5. Current evidence suggests that COVID-19 patients may complain from respiratory, physiological, and psychological impairment after hospital discharge 4. Furthermore, research has shown that around one-third of COVID-19 patients had severe respiratory failure and acute respiratory distress syndrome (ARDS), which can lead to persistent respiratory and physical impairment 6. Thus, lung tissue alterations, such as consolidation, thickening of the vascular wall , and pleural effusion have been reported among acute COVID-19 pneumonia patients 7. Finally, the increased risk of intensive care unit (ICU) acquired weakness has also been discussed in the literature as patients who experience severe respiratory failure end up on a mechanical ventilator and have extended ICU or hospital stays 8.

Despite this substantial body of research, there is still considerable debate regarding whether patients discharged from the hospital after a severe COVID-19 infection have fully recovered or whether they retain permanent lung damage or experience fibrotic lung changes. Studies have shown that up to 30% of patients who recover from severe COVID-19 pneumonia continue to experience breathlessness and require supplementary oxygen 9. While there is conflicting evidence regarding the actual pathophysiological mechanism through which a COVID-19 infection can predispose a patient to lung fibrosis, a meta-analysis suggested that a chronic viral infection can induce a mild and long-latency inflammatory response that contributes to the fibrotic response 10. In line with this, other studies have reported that ARDS can predispose patients to lung fibrosis; as a COVID-19 infection can cause ARDS, there is thus a risk of fibrosis, even after recovery 11.

Owing to the respiratory complications as a sequela of severe COVID-19 pneumonia, many recommendations have been published regarding respiratory rehabilitation in the post-acute phase. However, the efficacy of these recommendations is unclear. In addition, few studies have examined the effectiveness of pulmonary rehabilitation programs in the context of COVID-19, and thus, much of the published literature on this topic comprises editorial letters or recommendations from rehabilitation societies or organizations. Against this backdrop, the current report reviews published articles addressing pulmonary rehabilitation in patients with COVID-19 and highlighting the benefits of such rehabilitation for patient outcomes.

Pathophysiology mechanisms of COVID-19 infection to lung injury:

The virus that responsible for COVID-19 disease, SARS-CoV-2, is an enveloped virus. It infects the host cells through a series of viral spike proteins attached to the receptor on the host called angiotensin-converting enzyme-2 (ACE2) 12–14. Then, endocytosis occurred in which the viral genome is released into the host cell to establish the synthesis of the viral RNA through changes in the endoplasmic reticulum of the infected cell 15. Research has provided a list of host cells targeted by the SARS-CoV-2 virus, including type II pneumocytes, alveolar macrophages in the lungs, and basal epithelial cells in the nasal passages5. Many research identified different mechanism that activate proinflammatory and profibrotic pathways in the host cell after SARS-CoV-2 invasion 16,17. Thus, a reduction in the host cell ability to balance the renin-angiotensin system (RAS) is occurred as result of reduction in the expression of ACE2 that caused by cleavage of SARS-CoV-2 spike proteins18. Therefore, when the RAS is reduced at the cellular level, an increase in the activation of interleukin (IL)-6 and tumour necrosis factor-α (TNFα) occurred as well as the increase in recruitment of neutrophils and macrophages. This series of action cause direct endothelial cell injury^16,18. Biological research have listed IL-2, IL-7, IL-10, and TNFα as inflammatory cytokines which increased in COVID-19 patients^19–21.In addition , cellular injury occurs as result of viral replication and simulation of the immune response of infected cell,. This results in altered cell function and demise of type II alveolar epithelial cells, which suggested to be responsible for the beginning of the development of pulmonary fibrosis^21,22.

In terms of the disease severity, different SARS-CoV-2 infection phenotypes have been identified based on clinical and radiological characteristics 23. The first, Phenotype-1 is the most common and is characterized by mild respiratory symptoms, a normal chest radiograph, and the absence of hypoxemia; symptomatic treatment is used for such patients. Phenotype-2 is characterized by the presence of hypoxemia or multiple small ground-glass opacities on the chest radiograph. These patients require close respiratory monitoring because they may progress to Phenotype-3, which presents more significant hypoxemia, higher respiratory rates, and high IL-6 and other inflammatory marker levels 23. This type also requires close monitoring as patients may need to be intubated. Phenotype-4 is characterized by alveolar edema and normal/low lung compliance, meaning patients have severe hypoxemia requiring intubation 23,24. Treatment should include tidal volumes of 6 mL/kg PBW and moderate-to-high positive end-expiratory pressure (PEEP) as well as lateral or prone positioning. Phenotype-5 is characterized by an ARDS-like appearance, and management should follow standard ARDS guidelines. A protective ventilatory strategy and prone positioning are indicated 23,24.

Thus, the majority of patients with a severe manifestation of COVID-19 required respiratory support and ICU admission, where 88% of those required assisted ventilation by a mechanical ventilator25. There is a lack of consensus in the data regarding the respiratory mechanics and optimal mechanical ventilator setting in patients admitted to ICU for COVID-19 associated respiratory failure^3,26. Intubated patients with severe COVID-19 disease were placed on with high PEEP, increasing barotrauma incidence 27. Studies suggest that COVID-19 patients who progressed to ARDS have edema and atelectasis, which cause a change in lung volumes, resulting in over distention of the lung (called volutrauma), or an increase in the strain of the ventilated alveolar space( called atelectraum). Additionally, the alteration in lung tissue due to the pathological process of severe COVID-19 causes friability of the lung parenchyma and subsequently increases the risk of lung fibrosis27.

Pulmonary rehabilitation for post-COVID-19 infection:

Pulmonary rehabilitation, in general, considers a critical component in the management approach to enhance the shortness of breath and exercise tolerance, and ultimately the health status of patients with chronic lung disease28. The primary strategy of pulmonary rehabilitation programs is exercise training, education, and behaviour changes. All those strategies improve physical and psychological well-being, therefore promoting the long-term health quality of life 29. Different health settings utilize different approaches and structures of pulmonary rehabilitation programs; however, all programs share the key components of training include: endurance, interval, resistance/strength exercise of upper and lower limbs, walking , and self-management training. Most of those sessions usually implemented through outpatient programs 30. Since the pulmonary rehabilitation program includes many sessions for a long period, patient adherence is the major issue to achieve such a program's effectiveness 31.

The need for pulmonary rehabilitation in COVID-19:

The need for pulmonary rehabilitation for COVID-19 patients has been discussed in the literature. Specifically, during the acute phase of a severe COVID-19 infection, patients receive intensive medical management, including prolonged mechanical ventilation, sedation, and neuromuscular blocking agents. This intensive medical management is considered a risk factor for developing post-intensive care weakness 32. Studies have shown that many patients referred to pulmonary rehabilitation programs after severe COVID-19 have symptoms common to other ICU patients, including dyspnea, anxiety, prolonged pain, and reduced physical function and quality of life 33.

Consistent with SARS infection outcomes, many studies have hypothesized that the lung tissue damage and alteration that occur in severe COVID-19 may cause various degree of physical dysfunction34. Therefore, experiences with pulmonary rehabilitation in post-SARS patients provide supportive evidence for the implementation of pulmonary rehabilitation programs for COVID-19 patients 35. Therefore, COVID-19 patients tend to have the same problems as patients with chronic lung disease; however, COVID-19 patients, the need for a pulmonary rehabilitation program is critical to overcome breathlessness and fatigue, improve physical performance, and subsequently enhance the quality of life 36.

The main goal of pulmonary rehabilitation programs for COVID-19 survivors is usually endurance as these patients had a prolonged hospital stay and are thus at risk of developing ICU acquired weakness^8,28. Moreover, as dyspnea and a high respiratory rate are known predictors of severe disease or death, it is important to continue monitoring such patients closely. While many pulmonary rehabilitation programs focus on endurance, there is a need for more research on how to best quantify patients’ endurance level as part of an outcome assessment37. Meanwhile, many patients with COVID-19 require supplemental O2 for post-acute rehabilitation, and thus a secondary goal in rehabilitation programs is to wean them off O2. Third, prolonged bed rest and immobility contribute to the loss of strength, and studies have indicated that patients with COVID-19 have a greater muscle mass loss compared to pathologies with similar ICU and bed rest time38. This may be due to specific COVID-19 loads, the impact of the prolonged lack of muscle tissue oxygenation, and the physiological reaction to longer periods of increased respiratory rate and heart rate along with decreased PaO232. Finally, there is the issue of independence: most patients are discharged as early as possible to free up ICU and hospital beds, meaning that the patients may not yet be fully independent at home39.

With the growing body of evidence showing that COVID-19 survivors have pulmonary sequelae after the acute phase of the infection, an increasing number of studies have investigated the clinical outcomes among COVID-19 survivors, especially concerning the long-term effects^35,39,40. In relation to the abovementioned points on the functional deficits post COVID-19, various associations and committees have published recommendations for inpatient and outpatient pulmonary rehabilitation^37,41–43. Those recommendations have been utilized as essential clinical practice guidelines for effectively managing severe COVID-19 with ICU support. However, the main challenges for pulmonary rehabilitation, which mainly take the form of inpatient sessions, are the limited numbers of therapists compared to the number of patients as well as existing infection and hygiene measures, especially if the patients are isolated 44.

Reviewing the published research:

Most of the evidence assessing the impact of pulmonary rehabilitation programs on COVID-19 survivors has been published as reports by various organizations and pulmonary rehabilitation committees, although there have been a few prospective cohort and cross-sectional studies 36,39,40,44. Thus, the guidelines and recommendations for implementing pulmonary rehabilitation programs in the COVID-19 era have primarily come from organizations 41–43,45,46. Table 1 present the published studies on the effective of pulmonary rehabilitation on COVID-19 patients. At the beginning of the COVID-19 pandemic, several studies described the short-term effects of inpatient pulmonary rehabilitation for patients with severe COVID-19 infection admitted to ICU and placed on mechanical ventilation. For example, a cross-sectional survey recruited post-COVID-19 patients referred to a rehabilitation unit in Italy and assessed their pulmonary function and disability status 36. The study shared the experience of their pulmonary rehabilitation program and stressed the clinical importance of pulmonary rehabilitation programs for COVID-19 patients in the early stages of recovery 36.

In 2020, Spielmann et al. described the effect of a three-week standardized inpatient pulmonary rehabilitation program for hospitalized COVID-19 patients and compared their outcomes to the outcomes of patients who had other lung diseases and had undergone a similar pulmonary rehabilitation program in 2019 47. The study found improvements in physical performance, measured by Functional Independence Measure (FIM) and 6 Minute Walk Test (6-MWT), among hospitalized COVID-19 patients. This finding provides emerging evidence regarding clinical and functional improvements for severe COVID-19 and highlights the importance of post-acute pulmonary rehabilitation for COVID-19 recovery 47. Other studies have indicated that the length of time on ventilation, level of sedation, and function after extubation are the most important indicators of long-term recovery48. Furthermore, Puchner et al., who conducted a cohort study to assess the status of COVID-19patients enrolled in a pulmonary rehabilitation program, showed that more than 50% of their sample had pathological Forced expiratory volume in 1 second (FEV1), Forced vital capacity (FVC), and Total lung capacity (TLC) below < 80%. That study also found that 83% of study participants still showed reduced diffusing capacity of the lungs for carbon monoxide(DLCO) at the end of the rehabilitation program 40.

Beyond this, many studies have reported that patients have reductions in their maximum inspiratory pressure and diffusion capacity measures within the first year following their discharge from ICU 49. Those reductions in respiratory function manifest as increased work of breathing and an effective cough 50. Mo et al. found that patients discharged from hospital after severe COVID-19 pneumonia had impaired lung diffusion capacity and complained of dyspnea, chest pain, and general fatigue for weeks after hospital discharge 51. Moreover, another study reported that COVID-19 survivors who were referred to a pulmonary rehabilitation program still had residual infiltrates of the lung, which possibly progressed to fibrosis, leading to a limitation in gas exchange 41,52. The study further highlighted that COVID-19 survivors require close monitoring of their lung function and residual capacity to monitor changes in FEV1, FVC, FEV1/FVC%, and DLCO% 41. Additionally, respiratory and aerobic exercises has shown promise in helping to enhance endurance and quality of life of COVID-19 patients in addition to reduction in the anxiety and depression level 53.

Meanwhile, there is limited clinical trial based evidence regarding pulmonary rehabilitation for COVID-19 survivors. One randomized-controlled trial (RCT) assessed the effectiveness of a 10-min pulmonary rehabilitation session for six weeks on respiratory function, Health-related quality of life (HRQoL), mobility, and psychological function among elderly COVID-19 survivors discharged from hospital 39. The study's findings showed an improvement in respiratory function (FEV1/FVC), HRQoL, and in level of anxiety among their patients.

Recently, a scoping review highlighted pulmonary rehabilitation in COVID-19 patients, underlining the lack of data on this topic, although the recommendations published by various societies highlight the benefits of early pulmonary rehabilitation program initiation 54. The review strongly suggests implementing a plan for multidisciplinary rehabilitation programs to prevent the development of long-term consequences of COVID-19.

Conclusions:

This review has shed light on the need for more evidence of the beneficial effects of pulmonary rehabilitation programs on patients recovering from COVID-19 and their role in ensuring that this population can resume a functional life. However, to produce findings that can be translated into practice, the challenges inherent to this line of research need to be addressed. Specifically, the extant risk of infection, quarantine times, and physical barriers rules have added more challenges to the implementation of pulmonary rehabilitation sessions. In response to this, there has been much discussion of the role of home-based telemedicine in pulmonary rehabilitation 55,56. Overall, this field still has much to accomplish in the future to fully understand the long-term outcomes of COVID-19, also in the context of any future respiratory infection pandemic.

Key Points:

• Research suggested that chronic viral infection can induce an inflammatory response that contributes to the fibrotic response.

• The is a lack of solid evidence on the impact of pulmonary rehabilitation programs on COVID-19 survivors.

• Most of the studies highlighted the challenges to the implementation of pulmonary rehabilitation sessions.

REFERENCE:

1. Xu XW, Wu XX, Jiang XG, Xu KJ, Ying LJ, Ma CL, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: Retrospective case series. BMJ. 2020;368.

2. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–62.

3. Grasselli G, Zangrillo A, Zanella A, Antonelli M, Cabrini L, Castelli A, et al. Baseline Characteristics and Outcomes of 1591 Patients Infected with SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. JAMA - J Am Med Assoc. 2020;323(16):1574–81.

4. Halpin SJ, McIvor C, Whyatt G, Adams A, Harvey O, McLean L, et al. Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation. J Med Virol. 2021;93(2):1013–22.

5. McDonald LT. Healing after COVID-19: Are survivors at risk for pulmonary fibrosis? Am J Physiol - Lung Cell Mol Physiol. 2021;320(2):L257–65.

6. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506.

7. Wu J, Pan J, Teng D, Xu X, Feng J, Chen YC. Interpretation of CT signs of 2019 novel coronavirus (COVID-19) pneumonia. Eur Radiol. 2020;30(10):5455–62.

8. Cabañes-Martínez L, Villadóniga M, González-Rodríguez L, Araque L, Díaz-Cid A, Ruz-Caracuel I, et al. Neuromuscular involvement in COVID-19 critically ill patients. Clin Neurophysiol Off J Int Fed Clin Neurophysiol. 2020;131(12):2809–16.

9. Serafim RB, Póvoa P, Souza-Dantas V, Kalil AC, Salluh JIF. Clinical course and outcomes of critically ill patients with COVID-19 infection: a systematic review. Vol. 27, Clinical Microbiology and Infection. 2021. p. 47–54.

10. Sheng G, Chen P, Wei Y, Yue H, Chu J, Zhao J, et al. Viral Infection Increases the Risk of Idiopathic Pulmonary Fibrosis: A Meta-Analysis. Chest. 2020;157(5):1175–87.

11. Thille AW, Esteban A, Fernández-Segoviano P, Rodriguez JM, Aramburu JA, Vargas-Errázuriz P, et al. Chronology of histological lesions in acute respiratory distress syndrome with diff use alveolar damage: A prospective cohort study of clinical autopsies. Lancet Respir Med. 2013;1(5):395–401.

12. Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. 2020;181(2):281-292.e6.

13. Cameron A, Porterfield CA, Byron LD, Wang J, Pearson Z, Bohrhunter JL, et al. A multiplex microsphere IgG assay for SARS-CoV-2 using ACE2-mediated inhibition as a surrogate for neutralization. J Clin Microbiol. 2021;59(2).

14. Sun B, Feng Y, Mo X, Zheng P, Wang Q, Li P, et al. Kinetics of SARS-CoV-2 specific IgM and IgG responses in COVID-19 patients. Emerg Microbes Infect. 2020;9(1):940–8.

15. Escudero D, Boga JA, Fernández J, Forcelledo L, Balboa S, Albillos R, et al. SARS-CoV-2 analysis on environmental surfaces collected in an intensive care unit: keeping Ernest Shackleton’s spirit. Intensive care Med Exp. 2020;8(1):68.

16. Ragab D, Salah Eldin H, Taeimah M, Khattab R, Salem R. The COVID-19 Cytokine Storm; What We Know So Far. Vol. 11, Frontiers in Immunology. Frontiers Media S.A.; 2020.

17. Hong KS, Lee KH, Chung JH, Shin KC, Choi EY, Jin HJ, et al. Clinical Features and Outcomes of 98 Patients Hospitalized with SARS-CoV-2 Infection in Daegu, South Korea: A Brief Descriptive Study. Yonsei Med J. 2020;61(5):431–7.

18. Gozalbo-Rovira R, Gimenez E, Latorre V, Francés-Gómez C, Albert E, Buesa J, et al. SARS-CoV-2 antibodies, serum inflammatory biomarkers and clinical severity of hospitalized COVID-19 patients. J Clin Virol Off Publ Pan Am Soc Clin Virol. 2020;131:104611.

19. Notz Q, Schmalzing M, Wedekink F, Schlesinger T, Gernert M, Herrmann J, et al. Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome-An Observational Pilot Study. Front Immunol. 2020;11:581338.

20. Sun H, Guo P, Zhang L, Wang F. Serum interleukin-6 concentrations and the severity of COVID-19 pneumonia: A retrospective study at a single center in Bengbu City, Anhui Province, China, in January and February 2020. Med Sci Monit. 2020;26:e926941.

21. Pandolfi L, Fossali T, Frangipane V, Bozzini S, Morosini M, D’Amato M, et al. Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome. BMC Pulm Med. 2020;20(1):301.

22. Winters NI, Burman A, Kropski JA, Blackwell TS. Epithelial Injury and Dysfunction in the Pathogenesis of Idiopathic PulmonaryFibrosis. Vol. 357, American Journal of the Medical Sciences. Elsevier B.V.; 2019. p. 374–8.

23. Rello J, Storti E, Belliato M, Serrano R. Clinical phenotypes of SARS-CoV-2: Implications for clinicians and researchers. Vol. 55, European Respiratory Journal. European Respiratory Society; 2020.

24. Battaglini D, Robba C, Caiffa S, Ball L, Brunetti I, Loconte M, et al. Chest physiotherapy: An important adjuvant in critically ill mechanically ventilated patients with COVID-19. Vol. 282, Respiratory Physiology and Neurobiology. Elsevier B.V.; 2020. p. 103529.

25. Grasselli G, Cattaneo E, Florio G, Ippolito M, Zanella A, Cortegiani A, et al. Mechanical ventilation parameters in critically ill COVID-19 patients: a scoping review. Vol. 25, Critical Care. BioMed Central Ltd; 2021. p. 1–11.

26. Grasselli G, Pesenti A, Cecconi M. Critical Care Utilization for the COVID-19 Outbreak in Lombardy, Italy: Early Experience and Forecast during an Emergency Response. Vol. 323, JAMA - Journal of the American Medical Association. American Medical Association; 2020. p. 1545–6.

27. Gupta VK, Alkandari BM, Mohammed W, Tobar AM, Abdelmohsen MA. Ventilator associated lung injury in severe COVID-19 pneumonia patients – Case Reports: Ventilator associated lung injury in COVID-19. Eur J Radiol Open. 2021;8.

28. Spruit MA. Pulmonary rehabilitation. Vol. 23, European Respiratory Review. European Respiratory Society; 2014. p. 55–63.

29. M T, F G, DD S. Pulmonary Rehabilitation in a Post-COVID-19 World: Telerehabilitation as a New Standard in Patients with COPD. Int J Chron Obstruct Pulmon Dis. 2021;16.

30. Spruit MA, Pitta F, Garvey C, ZuWallack RL, Roberts CM, Collins EG, et al. Differences in content and organisational aspects of pulmonary rehabilitation programmes. Eur Respir J. 2014;43(5):1326–37.

31. Wadell K, Janaudis Ferreira T, Arne M, Lisspers K, Ställberg B, Emtner M. Hospital-based pulmonary rehabilitation in patients with COPD in Sweden-A national survey. Respir Med. 2013;107(8):1195–200.

32. Grigoletto I, Cavalheri V, de Lima FF, Ramos EMC. Recovery after COVID-19: The potential role of pulmonary rehabilitation. Vol. 24, Brazilian Journal of Physical Therapy. Revista Brasileira de Fisioterapia; 2020. p. 463–4.

33. Roberts P, Wertheimer J, Park E, Nuño M, Riggs R. Identification of Functional Limitations and Discharge Destination in Patients With COVID-19. Arch Phys Med Rehabil. 2021;102(3):351–8.

34. Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis GJ, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631–7.

35. Yang L-L, Yang T. Pulmonary rehabilitation for patients with coronavirus disease 2019 (COVID-19). Chronic Dis Transl Med. 2020;6(2):79–86.

36. CURCI C, PISANO F, BONACCI E, CAMOZZI DM, CERAVOLO C, BERGONZI R, et al. Early rehabilitation in post-acute COVID-19 patients: Data from an Italian COVID-19 Rehabilitation Unit and proposal of a treatment protocol. Eur J Phys Rehabil Med. 2020;56(5):633–41.

37. Spruit MA, Singh SJ, Garvey C, Zu Wallack R, Nici L, Rochester C, et al. An official American thoracic society/European respiratory society statement: Key concepts and advances in pulmonary rehabilitation. Am J Respir Crit Care Med. 2013;188(8).

38. Sagarra-Romero L, Viñas-Barros A. COVID-19: Short and Long-Term Effects of Hospitalization on Muscular Weakness in the Elderly. Int J Environ Res Public Health. 2020;17(23):1–12.

39. Liu K, Zhang W, Yang Y, Zhang J, Li Y, Chen Y. Respiratory rehabilitation in elderly patients with COVID-19: A randomized controlled study. Complement Ther Clin Pract. 2020;39.

40. Puchner B, Sahanic S, Kirchmair R, Pizzini A, Sonnweber B, Wöll E, et al. Beneficial effects of multi-disciplinary rehabilitation in postacute COVID-19: An observational cohort study. Eur J Phys Rehabil Med. 2021;57(2):189–98.

41. Glöckl R, Buhr-Schinner H, Koczulla AR, Schipmann R, Schultz K, Spielmanns M, et al. Recommendations from the German respiratory society for pulmonary rehabilitation in patients with COVID-19. Pneumologie. 2020;74(8):496–504.

42. Spruit MA, Holland AE, Singh SJ, Tonia T, Wilson KC, Troosters T. COVID-19: Interim guidance on rehabilitation in the hospital and post-hospital phase from a European Respiratory Society- And American Thoracic Society-coordinated international task force. Eur Respir J. 2020;56(6).

43. Singh S, Barradell A, Greening N, Bolton C, Jenkins G, Preston L, et al. The British Thoracic Society survey of rehabilitation to support recovery of the Post Covid-19 population. BMJ Open. 2020;

44. Spielmanns M, Pekacka-Egli AM, Schoendorf S, Windisch W, Hermann M. Effects of a comprehensive pulmonary rehabilitation in severe post-covid-19 patients. Int J Environ Res Public Health. 2021;18(5):1–14.

45. Zhao HM, Xie YX, Wang C. Recommendations for respiratory rehabilitation in adults with coronavirus disease 2019. Vol. 133, Chinese Medical Journal. Lippincott Williams and Wilkins; 2020. p. 1595–602.

46. Network R. Rehabilitation following COVID-19 in the pulmonary rehabilitation setting. 2020;(June).

47. Spielmanns M, Pekacka-Egli AM, Cecon M, Witassek F, Schoendorf S, Lutz D, et al. COVID-19 Outbreak During Inpatient Rehabilitation: Impact on Settings and Clinical Course of Neuromusculoskeletal Rehabilitation Patients. Am J Phys Med Rehabil. 2021;100(3):203–8.

48. Zampogna E, Paneroni M, Belli S, Aliani M, Gandolfo A, Visca D, et al. Pulmonary Rehabilitation in Patients Recovering from COVID-19. Respiration. 2021;100(5):416–22.

49. Smith JM, Lee AC, Zeleznik H, Scott JPC, Fatima A, Needham DM, et al. Home and community-based physical therapist management of adults with post-intensive care syndrome. Vol. 100, Physical Therapy. Oxford University Press; 2020. p. 1062–73.

50. Fan J, Liu X, Pan W, Douglas MW, Bao S. Epidemiology of coronavirus disease in Gansu Province, China, 2020. Emerg Infect Dis. 2020;26(6):1257–65.

51. Mo X, Jian W, Su Z, Chen M, Peng H, Peng P, et al. Abnormal pulmonary function in COVID-19 patients at time of hospital discharge. Vol. 55, European Respiratory Journal. European Respiratory Society; 2020.

52. Vitacca M, Nava S, Santus P, Harari S. Early consensus management for non-ICU acute respiratory failure SARS-CoV-2 emergency in Italy: From ward to trenches. Vol. 55, European Respiratory Journal. 2020.

53. Mohamed AA, Alawna M. Role of increasing the aerobic capacity on improving the function of immune and respiratory systems in patients with coronavirus (COVID-19): A review. Diabetes Metab Syndr Clin Res Rev. 2020;14(4):489–96.

54. Siddiq MAB, Rathore FA, Clegg D, Rasker JJ. Pulmonary rehabilitation in COVID-19 patients: A scoping review of current practice and its application during the pandemic. Vol. 66, Turkish Journal of Physical Medicine and Rehabilitation. Turkish Society of Physical Medicine and Rehabilitation; 2021. p. 480–94.

55. Wootton SL, King M, Alison JA, Mahadev S, Chan ASL. COVID-19 rehabilitation delivered via a telehealth pulmonary rehabilitation model: a case series. Respirol Case Reports. 2020;8(8):669.

56. Bryant MS, Bandi VD, Nguyen CK, Lan C, Henson HK, Sharafkhaneh A. Telehealth Pulmonary Rehabilitation for Patients With Severe Chronic Obstructive Pulmonary Disease. Fed Pract. 2019;36(9):430–5.