Our present study demonstrated that, although no significant alternations in 28-day, ICU, and hospital mortality rates, as well as patients’ lengths of stay in hospital and ICU were found, early physical and pulmonary rehabilitation in severely and critically ill patients with COVID-19 increased the duration of ventilator-free days during hospitalization, with no increased adverse events and complications. Additionally, early rehabilitation in severely ill COVID-19 patients enhanced the recovery of lung volume and diffusing capacity, accelerated patients’ return to independent functional status, decreased ICU-AW incidences, and increased muscle strength and exercise capacity at hospital discharge and one month after discharge. The improvements in lung diffusing capacity, muscle strength, life quality, and exercise capacity remained significant up to three months after hospital discharge. Therefore, the implementation of early physical and pulmonary rehabilitation was safe and effective for severely and critically ill patients with COVID-19 to promote their functional, physical and psychological recovery.
Skeletal muscle mass is known to be an important determinant factor for critical patients to overcome diseases in the ICU7. Loss of skeletal muscle mass, quality, and strength in the ICU is an independent mortality risk factor for critically ill patients, and muscle weakness affecting the limbs and respiratory muscles during ICU hospitalization is associated with poor outcomes, such as delayed recovery, hindered weaning from mechanical ventilation, decreased life quality, and increased financial costs15,16. Accumulated evidence has revealed that early ICU rehabilitation, including pulmonary rehabilitation to improve respiratory function and remove airway secretions, and physical rehabilitation to attenuate muscle weakness, has positive impacts on critically ill patients’ prognoses8,9,17−19. Therefore, early rehabilitation in the ICU is supposed to improve the clinical outcomes and functional recovery of severe COVID-19 patients. However, to our knowledge, a limited number of studies have reported the impacts of early physical and pulmonary rehabilitation on COVID-19 patients, especially for severe and critical cases. For example, one case report shared the early pulmonary rehabilitation experiences of a 41-year-old severe patient with SARS-CoV-2 pneumonia20. Another study found that a six-week respiratory rehabilitation program produced positive impacts on COVID-19 patients aged over 65 by improving respiratory functions, quality of life, and exercise endurance, as well as relieving anxiety21. However, no study has systematically assessed the effects of early physical and pulmonary rehabilitation on severe COVID-19 patients. In our present study, we found that implementing early rehabilitation in severe and critical patients with COVID-19 increased the amount of ventilator-free days during hospitalization, largely attributed to the removal of airway secretions and amelioration of respiratory failure. These results were consistent with most previous reports concerning the beneficial impacts of early physical medicine and rehabilitation on critically ill patients in the ICU22.
Previous study has found that lung functional impairments in the recovered patients with SARS-coronavirus pneumonia were common and could last for months or even years, among which impaired diffusing capacity and defected lung volume were the most common abnormalities1. In our present study, we witnessed varying degrees of declining DLCO, TLC, FEV1, FVC, and FEV1/FVC levels in the severe and critical COVID-19 patients at hospital discharge, consistent with a recent report revealing the diffusion capacity impairments and restrictive ventilatory defects in COVID-19 patients at hospital discharge23. Histological examinations of the lung tissue in COVID-19 patients confirmed the diffuse alveolar damages with hyaline membrane formation and fibromyxoid exudates24. Follow-up study lasting for one year found that the persistent functional limitation in the survived ARDS patients was largely a result of muscle wasting and weakness, due to their immobilization during hospitalization6.Thus, pulmonary alveolar edemas, interstitial fibrous proliferation, and muscle wasting collectively resulted in impaired lung function. Previous study found that respiratory rehabilitation could clearly enhance improvements in the respiratory functions of elderly COVID-19 patients21. However, we only found significant promotions in lung volume and diffusing capacity, potentially due to the differences in our patients’ disease severity, baseline comorbidities, and smoking history.
In our current study, the interventions of early rehabilitation therapy significantly improved independence functional outcomes at hospital discharge and one month after discharge, supporting the benefits and feasibility of these interventions on the restoration of functional independence. Our results are consistent with previous findings demonstrating that whole-body rehabilitation in the earliest days of critical illness result in better functional outcomes, as reflected by higher Barthel Index scores, more independent ADLs, and greater unassisted walking distance at hospital discharge9. After three months, the independence functions improved for all patients and the beneficial effects of rehabilitation therapy subsided. A variety of improvements in muscles, nerves, metabolism immunity, and psychological states may explain the long-term recovery.
The adverse impacts of skeletal muscle immobility are well-recognized, as individuals show skeletal muscle atrophic signs if immobilized for more than 72 hours, and loss of muscle mass and strength can be noted even in well-nourished healthy older adults within 10 days of bed rest25,26. Therefore, physical rehabilitation in the ICU for severe COVID-19 patients, especially those combined with ARDS, is supposed to be an important intervention to preserve muscle architecture, improve muscle strength, and decrease ICU-AW. In present study, we confirmed that early physical rehabilitation results in improvements in muscle strength and exercise capacity in the three-month follow-up, with decreases in ICU-AW incidences at hospital discharge and one month after discharge. Impaired muscle function may explain the compromised quality of life. Thus, we postulate that the observed improvements in life quality and physical function may partially be due to the remission of muscle weakness. These results are consistent with most reports supporting the beneficial effects of early mobilization and rehabilitation on greater muscle strength in critically ill patients17,22. However, one meta-analysis found that early mobilization and rehabilitation had no significant effects on muscle strength, quality of life, and ICU-AW incidences, perhaps due to the inadequate inclusion of published randomized controlled trials (RCT)27. As for the mechanisms of rehabilitation training on these benefits, in addition to conventional concepts, skeletal muscles are now considered as important endocrine tissues that secrete various bioactive molecules, called myokines, that act in an auto-, para-, and endocrine manner to regulate the physiological function of target tissues and contribute to the progression of diverse diseases28,29. Rehabilitation training is speculated to protect target organs against disorders through the regulation of myokines homoeostasis, but further studies are needed to explore the implications and underlying mechanisms of myokines as related to the beneficial effects of rehabilitation therapy on severe and critical COVID-19 patients.
Despite this study’s numerous strengths, we do have several limitations deserving consideration. Firstly, the sample size was relatively small with few non-survivor cases, limiting our sub-group or regression analysis. Secondly, as COVID-19 is a world public health emergency and there are insufficient clinical experience on rehabilitation therapy for severe COVID-19 cases, we varied the therapy’s intensity for both the intervention and control groups, according to patients’ medical stability and tolerance. Thus, we are currently conducting a retrospective study, rather than an RCT study. Thirdly, subsequent at-home rehabilitation training may have potentially biased our results and affected the outcomes.