The Effects of a Pulmonary Rehabilitation Programme on Functional Capacity and Strength of Respiratory Muscles in Patients with Post-COVID Syndrome

In late 2019, the WHO declared a COVID-19 pandemic (1), with the severity ranging from asymptomatic to mild forms of the disease, to multiple organ failure and death (2).

In addition to the acute phase, a distinction is also made with regard to post-COVID syndrome or long COVID. This refers to a duration of disease symptoms – such as shortness of breath, fatigue, chest pain, and cough – for more than two months after onset (3, 4). SARS-CoV-2 virus reduces respiratory muscle strength independently or in combination with other factors, resulting in shortness of breath in patients in acute and post-COVID phases (5). Pathophysiological mechanisms include direct myopathic effects on respiratory muscles (4) or damage to neurological control of breathing (6).

The pulmonary rehabilitation (PR) programme, based on 2013 recommendations of the American Thoracic Society (ATS) and European Respiratory Society (ERS), aims to improve the health status of patients with chronic respiratory diseases (7). Patients with chronic obstructive pulmonary disease commonly use PR, but it is effective with many other pulmonary diseases, such as COVID-19 and post-COVID syndrome. In the long term, it improves the physical and psychological health of patients with chronic lung diseases (7). It improves the quality of life by improving cardiorespiratory and bone-muscular function, reducing dyspnea and fatigue intensity (8). During rehabilitation, the patient’s condition is regularly assessed. Exercises are adjusted with a gradual increase in load, and the same tests are performed at the beginning and end of PR programme (9).

Exercises to strengthen respiratory muscles are an important part of PR programme for post-COVID patients (10). Various respiratory muscle strengthening devices are used in rehabilitation, such as an inspiratory muscle training (IMT) device, positive expiratory pressure device (PEP), and Respifit S (an inspiratory muscle training device). The IMT device increases the strength of the patient’s respiratory muscles and is more effective than breathing exercises (11), while IMT exercises improve respiratory muscle strength and lung function in COPD patients (12). The efficacy of these exercises has already been demonstrated in patients with some other diagnoses. Morgan et al. examined respiratory muscle-strengthening exercises in post-COVID-19 patients, and their review found that pulmonary function improved in all but one of included studies, and dyspnea and quality of life improved significantly (13). This led to a hypothesis that PR programmes positively affect functional capacity and respiratory muscle strength in patients with post-COVID syndrome. This study aimed to investigate a PR programme’s effects on lung functional capacity and respiratory muscles strength in patients with post-COVID syndrome.

Most patients (71.3%) started the rehabilitation programme more than four months after having COVID-19 (Figure 1).

Figure 1.

Over half of the patients had decreased respiratory muscle strength (<80%) and functional capacity before the PR programme. After rehabilitation, 51.3% and 16.3% of patients had PI_max and PE_max values <80% of the predicted threshold, respectively, whereas only 21.3% had a 6MWT distance <80% of the predicted reference value (Table 2).

The effects of PR on patients’ respiratory muscle strength (Table 3) showed significant differences (P<0.001), with small to large effect sizes. The effect and difference are very large for PImax. The mean value of PImax increased by 18.16 cmH2O and PEmax by 8.50 cmH2O. The results for all other pulmonary function parameters in patients with COVID-19 syndrome showed significant improvement after PR (P<0.05), except for the Tiffeneau index. However, the effect sizes of PR ranged from very small to small, with a Cohen’s d index from 0.18 to 0.48. PR significantly improved functional capacity as measured by 6MWT, with a large effect size. Peripheral oxygen saturation improved significantly, but the effect size was small. A significant reduction in dyspnea, as measured on the modified Borg scale, was observed after PR, with a small effect.

In Table 4, we compared the outcomes after PR between patient groups according to the time elapsed between onset of COVID-19 and start of rehabilitation. Significant differences (P<0.05) were observed for higher PI_max in patients who started rehabilitation after two to three months than in those who started rehabilitation more than four months after the onset of COVID-19. The lowest values of PI_max were measured in patients who started rehabilitation more than four months after disease onset. Post-hoc analysis showed that PI_max in terms of cmH2O was significantly higher in patients who started PR two to three months after disease onset than in patients who started rehabilitation more than four months after it (Tukey P=0.024). The same was true for PI_max in percentage terms (Tukey P=0.012). For PI_max, no significant difference was found between patients who started PR two to three months after COVID-19 and patients who started rehabilitation three to four months after COVID-19 (Tukey P=0.369). For PE_max, there was no significant difference with regard to the time when rehabilitation started after COVID-19. The time elapsed from disease onset to initiation of PR had no significant effect on other spirometric pulmonary function test results or DLCO, 6MWT, and dyspnea. A post-hoc analysis showed that patients who started PR two to three months after disease onset had a significantly higher heart rate than patients who started rehabilitation more than four months after it (Tukey P=0.038).

COVID-19 and post-COVID syndrome, relatively new clinical entities for acute and chronic patients’ health problems, have become subject of numerous studies. The results of this study support the clinical use of a PR programme with post-COVID-19 patients, since it significantly improved most indicators of pulmonary function.

At the end of rehabilitation, the values of FEV1, FVC, DLCO, 6MWT, and respiratory muscle strength improved significantly, with effect sizes ranging from small to large (Cohen’s d from 0.35 to 1.08). In contrast, the Tiffeneau index remained unchanged, as both the numerator (FEV1) and denominator (FVC) improved significantly. Lung function increased in litres from 4.14±1.28 to 4.33±1.29 for FVC and from 3.04±0.93 to 3.15±0.96 for FEV1. Functional capacity increased in metres from 442.76±96.22 to 503.11±105.15, with an increase in the predicted value from 77.7% to 87.7%. In addition to the significant effects of PR on lung function, a previous study of older adults who had recovered from COVID-19 confirmed a positive impact on other areas of health, such as quality of life and anxiety. In that study, a six-week PR programme included 10-minute exercises twice weekly to strengthen respiratory muscles and the diaphragm, as well as stretching exercises (21). After hospitalization, post-COVID patients usually have muscle weakness and difficulty breathing after exercise. For them, rehabilitation is crucial to improving fitness and muscle strength because the muscles of whole body are weakened in addition to respiratory muscles (22).

PR significantly improved PImax, PEmax, and respiratory muscle strength. A total of 71.3% of patients had a pathological value <80% of the predicted value for PImax at the first measurement, and 51.3% of them at the last measurement. For PEmax, pathological values were found in 35% of patients at the first measurement and in 6.3% of them at the last measurement. Vieira da Costa et al. confirmed the improvement of respiratory muscle strength after PR in a study of nine post-COVID patients with different clinical presentations, dry cough, shortness of breath, and chest pain (23). In addition to improving lung function and respiratory strength, the endurance of the respiratory muscles and diaphragm, main respiratory muscle, and quadriceps all improved (23). Villelabeitia-Jaureguizar et al. studied SARS-CoV-2 patients who were treated with invasive mechanical ventilation in an intensive care unit, and then performed low-intensity respiratory muscle exercises after discharge (24). The results suggest that low-intensity respiratory muscle training improves respiratory strength and quality of life associated with health status and shortness of breath.

In this study the COVID-19 patients who took part in the PR programme recovered better and faster than those who did not participate in it. Their muscle strength, balance, and psychosocial status also improved significantly compared to patients who suffered only respiratory failure. Long-term ICU treatment significantly damages muscle function in the short term, limits physical performance, and reduces quality of life. Al Chikhania at al. suggest that PR programmes may reduce posttraumatic stress (25). The increased PImax and PEmax values after PR indicate that improved inspiratory and expiratory muscle strength is associated with greater mobility of the chest wall and diaphragmatic movements (10, 26). Respiratory muscle training improves muscle strength, airway resistance, and diaphragm thickness. It also reduces dyspnea, as weakness of the respiratory muscles is associated with shortness of breath (10).

The development of fibrosis is partly genetically determined. The angiotensin-converting enzyme-2 gene is expressed in the myofiber membrane of the diaphragm, allowing infiltration of the SARS-CoV-2 virus and increasing gene expression involved in fibrosis (4,27). COVID-19 also changes the function of the diaphragm and decreases its thickness (27). A decrease in diaphragm muscle significantly increases the risk of pneumonia, and low thickness and density at CT are predictors for a severe form of COVID-19 (28). Diaphragm thickness at the end of expiration decreased In COVID-19 patients, and the thickening proportion increased (29). Various pathophysiological mechanisms are involved in the damage to the respiratory muscles that occurs with COVID-19, such as the decreased contractility of the respiratory muscles, myopathy of the respiratory muscles caused by the virus, unilateral paralysis of diaphragm due to unilateral injury of the phrenic nerve, severe atrophy and weakness due to dysfunction of the diaphragm, and baseline respiratory muscle weakness (4). COVID-19 may also affect neural control of breathing and cause unilateral diaphragm paralysis, unrelated to mechanical ventilation and normal lung parenchyma (6, 30).

Fibrous abnormalities and lung fibrosis affect about one-third of COVID-19 patients (31). Risk factors include older age, chronic comorbidities, use of mechanical ventilation during the acute phase of COVID-19, and female gender. The development and progression of pulmonary fibrosis is influenced by each individual’s genetic background, i.e., the genes involved in innate antiviral defence, inflammatory lung injury, and the ABO system of blood groups (31, 32). Aging increases lung parenchyma stiffness and facilitates pulmonary fibrosis progression (33). For all these reasons, it is obvious why exercise in PR alleviates the severe symptoms of post-COVID-19 pulmonary fibrosis (34).

The results are consistent with a systematic review, which showed that PR significantly improved exercise tolerance as determined by 6MWT (35). PR improves the pulmonary function parameters and reduces anxiety, depression, and symptoms of dyspnea and fatigue. Moreover, the lung function parameters and respiratory muscle strength were significantly better in patients who took part in a PR programme than in patients who did not (35).

The time between onset of COVID-19 and start of PR had no significant effects on most of the parameters of lung function, except PImax, suggesting that the time of starting PR is not as important clinically as simply starting rehabilitation in terms of achieving faster recovery and improvement in quality of life in post-COVID syndrome patients.

The PR programme is effective in patients recovering from severe acute respiratory syndrome (SARS). In these patients, pulmonary abnormalities are present in up to 75.4% of patients six months after onset of the disease (36), and abnormalities in pulmonary function are present in one-third one year after SARS (37). Some studies reported reductions in DLCO scores ranging from 11% to 45% among patients after one year, while the 6MWT results improved (38). Wu et al. showed radiological abnormalities resembling pulmonary fibrosis seven years after SARS (39). The results of studies on SARS patients, in whom the consequences of damage to pulmonary function are visible seven years after onset of the disease, point to the importance of a timely PR programme in post-COVID-19 patients. Although the short-term consequences of COVID-19, such as weakened lung function, decreased muscle strength, and reduced mobility, are described in detail, further studies are needed to determine whether COVID-19 permanently impairs lung function. In this way, rehabilitation programmes in the acute and later phases of the disease can be maximally individualized and thus enable the best possible quality of life for each person (40).

In the context of all the previously mentioned studies on patients who have recovered from COVID-19, the use of the PR programme has been shown to have numerous positive effects, with sufficient supporting evidence. This complex programme includes physical activity and breathing exercises that increase respiratory muscle strength and lung function. The results are clinically significant since, at the end of rehabilitation, the patients had the ability to walk a greater distance with a lower grade of dyspnea. The use of the correct breathing patterns and exercises helped the patients to make tremendous efforts and achieve a higher workload with less breathlessness. This underscores the importance of referring patients in the post-COVID phase for PR. Learning the correct breathing patterns, strengthening specific limb muscles, increasing fitness, strengthening the respiratory muscles, improving the pulmonary function parameters, and increasing the functional capacity all help to improve the quality of life. Corral et al. have shown that an inspiratory and expiratory muscle training programme effectively improves the quality of life of people with long-term COVID-19 symptoms (41). In addition, a systematic review with a meta-analysis found that rehabilitation interventions are associated with significant improvements in quality of life, functional exercise capacity, and dyspnea in post-COVID patients (42).

It should be noted that the programme investigated in this study is neither financially nor technically demanding for medical personnel. A clinical psychologist was included in the PR programme and had an important role in treating people with post-COVID syndrome, since anxiety and depression are not uncommon in this population (43). However, psychological monitoring of patients during PR has shown that this medical intervention can improve mental health.

PR significantly strengthens the respiratory muscles in patients with post-COVID syndrome, particularly in terms of PImax, by 18.16 litres, it improves lung functional capacity–FVC by 0.14 and FEV1 by 0.08, and reduces dyspnea by 0.95. Besides statistical significance, these positive effects on respiratory muscle strength have clinical relevance. The pulmonary function parameters of FVC, FEV1, and DLCOS significantly improved in the patients, as did endurance based on the results of the 6MWT test. The time elapsed between disease onset and starting the PR programme was not found to be significant in improving lung function, but it did affect respiratory muscle strength.