PR involves exercise training, education, and behavioral and lifestyle rehabilitation and is a promising intervention for facilitating recovery and enhancing QOL in patients with long COVID-19.15 Our observational study findings strongly support the beneficial effects of PR for PASC patients with varying degrees of disease severity. There were significant improvements in mobility, dyspnea scales, functionality, and mental health.
Our data provides robust evidence supporting the positive effect of PR on physical health in those suffering with long COVID-19. Despite their age and high baseline 6MWD, participants still improved their walking distance by nearly 2 standard deviations, which is above the average minimal clinically important difference (MCID) for the test.16 In a similar study conducted with 64 patients, 70% of participants 6MWD improved nearly twice the MCID from baseline (62.9 +/- 48.2) after 6 weeks of rehabilitation.17 Similarly, we saw a significant increase in other indices above their MCID; CR reps improved (8.83 to 13.13 reps, p < 0.001), TUG test time (12.76 to 9.50 seconds, p < 0.0001) and gait speed (1.03 m/s to 1.30 m/s, p < 0.0001).18–20 While the patients were still symptomatic, their QOL improved, and the improvements in these health indices after PR support it as an effective treatment for the physical symptoms of PASC. This is consistent with the improvements seen in populations of former critically ill patients who are recovering from acute respiratory distress syndrome and those with post-intensive care syndrome who experience slow recovery, long-term cognitive impairment, and functional disability.21,22
We also found that PR is associated with improved mental outcomes. Our study showed significant improvement in PASC patient HADS scores after PR, with only minor, statistically insignificant worsening in mean PHQ-9 scores. The benefits of PR for mental health have been confirmed in patients with several health conditions, such as COPD and asthma, and similar positive effects are being seen in patients with PASC.10,23,24 A prospective study of 50 patients showed marked improvements in QOL for those with severe/critical COVID-19 after rehabilitation, particularly in their SF-36 mental component scores.14 In our study, CHF, ILD, and receiving specific inpatient therapies were associated with higher HADS scores, suggesting a possible increase in psychological distress and resistance to improved anxiety and depression in patients with these factors. Active alcohol use, CKD, receiving specific inpatient therapies, and having multiple SARS-CoV-2 infections were also associated with higher PHQ-9 scores, which suggests that these factors may also worsen psychological health.
Beyond the stress induced by COVID-19 itself, public health measures, such as mass confinement and the ensuing financial losses, have substantially increased emotional distress and psychiatric illness risk. Our study showed significant improvement in HADS scores post-rehabilitation which is consistent with prior reported literature. A systematic review showed elevated rates of anxiety (6.3–50.9%), depression (14.6–48.3%), post-traumatic stress disorder (7–53.8%), and psychological stress (34.4–38%) in the general population during the pandemic.25 Post-recovery, COVID-19 patients commonly exhibit long-term anxiety and depression symptoms.26 A 2021 study tracking 1050 discharged COVID-19 patients revealed that those with positive PHQ-2 and trauma screening questionnaire (TSQ) scores were more likely to experience persistent dyspnea, myalgia, anorexia, and confusion at a 9-week follow-up (PHQ-2 80% vs 41.8%, TSQ 88.8% vs 42.9%, p < 0.001).27
Dyspnea, one of the most prevalent symptoms of PASC, is most likely multifactorial.28 This symptom is common, persistent, and has a negative impact on patient QOL, often leading to poor sleep and low mood.29 Our study highlights a significant decrease in MMRC, SOBQ, and CAT scores beyond their MCID. This is corroborated by a meta-analysis published by Ahmed et al.,30 which included 8 randomized controlled trials with 449 participants. Their findings revealed that PR significantly improves dyspnea and exercise capacity.30 However, in our study, antibody treatment and ICS were linked to increased SOBQ scores despite the overall SOBQ score reduction. Our study results confirm existing research showing that PR may improve dyspnea in patients with long COVID.
Comorbidities and risk factors like hypertension, DM, and previous SARS-CoV-2 infection have been shown to influence recovery rates, presenting challenges to patient mobility and psychological health and causing dyspnea.31,32 More specifically, conditions like hypertension, DM, COPD, CHF, ILD, multiple COVID-19 diagnoses, obstructive sleep apnea, and inpatient and outpatient COVID-specific therapies are associated with slower recovery and may limit improvement in mobility, dyspnea and psychological health.33 To our knowledge, our study presents the first insight into the effects of these factors on PASC and PR outcomes. The results of this study have unveiled potential avenues for future research on complex interactions between each of these risk factors to identify pathological mechanisms and ultimately restore a patient’s physical and psychological health after COVID-19.
It is important to note that our study cohort was predominantly White, whereas other races such as African Americans and Hispanics have been shown to have a higher risk of contracting COVID-19.34,35 This draws attention to the socioeconomic, ethnic, and health disparities associated with chronic respiratory diseases that may pose barriers to PR.36,37 The COVID-19 pandemic has greatly amplified and exposed the existing inequalities and social determinants of health in patients with chronic respiratory disease.38 These disparities may directly impact the uptake, attendance, and completion of PR and subsequent recovery from PASC. Clinicians and policymakers must consider these systemic differences in race and socioeconomic factors to optimize rehabilitation care for a diverse population.
Our study illuminates the need for continued longitudinal research on post-COVID-19 recovery, focusing on the long-term impacts of personalized PR for patients with PASC. It underscores the importance of integrating mental health services within these programs and investigating the efficacy of remote rehabilitation methods. There is potential benefit in exploring a proactive approach and starting rehabilitation immediately post-recovery. This study highlights a broader focus on QOL beyond clinical outcomes and the need to address health disparities in accessing PR. Lastly, an understanding of the cost-effectiveness of these interventions is crucial for resource allocation and policy making. Hence, future research may shed more light on the optimal management of patients with PASC, thereby reducing disease burden, streamlining health service utilization, and enhancing QOL.
Limitations and Strengths
Our retrospective study offers significant insights but faces several limitations. As an observational study, it lacks randomization and a control group, which are crucial for reducing biases and bolstering result validity. The limited sample size potentially impacts statistical power and the robustness of the study, limiting the wider applicability of our findings to all PASC patients. The study does not clearly distinguish improvements from natural recovery versus those from PR intervention. It also lacks long-term follow-up to assess lasting effects of the rehabilitation. The potential overlap of chronic fatigue syndrome with PASC is another limitation. Despite these constraints, the study's pragmatic approach in a real-world setting is an asset, and the average follow-up period of 3.8 months post-rehabilitation allows for a reasonable evaluation of outcomes. However, further randomized control trials with larger samples and longer-term follow-up are necessary to confirm and expand these findings.