key: cord-0707808-4na98m9v
authors: Soril, Lesley J.J.; Damant, Ronald W.; Lam, Grace Y.; Smith, Maeve P.; Weatherald, Jason; Bourbeau, Jean; Hernandez, Paul; Stickland, Michael K.
title: The effectiveness of pulmonary rehabilitation for Post-COVID symptoms: A rapid review of the literature
date: 2022-03-02
journal: Respir Med
DOI: 10.1016/j.rmed.2022.106782
sha: 7f0f8a023c253995c34ce52897cd294001c8b7ac
doc_id: 707808
cord_uid: 4na98m9v

BACKGROUND: Multi-disciplinary rehabilitation is recommended for individuals with post-acute sequelae of COVID-19 infection (i.e., symptoms 3–4 weeks after acute infection). There are emerging reports of use of pulmonary rehabilitation (PR) in the post-acute stages of COVID-19, however the appropriateness of PR for managing post-COVID symptoms remains unclear. To offer practical guidance with regards to post-COVID PR, a greater understanding of the clinical effectiveness literature is required. METHODS: A rapid review of the published literature was completed. An electronic database search of the literature published between July 1, 2020 and June 1, 2021 was performed in MEDLINE, Pubmed, and EMBASE. Primary studies evaluating the clinical effectiveness of PR for individuals with post-COVID symptoms were included. RESULTS: Nine studies evaluating the effectiveness of PR were identified; most were small, experimental or quasi-experimental studies, including 1 RCT, and were primarily of low quality. After attending PR, all studies reported improvements in exercise capacity, pulmonary function, and/or quality of life for individuals with post-COVID symptoms who had been hospitalized for their acute COVID-19 infection. Few studies evaluated changes in post-COVID symptom severity or frequency and, of these, improvements in dyspnea, fatigue, anxiety and depression were observed following PR. Further, no studies evaluated non-hospitalized patients or long-term outcomes beyond 3 months after initiating PR. CONCLUSIONS: With limited high-quality evidence, any recommendations or practical guidance for PR programmes for those with post-COVID symptoms should consider factors such as feasibility, current PR capacity, and resource constraints.

The SARS-CoV-2 coronavirus (COVID-19) has resulted in unparalleled morbidity, mortality (1) , and there is evolving evidence that a notable proportion of COVID-19 survivors experience residual and long-term effects.(2) Data published to-date indicate that symptoms appearing 3-4 weeks after acute COVID-19 infection can include dyspnea, fatigue, exercise intolerance, and worsened health-related quality of life (HRQL). (2) (3) (4) To manage these post-acute sequelae of SARS-CoV-2,(5) herein referred to as post-COVID symptoms, groups such as the World Health Organization recommend multi-disciplinary rehabilitation. Given that acute COVID-19 frequently includes respiratory complications, and the prevalence of post-COVID respiratory symptoms, (3, 4) many suggest that participation in a pulmonary rehabilitation (PR) programme may be appropriate for COVID-19 survivors.(5) To support the development of practical guidance for post-COVID PR, a rapid literature review was completed to determine the clinical effectiveness of PR for individuals with post-COVID symptoms.

A rapid review of the published literature was completed in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, (6) where applicable. An electronic database search of the literature published between July 1, 2020 and June 1, 2021 was completed in MEDLINE, Pubmed, and EMBASE. For the search strategy, medical subject headings (MeSH terms) for respiratory symptoms and conditions (e.g., dyspnea, cough, respiratory failure, airway disease) were combined with key word terms for "post-COVID" and the concept of "pulmonary rehabilitation". The search was limited to English language. Abstracts and full-texts were screened in duplicate. Articles were included if: they were primary studies designed as a J o u r n a l P r e -p r o o f randomized controlled trial (RCT), quasi-experimental study, observational cohort study, or implementation experience; secondary data from evidence syntheses; and focused on PR for patients with post-COVID symptoms. A program was considered as PR if it contained, at minimum, exercise and education/counselling.(7)

Nine studies were included (Supplementary Figure 1 ) (8) (9) (10) (11) (12) (13) (14) (15) (16) and study characteristics are summarized in Table 1 . Most studies were case reports or pilot (n=5) or controlled before and after (n=3); only 1 randomized controlled trial (RCT) was included. Sample sizes were small to moderate (<100 participants) and included primarily older participants (~60 years old or older). All study participants were hospitalized due to acute COVID-19 infection and, in 6 studies (8, 11, (14) (15) (16) participants were admitted to the intensive care unit (ICU) and/or required mechanical ventilation.

Details of PR programs and study findings are presented in Table 2 . Most PR were multidisciplinary, tailored to the participants' conditions or rehabilitation goals, and frequently consisted of exercise training, education, and/or counselling. All participants were admitted to PR after hospitalization due to acute COVID-19; only 4 studies reported the timing of admission (8, 9, 11, 15) which ranged from 10 to 125 days following onset of acute symptoms or COVID-19 diagnosis. The length of follow-up varied across studies, from 3 weeks to 3-months from the start of the PR.

Broadly, all studies reported improvements in post-COVID patient outcomes following PR ( Table 2) . The experimental and the controlled before and after studies commonly reported statistically significant improvements in exercise tolerance (e.g., 6-minute walk test distance J o u r n a l P r e -p r o o f [6MWD]), HRQL, and pulmonary function (e.g., forced vital capacity, forced vital capacity in one second, FEV1/FVC, and diffusion capacity for carbon monoxide). Select studies also reported improvements in dyspnea or other respiratory symptoms, fatigue, and anxiety and depression. No worsening of outcome measures, nor adverse events were reported (n=309 participants across included studies).

In the one RCT, 36 participants were randomized to the intervention (two 10-min PR sessions/week for 6 weeks) and demonstrated at 6-weeks post-PR significant improvements in 6MWD, HRQL, pulmonary function, and self-rated anxiety compared to their baseline values and to control participants (n=36; no rehabilitation intervention). (12) No statistically significant differences in functional independence measures or self-rating depression scores within (i.e., prepost) and between groups were observed. Limitations of this RCT include a small sample size, inclusion of only older adults (i.e., age 65 years or older), and unclear blinding of assessors and participants to the group allocation.(12)

We identified 9 primary studies that suggest that PR may lead to improvements in exercise capacity, HRQL, and/or pulmonary function among patients with post-COVID symptoms who had been hospitalized. The few studies that evaluated changes in post-COVID symptom severity or frequency reported improvements in dyspnea, fatigue, anxiety and depression. No studies evaluated non-hospitalized patients, healthcare resource utilization, nor longer-term outcomes beyond 3 months following PR. The included study populations were variable in terms of time post-acute COVID-19 infection. Although we did not perform a risk of bias or quality assessment, most studies were likely low quality due to smaller sample sizes, J o u r n a l P r e -p r o o f short follow-up, and/or non-randomized study designs. The reported findings should, therefore, be interpreted with caution.

Potential practical limitations to implementing post-COVID PR were also not addressed in the literature. In many jurisdictions, PR was halted due to the COVID-19 pandemic and/or delivered at reduced capacity due to the need to deliver PR virtually, leaving considerable waitlists for non-COVID respiratory patients to attend PR. Referring post-COVID patients to PR will likely place large demands on existing programs, increase waitlists or require substantial resources for expansion, and potentially deny individuals with respiratory conditions access to a well-established therapy. (17) QoL, based on SF-36 scores in 8 dimensions, significantly increased post-intervention for those in the intervention group and between the intervention and control groups, suggesting an improvement in QoL.

Anxiety and depression scores decreased post-intervention in the intervention group, but only anxiety was significantly decreased within and between intervention and control groups.

There was no statistically significant difference in ADL in the intervention group before or after the PR, nor compared with the control group. 

An interactive web-based dashboard to track COVID-19 in real time

Postacute COVID-19 syndrome

Assessment of the Frequency and Variety of Persistent Symptoms Among Patients With COVID-19: A Systematic Review

Characteristics and predictors of acute and chronic post-COVID syndrome: A systematic review and metaanalysis

The PRISMA 2020 statement: an updated guideline for reporting systematic reviews

statement: key concepts and advances in pulmonary rehabilitation

Recovering of oxygenation, physical function and disability in patients with COVID-19. Monaldi Arch Chest Dis

Feasibility of an Outpatient Training Program after COVID-19

An Improvised Pulmonary Telerehabilitation Program for Postacute COVID-19 Patients Would Be Feasible and Acceptable in a Low-Resource Setting

Early experiences of rehabilitation for individuals post-COVID to improve fatigue, breathlessness exercise capacity and cognition -A cohort study

Respiratory rehabilitation in elderly patients with COVID-19: A randomized controlled study

Preexisting cardiorespiratory comorbidity does not preclude the success of multidisciplinary rehabilitation in post-COVID-19 patients

Feasibility of telerehabilitation in survivors of COVID-19 pneumonia

Effects of a Comprehensive Pulmonary Rehabilitation in Severe Post-COVID-19 Patients

Cardiopulmonary rehabilitation in post-COVID-19 patients: case series

COVID-19: Interim Guidance on Rehabilitation in the Hospital and Post-Hospital Phase from a

Exertional intolerance and dyspnea with preserved lung function: an emerging long COVID phenotype?

We gratefully acknowledge the assistance of Joycelyn Jaca, Thomas