International Journal of

Environmental Research
and Public Health

Protocol
Pulmonary Rehabilitation in Patients with COVID-19—A
Protocol for Systematic Review and Meta-Analysis
Yanan Gao 1 , Huiming Huang 1 , Chunxia Ni 1 , Yong Feng 1 , Xiao Dong 1 , Yin Wang 1 and Junwu Yu 2, *

1 Faculty of Sport Science, Research Academy of Grand Health, Ningbo University, Ningbo 315211, China
2 Ningbo College of Health Sciences, Ningbo 315099, China
* Correspondence: [email protected]

Abstract: Introduction: Pulmonary rehabilitation (PR) is a well-established treatment for patients

with chronic lung disease; however, its role in patients with COVID-19 has not been systematically
studied. We provide a protocol outlining the methods and analyses that will be used in the systematic
review. Methods: The methodology of this systematic review protocol has been filed in PROSPERO
under the registration number CRD42022301418. Five electronic databases (PubMed, Web of Sci-
ence, Cochrane Library, EBSCO, and CNKI databases) will be searched from 2019 to 28 July 2022,
using pre-determined search terms. Eligibility criteria will be defined using a PICOS framework.
Pulmonary function, exercise capacity, and health-related quality of life will be the primary outcomes.
Quantitative findings will be narratively synthesized, whilst argument synthesis combined with
refutational analysis will be employed to synthesize qualitative data. Results: The results will be pre-
sented by both meta-analysis and qualitative analysis. Conclusion: This protocol describes what will
be the first systematic review to conduct a worldwide assessment of the effect of PR in patients with
COVID-19. Because this is a systematic review and meta-analysis, no ethical approval is needed. The
systematic review and meta-analysis will be published in a peer-reviewed journal and disseminated
Citation: Gao, Y.; Huang, H.; Ni, C.;
both electronically and in print.
Feng, Y.; Dong, X.; Wang, Y.; Yu, J.
Pulmonary Rehabilitation in Patients
with COVID-19—A Protocol for
Keywords: COVID-19; pulmonary rehabilitation; systematic review; exercise capacity; pulmonary
Systematic Review and function; quality of life
Meta-Analysis. Int. J. Environ. Res.
Public Health 2022, 19, 13982. https://
doi.org/10.3390/ijerph192113982
1. Introduction
Academic Editors: Adrian Midgley
and Paul B. Tchounwou The world is now in the middle of the COVID-19 pandemic. Globally, as of
2 August 2022, there have been 575,887,049 confirmed cases of COVID-19, including
Received: 13 August 2022 6,398,412 deaths, reported to WHO [1]. COVID-19 is an acute infectious illness that
Accepted: 21 October 2022
primarily affects the respiratory system and lungs, with severe lung damage being the
Published: 27 October 2022
leading cause of mortality [2]. Given the commonly severe involvement of multiple
Publisher’s Note: MDPI stays neutral organs and body functions during COVID-19, other abnormalities may persist after the
with regard to jurisdictional claims in acute phase has passed, potentially affecting patients’ well-being.
published maps and institutional affil- These issues can be addressed through pulmonary rehabilitation (PR). PR, defined as
iations. a comprehensive non-pharmacological strategy, is often remarkably successful in patients
with chronic obstructive pulmonary disease (COPD) [3]. However, COVID-19 is distinct
from other types of lung disease, and understanding the impact of PR on COVID-19 patients
is critical to developing better COVID-19 treatments.
Copyright: © 2022 by the authors.
According to the 2013 American Thoracic Society (ATS)/European Respiratory Society
Licensee MDPI, Basel, Switzerland.
(ERS) Statement [3], PR is “a comprehensive intervention based on a comprehensive patient
This article is an open access article
assessment and patient-tailored treatment, including but not limited to exercise training,
distributed under the terms and
education, and behavioral changes. PR aims at improving chronic respiratory, physical, and
conditions of the Creative Commons
Attribution (CC BY) license (https://
mental status of patients with disease, and promoting long-term adherence to health care
creativecommons.org/licenses/by/
behavior”. Since 2015, numerous clinical trials have provided data on safety and clinical
4.0/).
outcomes of planned PR models, including home rehabilitation [4]; telerehabilitation [5];

Int. J. Environ. Res. Public Health 2022, 19, 13982. https://doi.org/10.3390/ijerph192113982 https://www.mdpi.com/journal/ijerph
Int. J. Environ. Res. Public Health 2022, 19, 13982 2 of 14

interactive, web-based models [6]; mixed heart failure/PR models [7]; and so on [8]. The
comprehensive assessment of PR mainly includes five areas: exercise capacity, quality of
life, dyspnea, nutritional status, and occupational status [9].
PR is the cornerstone of the treatment of patients with chronic respiratory diseases [10].
There is direct evidence that PR can improve exercise capacity, reduce dyspnea, improve
health-related quality of life, and reduce hospitalization rates in chronic obstructive pul-
monary disease (COPD) patients [11,12]. There is now growing evidence that PR can im-
prove outcomes in other conditions such as interstitial lung disease [13], bronchiectasis [14],
and pulmonary hypertension [15]. Furthermore, education and psychological support in
PR can enhance patients’ cognition and comprehension of their diseases [16]. Therefore,
the extension of PR has great practical significance, and many nations or territories have
also issued guidelines and consensus statements for PR nursing in chronic respiratory
diseases [17–20].
In recent years, there have been several works discussing the effects of PR on COVID-19
patients. Gonzalez-Gerez et al. [21] found that PR can improve the physical condition, dys-
pnea, and perceived effort among people with mild to moderate COVID-19 symptoms in
the acute stage; however, long-term effects cannot be determined based on the results in the
study. A retrospective cohort study [22] found that PR could be used to promote exercise
capacity improvement after COVID-19. Their study, however, can only suggest a potential
association between PR and outcomes, not the causal effect of PR, and is highly biased.
Conducting high-quality clinical trials in a large number of patients is nearly impossible
due to the high contagiousness of COVID-19, and a systematic review and meta-analysis
are still lacking. It is still unclear how PR affects COVID-19 patients and whether this
impact is affected by the patient’s age, disease severity, stage of disease, type of PR, and the
program of PR.
A synthesis of the evidence of the association between PR and pulmonary function, ex-
ercise capacity, and health-related quality of life would contribute to a better understanding
of the relationship between PR and patients with COVID-19. Furthermore, investigating
the prognostic value of PR for the above outcomes would aid in better understanding the
mechanism of COVID-19 and making better clinical decisions. Unfortunately, most of the
current PR recommendations for COVID-19 rely on previous inferences from severe acute
respiratory syndrome (SARS) recovery [23].
Stronger conclusions can be drawn from a systematic review of the literature than
from any single study, and this protocol will outline the methods and analyses used in a
systematic review. The systematic review and meta-analysis will explore whether PR is an
effective intervention to improve the prognosis of patients with COVID-19.

2. Materials and Methods

2.1. Aims
2.1.1. Primary Aim
The aim of this systematic review and meta-analysis protocol is to evaluate the effect
of pulmonary rehabilitation (PR) on COVID-19 patients.

2.1.2. Review Questions

What are the effects of PR on COVID-19 patients compared to controls?
Which outcomes are significantly influenced by using PR?
Whether the effect of PR intervention is different on COVID-19 patients with different
disease severity and intervention frequency?
Which types and characteristics of interventions with PR were devised for
COVID-19 patients?
Whether PR is an effective intervention for improving the prognosis of patients with
COVID-19?
Int. J. Environ. Res. Public Health 2022, 19, 13982 3 of 14

2.2. Design
This review is conducted in accordance with the Preferred Reporting Items for Sys-
tematic Reviews and Meta-Analyses (PRISMA 2020 [24]) statement. The systematic review
protocol was prospectively registered at the International Prospective Register of Systematic
Reviews (PROSPERO, Registration No. CRD42022301418). The intent of the systematic
review, as registered in PROSPERO, was to evaluate the effects of PR in patients with
COVID-19, and to explore whether PR is an effective intervention for improving the
prognosis of patients with COVID-19. If the conditions for effect size merging are met,
meta-analysis will exist.

2.2.1. Inclusion and Exclusion Criteria

The criteria of this study will be summarized based on the participants, interventions,
comparisons, outcomes, and study design (PICOS) schema according to the Cochrane
handbook for systematic reviews of interventions.

Types of Studies
Include: All empirical research studies published in peer-reviewed journals that pro-
vide comparative quantitative data on our primary outcomes will be considered as eligible,
such as randomized controlled trials (RCTs), quasi-RCTs, non-randomized controlled trials,
and observational case-control and cohort studies. For relevant but unpublished studies,
research groups will be contacted with a request to provide summary data.
Exclude: We will exclude reviews, letters, poster presentations, editorials, case series,
and protocols.

Types of Participants
Include: All patients suffering from COVID-19 will be included regardless of stage of
disease, severity of illness, sex, age, race, education, and economic status. The diagnostic
criteria refer to clinical diagnosis and treatment guidelines issued by the United States [25]
and China [26].

Types of Interventions
Include: A broad range of PR will be included to gain a comprehensive overview
of current approaches to PR. Interventions will be included if they match the following
definition of PR: “the delivery of rehabilitation services which primarily takes advantage
of respiratory training, exercise training, education, and behavioral changes”. Respira-
tory rehabilitation-based exercise training interventions are also incorporated, such as
respiratory muscle training, diaphragm training, and traditional Chinese exercise training.
Telerehabilitation, face-to-face PR, in-person PR, supervised PR, and unsupervised PR will
all be included in the study.
Exclude: Respiratory rehabilitation with the assistance of a respiratory trainer. Exercise
training alone that is not based on respiratory rehabilitation, such as endurance and
aerobic training.

Types of Outcomes
Include: Outcomes that may be included are listed in Table 1.
Int. J. Environ. Res. Public Health 2022, 19, 13982 4 of 14

Table 1. Outcomes and Measurements Will be Included in the Review.

Outcomes Assessments and Indexes

Primary outcomes
Pulmonary function Pulmonary function tests (FVC, FEV1, PEF, VC)
Six-minute walk test, cardiopulmonary
Exercise capacity
exercise testing (VO2max, peak VO2)
Dyspnea Multidimensional dyspnea -12 scale, Borg scale
Health-related quality of life Quality-of-life inventory
Secondary outcomes
The number of hospitalizations and days in
Admission notes, progress notes
the hospital
Anxiety and depression The hospital anxiety and depression scale
Muscle strength and endurance tests (HGS,
Strength and endurance
1RM, sit-ups)
Sleep disorders Pittsburgh sleep quality index
Fatigue Multidimensional fatigue inventory
Anorexia Anorexia inventory
Blood pressure Sphygmomanometer
Heart rate Heart rate monitor
Body composition Body composition analyzer (BMI, MM, LBM)
Hematological and biochemical parameters Blood biochemical automatic analyzer (SPOZ)
CT imaging CT scanner
Abbreviation: FVC, forced vital capacity; FEV1, 1 s forced expiratory volume; PEF, peak expiratory flow;
VC, vital capacity; VO2max, maximal oxygen uptake; peak VO2, peak oxygen uptake; HGS, handgrip strength;
1RM, one-repetition maximum; BMI, body mass index; MM, muscle mass; LBM, lean body mass; SPOZ, oxygen
content of blood.
Exclude: Studies that do not contain data on either of the above outcomes.

2.3. Search Methods

2.3.1. Search Strategy
Electronic Searches
The review will involve searching the PubMed, Web of Science, Cochrane Library,
EBSCO, and CNKI databases from December 2019 to July 2022. Medical subject heading
(MeSH) terms will be adopted to search the database, mainly including ”COVID-19” AND
”Rehabilitation” AND ”Pulmonary” AND ”Trial”. Each database will use subject words
and free words to search. All searches will be limited to the English and Chinese languages,
but no geographical restrictions will be applied. Table 2 lists the search strategies and
search words of the PubMed database in detail. The search strategies of other databases
will convert the logical operators and search fields accordingly. Different search strategies
will be used for different language databases. PubMed is used as an example, and the
specific search strategy is detailed in Table 2.

Table 2. Search Strategy for PubMed.

Number Search Terms of Query

COVID-19[Mesh] OR COVID-2019[tiab] OR COVID19[tiab] OR COVID-19
pandemic[tiab] OR COVID-19 virus disease[tiab] OR SARS-CoV-2 infection[tiab] OR
#1
2019 novel coronavirus infection[tiab] OR coronavirus disease 2019[tiab] OR
2019-nCoV infection[tiab] OR COVID-19 virus infection[tiab]
severe acute respiratory syndrome coronavirus 2[Mesh] OR SARS-CoV-2[tiab] OR
2019-nCoV[tiab] OR 2019 novel coronavirus[tiab] OR COVID-19 virus[tiab] OR
#2
COVID19 virus[tiab] OR coronavirus disease 2019 virus[tiab] OR Corona Virus
Disease 2019[tiab]
#3 #1 OR #2
Pulmonary[Mesh] OR pulmonary rehabilitation[tiab] OR lung rehabilitation[tiab]
OR pulmonary rehabilitation exercise[tiab] OR pulmonary recovery[tiab] OR lung
#4
recovery[tiab] OR lung rehabilitation exercise[tiab] OR pulmonary rehabilitation
therapy[tiab]
Int. J. Environ. Res. Public Health 2022, 19, 13982 5 of 14

Table 2. Cont.

Number Search Terms of Query

Respiratory therapy[Mesh] OR pulmonary respiratory therapy[tiab] OR breathing
#5 therapy[tiab] OR respiratory muscle training[tiab] OR respiratory muscle
exercise[tiab] OR inspiratory muscle training[tiab] OR lung respiratory therapy[tiab]
#6 #4 OR #5
#7 #3 AND #6
randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized[tiab]
#8
OR clinical trials as topic[Mesh] OR trial[tiab]
#9 #7 AND #8

Additional Resources
We will also manually search the following resources to identify ongoing or com-
pleted clinical trials, such as Google Scholar (http://scholar.google.com), Baidu Scholar
(http://xueshu.baidu.com/), Clinical Trials (http://www.clinicaltrails.gov), and the
China Clinical Trials Registry (http://www.chictr.org/cn/).
2.3.2. Study Selection
EndNote (Version X9, Clarivate, Philadelphia, PA, USA) will be used for import,
grouping, deduplication, adding full text, and so on. After importing the reference into
EndNote, we will first filter out the literature by comparing the title, author, year, journal
name, volume, page number, and other information to remove duplicate references. Two
authors (Y.G., C.N.) trained in evidence-based medicine will conduct a one-by-one review
of the titles and summaries of the reference books according to the inclusion and exclusion
criteria and remove the references that obviously do not meet the inclusion criteria into the
exclusion folder. They will add the full text of the bibliographies, meeting the requirements
of the preliminary hearing. The two authors (Y.G., Y.F.) will read the contents of the research
design one by one in the full text of the literature, remove the literature that does not meet
the requirements to the exclusion folder, and record the reasons for exclusion in Excel. In
the screening process, the solution should be discussed first if there is any
Int. J. Environ. Res. Public Health 2022, 19, x FOR PEER REVIEW
disagreement. If
6 of 14
disagreements still exist, the author (H.H.) will assist in judgment. The literature screening
process is shown in Figure 1.

Figure 1. The
Figure 1.PRISMA flow diagram
The PRISMA of literature
flow diagram screening process.
of literature screening process.

2.3.3. Data Extraction

Data will be extracted by two independent reviewers (YG and HH) according to an
agreed data extraction form (Appendixes A–E). Any disagreements will be resolved by
consensus.
Int. J. Environ. Res. Public Health 2022, 19, 13982 6 of 14

2.3.3. Data Extraction

Data will be extracted by two independent reviewers (YG and HH) according to
an agreed data extraction form (Appendices A–E). Any disagreements will be resolved
by consensus.
Data to be extracted mainly include bibliographic information (e.g., author, title, year,
publication), demographics (e.g., sex, age, sample size), groups (e.g., group name, group
description, intervention frequency, intensity, duration, co-interventions), and outcomes
(e.g., time points measured/reported, definition, unit of measurement, imputation of
missing data). The specific data to be extracted are shown in Table 3.

Table 3. Variables to be extracted at the full-text stage.

Authors Reported conflict of interest

Title Study design
Year of publication Country
Bibliographic
Journal Setting(s)
Sources of funding Type of allocation sequence
Institutions and affiliations Inclusion and exclusion criteria
Age Severity of COVID-19
Sex Stage of disease
Demographics With or without complications
Sample size Description of health status
Physical activity levels
Pulmonary rehabilitation modalities
(e.g., telerehabilitation, face to face, Rehabilitation intensity
Pulmonary self-management)
rehabilita- Pulmonary rehabilitation program
tion (e.g., aerobic exercise, resistance Rehabilitation session volume (total
protocol exercise, nutrition, education) time of work and recovery intervals)
Duration, intensity, and modality
Exercise modality (e.g., treadmill, Pulmonary rehabilitation combined
stationary cycle) with other interventions (e.g.,
Number and duration of combination of group psychological
work/recovery intervals intervention and pulmonary
Control intervention rehabilitation)
Pulmonary function levels at baseline
Time points measured
and after pulmonary rehabilitation
Pulmonary Time points reported
function Follow-up time Pulmonary function levels at baseline
Measurement method and after follow-up
Unit of measurement
Exercise capacity at baseline and after
Time points measured
pulmonary rehabilitation
Exercise Time points reported
capacity Follow-up time Exercise capacity at baseline and after
Measurement method follow-up
Unit of measurement
Dyspnea levels at baseline and after
Time points measured
pulmonary rehabilitation
Time points reported
Dyspnea
Follow-up time Dyspnea levels at baseline and after
Types of questionnaires follow-up
Questionnaire scoring rules
Int. J. Environ. Res. Public Health 2022, 19, 13982 7 of 14

Table 3. Cont.

Quality-of life-levels at baseline and

Time points measured
Health- after pulmonary rehabilitation
related Time points reported
quality of Follow-up time Quality-of-life levels at baseline and
life Types of questionnaires after follow-up
Questionnaire scoring rules
Adverse effects (e.g., reasons for
Days in the hospital
dropout, dizziness)
Strength and endurance
Other Sleep disorders
Recruitment, retention, adherence,
variables Fatigue
outcome rates, and acceptability of
Blood pressure
intervention
Body composition
Hematological and biochemical
parameters

Authors will be contacted if data are missing or unclear in the selection of articles. If
sufficient information cannot be obtained in this way, we will analyze the available data
and the potential impact of insufficient data on the study results in the discussion.

2.4. Quality Appraisal

The identified trials will be assessed independently by two reviewers (Y.G. and C.N.).
For case-control and cohort studies, the risk of bias will be assessed using the Newcastle–
Ottawa Scale (NOS) [27]. Stars are awarded for each domain, which allows the study to be
graded into poor, fair, or good quality. For randomized controlled trials, quality assessment
will be carried out with the Cochrane Risk of Bias Tool [28]. Any disagreements will be
reviewed by the third reviewer (Y.F.) and resolved by discussion among all reviewers. If
the information about the risk of bias in the clinical trial is unclear, we will try to contact
the author by email.

2.5. Data Synthesis

It is anticipated that the included studies will vary significantly in type and method,
though meta-analyses will be conducted if data are available or situations allowed. Accord-
ing to the heterogeneity between studies, the method of data analysis and synthesis will
be determined. When we find obvious heterogeneity in the combined data, we will use
subgroup analysis, sensitivity analysis, and publication bias to investigate the source of
the heterogeneity.

2.5.1. Meta-Analysis
If the heterogeneity between the included studies is within the acceptable range, a
meta-analysis of the study results will be conducted. A Chi-square test (χ2 ) and I2 will
be used to analyze the heterogeneity between the clinical trials. If p > 0.1, I2 ≤ 50%, it
indicates that the heterogeneity between the clinical trials is within the acceptable range,
and a fixed-effect model will be used to analyze the data. If p ≤ 0.1, I2 > 50%, indicating
that the heterogeneity between clinical trials is considerable, subgroup analysis will be
needed to identify the source of heterogeneity, and the random-effect model will be used
to analyze the data. RevMan5.3 software (Cochrane Collaboration, Oxford, UK) will be
used to synthesize the study data. Mean difference (MD) or standardized mean difference
(SMD) and 95% confidence interval (CI) are used to describe the effect size of continuous
data (e.g., spirometry/mL, six-minute walk/min, VO2max/(mL/min/kg), strength/kg,
blood pressure/kPa, questionnaire scale scores). The Z test judges the effect size, and it has
statistical significance when p ≤ 0.05. The data synthesis results will be presented in the
form of forest plots.
Int. J. Environ. Res. Public Health 2022, 19, 13982 8 of 14

2.5.2. Descriptive Review

If the heterogeneity between the included studies is significant, we will make a de-
scriptive analysis of the study results. A Chi-square test (χ2 ) and I2 will be used to analyze
the heterogeneity between the clinical trials. If p ≤ 0.1, I2 > 75%, it indicates that the het-
erogeneity between the clinical trials is very significant, if the heterogeneity is substantial,
we will make a narrative qualitative summary. Study comparisons will be grouped (e.g.,
severity of disease, sex, age, types of intervention) to answer the research questions and
findings will be synthesized based on outcomes. The characteristics of included studies
will be presented in a narrative format, as recommended by PRISMA.

2.5.3. Subgroup Analysis

If there is a certain degree of heterogeneity between included clinical trials, subgroup
analysis can be used to determine the source of the heterogeneity. The subgroup analysis
will be conducted according to age, sex, country, severity of the disease, intervention length,
different outcome measurement time points, and different follow-up time points.

2.5.4. Sensitivity Analysis

The purpose of sensitivity analysis is to evaluate the bias variables by eliminating each
study one at a time. It will compute the sensitivity of each study over the whole project to
determine whether an individual study has a substantial influence on the outcomes.

2.6. Assessment of Publication Biases

We will assess publication bias by funnel plots for asymmetry when at least 10 trials
are available [29]. If the plot is asymmetric and there is no inverted funnel form, there may
be publication bias. The causes might be connected to the small sample size, allocation
concealment, and insufficient blind method implementation.

2.7. Ethical Considerations

As this study is only a systematic review and does not involve human or animal
experimentation or personal privacy, ethical approval is not required.

3. Results
The results of the systematic review will be published as a peer-reviewed article.

4. Discussion
Among patients with pulmonary diseases, rehabilitation helps reduce dyspnea, in-
crease exercise capacity, and improve health-related quality of life [3]. Therefore, rehabilita-
tion might be a valuable treatment in patients with COVID-19. Patients with COVID-19
often have pathological features, such as pulmonary interstitial or alveolar edema and
pulmonary inflammatory lymphoid infiltration, and are prone to acute respiratory dis-
tress syndrome (ARDS), causing lung injury [30]. Patients with severe COVID-19 may
experience significant decreases in lung function, potentially requiring mechanical ventila-
tion [31]. Respiratory and circulatory failure are common causes of death among COVID-19
patients [32]. Although the mechanisms of COVID-19-induced lung injury are still being
elucidated [33], pulmonary rehabilitation (PR) is necessary at any stage in the course of
the COVID-19.
Integrated into the individualized treatment of the patient, PR is designed to reduce
symptoms, optimize functional status, increase participation, and reduce healthcare costs
through stabilizing or reversing systemic manifestations of the disease [34]. PR has emerged
as a cost-effective intervention for managing chronic lung disease [35]. As evidence has
shown, PR improves the 6 min walking distance (6MWD), QoL, and respiratory symptoms
in patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease
(ILD) [36,37]. However, not all patients with pulmonary disease benefit from PR to the
Int. J. Environ. Res. Public Health 2022, 19, 13982 9 of 14

same degree. In both COPD and ILD patients, studies have shown that PR is not responsive
to disease rehabilitation [38,39].
Currently, studies focusing on PR in patients with COVID-19 are few. Many of the
difficult questions about PR have not been answered, such as whether PR is appropriate
for all COVID-19 patients, at which stage in the course of COVID-19 should PR be ad-
ministered, how specifically does PR work against COVID-19 compared to other types
of pneumonia, and so on. Although there are some data showing the impressive ben-
efits of PR participation, the effectiveness of rehabilitation has not been systematically
summarized yet.
Some international rehabilitation associations provided PR guidelines for COVID-19
patients. For example, the Chinese Association of Rehabilitation Medicine has established
different PR programs for patients with light, moderate, severe, and worse symptoms
during hospitalization and discharge [40]. The PR guideline from Turkey emphasizes that
exercise training is the most effective and compulsory method in achieving the goals of
PR [23]. Carda et al. [41] made suggestions for the PR program according to their clinical
experience of COVID-19, and they strongly advised the implementation of teleconsultation
and telerehabilitation devices and suggested that patients who had kept negative results of
COVID-19 for more than 7 days after their first diagnosis could be given access to PR. The
2020 British Thoracic Society [42] also updated the PR guideline for COVID-19 from fatigue,
mood disturbances, cognitive function, and support to reopening work. However, most of
the current PR guidelines adopted for patients with COVID-19 are based on the experience
gained during the response to the SARS epidemic in 2004. Therefore, more evidence is
needed to demonstrate the impact of PR and different PR designs on COVID-19 patients.
This protocol will represent the first systematic review and meta-analysis on effects of PR
in patients with COVID-19. A deep understanding of PR can alleviate the COVID-19 crisis
and optimize COVID-19 resource allocation. Therefore, the conclusions of the systematic
review will have direct practical implications and clinical relevance.

5. Limitations
There will be some limitations to this systematic review. First, the outbreak of
COVID-19 is sudden. It is impossible to formulate and implement a large-sample ran-
domized controlled trial in a short period, and the quality of clinical trials may not be high
enough, which affects the quality of evidence to a certain extent. Secondly, the different
types, frequency, intensity, and duration of PR may cause clinical heterogeneity. Thirdly,
this review will only include Chinese and English studies from the literature, which may
lead to selective bias. Although there are some limitations, the team members will still carry
out this review to provide some references and suggestions for clinical decision-making
and further clinical research.

6. Conclusions
Pulmonary rehabilitation (PR) is an effective tool of rehabilitation interventions for
COVID-19 patients. The findings of this systematic review and meta-analysis can help physical
therapists and the general public in actively addressing the challenges posed by COVID-19.

Author Contributions: Contributions to concept and design: Y.G., J.Y., H.H., C.N. and Y.F.; Data
analysis and interpretation: Y.G., C.N., Y.F., X.D. and Y.W.; Drafting the article: Y.G. and Y.F.; Revising
critically: Y.G. and J.Y. All authors have read and agreed to the published version of the manuscript.
Funding: This research was funded by the National Social Science Foundation of China, grant
number 18BTY100.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Data sharing is not applicable to this article as no new data were
created or analyzed in this study protocol.
Int. J. Environ. Res. Public Health 2022, 19, 13982 10 of 14

Acknowledgments: We thank all the participants for participating in this study.

Conflicts of Interest: The authors declare no conflict of interest.

Appendix A. General Information

General Information
Date form completed
First Author
Study title
DOI number
Year of publication
Published trial YES [ ] NO [ ]
Publication type
Author contacted YES [ ] NO [ ] time
Notes:

Appendix B. Trial Eligibility

Study Review Inclusion
Yes/No/Unclear Location in Text
Characteristics Criteria
Randomized trial
Type of study
Other design
(specify):
1. COVID-19 patients
Participants
2. Other:
Treatment in any type
Intervention
of PR
Decision: Included [ ]/excluded [ ]
Reason for exclusion
Notes:
Int. J. Environ. Res. Public Health 2022, 19, 13982 11 of 14

Appendix C. Methods
Location in
Descriptions as Stated in Report/Paper
Text
Country/Countries
Aim of study Aim: Not clearly defined [ ]
Start date
End date
Total number of groups
Number of participants in Intervention: ____ Control: _____
each group Other: ______
Number of participants that Intervention: ____ Control: _____
were analyzed Other:______
Duration of participation
What was/were the primary
1a. 1b. 1c.
outcome(s)
What was/were the
2a. 2b. 2c.
secondary outcome(s)
Time points where outcomes
Primary outcomes:
were measured
1a. 1b. 1c.
Secondary outcomes:
2a. 2b. 2c.
Notes:

Appendix D. Groups
Intervention Group (PR) Comparison Group
Description as Stated in Location Description as Stated in Location
Report/Paper in Text Report/Paper in Text
Group name
Mean: Mean:
Median: Median:
Age SD: Age SD:
Range: Range:
IQR: IQR:
Number of Number of
Sex Males [ ] Sex Males [ ]
Number of Number of
Females [ Females [
] ]
Race/Ethnicity Race/Ethnicity
Severity of Severity of
illness illness
Comorbidities Comorbidities
Int. J. Environ. Res. Public Health 2022, 19, 13982 12 of 14

Intervention Group (PR) Comparison Group

Description as Stated in Location Description as Stated in Location
Report/Paper in Text Report/Paper in Text
Group name
Other
treatment
received Control
(additional intervention
to PR)
Types of
PR
Frequency/intensity Frequency/intensity
Duration Duration
Co-
interventions
Notes:

Appendix E. Outcomes
Outcome 1 Outcome 2 Outcome 3
Description Location Description Location Description
Location
as Stated in in as Stated in in as Stated in
in Text
Report/Paper Text Report/Paper Text Report/Paper
Outcome
name
Time points
measured
Time points
reported
Outcome
definition
Person
measur-
ing/reporting
Unit of
measurement
Scales: upper
and lower
limits
Is Yes [ ] No [ Yes [ ] No [ Yes [ ] No [
outcome/tool ] ] ]
validated? Unclear [ ] Unclear [ ] Unclear [ ]
Imputation of
missing data
Assumed risk
estimate
Notes:
Int. J. Environ. Res. Public Health 2022, 19, 13982 13 of 14

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