Rehabilitation Interventions for Physical Capacity and Quality of Life in Adults With Post–COVID-19 Condition

This meta-analysis reviews studies investigating the association of rehabilitation interventions with physical capacity and quality of life in adults with post–COVID-19 condition (PCC).


* Named contact.
The named contact is the guarantor for the accuracy of the information in the register record.This may be any member of the review team.
Give the electronic email address of the named contact.pbobos@uwo.ca

Named contact address
Give the full institutional/organisational postal address for the named contact.
1151 Richmond Street 9. Named contact phone number.
Give the telephone number for the named contact, including international dialling code.+1-519-870-5145 10. * Organisational affiliation of the review.
Full title of the organisational affiliations for this review and website address if available.This field may be PROSPERO International prospective register of systematic reviews completed as 'None' if the review is not affiliated to any organisation.

Western University
Organisation web address: 11. * Review team members and their organisational affiliations.
Give the personal details and the organisational affiliations of each member of the review team.Affiliation refers to groups or organisations to which review team members belong.NOTE: email and country now MUST be entered for each person, unless you are amending a published record.Give the name and affiliation of any individuals or organisations who are working on the review but who are not listed as review team members.NOTE: email and country must be completed for each person, unless you are amending a published record.

* Review question.
State the review question(s) clearly and precisely.It may be appropriate to break very broad questions down into a series of related more specific questions.Questions may be framed or refined using PI(E)COS or similar where relevant.State the sources that will be searched (e.g.Medline).Give the search dates, and any restrictions (e.g.language or publication date).Do NOT enter the full search strategy (it may be provided as a link or attachment below.)

Are rehabilitation interventions effective at improving aerobic and respiratory function and quality of life, in
A systematic electronic search of the literature will be performed from January 2020 until December 2022, in PubMed, Scopus, CINAHL, and Clinical Trials Registry with no date restrictions.The following keywords will be used to identify potentially relevant studies: "covid-19", "long-covid", "post-covid", "sequelae", "exercise", "exercise therapy", "rehabilitation", "physical activity", "physical therapy", "randomized controlled trials", "RCT".In addition, we will conduct a manual search of the reference lists of the included studies to identify any potential studies missed in the electronic search.17.URL to search strategy.
Upload a file with your search strategy, or an example of a search strategy for a specific database, (including the keywords) in pdf or word format.In doing so you are consenting to the file being made publicly accessible.Or provide a URL or link to the strategy.Do NOT provide links to your search results.
Alternatively, upload your search strategy to CRD in pdf format.Please note that by doing so you are consenting to the file being made publicly accessible.Do not make this file publicly available until the review is complete 18. * Condition or domain being studied.
Give a short description of the disease, condition or healthcare domain being studied in your systematic review.
The main condition being studied are patients suffering from Long covid syndrome as defined by The World Health Organization (WHO).The WHO defines Long COVID or post COVID syndrome as a case definition of "symptoms occurring three or more months after acute SARS-CoV-2 infection that last for at least two months and is not explainable by an alternative condition".19.* Participants/population. Specify the participants or populations being studied in the review.The preferred format includes details of both inclusion and exclusion criteria.
We will include randomized trials that include patients with Long COVID syndrome as defined by The World Health Organization (WHO).Studies that include interventions during acute care will be excluded.20.* Intervention(s), exposure(s).

PROSPERO International prospective register of systematic reviews
Give full and clear descriptions or definitions of the interventions or the exposures to be reviewed.The preferred format includes details of both inclusion and exclusion criteria.
We will include studies that used aerobic, strength, conditioning and respiratory exercise interventions and treatment modalities.Studies that use a medication-only treatment will be excluded.21. * Comparator(s)/control.
Where relevant, give details of the alternatives against which the intervention/exposure will be compared (e.g.another intervention or a non-exposed control group).The preferred format includes details of both inclusion and exclusion criteria.
The interventions in the control groups can be either usual/standard care or waitlist/control.22. * Types of study to be included.
Give details of the study designs (e.g.RCT) that are eligible for inclusion in the review.The preferred format includes both inclusion and exclusion criteria.If there are no restrictions on the types of study, this should be stated.
We will only include randomised control trials.Studies that are self-controlled and do not include a control group will be excluded.Non-randomised, quasi-experimental and feasibility trials will be excluded.We will also exclude observational studies, case series, case reports and pilot studies.

Context.
Give summary details of the setting or other relevant characteristics, which help define the inclusion or exclusion criteria.

* Main outcome(s).
Give the pre-specified main (most important) outcomes of the review, including details of how the outcome is defined and measured and when these measurement are made, if these are part of the review inclusion criteria.
The main outcome will be performance-based aerobic function, measured with the 6-minute walking test.If similar measurements are used instead, such as a 3min-walking test or a 2-min walking test, we will extract the outcome measures and pool them using Standardised Mean Difference.The timepoint of the primary outcome will be directly post-intervention.

Measures of effect
Please specify the effect measure(s) for you main outcome(s) e.g.relative risks, odds ratios, risk difference, and/or 'number needed to treat.
The effect measures for the main outsome will be the standardised mean differences (SMD) of change scores with 95% credible intervals.We will use OpenBUGS and STATA (Stata Statistical Software: Release 16, StataCorp LLC) to perform the meta-analysis.

PROSPERO International prospective register of systematic reviews
List the pre-specified additional outcomes of the review, with a similar level of detail to that required for main outcomes.Where there are no additional outcomes please state 'None' or 'Not applicable' as appropriate to the review We will include long term performance-based aerobic function measured by the 6-minute walking test in our secondary outcomes.We will also include performance-based aerobic function measured by the 30-sec sit and stand test in both short and long-term follow-ups in our secondary outcomes.Other secondary outcomes will be patient-reported function, performance-based and patient reported respiratory function, Global Health Status and patient reported quality of life both in short and in long term follow-ups.If more than one effect measures are presented in a study for the same outcome, we will extract the one reported as the primary outcome in the study.We will also monitor adverse events and serious adverse events related to the interventions across all studies.Adverse events and non-adverse events unrelated to the interventions will not be included.

Measures of effect
Please specify the effect measure(s) for you additional outcome(s) e.g.relative risks, odds ratios, risk difference, and/or 'number needed to treat.
The effect measures for performance-based and patient-reported aerobic function, respiratory function, Global Health Status and quality of life (continuous outcomes) will be the standardised mean differences (SMD) of change scores with 95% credible intervals.We will use OpenBUGS and STATA (Stata Statistical Software: Release 16, StataCorp LLC) to perform a meta-analysis using the standardised mean difference with 95% credible intervals.The effect measured for the adverse events (dichotomous outcome) will be the risk ratios with 95% credible intervals (CrIs).

* Data extraction (selection and coding).
Describe how studies will be selected for inclusion.State what data will be extracted or obtained.State how this will be done and recorded.
The selection of individual studies will involve two independent reviewers who will perform a systematic electronic search of the databases.Two reviewers will identify potentially relevant articles, remove duplicates, and then screen titles and abstracts.The full text of any study marked include or uncertain will be obtained and the eligibility criteria will be applied.Two independent researchers will extract the data from the eligible included studies.Data extraction will include study, author, year, sample characteristics, intervention, comparison groups, aerobic function, respiratory function, Global Health Status, quality of life, and adverse or serious adverse events.

* Risk of bias (quality) assessment.
State which characteristics of the studies will be assessed and/or any formal risk of bias/quality assessment tools that will be used.

PROSPERO International prospective register of systematic reviews
Two independent authors will assess the included RCTs for risk of bias (ROB).The ROB assessment will be performed using the Cochrane Risk of Bias tool.The ROB tool is based on 7 items, random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias.The adequacy of each of the seven ROB domains will be rated as "low," "unclear," or "high" risk.We will summarize the assessment of ROB per study as Low ROB (if low ROB was judged for all the seven domains); as Unclear ROB (if unclear ROB was judged for one or more of the seven domains); and as High ROB (if high ROB was judged for one or more of the seven domains).The GRADE guidelines will be used to evaluate the certainty of evidence.The GRADE approach includes assessing ROB for study limitations, inconsistency, publication bias, imprecision, and indirectness.The rating of the quality of outcome across trials will be carried out to summarize the extent of our confidence (high, moderate, low, or very low).

* Strategy for data synthesis.
Describe the methods you plan to use to synthesise data.This must not be generic text but should be specific to your review and describe how the proposed approach will be applied to your data.If metaanalysis is planned, describe the models to be used, methods to explore statistical heterogeneity, and software package to be used.
For data synthesis we will use OpenBUGS (version 3.2.3,Cambridge, UK) and STATA (Stata Statistical Software: Release 16, StataCorp LLC).We will perform a pair-wise Bayesian random-effects metaanalyses using the normal likelihood to compare rehab interventions versus usual care, waitlist or no intervention using standardized mean difference with 95% credible intervals for continuous outcomes and risk ratio with 95% credible Intervals for binary ones.If meta-analysis is not possible, we will present the results in a narrative format.We will provide descriptive statistics of the patient groups, interventions, outcomes, and adverse effects of treatments.We will report all results using the intention-to-treat principle (the sample randomized in the study).If trials report standard error, we will transform it into standard deviation.For missing values such as standard deviation, we will use the following methods: 1.We convert 95% Confidence Intervals or Standard Error to Standard Deviation; 2. Digitizer software -Digitize a scanned graph or chart into (x, y)-data, will be used when data was presented in graphic form (http://www.digitizeit.de/).To facilitate analysis, data imputation rules will be used when necessary.We will assess small study effects with Harbord test and we will investigate the presence of publication bias with funnel plots.In the presence of publication bias we will impute the missing studies to account for publication bias in the meta-analysis.We will compare the observed and the imputed studies by using the nonparametric "trim and fill" method.We will use contour-enhanced funnel plot to assess if imputed studies fall in the region of statistical significance.29.* Analysis of subgroups or subsets.Select each language individually to add it to the list below, use the bin icon to remove any added in error.English There is not an English language summary 32.* Country.
Select the country in which the review is being carried out.For multi-national collaborations select all the countries involved.Canada 33.Other registration details.
Name any other organisation where the systematic review title or protocol is registered (e.g.Campbell, or The Joanna Briggs Institute) together with any unique identification number assigned by them.If extracted data will be stored and made available through a repository such as the Systematic Review Data Repository (SRDR), details and a link should be included here.If none, leave blank.34.Reference and/or URL for published protocol.
If the protocol for this review is published provide details (authors, title and journal details, preferably in Vancouver format) Add web link to the published protocol.
Or, upload your published protocol here in pdf format.Note that the upload will be publicly accessible.
No I do not make this file publicly available until the review is complete Please note that the information required in the PROSPERO registration form must be completed in full even if access to a protocol is given.Give words or phrases that best describe the review.Separate keywords with a semicolon or new line.Keywords help PROSPERO users find your review (keywords do not appear in the public record but are included in searches).Be as specific and precise as possible.Avoid acronyms and abbreviations unless these are in wide use.37. Details of any existing review of the same topic by the same authors.
If you are registering an update of an existing review give details of the earlier versions and include a full bibliographic reference, if available.38.* Current review status.
Update review status when the review is completed and when it is published.New registrations must be ongoing so this field is not editable for initial submission.
Please provide anticipated publication date Review_Ongoing 39.Any additional information.
Provide any other information relevant to the registration of this review.

PROSPERO
International prospective register of systematic reviews patients diagnosed with long-covid?16. * Searches.

35 .
Dissemination plans.Do you intend to publish the review on completion?Yes Give brief details of plans for communicating review findings.? PROSPERO International prospective register of systematic reviews 36.Keywords.
DetailsList actual or perceived conflicts of interest (financial or academic).None 14. Collaborators.

. Research strategy MEDLINE, Feb 10 th 2023 1 COVID-19/ or SARS-CoV-
40.Details of final report/publication(s) or preprints if available.Leave empty until publication details are available OR you have a link to a preprint (NOTE: this field is not editable for initial submission).List authors, title and journal details preferably in Vancouver format.Give the link to the published review or preprint.