Massage Therapy for Pulmonary Function in Patients Recovering From Covid-19: A Protocol for Systematic Review and Meta-analysis

Background:Starting in December 2019 in Wuhan (Hubei province, China), a novel coronavirus, designated SARS-CoV-2, has caused an international outbreak of a respiratory illness and rapidly evolved into a pandemic.Given the rapidly growing pandemic and the overwhelmedmedical system, the number of self ‐ quarantined and recovering patients is increasing.There is an urgentneed of alternative medicine to help patients relieve symptoms duringself ‐ quarantine, and possibly to help increase their chances of survivaland recovery from COVID-19.Massage (tuina) therapy is one of the widely employed complementary and alternative medicine interventions in the world.Long-term clinicalpractices and experiences have shown that massage therapy could signicantly contribute to the healing of most respiratory conditions and lung disease.This systematic review and meta-analysis will summarize the current evidence of tuina (massage) used as an intervention for pulmonary function in COVID-19 recovering patients. Methods:We will search the following electronic databases for randomized controlled trials to evaluate the effectiveness and safety of massage therapy inimproving pulmonary function ofCOVID-19 recovering patients: Wanfang and Pubmed Database, CNKI, CENTRAL, CINAHL, EMBASE and MEDLINE. Each database will be searched from inception to June 2020. The entire process will include study selection, data extraction, risk of bias assessment and meta-analyses. Discussion:This proposed systematic review will evaluate the existing evidence and explore the potential roleof massage therapyon the effectiveness and safety in pulmonary function of COVID-19 recovering patients.The outcomes will include the improvement of pulmonary function and adverse effect.

the effectiveness and safety of massage therapy inimproving pulmonary function ofCOVID-19 recovering patients: Wanfang and Pubmed Database, CNKI, CENTRAL, CINAHL, EMBASE and MEDLINE. Each database will be searched from inception to June 2020. The entire process will include study selection, data extraction, risk of bias assessment and meta-analyses.
Discussion:This proposed systematic review will evaluate the existing evidence and explore the potential roleof massage therapyon the effectiveness and safety in pulmonary function of COVID-19 recovering patients.The outcomes will include the improvement of pulmonary function and adverse effect.

PROSPERO registration number:CRD42020192107
Background Starting in December 2019 in Wuhan (Hubei province, China), a novel coronavirus, designated SARS-CoV-2, has caused an international outbreak of a respiratory illness and rapidly evolved into a pandemic [1,2].
Its widespread infectivity and strong pathogenicity has posed a huge threat to public health, seriously affecting social production and life [3,4]. The disease caused by this virus has been o cially named COVID-19 (coronavirus disease 2019) by the World Health Organization (WHO) [5]. The research conducted on the COVID-19 virus haselucidatea wide variety of clinical manifestations and the epidemiological characteristics of the affected population [6]. Most cases are asymptomatic or selflimiting, but the clinical spectrum extends to severe progressive pneumonia with acute respiratory distress syndrome, a life-threatening condition requiring mechanical ventilation and intensive care support [7].The COVID-19 virus remains a global healthcare emergency as the number of cases and fatality continue to rise. As more information is being gathered, understanding of the virus will improve better diagnosis, prevention and treatment options for patients exposed or experiencing symptoms from the disease [8].
Complementary and alternative medicine (CAM) is considered as an adjunct to treat chronic or serious diseases and to self-manage long-term health complaints [9].Traditional Chinese medicine (TCM), a main form of complementary and alternative medicine, is an ancient and holistic approach to health and healing [10]. TCM has unique theory and a long history of clinical practice with reliable e cacy and few side effects [11].Massage (tuina) therapy is one of the widely employed complementary and alternative medicine interventions in the world. As a useful therapy implemented on human's skin, muscles and joints, massage has unique advantages in the eld of medicine [12]. It can act on the subcutaneous muscular layer, enhance the local blood circulation and tissue metabolism of the skin, thus exert its effects on diverse systems and alleviate aversive symptoms. Long-term clinicalpractices and experiences have shown that massage therapy could signi cantly contribute to the healing of most respiratory conditions and lung disease.
This systematic review and meta-analysis will summarize the current evidence of tuina (massage) used as an intervention for patients recovering from COVID-19.

Methods
This systematic review protocol has been registered on PROSPERO (ID: CRD42020192107). The protocol follows the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol (PRISMA-P) statement guidelines [13]. We will describe the changes in our full review if needed.

Type of studies
This review will include clinical RCTs of massage therapy for pulmonary function in patients recovering from COVID-19 without any language or publication status restrictions.Non-RCTs, quasi-RCTs, case series, case reports, crossover studies, uncontrolled trials, and laboratory studies will not be included.

Type of participants
Patients diagnosed with COVID-19 of all ages and racial groups and have recovered will be included.

Type of interventions
Interventions will include any type of clinically performed massage for improvement of pulmonary The in uence of massage on the pulmonary function and quality of life in convalescent patients.Comparison of improvement in main symptoms such as cough and chest tightness before and after treatment, changes in lung imaging, changes in serum leukocyte content; compare the differences in the scores of the World Health Organization's Quality of Life Rating Scale (WHOQOL-100) before and after treatment.
Secondary outcomes: Accompanying symptoms (such as myalgia, expectoration, stu ness, runny nose, pharyngalgia, anhelation, chest distress, dyspnea, crackles, headache, nausea, vomiting, anorexia, diarrhea) disappear rate, negative COVID-19 results rate on two consecutive occasions (not on the same day), CT image improvement, average hospitalization time, occurrence rate of common type to severe form, clinical cure rate, and mortality.

3.4.2.Additional outcome(s)
Safety measurements and adverse events. We will use EndNote X9 software to manage the records of searched electronic databases. The initial selection will involve scanning of the titles and abstracts of the retrieved studies. The full text of relevant studies will then be reviewed for study inclusion, in accordance with the inclusion criteria, by 2 authors (KLZ and SD). Potentially relevant articles will be reviewed independently by 2 authorsto determine if they meet the prespeci ed criteria. Any disagreement between authors will be resolved by consensus with a third author. The study selection procedure will follow and be recorded in the PRISMA ow chart. All the evidence will be assessed by The Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Data extraction and management.
According to the inclusion criteria, a standard data collection form will be made before data extraction.
The following data will be extracted by 2 authors (KLZ and SD): General information: Research identi cation, publication year, the title of the study, rst author; Study methods: study design, sample size, randomization method, allocation concealment, blinding, incomplete report or selecting report, other sources of bias; Participants: Inclusion and exclusion criteria; Intervention: motion details, treatment duration, and frequency; Control: Type of control methods, motion details, treatment duration, and frequency; Outcomes: Included outcome measures.

Risk of bias assessment.
The risk of bias in included studies will be assessed independently by 2 reviewers (KLZ and SD) using the Cochrane Risk of Bias Tool, with any disagreements resolved by consensus or by discussion with a third reviewer. All judgments will be fully described, and the conclusions will be presented in the Risk of Bias gures and will be incorporated into the interpretation of review ndings, by means of sensitivity analysis.
The risk of bias of each domain will be graded as adequate, unclear, or inadequate. We intend to use the concealment of allocation grading in investigation of any heterogeneity and in sensitivity analysis. Other aspects of study quality including the extent of blinding (if appropriate), losses to follow up, noncompliance, whether the outcome assessment was standardized, and whether an intention to treat analysis was undertaken, will be presented in the risk of bias table describing the included studies and will provide a context for discussing the reliability of the results.

Data analysis.
We will use Stata Software [Computer program] (Version 15.1) to process the meta-analysis. Weighted mean difference(WMD)will be used for continuous variable data, and the combined statistical effects of these two are combined. The X 2 test will be adopted to analyze whether there is heterogeneity in each of the included research questions. I 2 >50% is a criterion for signi cant judgment. The xed effect model is adopted if I 2 ≤50%, which is considered to have homogeneity between the studies. The random effect model is adopted if I 2 >50%, which is considered to have heterogeneity among the studies. The effect size is expressed as 95% con dence interval (CI), and P<0.05 is considered to be statistically signi cant.
Sensitivity analyses: heterogeneity may be due to the presence of 1 or more outlier studies with results that con ict with the rest of the studies. We will perform sensitivity analyses excluding outlier studies. In addition, we plan to perform sensitivity analysis to explore the in uence of trial quality on effectestimates. The quality components of methodology include adequacy of generation of allocation sequence, concealment of allocation, and the use of intention-to-treat analysis.
Meta-regression analyses: if data permits, we will perform the meta-regression analyses.

Publication bias.
If su cient number of trials (more than 10 trials) are found, we will generate funnel plots (effect size against standard error) to investigate publication bias.

Ethics and dissemination.
The results of this review will be disseminated through peer-reviewed publication. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process.

Discussion
The novel coronavirus disease 2019 (COVID-19) has grown to be a global public health emergency since patients were rst detected in Wuhan, China [14]. Accumulating evidence revealed that COVID-19 causes a broad spectrum of diseases that affects multiple organs including the lung, heart and kidney with reported cardiomyopathy and kidney injury [15][16].The COVID-19-related disease can lead to pneumonia, acute respiratory distress syndrome (ARDS) and congestive heart failure [17].Detection of viral genomicmaterials is the gold standard for diagnosis.Until now, there is no available speci c drugs or vaccines can cure the patients with COVID-19 infection [18].Current treatment for patientswith lung injuries is supportive, but with a high case fatality rate of22% to as high as 88% for ICU patients [19][20][21].Most of the prescribed alternative medicines are, however, neither speci cnor highly effective for COVID-19 treatment.Given the rapidly growing pandemic and the overwhelmedmedical system, the number of self-quarantined and recovering patients is increasing.There is an urgentneed of alternative medicine to help patients relieve symptoms duringself-quarantine, and possibly to help increase their chances of survivaland recovery from COVID-19.
During the SARS epidemics, traditional Chinese medicine (TCM)treatments were con rmed to have evident effects in successfullypreventing and treating SARS [22][23][24]. Furthermore, TCM combined with western medicine treatment can reduce adverse events and other complications induced by glucocorticoid, antibiotic, and antiviral treatments [25,26].Evidence clearly indicated that TCM combined with western medicine can signi cantly alleviate symptoms of SARS, including decreasing body temperature, cough and breathing di culties, improving absorption of pulmonary in ltration, and quality of life [27].Based on previous experience, we suggest that massage therapy, with unique advantagesand few reported side effects, may be a promising candidate as an alternativemedicine to help relieve severe symptoms of COVID-19 duringself-quarantine and recovery.
In conclusion, this is the rst systematic review to examine empiricalevidence of massage therapy for pulmonary function recovery in COVID-19. It will provide an overview of the application of massage therapy for COVID-19 convalescentpatients and assess the strengths and limitations of current evidence.This review will bring massage therapy to the tablefor discussion about its potential as an alternative medicine to attenuatepulmonary function in patients recovering from COVID-19.