Quality of and Recommendations for Relevant Clinical Practice Guidelines for COVID-19 Management: A Systematic Review and Critical Appraisal

Background: The morbidity and mortality of coronavirus disease 2019 (COVID-19) are still increasing. This study aimed to assess the quality of relevant COVID-19 clinical practice guidelines (CPGs) and to compare the similarities and differences between recommendations. Methods: A comprehensive search was conducted using electronic databases (PubMed, Embase, and Web of Science) and representative guidelines repositories from December 1, 2019, to August 11, 2020 (updated to April 5, 2021), to obtain eligible CPGs. The Appraisal of Guidelines for Research and Evaluation (AGREE II) tool was used to evaluate the quality of CPGs. Four authors extracted relevant information and completed data extraction forms. All data were analyzed using R version 3.6.0 software. Results: In total, 39 CPGs were identified and the quality was not encouragingly high. The median score (interquartile range, IQR) of every domain from AGREE II for evidence-based CPGs (EB-CPGs) versus (vs.) consensus-based CPG (CB-CPGs) was 81.94% (75.00–84.72) vs. 58.33% (52.78–68.06) in scope and purpose, 59.72% (38.89–75.00) vs. 36.11% (33.33–36.11) in stakeholder involvement, 64.58% (32.29–71.88) vs. 22.92% (16.67–26.56) in rigor of development, 75.00% (52.78–86.81) vs. 52.78% (50.00–63.89) in clarity of presentation, 40.63% (22.40–62.50) vs. 20.83% (13.54–25.00) in applicability, and 58.33% (50.00–100.00) vs. 50.00% (50.00–77.08) in editorial independence, respectively. The methodological quality of EB-CPGs were significantly superior to the CB-CPGs in the majority of domains (P < 0.05). There was no agreement on diagnosis criteria of COVID-19. But a few guidelines show Remdesivir may be beneficial for the patients, hydroxychloroquine +/– azithromycin may not, and there were more consistent suggestions regarding discharge management. For instance, after discharge, isolation management and health status monitoring may be continued. Conclusions: In general, the methodological quality of EB-CPGs is greater than CB-CPGs. However, it is still required to be further improved. Besides, the consistency of COVID-19 recommendations on topics such as diagnosis criteria is different. Of them, hydroxychloroquine +/– azithromycin may be not beneficial to treat patients with COVID-19, but remdesivir may be a favorable risk-benefit in severe COVID-19 infection; isolation management and health status monitoring after discharge may be still necessary. Chemoprophylaxis, including SARS-CoV 2 vaccines and antiviral drugs of COVID-19, still require more trials to confirm this.


INTRODUCTION
The morbidity and mortality associated with coronavirus disease 2019  are still increasing at present. According to the official website of World Health Organization (WHO), by 10 April 2021, there have been 134,308,070 confirmed cases of COVID-19, including 2,907,944 deaths worldwide (1). Containing the spread poses a challenge because of the rising number of infected people with high mortality and the highly contagious nature of COVID-19. Clinical practice guidelines (CPGs) have been defined as "statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and a risk-benefit assessment of alternative care options" (2), and they play an important role in guiding clinical decisions about prevention, diagnosis, treatment and care. Some professional association, guideline development groups have issued successively COVID-19 management guidelines.
Previous reviews have also concentrated on methodological quality and recommendations for COVID-19 guidelines, but these have covered a narrow range of topics (3)(4)(5)(6). The methods and reporting quality of practice guidelines for five different viruses causing public health emergencies of international concern, including the severe acute respiratory syndrome coronavirus 2, tended to be low, particularly in stakeholder involvement and applicability. There was also poor quality of recommendations for the use of antiviral drugs such as lopinavir-ritonavir, convalescent plasma, and intravenous immunoglobulins. Reverse transcription-polymerase chain reaction (RT-PCR) and Computed tomography (CT) were the most common diagnostic methods for COVID-19. Besides, there was no effective treatment against COVID-19; supportive therapy (mainly rest in bed, ensuring adequate calories, maintaining water-electrolyte balance, oxygen therapy, etc.) is the most significant treatment plan. Live evidence related to COVID-19 is still appearing on a daily basis, and live recommendations on chemoprophylaxis, diagnosis, and antiviral therapy are also being continuously updated. As for discharged patients, a small proportion of patients experienced reappearance of a positive test for SARS-CoV-2 during convalescence (7)(8)(9). As the number of cured patients increases, criteria for discharge management is also an important issue.
Thus, this review, based on a comprehensive literature search, has been conducted to compare the variations in recommendations within prophylaxis, diagnosis, antiviral treatment, and discharge management of COVID-19 and to assess their methodological quality. We aim to provide relatively more reliable suggestions for decision-making bodies regarding possible health problems to satisfy the needs of the public, providing guidance for government departments and COVID-19 prevention and control institutions.

METHODS
The review was performed according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines (10).

Search Strategy
We searched PubMed, Embase, and Web of Science. Additionally, eight representative guideline repositories were searched: World Health Organization (WHO), National Institute for Health and Care Excellence (NICE), Guidelines International Network (GIN), National Institutes of Health (NIH), Scottish Intercollegiate Guidelines Network (SIGN), Association of American Medical Colleges (AAMC), ECRI Guideline Trust, and Biochemical Genetic and Genomic (BIGG). A list of the websites with COVID-19 guidelines is presented in Supplementary Table 1. The search dates were from December 1, 2019, to August 11, 2020 (updated to April 5, 2021). The key words mainly included "severe acute respiratory syndrome coronavirus 2 or SARS-COV-2 or COVID-19 or COVID19 or 2019 coronavirus or 2019 novel coronavirus or 2019-nCoV or Novel coronavirus pneumonia or NCP or coronavirus disease-19 or coronavirus disease 2019" AND "guideline or guidance or recommendation or clinical practice guideline or consensus." MeSH terms were used to search Title/Abstract. Furthermore, taking PubMed as an example, the retrieval strategy is shown in Supplementary Figure 1.

Guidelines Identification
All guidelines related to COVID-19 published in English were included if they met the following criteria: (1) explicit recommendations on COVID-19 management (Which kind of agent can prevent COVID-19? Which strategy can be used to diagnose COVID-19 and identify and risk stratify patients with  suspected or confirmed COVID-19? Which drugs can be used to  treat patients with COVID-19? What are the discharge criteria for  COVID-19, and what indicators are there for follow-up attention  after discharge?); (2) evidence-based clinical practice guidelines (EB-CPGs) or consensus-based guidelines (CB-CPGs); and (3) updated versions of CPGs if multiple versions of the guidelines exists. To determine the eligible guidelines, EB-CPGs were defined as having recommendations based on a systematic literature search and literature quality assessment or grade for evidence and recommendation; CB-CPGs were defined as having recommendations developed by multidisciplinary experts (such as frontline clinicians) based on their experience or the existing literature using a consensus method rather than a systematic review.

Data Extraction
Four reviewers independently extracted the details of the guidelines relevant to their characteristics using a standardized data collection form. Extracted data included guideline title, date of publication, publication country/region, guideline developers, target population, development method (evidencebased or consensus-based), topic, funding, and the related recommendations. Another reviewer examined the data extraction forms to make sure no errors had occurred. Disagreements were resolved by consensus.

Methodological Quality Appraisal
Two reviewers independently evaluated the quality of each included guideline using the widely accepted CPG assessment tool-AGREE II, which is composed of 23 items within 6 domains including "scope and purpose, " "stakeholder involvement, " "rigor of development, " "clarity of presentation, " "applicability, " and "editorial independence" (11,12). Details of each domain are shown in Supplementary Table 2. Each item was scored from 1 (strongly disagree) to 7 (strongly agree). We calculated each domain score for every eligible CPG individually using the following formula provided by the AGREE II tool: (obtained score-minimal possible score)/(maximal possible score-minimal possible score) × 100% (11).

Guideline Recommendations Synthesis
We performed a textual descriptive synthesis to analyze eligible CPGs from four aspects: chemoprophylaxis; diagnosis; antiviral therapy; and discharge management.

Statistical Analysis
Descriptive statistical analyses were performed. Data for each AGREE II domain of every included CPG were presented as medians and interquartile ranges (IQRs). The scores of EB-CPGs and CB-CPGs in each domain were compared using Wilcoxon Rank-Sum Test. A P < 0.05 was regarded as significance. Intraclass correlation coefficients (ICCs) with a 95% confidence interval (CI) were calculated to evaluate the agreement among two assessors for each domain. The degree of agreement between 0.00 and 0.40 was considered poor, 0.41 to 0.75 was good, and 0.75 to 1.00 was excellent (13). All the data were analyzed using R version 3.6.0 software (The R Foundation for Statistical Computing, Vienna, Austria) for Windows. Figure 1 presents the flow chart of guidelines identification, and 39 CPGs were eventually included (14-52).

Characteristics of Included Guidelines
As Supplementary Table 3 shows, the guidelines were published from February 6, 2020, to April 5, 2021. Of them, 15 guidelines were CB-CPGs and 24 were EB-CPGs, and 15 received funding support. Among the recommendations in these 39 CPGs, 8 were on chemoprophylaxis, 18 on diagnosis, 1 on identification and triage of patients with COVID-19, 25 on antiviral drugs, and 6 on discharge. The guidelines were mainly developed by the United States, China, or other international organization or cooperation (See Figure 2).

Guidelines' Quality
The ICC values for all six domains of AGREE II were over 0.75, indicating a high consistency on the scores between the two assessors. As shown in Supplementary Table 4, Table 1, Figure 3, the final domain score of every guideline across all domains ranged from 0% (Domain 6 of editorial independence in 1 guidelines) (51) to 100% (Domain 6 in 11 guidelines) (16,19,25,29,31,32,34,44,(46)(47)(48). Regarding the score of each domain across all guidelines, for EB-CPGs, the score of Domain 5 (applicability) was the lowest with a median score of 40
As presented in Tables 5A,B, four EB-CPGs (29,34,36,51) and two CB-CPGs (35, 52) concentrated on the discharge management of COVID-19. The criteria were mainly based on temperature returning to normal more than 3 days, improvement in respiratory symptoms and negative results from two successive nucleic acid test of respiratory samples (with a sampling interval of at least 1 day). Besides, three EB-CPGs (29,34,51) and one CB-CPG (35) described the relevant precautions after discharge. For example, isolation management should be continued, and the patients should wear a mask if necessary.

DISCUSSION
EB-CPGs and CB-CPGs play an important role in this pandemic, which is constantly being updated. The first EB-CPGs were published on Feb 6, 2020 (53); the first protocol of the updated  EB-CPG was released on March 7, 2020 (54). Finally, 39 CPGs were included in this review. The methodological quality of EB-CPGs is better than CB-CPGs because the median score with IQR is statistically significantly higher in EB-CPGs for domains of the AGREE II assessment tool in general. However, they all still need to be further improved, especially in the areas of gathering and synthesizing reliable the latest up-to-date information, involving the target population in guideline development and improving the implementability of the recommendations. Recommendations relevant to chemoprophylaxis, diagnosis, antiviral drugs, and discharge management of COVID-19 showed small differences. COVID-19 is a newly identified infectious disease, which poses a significant threat to both the general population and  Not reported *When SARS-CoV-2 infection requires laboratory confirmation for clinical or epidemiological purposes, testing for SARS-CoV-2 IgG or total antibody 3 to 4 weeks after symptom onset to detect evidence of past SARS-CoV-2 infection;using IgG antibody to provide evidence of COVID-19 infection in symptomatic patients with a high clinical suspicion and repeatedly negative NAAT testing; In pediatric patients with multisystem inflammatory syndrome, using both IgG antibody and NAAT to provide evidence of current or past COVID-19 infection; **Not recommended as the sole basis; ***SARS-CoV-2 antibody tests are not recommended for diagnosis of current infection with COVID-19; ****For symptomatic patients with suspected COVID-19, using chest imaging for the diagnostic workup of COVID-19 when RT-PCR testing is not available; RT-PCR testing is available but results are delayed; and initial RT-PCR testing is negative but with high clinical of suspicion of COVID-19; *****CT scan should not be used routinely in the diagnosis of COVID-19 in children; ******Pregnant women with suspected COVID-19 infection; *******Not recommend routine serological testing to diagnose active COVID-19 in symptomatic pregnant women with negative RT-PCR; ********Not currently recommend using chest CT scans or X-rays as a first-line test for diagnosing COVID-19 in symptomatic pregnant women. EB-CPG, Evidence-based guideline; CB-CPG, Consensus-based guideline; CXR, chest radiography; chest CT, chest computed tomography. Etiological criteria: testing positive for SARS-CoV-2 by real-time polymerase chain reaction (PCR) and highly homologous genetic sequencing of respiratory tract or blood samples with the known SARS-CoV-2; Serological criteria: positive results of serum-specific antibodies IgM and IgG test, specifying serum-specific antibody IgG changed from negative to positive or increased four-fold or higher from that in the acute phase during the recovery period; Epidemiological history: involved noting whether the patients had a travel or residence history in a community with infected cases reported in China or a country or region with a serious epidemic, a history of contacting patients infected with SARS-Cov-2, a history of contacting patients with fever or respiratory symptoms from communities with reported cases in China or countries or regions with serious epidemics, clustered cases within 14 days prior to disease onset. Clinical manifestations: mainly consisted of fever, fatigue, dry cough, and/or other respiratory symptoms; COVID 19 imaging features and, in the early stage of the disease, the total number of leukocytes was normal or decreased, and the lymphocyte count was decreased.        (51) ****** ***** ****** ***** ***** ***
Frontiers in Medicine | www.frontiersin.org  Not reported *Afebrile for ≥24 h; **Substantially improved respiratory symptoms; ***Temperature returned to normal for more than 3 days; ****Significant absorption of pulmonary chest lesions; *****Two consecutive negative nucleic acid tests from sputum, nasopharyngeal swabs, or other respiratory tract samples (at least 24 h between samples); ******For hospitalized patients with COVID-19 whose symptoms are resolved, not using chest imaging in addition to clinical and/or laboratory assessment to inform the decision regarding discharge. EB-CPG, Evidence-based guideline; CB-CPG, Consensus-based guideline.
health care workers. In the early stage of the pandemic, the absolute lack of direct evidence is the biggest challenge for guideline development. A large number of CB-CPGs and EB-CPGs in accordance with experience of frontline health professionals, such as experts in infectious disease, medical imaging, and clinical immunology, have put forward valuable suggestions to guide clinical practice. Although the methodological quality of EB-CPGs is higher than CB-CPGs in general, they all have deficiencies in the following aspects, including obtaining the views and preferences of the target population, considering benefits and risks when formulating recommendations, introducing a detailed update plan, and providing implementation strategy for the recommendations or methods for managing potential conflicts of interest, similar to Dagens' , Luo' , and Zhao' studies (3,4,6). In view of the above topics, there are some examples of good practice, for example, conducting interviews and group surveys to collect information on treatment evidence from frontline experts fighting the disease (34); inviting patients recovering from COVID-19 to get involved in the guideline development panel (45); critically assessing new studies where these supersede previous outdated recommendations (14); providing available recommendation summaries in user-friendly and multilayered formats for clinicians and patients through the MAGIC app (55) or the provision of consultation decision aids to facilitate shared decision-making (45); and using the GRADEpro guideline development tool online software to conduct evidence-based CPGs (56). The methodology for guideline development to deal with public health emergencies is still a challenge, and methods for their development which ensure the rigor, timeliness and implementability of recommendations is a problem to be further explored by methodologists.
Recommendations relevant to chemoprophylaxis, diagnosis, antiviral treatments, and discharge management of COVID-19 varied in the guidelines. Chemoprophylaxis may be beneficial to reduce COVID-19 spread, which is important when lacking specific vaccines due to the high social and economic costs caused by social distancing of entire populations and blockade of entire cities. This method has been applied to other respiratory viruses; for example, healthcare workers who were exposed to high risk groups fought against the Middle East respiratory syndrome coronavirus using lopinavir-ritonavir plus ribavirin in South Korea (57). Unfortunately, there are still no effective and verified drugs for COVID-19 prophylaxis in the guidelines. However, a  (51) ****** *******

Recommended
Not reported *Following local/regional/national deisolation, or ability to self-isolate adequately for a minimum of 10 days following the onset of symptoms, if applicable; **All patients and caregivers receive comprehensive education on adequate hygiene and the importance of mask-wearing, including for close contacts; ***Taking into consideration the capability of primary caregivers to provide the necessary care to meet the psychological, physical, and neurocognitive needs; ****Discharged patients may be quarantined for 2 weeks; *****PCR tests can be performed at 2 and 4 weeks after discharge; ******Early discharge to home may be followed by a telephonic follow-up or home visit by a designated nurse; *******Mothers should practice respiratory hygiene and wear a mask while breastfeeding and providing other care to the baby; they should routinely clean and disinfect all the surfaces; ********At 6-8 weeks following discharge, a formal assessment of physical and emotional functioning for patients with COVID-19; a formal psychological assessment for COVID-19 survivors with symptoms of psychological distress; *********At 6-8 weeks following discharge, doing regular daily activities in the first 6-8 weeks after hospital discharge; nutritional support for COVID-19 survivors with loss of lower-limb muscle mass, a musclestrengthening programme for COVID-19 survivors with loss of lower-limb muscle mass and/or function; a comprehensive pulmonary rehabilitation programme for COVID-19 survivors with pre-existing/ongoing lung function impairment; a comprehensive rehabilitation programme for COVID-19 survivors with a need for rehabilitative interventions. EB-CPG, Evidence-based guideline; CB-CPG, Consensus-based guideline.
retrospective cohort study on family members and health care workers who were exposed to patients diagnosed with SARS-CoV-2 suggested that Arbidol could reduce risk of infection with the disease in hospital and family settings (58). SARS-CoV 2 vaccines may be beneficial for the prevention of COVID-19. The effectiveness and safety of them are still continuously ongoing trials. For instance, estimated BNT162b2 and mRNA-1273 COVID-19 vaccines effectiveness for prevention of infection was 90% for full immunization and 80% for partial immunization (59). Most commonly reported adverse effects of COVID-19 mRNA-1273 vaccine were localized pain, generalized weakness, headache, and myalgia (60). New evidence may inform decision making on chemoprophylaxis for healthcare personnel by policy makers in the future. Diagnostic criteria for COVID-19 were not identical across the guidelines. What is more consistent is confirmation of diagnosis by testing positive for SARS-CoV-2 by real-time PCR. The main differences are the inclusion of other features, such as epidemiological history, serological tests, and clinical manifestations, as one of the bases for the diagnosis. Early studies have confirmed that 49-66% patients had contact with personnel in outbreak area (61). Up to now, asymptomatic infection of SARS-CoV-2 has become a worldwide concern. A recent study indicated that these cases may account for 60% of all infections and may trigger new outbreaks (62). Asymptomatic cases were significantly younger than those with symptomatic patients, had similar common incidence rate, and were more likely to come from high altitude and low mobility areas, with better history of epidemiology (63). Careful examination of the epidemiological history would help to identify asymptomatic patients that may have delayed symptoms after diagnosis. In addition, stability issues of RT-PCR testing of COVID-19 for hospitalized patients clinically diagnosed with SARS-CoV-2 are a problem. Li et al. reported a potentially high false negative rate of RT-PCR where results from several tests from the same patients at different points were inconsistent during the course of their diagnosis and treatment (64). Current systematic reviews have confirmed that the detection of anti-SARS-CoV-2 IgG and IgM had high diagnostic efficiency (2,282 patients with SARS-CoV-2 and 1,485 healthy persons or patients without SARS-CoV-2) (65) and a high sensitivity of chest CT for the detection of COVID-19 in regions with severe (3,186 patients) (66). The presentation of COVID-19 symptoms (such as fever, cough, myalgia/fatigue, leukocyte, and neutrophil counts) might be regarded as a surrogate marker for the disease' presence and severity (67,68). Therefore, serological criteria, epidemiological history, clinical manifestations, and chest x-ray/CT should also be used for to assist diagnosis for COVID-19 infection during the current epidemic, counteracting possible false negative RT-PCR results if available.
Studies published after the deadline for analysis have been included here. Although there were no consistent recommendations on the usage of antiviral drugs, it does offer a few valuable suggestions, including antiviral drugs, such as hydroxychloroquine and remdesivir, for COVID-19. The majority of EB-CPGs did not recommend hydroxychloroquine +/-azithromycin to treat patients with COVID-19 because higher certainty benefits (e.g., mortality reduction) are now highly unlikely even if additional high quality randomized controlled trials would become available (14,15,18,20,21,40,45). Remdesivir is an antiviral drug with potent in vitro activity against a range of RNA viruses including MERS-CoV, SARS-CoV, there may be a favorable risk-benefit profile for remdesivir compared with no antiviral treatment in severe COVID-19 infection with limited safety data currently available for the drug (14-16, 20, 21, 24, 25, 34, 37, 47). In addition, Traditional Chinese medicine treatment may be beneficial for the treatment of COVID-19, including Lianhua Qingwen granules/capsules and Huashi Baidu granules. More new evidence concentrating on antiviral therapy continuously emerges. For example, early application of lopinavir / ritonavir+interferon-α can reduce the shedding time of sars-cov-2 (69); Early initiation with interferon) β-1b, lopinavir, ribavirin combination therapy were more safe and effective than lopinavir alone in relieving symptoms, shortening length of stay in patients with mild to moderate COVID-19 (70); Lianhua Qingwen combined with Western medicine may have a significant effect and fewer side effects in the treatment of common patients with new coronavirus pneumonia (71). The new evidence above will help to update the recommendations of the guidelines.
The phenomenon that some discharge patients have tested positive for COVID-19 again after recovery has attracted a lot of attention. The included guidelines provided different suggestions on discharge criteria and precautions after discharge. As previously stated, Chest CT and X ray can be beneficial for COVID-19 diagnosis. Viral RNA was detected in 48.1% of patients' feces, even in the feces who have been diagnosed with negative results in respiratory tract samples (72). Thus, a nucleic acid test of upper airway specimens (nasopharyngeal and pharyngeal swabs) and fecal stool can be considered along with other criteria. Additionally, it may be necessary to continue isolation management and health status monitoring. A follow-up study for 651 patients recovered from COVID-19 revealed that 3% of the patients were positive for SARS-CoV-2 by RTqPCR in routine physical examination and the median time from discharge to retest with postive results was 15.0 days (73). Thus, the COVID-19 pandemic is a rapidly changing situation. The recommendations in the guidelines are also continuously changing. The evidence-based living guidelines are pursed (74,75).
A strength of this review lies in the updated study (up to April 5, 2021) concentrating on hot topics, including chemoprophylaxis, diagnosis, antiviral therapy and discharge management of COVID-19 guidelines, at the same time and summarizing the recommendations. In addition, we defined the CPGs, distinguished EB-CPGs and CB-CPGs in order to gain the valuable recommendations developed by multidisciplinary experts and based on best evidence. However, there are several inevitable limitations in this current study. First, we did not compare the evidence and recommendation levels or different grade systems used in EB-CPGs. With new evidence emerging over time, some CPGs will be updated and evidence and recommendation levels may be changed or improved later. Second, we only searched the three medical databases and eight representative guidelines repositories, and some eligible EB-CPGs and CB-CPGs will thus have been missed.

CONCLUSION
In general, the methodological quality of EB-CPGs is greater than CB-CPGs. But we still need to pay attention to gathering and synthesizing reliable the latest up-to-date information, involving the target population in guideline development and improving the implementability of the recommendations. As for the recommendations of COVID-19, SARS-CoV 2 vaccines are still going through ongoing trials; various diagnosis strategies, including serological criteria and CT for COVID-19, may be more effective if available; hydroxychloroquine +/-azithromycin may be not beneficial to treat patients with COVID-19, but remdesivir may be a favorable risk-benefit in severe COVID-19 infection; and isolation management and health status monitoring after discharge may be still necessary. Thus, chemoprophylaxis and antiviral drugs of COVID-19 still need more trials for confirmation.

DATA AVAILABILITY STATEMENT
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.

AUTHOR CONTRIBUTIONS
Y-YW and X-TZ designed the study and formulated inclusion criteria. Y-YW, QS, HZ, QH, and B-HL searched and identified eligible guidelines. HZ, B-HL, M-ZL, and S-HH extracted important information. M-ZL and QS evaluated the quality of each included guideline using AGREE II. X-TZ and Y-HJ examined the data extraction forms. Y-YW, QH, and S-HH analyzed the data. Y-YW, X-TZ, XY, and Y-HJ contributed to discussed the findings. Y-YW, X-TZ, XY, and Y-HJ developed the final manuscript. All authors have read and approved the manuscript.

FUNDING
This work was supported (in part) by the Emergency Special Project for COVID-19 of Wuhan Municipal Health Commission (EG20A02).