Coronavirus disease (COVID-19): a scoping review.

BackgroundIn December 2019, a pneumonia caused by a novel coronavirus (SARS-CoV-2) emerged in Wuhan, China and has rapidly spread around the world since then.AimThis study aims to understand the research gaps related to COVID-19 and propose recommendations for future research.MethodsWe undertook a scoping review of COVID-19, comprehensively searching databases and other sources to identify literature on COVID-19 between 1 December 2019 and 6 February 2020. We analysed the sources, publication date, type and topic of the retrieved articles/studies.ResultsWe included 249 articles in this scoping review. More than half (59.0%) were conducted in China. Guidance/guidelines and consensuses statements (n = 56; 22.5%) were the most common. Most (n = 192; 77.1%) articles were published in peer-reviewed journals, 35 (14.1%) on preprint servers and 22 (8.8%) posted online. Ten genetic studies (4.0%) focused on the origin of SARS-CoV-2 while the topics of molecular studies varied. Nine of 22 epidemiological studies focused on estimating the basic reproduction number of COVID-19 infection (R0). Of all identified guidance/guidelines (n = 35), only ten fulfilled the strict principles of evidence-based practice. The number of articles published per day increased rapidly until the end of January.ConclusionThe number of articles on COVID-19 steadily increased before 6 February 2020. However, they lack diversity and are almost non-existent in some study fields, such as clinical research. The findings suggest that evidence for the development of clinical practice guidelines and public health policies will be improved when more results from clinical research becomes available.

The role of acupuncture and moxibustion in the treatment, prevention, and rehabilitation of patients with COVID-19: A scoping review.

Introduction: This study aims to summarize the available evidence and guideline/consensus recommendations for acupuncture and moxibustion in the treatment, prevention and rehabilitation of patients with coronavirus disease 2019 (COVID-19). Methods: A scoping review was performed. Eight electronic databases and other related websites were searched. All studies related to acupuncture and moxibustion for COVID-19 were considered. Descriptive analysis was applied to analyze the all included studies and guideline recommendations. Results: We ultimately included 131 eligible studies. The main topics of the included studies were the treatment (82.4%) and prevention (38.9%) of COVID-19. The most included studies were literature reviews (65, 49.6%), protocols of systematic reviews (20, 15.3%), and guidelines and consensuses (18, 13.7%). The 18 (13.7%) COVID-19 guidelines and consensuses included 47 recommendations on acupuncture and moxibustion, which focused on the treatment (21/47, 44.7%), rehabilitation (17/47, 36.2%) and prevention (6, 12.8%) of COVID-19 patients. Zusanli (ST36), Feishu (BL13), Guanyuan (RN4) were recommended mostly for the treatment, rehabilitation and prevention respectively. Conclusion: Acupuncture and moxibustion are effective in the treatment of COVID-19 patients to some extent. However, more high-quality of clinical trials still needed to determine the feasibility of acupuncture and moxibustion in COVID-19 patients to better guide clinical practice. Study registration: Open Science Framework Registries (Registration DOI: 10.17605/OSF.IO/Z35WN; https://osf.io/z35wn).

Analysis of COVID-19 Guideline Quality and Change of Recommendations: A Systematic Review

Background Hundreds of coronavirus disease 2019 (COVID-19) clinical practice guidelines (CPGs) and expert consensus statements have been developed and published since the outbreak of the epidemic. However, these CPGs are of widely variable quality. So, this review is aimed at systematically evaluating the methodological and reporting qualities of COVID-19 CPGs, exploring factors that may influence their quality, and analyzing the change of recommendations in CPGs with evidence published. Methods We searched five electronic databases and five websites from 1 January to 31 December 2020 to retrieve all COVID-19 CPGs. The assessment of the methodological and reporting qualities of CPGs was performed using the AGREE II instrument and RIGHT checklist. Recommendations and evidence used to make recommendations in the CPGs regarding some treatments for COVID-19 (remdesivir, glucocorticoids, hydroxychloroquine/chloroquine, interferon, and lopinavir-ritonavir) were also systematically assessed. And the statistical inference was performed to identify factors associated with the quality of CPGs. Results We included a total of 92 COVID-19 CPGs developed by 19 countries. Overall, the RIGHT checklist reporting rate of COVID-19 CPGs was 33.0%, and the AGREE II domain score was 30.4%. The overall methodological and reporting qualities of COVID-19 CPGs gradually improved during the year 2020. Factors associated with high methodological and reporting qualities included the evidence-based development process, management of conflicts of interest, and use of established rating systems to assess the quality of evidence and strength of recommendations. The recommendations of only seven (7.6%) CPGs were informed by a systematic review of evidence, and these seven CPGs have relatively high methodological and reporting qualities, in which six of them fully meet the Institute of Medicine (IOM) criteria of guidelines. Besides, a rapid advice CPG developed by the World Health Organization (WHO) of the seven CPGs got the highest overall scores in methodological (72.8%) and reporting qualities (83.8%). Many CPGs covered the same clinical questions (it refers to the clinical questions on the effectiveness of treatments of remdesivir, glucocorticoids, hydroxychloroquine/chloroquine, interferon, and lopinavir-ritonavir in COVID-19 patients) and were published by different countries or organizations. Although randomized controlled trials and systematic reviews on the effectiveness of treatments of remdesivir, glucocorticoids, hydroxychloroquine/chloroquine, interferon, and lopinavir-ritonavir for patients with COVID-19 have been published, the recommendations on those treatments still varied greatly across COVID-19 CPGs published in different countries or regions, which may suggest that the CPGs do not make sufficient use of the latest evidence. Conclusions Both the methodological and reporting qualities of COVID-19 CPGs increased over time, but there is still room for further improvement. The lack of effective use of available evidence and management of conflicts of interest were the main reasons for the low quality of the CPGs. The use of formal rating systems for the quality of evidence and strength of recommendations may help to improve the quality of CPGs in the context of the COVID-19 pandemic. During the pandemic, we suggest developing a living guideline of which recommendations are supported by a systematic review for it can facilitate the timely translation of the latest research findings to clinical practice. We also suggest that CPG developers should register the guidelines in a registration platform at the beginning for it can reduce duplication development of guidelines on the same clinical question, increase the transparency of the development process, and promote cooperation among guideline developers all over the world. Since the International Practice Guideline Registry Platform has been created, developers could register guidelines prospectively and internationally on this platform.

Guidelines for the prevention and management of children and adolescents with COVID-19.

Children are the future of the world, but their health and future are facing great uncertainty because of the coronavirus disease 2019 (COVID-19) pandemic. In order to improve the management of children with COVID-19, an international, multidisciplinary panel of experts developed a rapid advice guideline at the beginning of the outbreak of COVID-19 in 2020. After publishing the first version of the rapid advice guideline, the panel has updated the guideline by including additional stakeholders in the panel and a comprehensive search of the latest evidence. All recommendations were supported by systematic reviews and graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Expert judgment was used to develop good practice statements supplementary to the graded evidence-based recommendations. The updated guideline comprises nine recommendations and one good practice statement. It focuses on the key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin (IVIG) for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health. CONCLUSION: This updated evidence-based guideline intends to provide clinicians, pediatricians, patients and other stakeholders with evidence-based recommendations for the prevention and management of COVID-19 in children and adolescents. Larger studies with longer follow-up to determine the effectiveness and safety of systemic glucocorticoids, IVIG, noninvasive ventilation, and the vaccines for COVID-19 in children and adolescents are encouraged. WHAT IS KNOWN: • Several clinical practice guidelines for children with COVID-19 have been developed, but only few of them have been recently updated. • We developed an evidence-based guideline at the beginning of the COVID-19 outbreak and have now updated it based on the results of a comprehensive search of the latest evidence. WHAT IS NEW: • The updated guideline provides key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health.

Clinical manifestations of COVID-19: An overview of 102 systematic reviews with evidence mapping.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has rapidly spread worldwide, but there is so far no comprehensive analysis of all known symptoms of the disease. Our study aimed to present a comprehensive picture of the clinical symptoms of COVID-19 using an evidence map. METHODS: We systematically searched MEDLINE via PubMed, Web of Science, Embase, and Cochrane library from their inception to March 16, 2021. We included systematic reviews reporting the clinical manifestations of COVID-19 patients. We followed the PRISMA guidelines, and the study selection, data extraction, and quality assessment were done by two individuals independently. We assessed the methodological quality of the studies using AMSTAR. We visually presented the clinical symptoms of COVID-19 and their prevalence. RESULTS: A total of 102 systematic reviews were included, of which, 68 studies (66.7%) were of high quality, 19 studies (18.6%) of medium quality, and 15 studies (14.7%) of low quality. We identified a total of 74 symptoms including 17 symptoms of the respiratory system, 21 symptoms of the neurological system, 10 symptoms of the gastrointestinal system, 16 cutaneous symptoms, and 10 ocular symptoms. The most common symptoms were fever (67 studies, ranging 16.3%-91.0%, pooled prevalence: 64.6%, 95%CI, 61.3%-67.9%), cough (68 studies, ranging 30.0%-72.2%, pooled prevalence: 53.6%, 95%CI, 52.1%-55.1%), muscle soreness (56 studies, ranging 3.0%-44.0%, pooled prevalence: 18.7%, 95%CI, 16.3%-21.3%), and fatigue (52 studies, ranging 3.3%-58.5%, pooled prevalence: 29.4%, 95%CI, 27.5%-31.3%). The prevalence estimates for COVID-19 symptoms were generally lower in neonates, children and adolescents, and pregnant women than in the general populations. CONCLUSION: At least 74 different clinical manifestations are associated with COVID-19. Fever, cough, muscle soreness, and fatigue are the most common, but attention should also be paid to the rare symptoms that can help in the early diagnosis of the disease.

Herbal Medicine Intervention for the Treatment of COVID-19: A Living Systematic Review and Cumulative Meta-Analysis.

Background: Integrative herbal medicine has been reported to have beneficial effects in the treatment of coronavirus disease 2019 (COVID-19). Aim: To compile up-to-date evidence of the benefits and risks of herbal medicine for the treatment of COVID-19 symptoms. Methods: Eleven databases, including PubMed, Cochrane Register of Controlled Trials (CENTRAL), Embase, Allied and Complementary Medicine Database (AMED), Chinese National Knowledge Infrastructure Database (CNKI), Wanfang Database, and Chinese Science and Technique Journals Database (VIP), Research Information Service System (RISS), Korean Medical database (KMBase), Korean Association of Medical Journal database (KoreaMed), and OASIS database, were searched from 15 June, 2020, until 28 March 2022. Randomized controlled trials (RCTs), published in any language, reporting the efficacy and safety outcomes of herbal medicine in patients of all ages with a PCR-confirmed diagnosis of COVID-19 were included in this analysis. Data extraction and quality assessments were performed independently. Results: Random-effects meta-analyses showed evidence of favorable effects of treatment with herbal medicine when added to standard treatment, versus standard treatment alone, on the total effective rate (p = 0.0001), time to remission from fever (p < 0.00001), rate of remission from coughing (p < 0.0001), fatigue (p = 0.02), sputum production (p = 0.004), improvement of manifestations observed on chest computed tomography scans (p < 0.00001), incidence of progression to severe COVID-19 (p = 0.003), all-cause mortality (p = 0.003), time to a negative COVID-19 coronavirus test (p < 0.0001), and duration of hospital stay (p = 0.0003). There was no evidence of a difference between herbal medicine added to standard treatment, versus standard treatment alone, on the rate of remission from symptoms such as a fever, sore throat, nasal congestion and discharge, diarrhea, dry throat, chills, and the rate of conversion to a negative COVID-19 coronavirus test. Meta-analysis showed no evidence of a significant difference in adverse events between the two groups. There was an unclear risk of bias across the RCTs included in this analysis, indicating that most studies had methodological limitations. Conclusion: Current evidence suggests that herbal medicine added to standard treatment has potential benefits in the treatment of COVID-19 symptoms but the certainty of evidence was low.

Use of non-steroidal anti-inflammatory drugs and adverse outcomes during the COVID-19 pandemic: A systematic review and meta-analysis.

Background: There are concerns that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of adverse outcomes among patients with coronavirus COVID-19. This study aimed to synthesize the evidence on associations between the use of NSAIDs and adverse outcomes. Methods: A systematic search of WHO COVID-19 Database, Medline, the Cochrane Library, Web of Science, Embase, China Biology Medicine disc, China National Knowledge Infrastructure, and Wanfang Database for all articles published from January 1, 2020, to November 7, 2021, as well as a supplementary search of Google Scholar. We included all comparative studies that enrolled patients who took NSAIDs during the COVID-19 pandemic. Data extraction and quality assessment of methodology of included studies were completed by two reviewers independently. We conducted a meta-analysis on the main adverse outcomes, as well as selected subgroup analyses stratified by the type of NSAID and population (both positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or not). Findings: Forty comparative studies evaluating 4,867,795 adult cases were identified. Twenty-eight (70%) of the included studies enrolled patients positive to SARS-CoV-2 tests. The use of NSAIDs did not reduce mortality outcomes among people with COVID-19 (number of studies [N] = 29, odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.75 to 1.14, I2  = 89%). Results suggested that the use of NSAIDs was not significantly associated with higher risk of SARS-CoV-2 infection in patients with or without COVID-19 (N = 10, OR = 0.96, 95% CI: 0.86 to 1.07, I2  = 78%; N = 8, aOR = 1.01, 95% CI: 0.94 to 1.09, I2  = 26%), or an increased probability of intensive care unit (ICU) admission (N = 12, OR = 1.28, 95% CI: 0.94 to 1.75, I2  = 82% ; N = 4, aOR = 0.89, 95% CI: 0.65 to 1.22, I2  = 60%), requiring mechanical ventilation (N = 11, OR = 1.11, 95% CI: 0.79 to 1.54, I2  = 63%; N = 5, aOR = 0.80, 95% CI: 0.52 to 1.24, I2  = 66%), or administration of supplemental oxygen (N = 5, OR = 0.80, 95% CI: 0.52 to 1.24, I2  = 63%; N = 2, aOR = 1.00, 95% CI: 0.89 to 1.12, I2  = 0%). The subgroup analysis revealed that, compared with patients not using any NSAIDs, the use of ibuprofen (N = 5, OR = 1.09, 95% CI: 0.50 to 2.39; N = 4, aOR = 0.95, 95% CI: 0.78 to 1.16) and COX-2 inhibitor (N = 4, OR = 0.62, 95% CI: 0.35 to 1.11; N = 2, aOR = 0.73, 95% CI: 0.45 to 1.18) were not associated with an increased risk of death. Interpretation: Data suggests that NSAIDs such as ibuprofen, aspirin and COX-2 inhibitor, can be used safely among patients positive to SARS-CoV-2. However, for some of the analyses the number of studies were limited and the quality of evidence was overall low, therefore more research is needed to corroborate these findings. Funding: There was no funding source for this study.

Improving Data Surveillance Resilience Beyond COVID-19: Experiences of Primary heAlth Care quAlity Cohort In ChinA (ACACIA) Using Unannounced Standardized Patients.

We analyzed COVID-19 influences on the design, implementation, and validity of assessing the quality of primary health care using unannounced standardized patients (USPs) in China. Because of the pandemic, we crowdsourced our funding, removed tuberculosis from the USP case roster, adjusted common cold and asthma cases, used hybrid online-offline training for USPs, shared USPs across provinces, and strengthened ethical considerations. With those changes, we were able to conduct fieldwork despite frequent COVID-19 interruptions. Furthermore, the USP assessment tool maintained high validity in the quality checklist (criteria), USP role fidelity, checklist completion, and physician detection of USPs. Our experiences suggest that the pandemic created not only barriers but also opportunities to innovate ways to build a resilient data collection system. To build data system reliance, we recommend harnessing the power of technology for a hybrid model of remote and in-person work, learning from the sharing economy to pool strengths and optimize resources, and dedicating individual and group leadership to problem-solving and results. (Am J Public Health. 2022;112(6):913-922. https://doi.org/10.2105/AJPH.2022.306779).

Risk of COVID-19 Transmission Aboard Aircraft: An Epidemiological Analysis Based on the National Health Information Platform.

OBJECTIVES: This study aims to investigate the risk of COVID-19 transmission on aircraft. METHODS: We obtained data on all international flights to Lanzhou, China, from June 1, 2020, to August 1, 2020, through the Gansu Province National Health Information Platform and the official website of the Gansu Provincial Center for Disease Control and Prevention. We then performed the statistical analysis. RESULTS: Three international flights arrived in Lanzhou. The flights had a total of 700 passengers, of whom 405 (57.9%) were male, and 80 (11.4%) were children under the age of 14 years. Twenty-seven (3.9%) passengers were confirmed to have COVID-19. Confirmed patients were primarily male (17, 65.4%) with a median age of 27.0 years. Most confirmed cases were seated in the middle rows of economy class or near public facility areas such as restrooms and galleys. The prevalence of COVID-19 did not differ between passengers sitting in the window, aisle, or middle seats. However, compared with passengers sitting in the same row up to 2 rows behind a confirmed case, passengers seated in the 2 rows in front of a confirmed case were at a slightly higher risk of being infected. CONCLUSIONS: COVID-19 may be transmitted during a passenger flight, although there is still no direct evidence.

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The coronavirus disease 2019 (COVID-19) continues to spread around the world, and how to build an immune barrier against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the population is the work we need to do for a long time in the future. The vaccination is an important strategy to construct and improve the herd immunity barrier. Therefore, our country is currently actively and extensively implementing the anti-epidemic policy of SARS-CoV-2 vaccination. However, because of insufficient data on the safety of the SARS-CoV-2 vaccine in the population, especially the lack of clinical research in pregnant and lactating women, China has adopted a conservative approach on whether women in this special physiological period receive SARS-CoV-2 vaccine based on the safe consideration. However, with the widespread application of the SARS-CoV-2 vaccine in the prevention and control of the global epidemic, and the emergence of a large number of clinical research evidences at home and abroad, if we still exclude pregnant and lactating women from the vaccinated population, this part of the population will be fully exposed to the SARS-CoV-2 threat, which will weak the national prevention and control policy. Therefore, it is necessary to reconsider the vaccination of people in this special physiological period based on the experience of vaccination at home and abroad.

Potentially effective drugs for the treatment of COVID-19 or MIS-C in children: a systematic review.

The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C. We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C. A total of nine cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that after the treatment, 54.7% (95%CI, 10.3 to 99.1%) experienced adverse events, 5.6% (95%CI, 1.2 to 10.1%) died, and 27.0% (95%CI, 0 to 73.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, most of the included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone. CONCLUSIONS: Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines. WHAT IS KNOWN: • The efficacy and safety of using potential drugs such as remdesivir, glucocorticoid, and intravenous immunoglobulin (IVIG) in treating children and adolescents with COVID-19/MIS-C are unclear. WHAT IS NEW: • Overall, the current evidence cannot adequately demonstrate the effectiveness and safety of using remdesivir, glucocorticoids, and IVIG in treating children and adolescents with COVID-19 or MIS-C. • We are calling for the publication of high-quality clinical trials and provide substantial evidence for the development of guidelines.

Did patients with COVID-19 receive timely treatment in the early epidemic?-a systematic review and meta-analysis.

BACKGROUND: Corona virus disease 2019 (COVID-19) showed a significant difference in case fatality rate between different regions at the early stage of the epidemic. In addition to the well-known factors such as age structure, detection efficiency, and race, there was also a possibility that medical resource shortage caused the increase of the case fatality rate in some regions. METHODS: Medline, Cochrane Library, Embase, Web of Science, CBM, CNKI, and Wanfang of identified articles were searched through 29 June 2020. Cohort studies and case series with duration information on COVID-19 patients were included. Two independent reviewers extracted the data using a standardized data collection form and assessed the risk of bias. Data were synthesized through description and analysis methods including a meta-analysis. RESULTS: A total of 109 articles were retrieved. The time interval from onset to the first medical visit of COVID-19 patients in China was 3.38±1.55 days (corresponding intervals in Hubei province, non-Hubei provinces, Wuhan, Hubei provinces without Wuhan were 4.22±1.13, 3.10±1.57, 4.20±0.97, and 4.34±1.72 days, respectively). The time interval from onset to the hospitalization of COVID-19 patients in China was 8.35±6.83 days (same corresponding intervals were 12.94±7.43, 4.17±1.45, 14.86±7.12, and 5.36±1.19 days, respectively), and when it was outside China, this interval was 5.27±1.19 days. DISCUSSION: In the early stage of the COVID-19 epidemic, patients with COVID-19 did not receive timely treatment, resulting in a higher case fatality rate in Hubei province, partly due to the relatively insufficient and unequal medical resources. This research suggested that additional deaths caused by the out-of-control epidemic can be avoided if prevention and control work is carried out at the early stage of the epidemic. TRIAL REGISTRATION: CRD42020195606.

Guidelines on the treatment with integrated traditional Chinese medicine and western medicine for severe coronavirus disease 2019.

Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the "WHO handbook for guideline development", the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT).

[Proposal of Living Evidence-based Guideline for Combination of Traditional Chinese and Western Medicine for Treatment of COVID-19].

In order to standardize the clinical diagnosis and treatment decision-making with traditional Chinese medicine for pa-tients of coronavirus disease 2019(COVID-19) and put the latest clinical study evidence into clinical practice, the international trust-worthy traditional Chinese medicine recommendations( TCM Recs) working group started the compilation of Living Evidence-based Guideline for Combination of Traditional Chinese and Western Medicine for Treatment of COVID-19 on the basis of the standards and re-quirements of WHO handbook, GRADE and RIGHT. This proposal mainly introduces the formulation methods and processes of the living guidelines in details, such as the composition of the working group, the collection and identification of clinical issues and out-comes, the production of the living systematic review and the consensus of recommendations. The guidelines will continue to monitor the clinical study evidences of TCM in the prevention and treatment of COVID-19, and conduct regular evidence updating, retrieval and screening. When there is new study evidence, the steering committee will evaluate the possibility of the evidence to change clinical practice or previous recommendations, so as to decide whether the recommendations for the guidelines shall be implemented or upda-ted. The main criteria considered in the guideline updating are as follows:(1) There are new high-quality randomized controlled trial(RCT) evidences for TCM uninvolved in the previous edition of the guidelines;(2) as for the TCM involved in the guidelines, living sys-tematic review shows that new evidence may change the direction or strength of the existing recommendations. The specific implementation of the living evidence-based guidelines will take this proposal as the study basis and framework, in order to ensure the standardization of the formulation process and methods. This will be the first exploration of the methodology for living guidelines in the field of TCM.

Risk factors for poor prognosis in children and adolescents with COVID-19: A systematic review and meta-analysis.

BACKGROUND: This study provides the first systematic review and meta-analysis to identify the predictors of unfavorable prognosis of COVID-19 in children and adolescents. METHODS: We searched literature databases until July 2021 for studies that investigated risk factors for unfavorable prognosis of children and adolescents with COVID-19. We used random-effects models to estimate the effect size with 95% confidence interval (CI). FINDINGS: We identified 56 studies comprising 79,104 individuals. Mortality was higher in patients with multisystem inflammatory syndrome (MIS-C) (odds ratio [OR]=58.00, 95% CI 6.39-526.79) and who were admitted to intensive care (OR=12.64, 95% CI 3.42-46.68). Acute respiratry distress syndrme (ARDS) (OR=29.54, 95% CI 12.69-68.78) and acute kidney injury (AKI) (OR=55.02, 95% CI 6.26-483.35) increased the odds to be admitted to intensive care; shortness of breath (OR=16.96, 95% CI 7.66-37.51) increased the need of respiratory support; and neurological diseases (OR=5.16, 95% CI 2.30-11.60), C-reactive protein (CRP) level ≥80 mg/L (OR=11.70, 95% CI 4.37-31.37) and D-dimer level ≥0.5ug/mL (OR=20.40, 95% CI 1.76-236.44) increased the odds of progression to severe or critical disease. INTERPRETATION: Congenital heart disease, chronic pulmonary disease, neurological diseases, obesity, MIS-C, shortness of breath, ARDS, AKI, gastrointestinal symptoms, elevated CRP and D-dimer are associated with unfavourable prognosis in children and adolescents with COVID-19.

Integrating Chinese and western medicine for COVID-19: A living evidence-based guideline (version 1).

BACKGROUND: The coronavirus disease 2019 (COVID-19) has turned into a pandemic and resulted in huge death tolls and burdens. Integrating Chinese and western medicine has played an important role in the fight against the COVID-19 pandemic. PURPOSE: We aimed to develop a living evidence-based guideline of integrating Chinese and western medicine for COVID-19. STUDY DESIGN: Living evidence-based guideline. METHODS: This living guideline was developed using internationally recognized and accepted guideline standards, dynamically monitoring the release of new clinical evidence, and quickly updating the linked living systematic review, evidence summary tables, and recommendations. Modified Delphi method was used to reach consensus for all recommendations. The certainty of the evidence, resources, and other factors were fully considered, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the certainty of evidence and the strength of recommendations. RESULTS: The first version of this living guidance focuses on patients who are mild or moderate COVID-19. A multidisciplinary guideline development panel was established. Ten clinical questions were identified based on the status of evidence and a face-to-face experts' consensus. Finally, nine recommendations were reached consensus, and were formulated from systematic reviews of the benefits and harms, certainty of evidence, public accessibility, policy supports, feedback on proposed recommendations from multidisciplinary experts, and consensus meetings. CONCLUSION: This guideline panel made nine recommendations, which covered five traditional Chinese medicine (TCM) prescription granules/decoction (MXXFJD, QFPD, XFBD, TJQW, and JWDY), three Chinese patent medicines (LHQW granules/capsule, JHQG granules, and LHQK granules), and one Chinese herbal injection (XBJ injection). Of them, two were strongly recommended (LHQW granules/capsule and QFPD decoction), and five were weakly recommended (MXXFJD decoction, XFBD decoction, JHQG granules, TJQW granules, and JWDY decoction) for the treatment of mild and moderate COVID-19; two were weakly recommended against (XBJ injection and LHQK granules) the treatment of mild and moderate COVID-19. The users of this living guideline are most likely to be clinicians, patients, governments, ministries, and health administrators.

Safety, Immunogenicity, and Efficacy of COVID-19 Vaccines in Children and Adolescents: A Systematic Review.

AIM: To identify the safety, immunogenicity, and protective efficacy of COVID-19 vaccines in children and adolescents. METHODS: We conducted a systematic review of published studies and ongoing clinical studies related to the safety, immunogenicity, and efficacy of COVID-19 vaccine in children or adolescents (aged < 18 years). Databases including PubMed, Web of Science, WHO COVID-19 database, and China National Knowledge Infrastructure (CNKI) were searched on 23 July 2021. International Clinical Trials Registry Platform (ICTRP) was also searched to identify ongoing studies. RESULTS: Eight published studies with a total of 2852 children and adolescents and 28 ongoing clinical studies were included. Of the eight published studies, two were RCTs, two case series, and four case reports. The investigated COVID-19 vaccines had good safety profiles in children and adolescents. Injection site pain, fatigue, headache, and chest pain were the most common adverse events. A limited number of cases of myocarditis and pericarditis were reported. The RCTs showed that the immune response to BNT162b2 in adolescents aged 12-15 years was non-inferior to that in young people aged 16-25 years, while with 3 µg CoronaVac injection the immune response was stronger than with 1.5 µg. The efficacy of BNT162b2 was 100% (95% CI: 75.3 to 100), based on one RCT. Of the 28 ongoing clinical studies, twenty-three were interventional studies. The interventional studies were being conducted in fifteen countries, among them, China (10, 43.5%) and United States(9, 39.1%) had the highest number of ongoing trials. BNT162b2 was the most commonly studied vaccine in the ongoing trials. CONCLUSION: Two COVID-19 vaccines have potential protective effects in children and adolescents, but awareness is needed to monitor possible adverse effects after injection. Clinical studies of the COVID-19 vaccination in children and adolescents with longer follow-up time, larger sample size, and a greater variety of vaccines are still urgently needed.