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).

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.

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.

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.

Mortality and Clinical Interventions in Critically ill Patient With Coronavirus Disease 2019: A Systematic Review and Meta-Analysis.

Objective: The aims of this systematic review and meta-analysis were to summarize the current existing evidence on the outcome of critically ill patients with COVID-19 as well as to evaluate the effectiveness of clinical interventions. Data Sources: We searched MEDLINE, the Cochrane library, Web of Science, the China Biology Medicine disc, China National Knowledge Infrastructure, and Wanfang Data from their inception to May 15, 2021. The search strings consisted of various search terms related to the concepts of mortality of critically ill patients and clinical interventions. Study Selection: After eliminating duplicates, two reviewers independently screened all titles and abstracts first, and then the full texts of potentially relevant articles were reviewed to identify cohort studies and case series that focus on the mortality of critically ill patients and clinical interventions. Main Outcomes and Measures: The primary outcome was the mortality of critically ill patients with COVID-19. The secondary outcomes included all sorts of supportive care. Results: There were 27 cohort studies and six case series involving 42,219 participants that met our inclusion criteria. All-cause mortality in the intensive care unit (ICU) was 35% and mortality in hospital was 32% in critically ill patients with COVID-19 for the year 2020, with very high between-study heterogeneity (I 2 = 97%; p < 0.01). In a subgroup analysis, the mortality during ICU hospitalization in China was 39%, in Asia-except for China-it was 48%, in Europe it was 34%, in America it was 15%, and in the Middle East it was 39%. Non-surviving patients who had an older age [-8.10, 95% CI (-9.31 to -6.90)], a higher APACHE II score [-4.90, 95% CI (-6.54 to -3.27)], a higher SOFA score [-2.27, 95% CI (-2.95 to -1.59)], and a lower PaO2/FiO2 ratio [34.77, 95% CI (14.68 to 54.85)] than those who survived. Among clinical interventions, invasive mechanical ventilation [risk ratio (RR) 0.49, 95% CI (0.39-0.61)], kidney replacement therapy [RR 0.34, 95% CI (0.26-0.43)], and vasopressor [RR 0.54, 95% CI (0.34-0.88)] were used more in surviving patients. Conclusions: Mortality was high in critically ill patients with COVID-19 based on low-quality evidence and regional difference that existed. The early identification of critical characteristics and the use of support care help to indicate the outcome of critically ill patients.

A Comparison of Lung Ultrasound and Computed Tomography in the Diagnosis of Patients with COVID-19: A Systematic Review and Meta-Analysis.

Background Lung ultrasound (LUS) and computed tomography (CT) can both be used for diagnosis of interstitial pneumonia caused by coronavirus disease 2019 (COVID-19), but the agreement between LUS and CT is unknown. Purpose to compare the agreement of LUS and CT in the diagnosis of interstitial pneumonia caused by COVID-19. Materials and Methods We searched PubMed, Cochrane library, Embase, Chinese Biomedicine Literature, and WHO COVID-19 databases to identify studies that compared LUS with CT in the diagnosis of interstitial pneumonia caused by COVID-19. We calculated the pooled overall, positive and negative percent agreements, diagnostic odds ratio (DOR) and the area under the standard receiver operating curve (SROC) for LUS in the diagnosis of COVID-19 compared with CT. Results We identified 1896 records, of which nine studies involving 531 patients were finally included. The pooled overall, positive and negative percentage agreements of LUS for the diagnosis of interstitial pneumonia caused by COVID-19 compared with CT were 81% (95% confidence interval [CI] 43-99%), 96% (95% CI, 80-99%, I2 = 92.15%) and 80% (95%CI, 60-92%, I2 = 92.85%), respectively. DOR was 37.41 (95% CI, 9.43-148.49, I2 = 63.9%), and the area under the SROC curve was 0.94 (95% CI, 0.92-0.96). The quality of evidence for both specificity and sensitivity was low because of heterogeneity and risk of bias. Conclusion The level of diagnostic agreement between LUS and CT in the diagnosis of interstitial pneumonia caused by COVID-19 is high. LUS can be therefore considered as an equally accurate alternative for CT in situations where molecular tests are not available.

Consistency of recommendations and methodological quality of guidelines for the diagnosis and treatment of COVID-19.

OBJECTIVE: Since the beginning of the COVID-19 epidemic, a large number of guidelines on diagnosis and treatment of COVID-19 have been developed, but the quality of those guidelines and the consistency of recommendations are unclear. The objective of this study is to evaluate the quality of the diagnosis and treatment guidelines on COVID-19 and analyze the consistency of the recommendations of these guidelines. METHODS: We searched for guidelines on diagnosis and/or treatment of COVID-19 through PubMed, CBM, CNKI, and WanFang Data, from January 1, 2020 to August 31, 2020. In addition, we also searched official websites of the US CDC, European CDC and WHO, and some guideline collection databases. We included diagnosis and/or treatment guidelines for COVID-19, including rapid advice guidelines and interim guidelines. Two trained researchers independently extracted data and four trained researchers evaluated the quality of the guidelines using the AGREE II instruments. We extracted information on the basic characteristics of the guidelines, guideline development process, and the recommendations. We described the consistency of the direction of recommendations for treatment and diagnosis of COVID-19 across the included guidelines. RESULTS: A total of 37 guidelines were included. Most included guidelines were assessed as low quality, with only one of the six domains of AGREE II (clarity of presentation) having a mean score above 50%. The mean scores of three domains (stakeholder involvement, the rigor of development and applicability) were all below 30%. The recommendations on diagnosis and treatment were to some extent consistent between the included guidelines. Computed tomography (CT), X-rays, lung ultrasound, RT-PCR, and routine blood tests were the most commonly recommended methods for COVID-19 diagnosis. Thirty guidelines were on the treatment of COVID-19. The recommended forms of treatment included supportive care, antiviral therapy, glucocorticoid therapy, antibiotics, immunoglobulin, extracorporeal membrane oxygenation (ECMO), convalescent plasma, and psychotherapy. CONCLUSIONS: The methodological quality of currently available diagnosis and treatment guidelines for COVID-19 is low. The diagnosis and treatment recommendations between the included guidelines are highly consistent. The main diagnostic methods for COVID-19 are RT-PCR and CT, with ultrasound as a potential diagnostic tool. As there is no effective treatment against COVID-19 yet, supportive therapy is at the moment the most important treatment option.

Traditional Chinese Medicine guidelines for coronavirus disease 2019.

OBJECTIVE: To summarize the evidence from Traditional Chinese Medicine (TCM) practice in the treatment of coronavirus disease 2019 (COVID-19) and provide timely clinical practice guidance. METHODS: The guidelines were developed in accordance with the World Health Organization rapid guideline process. The evidence on TCM for COVID-19 from published guidelines, direct and indirect published clinical evidence, first hand clinical data, and expert experience and consensus were collected. The grading of recommendations assessment, development and evaluation (GRADE) method was used to grade the evidence and make the recommendations. RESULTS: Based on the available evidence, the guidelines recommended 17 Chinese medicines for COVID-19: 2 Chinese herbal granules, 7 Chinese patent medicines, and 8 Chinese herbal injections. CONCLUSION: As the literature search was conducted on March, any subsequent versions of these guidelines require an up-to-date literature review. We hope that the evidence summary in these will be helpful in global efforts to address COVID-19.

Development of Rapid Advice Guidelines for the Treatment of Coronavirus Disease 2019 with Traditional Chinese Medicine.

The worldwide spread of the 2019 novel coronavirus has become a profound threat to human health. As the use of medication without established effectiveness may result in adverse health consequences, the development of evidence-based guidelines is of critical importance for the clinical management of coronavirus disease (COVID-19). This research presents methods used to develop rapid advice guidelines on treating COVID-19 with traditional Chinese medicine (TCM). We have followed the basic approach for developing WHO rapid guidelines, including preparing, developing, disseminating and updating each process. Compared with general guidelines, this rapid advice guideline is unique in formulating the body of evidence, as the available evidence for the treatment of COVID-19 with TCM is from either indirect or observational studies, clinical first-hand data together with expert experience in patients with COVID-19. Therefore, our search of evidence not only focuses on clinical studies of treating COVID-19 with TCM but also of similar diseases, such as pneumonia and influenza. Grading of recommendations assessment, development and evaluation (GRADE) methodology was adopted to rate the quality of evidence and distinguish the strength of recommendations. The overall certainty of the evidence is graded as either high, moderate, low or very low, and to give either "strong" or "weak" recommendations of each TCM therapy. The output of this paper will produce the guideline on TCM for COVID-19 and will also provide some ideas for evidence collection and synthesis in the future development of rapid guidelines for COVID-19 in TCM as well as other areas.

The add-on effect of Chinese herbal medicine on COVID-19: A systematic review and meta-analysis.

BACKGROUND: Chinese herbal medicine (CHM) is thought to be a potential intervention in the treatment of coronavirus disease (COVID-19). PURPOSE: This study aimed to investigate the efficacy and safety of CHM or CHM combination therapy for COVID-19. STUDY DESIGN: Systematic review and meta-analysis METHODS: We searched for relevant studies in the CNKI, CBM, Wanfang Data, PubMed, Cochrane Library, Embase, and other resources from their inception to April 15, 2020. Randomized controlled trials, cohort studies, and case-control studies on CHM or CHM combination therapy for COVID-19 were included. Meta-analysis was performed according to the Cochrane Handbook. RESULTS: Overall, 19 studies with 1474 patients were included. Meta-analysis showed that the overall clinical effectiveness (OR = 2.67, 95% CI 1.83-3.89, I2 = 0%), improvement in the CT scan (OR = 2.43, 95% CI 1.80-3.29, I2 = 0%), percentage of cases turning to severe/critical (OR = 0.40, 95% CI 0.24-0.67, I2 = 17.1%), reverse transcription-polymerase chain reaction (RT-PCR) negativity rate (OR = 2.55, 95% CI 1.06-6.17, I2 = 56.4%) and disappearance rate of symptoms (fever, cough, and fatigue) were superior by combined CHM treatment of COVID-19. However, there was no statistical difference between the two groups in terms of length of hospital stay (WMD = -0.46, 95% CI -3.87 - 2.95, I2 = 99.5%), and rate of adverse effects (OR = 1.21, 95% CI 0.48-3.07, I2 = 43.5%). The quality of evidence was very low to low. CONCLUSION: The combined treatment of COVID-19 with Chinese and Western medicine may be effective in controlling symptoms and reducing the rate of disease progression due to low quality evidence.

Supportive care for patient with respiratory diseases: an umbrella review.

BACKGROUND: Supportive treatment is an important and effective part of the management for patients with life-threatening diseases. This study aims to identify and evaluate the forms of supportive care for patients with respiratory diseases. METHODS: An umbrella review of supportive care for patient with respiratory diseases was undertaken. We comprehensively searched the following databases: Medline, EMBASE, Web of Science, CNKI (China National Knowledge Infrastructure), Wanfang Data and CBM (SinoMed) from their inception to 31 March 2020, and other sources to identify systematic reviews and meta-analyses related to supportive treatments for patient with respiratory diseases including Coronavirus Disease 2019 (COVID-19), severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and influenza. We assessed the methodological quality using the AMSTAR score and the quality of the evidence for the primary outcomes of each included systematic review and meta-analysis. RESULTS: We included 18 systematic reviews and meta-analyses in this study. Most studies focused on the respiratory and circulatory support. Ten studies were of high methodological quality, five studies of medium quality, and three studies of low quality. According to four studies extracorporeal membrane oxygenation did not reduce mortality in adults [odds ratio/relative risk (OR/RR) ranging from 0.71 to 1.28], but two studies reported significantly lower mortality in patients receiving venovenous extracorporeal membrane oxygenation than in the control group (OR/RR ranging from 0.38 to 0.73). Besides, monitoring of vital signs and increasing the number of medical staff may also reduce the mortality in patients with respiratory diseases. CONCLUSIONS: Our overview suggests that supportive care may reduce the mortality of patients with respiratory diseases to some extent. However, the quality of evidence for the primary outcomes in the included studies was low to moderate. Further systematic reviews and meta-analyses are needed to address the evidence gap regarding the supportive care for SARS, MERS and COVID-19.

Effectiveness and safety of glucocorticoids to treat COVID-19: a rapid review and meta-analysis.

BACKGROUND: Glucocorticoids are widely used in the treatment of various pulmonary inflammatory diseases, but they are also often accompanied by significant adverse reactions. Published guidelines point out that low dose and short duration systemic glucocorticoid therapy may be considered for patients with rapidly progressing coronavirus disease 2019 (COVID-19) while the evidence is still limited. METHODS: We comprehensively searched electronic databases and supplemented the screening by conducting a manual search. We included randomized controlled trials (RCTs) and cohort studies evaluating the effectiveness and safety of glucocorticoids in children and adults with COVID-19, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and conducted meta-analyses of the main indicators that were identified in the studies. RESULTS: Our search retrieved 23 studies, including one RCT and 22 cohort studies, with a total of 13,815 patients. In adults with COVID-19, the use of systemic glucocorticoid did not reduce mortality [risk ratio (RR) =2.00, 95% confidence interval (CI): 0.69 to 5.75, I2=90.9%] or the duration of lung inflammation [weighted mean difference (WMD) =-1 days, 95% CI: -2.91 to 0.91], while a significant reduction was found in the duration of fever (WMD =-3.23 days, 95% CI: -3.56 to -2.90). In patients with SARS, glucocorticoids also did not reduce the mortality (RR =1.52, 95% CI: 0.89 to 2.60, I2=84.6%), duration of fever (WMD =0.82 days, 95% CI: -2.88 to 4.52, I2=97.9%) or duration of lung inflammation absorption (WMD =0.95 days, 95% CI: -7.57 to 9.48, I2=94.6%). The use of systemic glucocorticoid therapy prolonged the duration of hospital stay in all patients (COVID-19, SARS and MERS). CONCLUSIONS: Glucocorticoid therapy was found to reduce the duration of fever, but not mortality, duration of hospitalization or lung inflammation absorption. Long-term use of high-dose glucocorticoids increased the risk of adverse reactions such as coinfections, so routine use of systemic glucocorticoids for patients with COVID-19 cannot be recommend.

Chest computed tomography for the diagnosis of patients with coronavirus disease 2019 (COVID-19): a rapid review and meta-analysis.

BACKGROUND: The outbreak of the coronavirus disease 2019 (COVID-19) has had a massive impact on the whole world. Computed tomography (CT) has been widely used in the diagnosis of this novel pneumonia. This study aims to understand the role of CT for the diagnosis and the main imaging manifestations of patients with COVID-19. METHODS: We conducted a rapid review and meta-analysis on studies about the use of chest CT for the diagnosis of COVID-19. We comprehensively searched databases and preprint servers on chest CT for patients with COVID-19 between 1 January 2020 and 31 March 2020. The primary outcome was the sensitivity of chest CT imaging. We also conducted subgroup analyses and evaluated the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: A total of 103 studies with 5,673 patients were included. Using reverse transcription polymerase chain reaction (RT-PCR) results as reference, a meta-analysis based on 64 studies estimated the sensitivity of chest CT imaging in COVID-19 was 99% (95% CI, 0.97-1.00). If case reports were excluded, the sensitivity in case series was 96% (95% CI, 0.93-0.99). The sensitivity of CT scan in confirmed patients under 18 years old was only 66% (95% CI, 0.15-1.00). The most common imaging manifestation was ground-glass opacities (GGO) which was found in 75% (95% CI, 0.68-0.82) of the patients. The pooled probability of bilateral involvement was 84% (95% CI, 0.81-0.88). The most commonly involved lobes were the right lower lobe (84%, 95% CI, 0.78-0.90) and left lower lobe (81%, 95% CI, 0.74-0.87). The quality of evidence was low across all outcomes. CONCLUSIONS: In conclusion, this meta-analysis indicated that chest CT scan had a high sensitivity in diagnosis of patients with COVID-19. Therefore, CT can potentially be used to assist in the diagnosis of COVID-19.

Potential effectiveness and safety of antiviral agents in children with coronavirus disease 2019: a rapid review and meta-analysis.

BACKGROUND: The COVID-19 outbreak presents a new, life-threatening disease. Our aim was to assess the potential effectiveness and safety of antiviral agents for COVID-19 in children. METHODS: Electronic databases (MEDLINE, Embase, Web of Science, the Cochrane library, CBM, CNKI, and Wanfang Data) from their inception to March 31, 2020 were searched for randomized controlled trials (RCTs), clinical controlled trials and cohort studies of interventions with antiviral agents for children (less than 18 years of age) with COVID-19. RESULTS: A total of 23 studies with 6,008 patients were included. There was no direct evidence and all of evidence were indirect. The risks of bias in all studies were moderate to high in general. The effectiveness and safety of antiviral agents for children with COVID-19 is uncertain: For adults with COVID-19, lopinavir/ritonavir had no effect on mortality [risk ratio (RR) =0.77; 95% confidence interval (CI), 0.45 to 1.30]. Arbidol and hydroxychloroquine (HCQ) had no benefit on probability of negative PCR test (RR =1.27; 95% CI, 0.93 to 1.73; RR =0.93; 95% CI, 0.73 to 1.18) respectively. For adults with SARS, interferon was associated with reduced corticosteroid dose [weighted mean difference (WMD) = -0.14 g; 95% CI, -0.21 to -0.07] but had no effect on mortality (RR =0.72; 95% CI, 0.28 to 1.88); ribavirin did not reduce mortality (RR =0.68; 95% CI, 0.43 to 1.06) and was associated with high risk of severe adverse reactions; and oseltamivir had no effect on mortality (RR =0.87; 95% CI, 0.55 to 1.38). Ribavirin combined with interferon was also not effective in adults with MERS and associated with adverse reactions. CONCLUSIONS: There is no evidence showing the effectiveness of antiviral agents for children with COVID-19, and the clinical efficacy of existing antiviral agents is still uncertain. We do not suggest clinical routine use of antivirals for COVID-19 in children, with the exception of clinical trials.

Breastfeeding of infants born to mothers with COVID-19: a rapid review.

BACKGROUND: Existing recommendations on whether mothers with COVID-19 should continue breastfeeding are still conflicting. We aimed to conduct a rapid review of mother-to-child transmission of COVID-19 during breastfeeding. METHODS: We systematically searched Medline, Embase, Web of Science, Cochrane Library, China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang, and preprint articles up to March 2020. We included studies relevant to transmission through milk and respiratory droplets during breastfeeding of mothers with COVID-19, SARS, MERS and influenza. Two reviewers independently screened studies for eligibility, extracted data, assessed risk of bias and used GRADE to assess certainty of evidence. RESULTS: A total of 4,481 records were identified in our literature search. Six studies (five case reports and one case series) involving 58 mothers (16 mothers with COVID-19, 42 mothers with influenza) and their infants proved eligible. Five case reports showed that the viral nucleic acid tests for all thirteen collected samples of breast milk from mothers with COVID-19 were negative. A case series of 42 influenza infected postpartum mothers taking precautions (hand hygiene and wearing masks) before breastfeeding showed that no neonates were infected with influenza during one-month of follow-up. CONCLUSIONS: The current evidence indicates that SARS-CoV-2 viral nucleic acid has not been detected in breast milk. The benefits of breastfeeding may outweigh the risk of SARS-CoV-2 infection in infants. Mothers with COVID-19 should take appropriate precautions to reduce the risk of transmission via droplets and close contact during breastfeeding.

Effectiveness of intravenous immunoglobulin for children with severe COVID-19: a rapid review.

BACKGROUND: Intravenous immunoglobulin (IVIG) is usually used as supportive therapy, but the treatment of COVID-19 by IVIG is controversial. This rapid review aims to explore the clinical effectiveness and safety of IVIG in the treatment of children with severe COVID-19. METHODS: We systematically searched the literature on the use of IVIG in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), including both adults and children. We assessed the risk of bias and quality of evidence and reported the main findings descriptively. RESULTS: A total of 1,519 articles were identified by initial literature search, and finally six studies met our inclusion criteria, included one randomized controlled trial (RCT), four case series and one case report involving 198 patients. One case series showed the survival of COVID-19 patients with acute respiratory distress syndrome (ARDS) was not improved by IVIG. One case report showed high-dose IVIG could improve the outcome of COVID-19 adults. Three observational studies showed inconsistent results of the effect of IVIG on SARS patients. One RCT showed that IVIG did not reduce mortality or the incidence of nosocomial infection in adults with severe SARS. The quality of evidence was between low and very low. CONCLUSIONS: The existing evidence is insufficient to support the efficacy or safety of IVIG in the treatment of COVID-19.

Nosocomial infections among patients with COVID-19, SARS and MERS: a rapid review and meta-analysis.

BACKGROUND: COVID-19, a disease caused by SARS-CoV-2 coronavirus, has now spread to most countries and regions of the world. As patients potentially infected by SARS-CoV-2 need to visit hospitals, the incidence of nosocomial infection can be expected to be high. Therefore, a comprehensive and objective understanding of nosocomial infection is needed to guide the prevention and control of the epidemic. METHODS: We searched major international and Chinese databases: Medicine, Web of Science, Embase, Cochrane, CBM (China Biology Medicine disc), CNKI (China National Knowledge Infrastructure) and Wanfang database for case series or case reports on nosocomial infections of COVID-19, SARS (severe acute respiratory syndromes) and MERS (Middle East respiratory syndrome) from their inception to March 31st, 2020. We conducted a meta-analysis of the proportion of nosocomial infection patients in the diagnosed patients, occupational distribution of nosocomial infection medical staff. RESULTS: We included 40 studies. Among the confirmed patients, the proportions of nosocomial infections with early outbreaks of COVID-19, SARS, and MERS were 44.0%, 36.0%, and 56.0%, respectively. Of the confirmed patients, the medical staff and other hospital-acquired infections accounted for 33.0% and 2.0% of COVID-19 cases, 37.0% and 24.0% of SARS cases, and 19.0% and 36.0% of MERS cases, respectively. Nurses and doctors were the most affected among the infected medical staff. The mean numbers of secondary cases caused by one index patient were 29.3 and 6.3 for SARS and MERS, respectively. CONCLUSIONS: The proportion of nosocomial infection in patients with COVID-19 was 44% in the early outbreak. Patients attending hospitals should take personal protection. Medical staff should be awareness of the disease to protect themselves and the patients.

Application of telemedicine during the coronavirus disease epidemics: a rapid review and meta-analysis.

BACKGROUND: As COVID-19 has become a global pandemic, early prevention and control of the epidemic is extremely important. Telemedicine, which includes medical advice given over telephone, Internet, mobile phone applications or other similar ways, may be an efficient way to reduce transmission and pressure on medical institutions. METHODS: We searched MEDLINE, Web of Science, Embase, Cochrane, CBM, CNKI and Wanfang databases for literature on the use of telemedicine for COVID-19, SARS and MERS from their inception to March 31st, 2020. We included studies about the content of the consultation (such as symptoms, therapy and prevention, policy, public service), screening of suspected cases, the provision of advice given to those people who may have symptoms or contact history. We conducted meta-analyses on the main outcomes of the studies. RESULTS: A total of 2,041 articles were identified after removing duplicates. After reading the full texts, we finally included nine studies. People were most concerned about symptoms (64.2%), epidemic situation and public problems (14.5%), and psychological problems (10.3%) during COVID-19 epidemic. During the SARS epidemic, the proportions of people asking for consultation for symptoms, prevention and therapy, and psychological problems were 35.0%, 22.0%, and 23.0%, respectively. Two studies demonstrated that telemedicine can be used to screen the suspected patients and give advice. One study emphasized the limited possibilities to follow up people calling hotlines and difficulties in identifying all suspect cases. CONCLUSIONS: Telemedicine services should focus on the issues that the public is most concerned about, such as the symptoms, prevention and treatment of the disease, and provide reasonable advice to patients with symptoms or people with epidemic history.