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.

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.

Erratum to rapid advice guidelines for management of children with COVID-19.

[This corrects the article DOI: 10.21037/atm-20-3754.].

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.

Public health education for parents during the outbreak of COVID-19: a rapid review.

BACKGROUND: It is well-known that public health education plays a crucial role in the prevention and control of emerging infectious diseases, but how health providers should advise families and parents to obtain health education information is a challenging question. With coronavirus disease 2019 (COVID-19) spreading around the world, this rapid review aims to answer that question and thus to promote evidence-based decision making in health education policy and practice. METHODS: We systematically searched the literature on health education during COVID-19, severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS) epidemics in Medline (via PubMed), Cochrane Library, EMBASE, Web of Science, China Biology Medicine disc (CBM), China National Knowledge Infrastructure (CNKI), and Wanfang Data from their inception until March 31, 2020. The potential bias of the studies was assessed by Joanna Briggs Institute Prevalence Critical Appraisal Tool. RESULTS: Of 1,067 papers found, 24 cross-sectional studies with a total of 35,967 participants were included in this review. The general public lacked good knowledge of SARS and MERS at the early stage of epidemics. Some people's knowledge, attitude and practice (KAP) of COVID-19 had been improved, but the health behaviors of some special groups including children and their parents need to be strengthened. Negative emotions including fear and stigmatization occurred during the outbreaks. Reliable health information was needed to improve public awareness and mental health for infectious diseases. Health information from nonprofit, government and academic websites was more accurate than privately owned commercial websites and media websites. CONCLUSIONS: For educating and cultivating children, parents should obtain information from the official websites of authorities such as the World Health Organization (WHO) and national Centers for Disease Control, or from other sources endorsed by these authorities, rather than from a general search of the internet or social media.

Efficacy and safety of antibiotic agents in children with COVID-19: a rapid review.

BACKGROUND: The aim of this review was to evaluate the efficacy and safety of antibiotic agents in children with COVID-19, as well as to introduce the present situation of antibiotics use and bacterial coinfections in COVID-19 patients. METHODS: We searched Cochrane library, Medline, Embase, Web of Science, CBM, Wanfang Data and CNKI from their inception to March 31, 2020. In addition, we searched related studies on COVID-19 published before March 31, 2020 through Google Scholar. We evaluated the risk of bias of included studies, and synthesized the results using a qualitative synthesis. RESULTS: Six studies met our inclusion criteria. Five studies on SARS showed an overall risk of death of 7.2% to 20.0%. One study of SARS patients who used macrolides, quinolones or beta lactamases showed that the mean duration of hospital stay was 14.2, 13.8 and 16.2 days, respectively, and their average duration of fever was 14.3, 14.0 and 16.2 days, respectively. One cohort study on MERS indicated that macrolide therapy was not associated with a significant reduction in 90-day mortality (adjusted OR 0.84, 95% CI: 0.47-1.51, P=0.56) and improvement in MERS-CoV RNA clearance (adjusted HR 0.88, 95% CI: 0.47-1.64, P=0.68). According to the findings of 33 studies, the proportion of antibiotics use ranged from 19.4% to 100.0% in children and 13.2% to 100.0% in adults, despite the lack of etiological evidence. The most commonly used antibiotics in adults were quinolones, cephalosporins and macrolides and in children meropenem and linezolid. CONCLUSIONS: The benefits of antibiotic agents for adults with SARS or MERS were questionable in the absence of bacterial coinfections. There is no evidence to support the use of antibiotic agents for children with COVID-19 in the absence of bacterial coinfection.

Clinical characteristics of children with COVID-19: a rapid review and meta-analysis.

BACKGROUND: Most guidelines on COVID-19 published so far include recommendations for patients regardless of age. Clinicians need a more accurate understanding of the clinical characteristics of children with COVID-19. METHODS: We searched studies reporting clinical characteristics in children with COVID-19 published until March 31, 2020. We screened the literature, extracted the data and evaluated the risk of bias and quality of evidence of the included studies. We combined some of the outcomes (symptoms) in a single-arm meta-analysis using a random-effects model. RESULTS: Our search retrieved 49 studies, including 25 case reports, 23 case series and one cohort study, with a total of 1,667 patients. Our meta-analysis showed that most children with COVID-19 have mild symptoms. Eighty-three percent of the children were within family clusters of cases, and 19% had no symptoms. At least 7% with digestive symptoms. The main symptoms of children were fever [48%, 95% confidence interval (CI): 39%, 56%] and cough (39%, 95% CI: 30%, 48%). The lymphocyte count was below normal level in only 15% (95% CI: 8%, 22%) of children which is different from adult patients. 66% (95% CI: 55%, 77%) of children had abnormal findings in CT imaging. CONCLUSIONS: Most children with COVID-19 have only mild symptoms, and many children are asymptomatic. Fever and cough are the most common symptoms in children. Vomiting and diarrhea were not common in children. The lymphocyte count is usually within the normal range in children.