Coronavirus Disease 2019(COVID-19) In Children: Acaseseries Study And Development Of Evidence-based Guideline

PART 1COVID-19 IN CHILDREN: ACASE SERIESSTUDY FROM THE WEST OF CHINAObjectives:To investigate the clinical characteristics of children COVID-19 and the positive duration of SARS-Co V-2 nucleic acid test,so as to provide the baseline for management and the rationale of reasonable quarantine period.Methods: We used a multicenter retrospective case series studydesign to collect case history data and follow-up record,from seven COVID-19 designated hospitals in four provinces of western China.Epidemic exposure history,symptoms,laboratory tests,imaging examinations,treatment,and clinical outcomes were extracted.Chart reviewdata were reported by descriptive and exploratory subgroup analyses.Subgroup analysis included different age,gender,clinical symptoms and imaging changes.Results: From January 24,2020 to February 12,2020,a total of 32 confirmed children COVID-19 cases were included,with an average age of 9 years(SD=4.7 years),of which 10(31%)< 6 years,11(34%)aged 6-12 years,and 11(34%)aged 12-18 years.Seventeen cases(53%)were male.The most common symptoms were fever(38%)and cough(57%).Chest CT(Computed Tomography)findings were abnormal in 19 patients(59%): 3(19%)showed bilateral pneumonia,8(25%)showed unilateral pneumonia,and 8(25%)showed multiple mottling and ground glass-glassopacity.Twelve cases(38%)had a history of living or traveling to the epidemic area,and 29 cases(91%)were family cluster cases.Laboratory tests such as blood routine,liver function and inflammatory markers were overwhelmingly within the normal range.All casesreceived antiviral treatment,which interferon(94%)and lopinavir/ritonavir(47%)were most commonly used.There were no significant differences in clinical symptoms and CT results among different age groups(<6,6-12 and 12-18years)and genders(P>0.05).According to clinical symptoms and imaging changes,the cases were divided into "asymptomatic group" and "symptomatic or abnormal CT group".There were 6 cases in the asymptomatic group and 26 cases in the symptomatic or abnormal CT group.White blood cell(WBC)and neutrophil counts were higher in the asymptomatic infection group than in the symptomatic or abnormal CT group.After discharge,all cases recoveredwithout any death or severe case.The mean positiveduration of SARS-Co V-2 nucleic acid test was 15.4 days(SD=7.2 days),and it was close to that of the asymptomatic group and the symptomatic or abnormal CT group,and there was no statistical difference between the two groups (P>0.05).Correlation analysis found a significant negative correlation between lymphocyte count and the positive duration of SARS-Co V-2 nucleic acid testing(R=-0.448,P=0.013).Conclusions: Based on the case series study with small sample size,it was found that the symptoms of children COVID-19 were mild and the prognosis was fine after antiviral treatment and other supportive care.Current evidence supports the quarantine period of asymptomatic cases for the same as those with symptoms.Preliminary data found that lymphocyte count in children COVID-19 cases was negatively correlated with the positive duration of SARS-Co V-2 nucleic acid test,and this result andits mechanism need to be further studied.PART 2HEALTH EDUCATION FOR PARENTS DURING THE OUTBREAK OF COVID-19: A RAPID REVIEWObjectives: 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,and also is a question for our rapid advice guideline for management of children COVID-19(Coronavirus disease 2019).With 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: As a public health emergency,there are few published studies on COVID-19,so we will also include studies published during the epidemics of Severe Acute Respiratory Syndrome(SARS)and Middle East Respiratory Syndrome(MERS).We systematically searched the literature on health education during COVID-19,SARS and MERS epidemics in Medline(via Pub Med),Cochrane Library,EMBASE,Web of Science,CBM(China Biology Medicine disc),CNKI(China National Knowledge Infrastructure),and Wanfang Data from their inception until March 31,2020.After the inclusion of relevant studies,data from literature was extracted,and the studies on the same topic and design were summarized narratively.The potential bias of the studies was assessed by Joanna Briggs Institute Prevalence Critical Appraisal Tool.Theconfidence ofqualitative findingswere evaluated by GRADE-CERQual.Results: Of 1067 papers found,24 cross-sectional studies with a total of 35,967 participants were included in this review.Six anonymous online surveys were conducted on public awareness of COVID-19,and other 18 were published during the SARS and MERS epidemics.All studies were targeted to residents or the general public in epidemic areas,not specifically to parents.Through research topic analysis,we found that the included studies could be summarized into four main themes:(1)The public lack of awareness of infectious diseases.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.(2)The communication mode and reliability of health education.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.(3)The effect of health education.Several studies have shown that health education can improve public awareness and behavior during the outbreak of emerging infectious diseases,and it also helped keep the public optimistic.(4)Health education programs launched after SARS in 2003.Since the SARS epidemic,different international organizations and institutions have initiated at least three health educationprograms to promote public awareness of emerging infectious diseases.Conclusions: Our rapid review provides evidence of the importance and urgency of health education.Boosting health education to improve public health awareness for infectious diseases is urgently needed,especially for some vulnerable groups.Considering that information from the social media may be unreliable,the public including parents should obtain information from the official websites of authorities such as the World Health Organization(WHO)and national Center for Disease Control(CDC),or from other sources endorsed by these authorities,rather than from a general search of the internet or social media.For educating and cultivating children,parents need to educate their children with evidence-based information on COVID-19 and help them practice preventive measures and hygiene behaviors.PART 3 THE DEVELOPMENT OF RAPID ADVICE GUIDELINES FOR MANAGEMENT OF CHILDREN WITH COVID-19Objectives: As the COVID-19 spreadprogressively,an increasing number of children were likely to be affected by the pandemic.Health care providers urgently needed guidelines to managechildren with COVID-19.Therefore,our research team will develop a rapid advice guideline for children COVID-19,whichcould provide evidence-based and practicalrecommendationsinthemost countries.Methods: The guideline will be developed in accordance with the WHO definition for rapid advice guideline.A multidisciplinary and international team will be formed to reach the recommendations in the public health emergency.Recommendations will be supported by evidence based on our rapid reviews conducted.The GARDE(Grading of Recommendations Assessment,Development and Evaluation)methodology will be used for formulating the strength of recommendation and level of evidence.Initial recommendations will be reached consensus using the Delphi voting method.The Guidelines will be reported according to the RIGHT(Reporting Items for Practice Guidelines in Healthcare).Results: Twenty initial clinical questions were raised by the guideline development group,and 10 clinical questions were finally included and to be answered by the guideline.The evidence team developed rapid reviewsthrough systematic searches,and the core experts made initial recommendations based on the rapid reviews.After two rounds of Delphi voting,10 recommendations were formed after fully considering the expert comments,valuing patient preferences,and balancing the costs and benefits of the intervention.(1)For evaluation and diagnosis of children with COVID-19,we believe home observation is an important and appropriate option since most children infected with SARS-Co V-2 are often asymptomatic and present with milder symptoms than adults.(2)CT scan should not be used routinely as an imaging test for diagnosis.(3)Regarding pharmacotherapy,there is no direct clinical evidence for the effectiveness of antiviral drugs,antimicrobial agents,corticosteroids or IVIG in the treatment of children with COVID-19.Considering the potential side effects,resource availability,and patients’ preferences related to these interventions,none of these drugs were recommended,except within the context of a clinical trial.(4)Breastfeeding mothers should continue to breastfeed,if their condition permits,but with appropriate protection.(5)Children should first be screened and their families referred for consultation by telemedicine by telephone or Internet,which can promote the rational use of medical resources and reduce the risk of nosocomial infection.(6)Parents and guardians should obtain reliable health information regularly from official channels and communicate this to their children.Conclusions: This rapid advice guideline improved the management level of children COVID-19 in the context of the public health emergency.Through the development of rapid advice guideline,the experience for response to public health emergency has been accumulated.PART 4 MULTISYSTEM INFLAMMATORY SYNDROME IN CHILDREN DURING THE COVID-19 PANDEMIC: A SYSTEMATIC REVIEW OF PUBLISHED CASE STUDIESObjectives: A large number of cases have been reported recently on multisystem inflammatory syndrome in children(MIS-C),a newly emerged disease that seemed to correlate with coronavirus disease 2019(COVID-19).The aim of this review was to describe the clinical features,treatment and outcomes of MIS-C,as well as to assess the risk of bias of published case studies,analyzing their reporting quality.Methods: We searched all articles reporting on multisystem inflammatory condition in children and adolescents in the context of COVID-19 through MEDLINE(via Pub Med),Web of Science,China Biology Medicine disc(CBM)and China National Knowledge Infrastructure(CNKI)from their inception to June 17,2020.We used IHE and CARE checklists to evaluate the risk of bias and reporting quality of the included studies.We combined the data of clinical manifestations,imaging findings,treatments and outcomes using STATA version 15.Results: Twenty-four studies were included,with a total of 270 participants.Most cases were from Europe and the United States,and the terms of MIS-C in different articles were varied.Fever and gastrointestinal symptoms were the most experienced symptoms.Shock,rash,conjunctivitis,lips or oral cavity changes,hand and feet anomalies,and lymphadenopathywere observed,while respiratory symptoms seemed relatively infrequent.Seventy-eight percent to 100% of patients had evidence of SARS-Co V-2 infection,and patients positive for SARS-Co V-2 by serology [86%(95% CI: 78%,95%)] were more than those by RT-PCR [36%(95% CI: 26%,46%)].Most patients had one or more increased inflammatory markers including C-reactive protein(CRP),procalcitonin(PCT),erythrocyte sedimentation rate(ESR),ferritin,interleukin-6(IL-6),and D-dimer,accompanied by neutrophilia and lymphopenia.Impaired cardiac function was seen from elevated biomarkers and abnormal echocardiography.Intravenous immunoglobulin(IVIG),anticoagulants,inotropic agents and glucocorticoids were the main treatments,along with other intensive supportive care.Overall,the outcomes of MIS-C were favorable,and only one death was recorded.In terms of the quality assessment of included studies,most of the case studies did not follow the standard reporting checklist,so that they failed to get higher scores in the risk of bias assessment.Conclusions: Patients with MIS-C present with symptoms more severe than children with COVID-19,with fever and gastrointestinal symptoms as the primary manifestations and multisystem involvement,particularly cardiovascular system.Longer follow-up and further research for the pathophysiology of MIS-C are urgently needed.In addition,attention should be paid to the quality of case studies to improve the completeness and transparency of scientific reports.