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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.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.• 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.• 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.

BACKGROUND AND AIMS: With an increasing number of Clinical Practice Guidelines (CPGs) addressing primary prevention of food allergy and atopic dermatitis, it is timely to undertake a comprehensive assessment of the quality and consistency of recommendations and evaluation of their implementability in different geographical settings.METHODS: We systematically reviewed CPGs from 8 international databases and extensive website searches. Seven reviewers screened records in any language and then used the AGREE II and AGREE REX instruments to critically appraise CPGs published between January 2011 and April 2022.RESULTS: Our search identified 2138 relevant articles, of which 30 CPGs were eventually included. Eight (27%) CPGs were shortlisted based on our predefined quality criteria of achieving scores >70% in the "Scope and Purpose" and "Rigour of Development" domains of the AGREE II instrument. Among the shortlisted CPGs, scores on the "Applicability" domain were generally low, and only 3 CPGs rated highly in the "Implementability" domain of AGREE-REX, suggesting that the majority of CPGs fared poorly on global applicability. Recommendations on maternal diet and complementary feeding in infants were mostly consistent, but recommendations on use of hydrolysed formula and supplements varied considerably.CONCLUSION: The overall quality of a CPG for Food Allergy and Atopic Dermatitis prevention did not correlate well with its global applicability. It is imperative that CPG developers consider stakeholders' preferences, local applicability, and adapt existing recommendations to each individual population and healthcare system to ensure successful implementation. There is a need for development of high-quality CPGs for allergy prevention outside of North America and Europe.PROSPERO REGISTRATION NUMBER: CRD42021265689.

Despite distinct nasopharyngeal microbiome (NPM) profiles between asthmatics and healthy subjects, little is known about the NPM dynamics and its relation to childhood asthma exacerbation (AE). We investigated NPM changes by longitudinally collecting 135 flocked nasopharyngeal swabs (FNPSs) from 33 school-age asthmatic children at six time points (2 to 4-week intervals) from September to December 2017 in Hong Kong. Subjects were categorized into AE and stable asthma (AS) groups according to whether they experienced any exacerbation during follow-up. One-off FNPSs from nine nonasthmatic children were included as controls. Microbiota profiles were analyzed using 16S rRNA gene sequencing. All 144 NPMs were classified into six microbiome profile groups (MPGs), each dominated by

The exponential spread of COVID‐19 worldwide is evident, with devastating outbreaks primarily in the United States, Spain, Italy, the United Kingdom, France, Germany, Turkey and Russia. As of 1 May 2020, a total of 3,308,386 confirmed cases have been reported worldwide, with an accumulative mortality of 233,093. Due to the complexity and uncertainty of the pathology of COVID‐19, it is not easy for front‐line doctors to categorise severity levels of clinical COVID‐19 that are general and severe/critical cases, with consistency. The more than 300 laboratory features, coupled with underlying disease, all combine to complicate proper and rapid patient diagnosis. However, such screening is necessary for early triage, diagnosis, assignment of appropriate level of care facility, and institution of timely intervention. A machine learning analysis was carried out with confirmed COVID‐19 patient data from 10 January to 18 February 2020, who were admitted to Tongji Hospital, in Wuhan, China. A softmax neural network‐based machine learning model was established to categorise patient severity levels. According to the analysis of 2662 cases using clinical and laboratory data, the present model can be used to reveal the top 30 of more than 300 laboratory features, yielding 86.30% blind test accuracy, 0.8195 F1‐score, and 100% consistency using a two‐way patient classification of severe/critical to general. For severe/critical cases, F1‐score is 0.9081 (i.e. recall is 0.9050, and precision is 0.9113). This model for classification can be accomplished at a mini‐second‐level computational cost (in contrast to minute‐level manual). Based on available COVID‐19 patient diagnosis and therapy, an artificial intelligence model paradigm can help doctors quickly classify patients with a high degree of accuracy and 100% consistency to significantly improve diagnostic and classification efficiency. The discovered top 30 laboratory features can be used for greater differentiation to serve as an essential supplement to current guidelines, thus creating a more comprehensive assessment of COVID‐19 cases during the early stages of infection. Such early differentiation will help the assignment of the appropriate level of care for individual patients.

Microbiome mediates early life immune deviation in asthma development. Recurrent wheeze (RW) in pre-school years is a risk factor for asthma diagnosis in school-age children. Dysbiosis exists in asthmatic airways, while its origin in pre-school years and relationship to RW is not clearly defined. This study investigated metagenomics of nasopharyngeal microbiome in pre-school children with RW. We applied whole-genome shotgun sequencing and human rhinovirus (HRV) detection on nasopharyngeal samples collected from three groups of pre-school children: (i) RW group: 16 children at-risk for asthma who were hospitalized for RW, (ii) inpatient control (IC): 18 subjects admitted for upper respiratory infection, and (iii) community control (CC): 36 children without respiratory syndromes. Sequence reads were analyzed by MetaPhlAn2 and HUMAnN2 algorithm for taxonomic and functional identification. Linear discriminant analysis effect size (LEfSe) analysis was used to identify discriminative features. We identified that Moraxella catarrhalis and Dolosigranulum pigrum were predominant species in nasopharynx. RW had lower alpha diversity (Shannon diversity index) than CC (0.48 vs. 1.07; Padj = 0.039), characterized by predominant Proteobacteria. LEfSe analysis revealed D. pigrum was the only discriminative species across groups (LDA = 5.57, P = 0.002), with its relative abundance in RW, IC, and CC being 9.6, 14.2, and 37.3%, respectively (P < 0.05). LEfSe identified five (ribo)nucleotides biosynthesis pathways to be group discriminating. Adjusting for HRV status, pre-school children with RW have lower nasopharyngeal biodiversity, which is associated with Proteobacteria predominance and lower abundance of D. pigrum. Along with discriminative pathways found in RW and CC, these microbial biomarkers help to understand RW pathogenesis.

A proportion of asthmatic children outgrow their disease by adulthood, but there are limited data on predictors for asthma persistence. This prospective study characterized the trajectory of spirometric indices and identified predictors for the persistence of childhood asthma.Chinese asthmatic children aged 6-15 years from pediatric allergy clinic underwent annual visits for ≥5 years and until their adulthood. Pre-bronchodilator spirometry and anti-asthma medications were recorded at baseline and then at least annually. Asthma resolution was defined when patients were free from asthma symptoms and use of anti-asthma drugs for ≥2 years. Logistic regression was used to identify predictors for asthma persistence. Generalized estimating equation was used to analyze longitudinal changes in lung function parameters in relation to asthma persistence.181 asthmatic children aged [mean (SD)] 10.0 (2.7) years were followed for [mean (SD)] 12.5 (2.8) years. One third of them outgrew asthma during follow-up. Female was 3.36 times more likely to have persistent asthma. Inhaled corticosteroid (ICS) treatment ever and frequent asthma exacerbation (AE) predicted asthma persistence with respective odds ratios of 3.19 (95% confidence interval [CI] 1.44-7.09) and 3.05 (95% CI 1.39-6.68). Persistent asthma was inversely associated with baseline forced expiratory volume in 1-second (FEVFemale, ICS ever, and frequent AE predicted persistent asthma. Patients with persistent asthma had lower forced expiratory indices and poorer lung function growth into adulthood.

In December 2019, an infectious disease, caused by a novel coronavirus, emerged in Wuhan City, China. The disease was later named coronavirus disease 2019 (COVID-19) and the virus causing it was named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The rapid spread of COVID-19 worldwide has brought great challenges to local and global public health security and health systems. On March 12, 2020, the World Health Organization (WHO) declared the coronavirus outbreak a global pandemic and raised the risk of a global SARS-CoV-2 outbreak to “very high” (1-6). COVID-19, and its pathogen SARS-CoV-2, represent a novel infectious disease and all populations are therefore susceptible to infection. Its basic reproductive number R0 has been estimated at 3.3 (range 1.4 to 6.5), which is similar to SARS and much higher than Middle East respiratory syndrome (MERS) or influenza (7-10). By April 15, around two million confirmed cases had been reported over 200 countries worldwide. The exact number of patients under the age of 18 remains unknown, but their percentage among all cases is estimated to be less than 2% (11,12). Evidence indicates that the family cluster is the main source of COVID-19 infection for children (13). In contrast to adults, most infected children are asymptomatic or have only mild clinical manifestations. The existing COVID-19 clinical practice guidelines for public health policies have mostly focused on the prevention, diagnosis and treatment in adults, with little attention paid to children. Few of them are based on evidence from systematic reviews (14). Based on the above considerations, an international multidisciplinary working group developed this rapid advice guideline for management of children with COVID-19 using the methods and process proposed by the WHO and GRADE working group (15-17). We present the following article in accordance with the RIGHT reporting checklist (available at http://dx.doi.org/10.21037/atm-20-3754).

High-frequency action potentials are mediated by voltage-gated sodium channels, composed of one large α subunit and two small β subunits, encoded mainly by SCN1A, SCN2A, SCN3A, SCN1B, and SCN2B genes in the brain. These play a key role in epilepsy, with the most commonly mutated gene in epilepsy being SCN1A. We examined whether polymorphisms in the above genes affect epilepsy risk in 1,529 epilepsy patients and 1,935 controls from four ethnicities or locations: Malay, Indian, and Chinese, all from Malaysia, and Chinese from Hong Kong. Of patients, 19 % were idiopathic, 42 % symptomatic, and 40 % cryptogenic. We genotyped 43 polymorphisms: 27 in Hong Kong, 28 in Malaysia, and 12 in both locations. The strongest association with epilepsy was rs3812718, or SCN1A IVS5N+5GA: odds ratio (OR) = 0.85 for allele G (p = 0.0009) and 0.73 for genotype GG versus AA (p = 0.003). The OR was between 0.76 and 0.87 for all ethnicities. Meta-analysis confirmed the association (OR = 0.81 and p = 0.002 for G, and OR = 0.67 and p = 0.007 for GG versus AA), which appeared particularly strong for Indians and for febrile seizures. Allele G affects splicing and speeds recovery from inactivation. Since SCN1A is preferentially expressed in inhibitory neurons, G may decrease epilepsy risk. SCN1A rs10188577 displayed OR = 1.20 for allele C (p = 0.003); SCN2A rs12467383 had OR = 1.16 for allele A (p = 0.01), and displayed linkage disequilibrium with rs2082366 (r (2) = 0.67), whose genotypes tended toward association with SCN2A brain expression (p = 0.10). SCN1A rs2298771 was associated in Indians (OR = 0.56, p = 0.005) and SCN2B rs602594 with idiopathic epilepsy (OR = 0.62, p = 0.002). Therefore, sodium channel polymorphisms are associated with epilepsy.

Infectious disease used to be the most common cause of morbidity and mortality in the past. With improvement of hygiene and vaccination as well as other infection control measures, non-communicable diseases have taken over as the major causes of morbidity and mortality in most developed countries. Many of these non-communicable diseases are also increasing rapidly in developed and developing countries in Asia [1-3]. Among them, allergic diseases are the most common chronic diseases especially affecting the young population and children. Asia-Pacific is one of the most densely populated regions of the world and the population within the region is relatively younger as compared to countries in North America and Western Europe. Allergic diseases are known to be more common in highly developed countries where up to half of the population may suffer from one or more allergic conditions [4, 5]. The region is unique that there are highly developed regions such as Korea, Japan, Australia, and Singapore while other places are in different degrees of economic development. However, research on allergic diseases is rather limited in many of these places as it has been perceived to be uncommon in some of these places. Community surveys also revealed that conditions like asthma and allergic rhinitis are sub-optimally controlled in a large majority of patients [6]. We must ask ourselves why allergic diseases are uncommon in some of these places and why the levels of control of sufferers of allergic diseases are rather poor across Asia. Environmental pollution, including indoor and outdoor pollution, is a major problem in many places in Asia associated with the rapid urbanization as people are moving away from their rural environment to move into the cities and the ever increasing number of motor vehicles in many Asian cities [7]. Indoor environmental population related to biomass combustion may be an important modifiable factor associated with allergic airway diseases in the developing regions across Asia Pacific [8]. Not surprising, prevalence rates of asthma and allergies are increasing rapidly as documented by several recent studies in the region [4, 9]. There is little doubt that changing environmental conditions are some of the most important reasons explaining the high prevalence of allergies in the developed world. The spectrum of food allergies is also very different within Asia when compared to what has been described in the Western literature. For example, peanut allergy is very uncommon in many Asian countries despite being widely consumed by many population groups in the region [10]. Due to the diversity of genetic background of the people and the varied environmental exposure in different parts of the Asia-Pacific, this region should be able to provide plenty of opportunities to determine the genetic and environmental causes of different allergic conditions. Furthermore, many of the research findings from Europe and North America may not be directly applicable to the populations in Asia as demonstrated by genetic studies of allergic diseases. There are certainly many talents in the research arena within the field of allergy in the region as illustrated by many original studies and reviews published in this issue of Asia Pacific Allergy. Their research spans from genetics, basic mechanisms, clinical and experimental treatment to epidemiology studies. Large consortium-based research along with better funding opportunities similar to those of NIH in the US or European Commission will be needed to solve some of the many puzzles of allergic diseases in the Asia-Pacific region.