query: what are the health outcomes for children who contract COVID-19?

positive: Coronavirus Disease (COVID-19) in Children - What We Know So Far and What We Do Not? Pediatric coronavirus disease - 19 (COVID-19) infection is relatively mild when compared to adults, and children are reported to have a better prognosis Mortality in children appears rare Clinical features of COVID-19 in children include fever and cough, but a large proportion of infected children appears to be asymptomatic and may contribute to transmission It remains unclear why children and young adults are less severely affected than older individuals, but this might involve differences in immune system function in the elderly and/or differences in the expression/function of the cellular receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) - Angiotensin converting enzyme 2 (ACE2) Laboratory findings and chest imaging may not be specific in children with COVID-19 Diagnosis is by Reverse transcriptase-Polymerase chain reaction (RT-PCR) testing of upper or lower respiratory tract secretions This review additionally considers COVID-19 in immunosuppressed children, and also suggests a management algorithm for the few children who appear to present with life threatening infection, including the potential use of antiviral and immunomodulatory treatment The most significant threat to global child health from SARS-CoV-2 is unlikely to be related to COVID 19 in children, but rather the socio-economic consequences of a prolonged pandemic

positive: The dual impact of ACE2 in COVID-19 and ironical actions in geriatrics and pediatrics with possible therapeutic solutions The novel corona virus disease has shaken the entire world with its deadly effects and rapid transmission rates, posing a significant challenge to the healthcare authorities to develop suitable therapeutic solution to save lives on earth. The review aims to grab the attention of the researchers all over the globe, towards the role of ACE2 in COVID-19 disease. ACE2 serves as a molecular target for the SARS-CoV-2, to enter the target cell, by interacting with the viral glycoprotein spikes. However, the complexity began when numerous studies identified the protective response of ACE2 in abbreviating the harmful effects of vasoconstrictor, anti-inflammatory peptide, angiotensin 2, by mediating its conversion to angiotensin-(1–7), which exercised antagonistic actions to angiotensin 2. Furthermore, certain investigations revealed greater resistance among children as compared to the geriatrics, towards COVID-19 infection, despite the elevated expression of ACE2 in pediatric population. Based upon such evidences, the review demonstrated possible therapeutic interventions, targeting both the protective and deleterious effects of ACE2 in COVID-19 disease, primarily inhibiting ACE2-virus interactions or administering soluble ACE2. Thus, the authors aim to provide an opportunity for the researchers to consider RAAS system to be a significant element in development of suitable treatment regime for COVID-19 pandemic.

positive: Observational Research in Childhood Infectious Diseases (ORChID): a dynamic birth cohort study INTRODUCTION: Even in developed economies infectious diseases remain the most common cause of illness in early childhood. Our current understanding of the epidemiology of these infections is limited by reliance on data from decades ago performed using low-sensitivity laboratory methods, and recent studies reporting severe, hospital-managed disease. METHODS AND ANALYSIS: The Observational Research in Childhood Infectious Diseases (ORChID) study is an ongoing study enrolling a dynamic birth cohort to document the community-based epidemiology of viral respiratory and gastrointestinal infections in early childhood. Women are recruited antenatally, and their healthy newborn is followed for the first 2 years of life. Parents keep a daily symptom diary for the study child, collect a weekly anterior nose swab and dirty nappy swab and complete a burden diary when a child meets pre-defined illness criteria. Specimens will be tested for a wide range of viruses by real-time PCR assays. Primary analyses involves calculating incidence rates for acute respiratory illness (ARI) and acute gastroenteritis (AGE) for the cohort by age and seasonality. Control material from children when they are without symptoms will allow us to determine what proportion of ARIs and AGE can be attributed to specific pathogens. Secondary analyses will assess the incidence and shedding duration of specific respiratory and gastrointestinal pathogens. ETHICS AND DISSEMINATION: This study is approved by The Human Research Ethics Committees of the Children's Health Queensland Hospital and Health Service, the Royal Brisbane and Women's Hospital and The University of Queensland. TRIAL REGISTRATION: clinicaltrials.gov NCT01304914.

positive: Clinical and CT features in pediatric patients with COVID-19 infection: Different points from adults PURPOSE: To discuss the different characteristics of clinical, laboratory, and chest computed tomography (CT) in pediatric patients from adults with 2019 novel coronavirus (COVID-19) infection. METHODS: The clinical, laboratory, and chest CT features of 20 pediatric inpatients with COVID-19 infection confirmed by pharyngeal swab COVID-19 nucleic acid test were retrospectively analyzed during 23 January and 8 February 2020. The clinical and laboratory information was obtained from inpatient records. All the patients were undergone chest CT in our hospital. RESULTS: Thirteen pediatric patients (13/20, 65%) had an identified history of close contact with COVID-19 diagnosed family members. Fever (12/20, 60%) and cough (13/20, 65%) were the most common symptoms. For laboratory findings, procalcitonin elevation (16/20, 80%) should be pay attention to, which is not common in adults. Coinfection (8/20, 40%) is common in pediatric patients. A total of 6 patients presented with unilateral pulmonary lesions (6/20, 30%), 10 with bilateral pulmonary lesions (10/20, 50%), and 4 cases showed no abnormality on chest CT (4/20, 20%). Consolidation with surrounding halo sign was observed in 10 patients (10/20, 50%), ground-glass opacities were observed in 12 patients (12/20, 60%), fine mesh shadow was observed in 4 patients (4/20, 20%), and tiny nodules were observed in 3 patients (3/20, 15%). CONCLUSION: Procalcitonin elevation and consolidation with surrounding halo signs were common in pediatric patients which were different from adults. It is suggested that underlying coinfection may be more common in pediatrics, and the consolidation with surrounding halo sign which is considered as a typical sign in pediatric patients.

positive: Clinical features of pediatric patients with COVID-19: a report of two family cluster cases BACKGROUND: Coronovirus disease 2019 (COVID-19) has spread rapidly across the globe. People of all ages are susceptible to COVID-19. However, literature reports on pediatric patients are limited. METHODS: To improve the recognition of COVID-19 infection in children, we retrospectively reviewed two confirmed pediatric cases from two family clusters. Both clinical features and laboratory examination results of the children and their family members were described. RESULTS: The two confirmed children only presented with mild respiratory or gastrointestinal symptoms. Both of them had normal chest CT images. After general and symptomatic treatments, both children recovered quickly. Both families had travel histories to Hubei Province. CONCLUSIONS: Pediatric patients with COVID-19 are mostly owing to family cluster or with a close contact history. Infected children have relatively milder clinical symptoms than infected adults. We should attach importance to early recognition, early diagnosis, and early treatment of infected children.

positive: Recommendations for treatment of childhood non-severe pneumonia WHO recommendations for early antimicrobial treatment of childhood pneumonia have been effective in reducing childhood mortality, but the last major revision was over 10 years ago. The emergence of antimicrobial resistance, new pneumonia pathogens, and new drugs have prompted WHO to assemble an international panel to review the literature on childhood pneumonia and to develop evidence-based recommendations for the empirical treatment of non-severe pneumonia among children managed by first-level health providers. Treatment should target the bacterial causes most likely to lead to severe disease, including Streptoccocus pneumoniae and Haemophilus influenzae. The best first-line agent is amoxicillin, given twice daily for 3–5 days, although co-trimoxazole may be an alternative in some settings. Treatment failure should be defined in a child who develops signs warranting immediate referral or who does not have a decrease in respiratory rate after 48–72 h of therapy. If failure occurs, and no indication for immediate referral exists, possible explanations for failure should be systematically determined, including non-adherence to therapy and alternative diagnoses. If failure of the first-line agent remains a possible explanation, suitable second-line agents include high-dose amoxicillin–clavulanic acid with or without an affordable macrolide for children over 3 years of age.

positive: Clinical Characteristics and Outcomes of Hospitalized and Critically Ill Children and Adolescents with Coronavirus Disease 2019 (COVID-19) at a Tertiary Care Medical Center in New York City OBJECTIVE: To describe the clinical profiles and risk factors for critical illness in hospitalized children and adolescents with COVID-19. STUDY DESIGN: Children 1 month to 21 years with COVID-19 from a single tertiary care children’s hospital between March 15-April 13, 2020 were included. Demographic and clinical data were collected. RESULTS: 67 children tested positive for COVID-19; 21 (31.3%) were managed as outpatients. Of 46 admitted patients, 33 (72%) were admitted to the general pediatric medical unit and 13 (28%) to the pediatric intensive care unit (PICU). Obesity and asthma were highly prevalent but not significantly associated with PICU admission (p=0.99). Admission to the PICU was significantly associated with higher C-reactive protein, procalcitonin, and pro-B type natriuretic peptide levels and platelet counts (p<0.05 for all). Patients in the PICU were more likely to require high-flow nasal cannula (p=0.0001) and were more likely to have received Remdesivir through compassionate release (p<0.05). Severe sepsis and septic shock syndromes were observed in 7 (53.8%) PICU patients. Acute respiratory distress syndrome (ARDS) was observed in 10 (77%) PICU patients, 6 of whom (46.2%) required invasive mechanical ventilation for a median of 9 days. Of the 13 patients in the PICU, 8 (61.5%) were discharged home, and 4 (30.7%) patients remain hospitalized on ventilatory support at day 14. One patient died after withdrawal of life-sustaining therapy because of metastatic cancer. CONCLUSIONS: We describe a higher than previously recognized rate of severe disease requiring PICU admission in pediatric patients admitted to the hospital with COVID-19.

positive: Public health initiatives from hospitalized patients with COVID-19, China Abstract Background Since December 2019, when it first occurred in Wuhan, China, coronavirus disease 2019 (COVID-19) has spread rapidly worldwide via human-to-human transmission. We aimed to describe the epidemiological and demographic features of COVID-19 outside Wuhan. Methods A single-center case series of 136 consecutive (from January 16 to February 17, 2020) patients with confirmed COVID-19 hospitalized in The First People's Hospital of Jingzhou, China, was retrospectively analyzed. Outcomes were followed up until February 19, 2020. Results Of the 136 patients (median age, 49 years; interquartile range [IQR], 33–63 years; range, 0.3–83 years), 91 (67%) had been to Wuhan or contacted persons from Wuhan. Forty-five (33.1%) were familial clusters. The median incubation period was 6 days (IQR: 4–11 days). All children had an exact exposure history, family members with COVID-19, and “Mild/Moderate” symptoms at admission. Among the 64 elderly patients, 14 (21.9%) had no exposure history, and 43 (67.2%) had a chronic illness. All 11 (8.1%) “Severe/Very severe” illness at onset cases and 5 (3.7%) fatal cases were elderly patients. The duration from symptom onset to admission was positively correlated with the duration from symptom onset to endpoint. Overall, patients with a longer incubation period had more severe outcomes. Conclusion As high-risk susceptible groups, strong protection should be implemented for children and the elderly. Universal screening should be performed for people with a clear exposure history, even lacking apparent symptoms. Given the rapid progression of COVID-19, people should be admitted quickly following symptom onset.

positive: Promoting and supporting children's health and healthcare during COVID-19 - International Paediatric Association Position Statement

positive: Biomarkers in Pediatric ARDS: Future Directions Acute respiratory distress syndrome (ARDS) is common among mechanically ventilated children and accompanies up to 30% of all pediatric intensive care unit deaths. Though ARDS diagnosis is based on clinical criteria, biological markers of acute lung damage have been extensively studied in adults and children. Biomarkers of inflammation, alveolar epithelial and capillary endothelial disruption, disordered coagulation, and associated derangements measured in the circulation and other body fluids, such as bronchoalveolar lavage, have improved our understanding of pathobiology of ARDS. The biochemical signature of ARDS has been increasingly well described in adult populations, and this has led to the identification of molecular phenotypes to augment clinical classifications. However, there is a paucity of data from pediatric ARDS (pARDS) patients. Biomarkers and molecular phenotypes have the potential to identify patients at high risk of poor outcomes, and perhaps inform the development of targeted therapies for specific groups of patients. Additionally, because of the lower incidence of and mortality from ARDS in pediatric patients relative to adults and lack of robust clinical predictors of outcome, there is an ongoing interest in biological markers as surrogate outcome measures. The recent definition of pARDS provides additional impetus for the measurement of established and novel biomarkers in future pediatric studies in order to further characterize this disease process. This chapter will review the currently available literature and discuss potential future directions for investigation into biomarkers in ARDS among children.

positive: Severe acute respiratory syndrome in children. BACKGROUND Severe acute respiratory syndrome (SARS) is a febrile, respiratory tract illness caused by infection with the newly identified SARS-associated coronavirus. A notable feature of the 2003 global SARS outbreak was the relative paucity of cases reported among children. We reviewed the epidemiologic and clinical features of SARS in children and discuss implications of these findings for diagnosis, treatment and prevention of SARS. METHODS We performed a literature search to identify reports of pediatric (younger than 18 years of age) patients meeting the World Health Organization case definitions for SARS and abstracted relevant clinical and epidemiologic information. RESULTS We identified 6 case series reporting 135 pediatric SARS patients (80 laboratory-confirmed, 27 probable and 28 suspect) from Canada, Hong Kong, Taiwan and Singapore. Among laboratory-confirmed and probable SARS cases, the most common symptoms included fever (98%), cough (60%) and nausea or vomiting (41%); 97% had radiographic abnormalities. The clinical presentation of SARS in patients older than 12 years of age was similar to that in adults. However, patients 12 years of age or younger had milder disease and were less likely than older children to be admitted to an intensive care unit, receive supplemental oxygen or be treated with methylprednisolone. No deaths were reported among children or adolescents with SARS, and at 6 months after illness only mild residual changes were reported in exercise tolerance and pulmonary function. There is only 1 published report of transmission of SARS virus from a pediatric patient. CONCLUSIONS Children and adolescents are susceptible to SARS-associated coronavirus infection, although the clinical course and outcome are more favorable in children younger than 12 years of age compared with adolescents and adults. Transmission of SARS from pediatric patients appears to be uncommon but is possible.

positive: Severe acute respiratory syndrome in children: experience in a regional hospital in Hong Kong. OBJECTIVE To report the clinical, laboratory, and radiologic features of children with severe acute respiratory syndrome (SARS) and to examine the difference between the younger and older age groups. DESIGN Retrospective descriptive cohort study. SETTING A regional hospital in Hong Kong. PATIENTS Children younger than 18 yrs with SARS. RESULTS Twenty-one children were included, with a mean age of 10.7 +/- 5.1 yrs. Children with SARS presented with fever, nonproductive cough, malaise, chills, headache, myalgia, and loss of appetite. Examination of the chest showed minimal auscultatory findings. Common laboratory findings included lymphopenia, thrombocytopenia, and mild elevations of activated partial thromboplastin time, alanine transaminase, lactic dehydrogenase, and creatine phosphokinase. Bacteriologic and virologic studies were all negative for common pathogens. Unilateral focal opacity was the commonest finding in chest radiography. High-resolution computerized tomography of the thorax was an early diagnostic tool if the chest radiograph was negative. The clinical course was less severe in comparison with adult patients. However, adolescents (age, > or =12 yrs) resembled adults in their clinical features. When compared with the younger age group, the adolescents had significantly higher temperatures, more constitutional upset, and a greater need for steroid treatment. Children younger than 12 yrs seemed less ill but had more coughing. On the whole, the outcome was favorable. CONCLUSION Severe acute respiratory syndrome affects children, but the course is less severe. Nevertheless, the disease could have a significant psychosocial impact on children because of the potential seriousness of the disease in their adult family members.

positive: VIRAL ETIOLOGY AND OUTCOME OF SEVERE LOWER RESPIRATORY TRACT INFECTIONS AMONG CRITICALLY ILL CHILDREN ADMITTED TO THE PICU ABSTRACT Objective: To determine the viral etiology of severe lower respiratory tract infections (LRTIs), their clinical significance and prognosis among critically ill children. Design: A prospective descriptive study was carried out. Setting: Pediatric Intensive Care Unit (PICU) of Istanbul Medeniyet University, Goztepe Training and Research Hospital, Istanbul, Turkey. Patients: A total of 115 patients hospitalized in the PICU were evaluated for inclusion in the study. Children with underlying comorbidities and those who did not require mechanical ventilation were excluded. Main variables of interest: Demographic, clinical, laboratory test and radiographic data were recorded. Results: A total of 63 patients were eligible for the study. The most common diagnosis was bronchiolitis (57.1%). Respiratory syncytial virus (RSV) was the most frequent causal virus (36.5%). The most common complication was acute respiratory distress syndrome (ARDS) (28.6%). Multiple viral infection was identified in 20.6% of the patients, the most common in this subgroup being rhinovirus. Patients with bocavirus infection had a higher likelihood of needing invasive mechanical ventilation (IMV) at presentation. Children who died were likely to be < 12 months old, have ARDS, hepatitis, pneumomediastinum, multiple viral infection, and required IMV support with an increased duration of MV. Additionally, they were found to have a high Pediatric Risk of Mortality III score, Predicted Death Rate and increased need for inotropic support at admission. Conclusions: Our study showed critically ill children with LRTI without known risk factors to have high mortality when aged < 12 months, in the presence of multiple agents and when certain complications (ARDS, hepatitis) and X-ray findings were identified.

positive: Coronavirus Disease 2019 in Children: Characteristics, Antimicrobial Treatment, and Outcomes Abstract Background At present, coronavirus disease 2019 (COVID-19) has spread in many countries. We conducted this study to help paediatricians To help pediatricians understand the conditions of COVID-19 in children, we conducted this study. Methods We retrospectively summarized the characteristics, treatment and outcomes of pediatric cases in Wuhan children's hospital which was the only designated hospital for children with COVID-19 in Hubei Province. A Cox proportional hazards regression analysis was used to evaluate factors associated with clinical outcomes. Results As of February 29, 75 children had been discharged, of which only one was has severe pneumonia and one was critical cases. Children younger than 2 years were more susceptible to COVID-19. All patients have received interferon-α nebulization, and eight cases including the severe and critical cases were co-administrated ribavirin. Five patients with mild pneumonia were given arbidol. Twenty-three patients were given traditional Chinese medicine (TCM). The average length of stay (LOS) and the time of SARS-CoV-2 clearance were 10.57 and 6.39 days, respectively. None of the factors was associated with LOS or time of SARS-CoV-2 clearance. Conclusions The severity of COVID-19 in pediatric cases were milder than adults. The efficacy of the antiviral therapy in children with COVID-19 remains to be evaluated.

positive: Simulated Assessment of Pharmacokinetically Guided Dosing for Investigational Treatments of Pediatric Patients With Coronavirus Disease 2019 Importance: Children of all ages appear susceptible to severe acute respiratory syndrome coronavirus 2 infection. To support pediatric clinical studies for investigational treatments of coronavirus disease 2019 (COVID-19), pediatric-specific dosing is required. Objective: To define pediatric-specific dosing regimens for hydroxychloroquine and remdesivir for COVID-19 treatment. Design, Setting, and Participants: Pharmacokinetic modeling and simulation were used to extrapolate investigated adult dosages toward children (March 2020-April 2020). Physiologically based pharmacokinetic modeling was used to inform pediatric dosing for hydroxychloroquine. For remdesivir, pediatric dosages were derived using allometric-scaling with age-dependent exponents. Dosing simulations were conducted using simulated pediatric and adult participants based on the demographics of a white US population. Interventions: Simulated drug exposures following a 5-day course of hydroxychloroquine (400 mg every 12 hours × 2 doses followed by 200 mg every 12 hours × 8 doses) and a single 200-mg intravenous dose of remdesivir were computed for simulated adult participants. A simulation-based dose-ranging study was conducted in simulated children exploring different absolute and weight-normalized dosing strategies. Main Outcomes and Measures: The primary outcome for hydroxychloroquine was average unbound plasma concentrations for 5 treatment days. Additionally, unbound interstitial lung concentrations were simulated. For remdesivir, the primary outcome was plasma exposure (area under the curve, 0 to infinity) following single-dose administration. Results: For hydroxychloroquine, the physiologically based pharmacokinetic model analysis included 500 and 600 simulated white adult and pediatric participants, respectively, and supported weight-normalized dosing for children weighing less than 50 kg. Geometric mean-simulated average unbound plasma concentration values among children within different developmental age groups (32-35 ng/mL) were congruent to adults (32 ng/mL). Simulated unbound hydroxychloroquine concentrations in lung interstitial fluid mirrored those in unbound plasma and were notably lower than in vitro concentrations needed to mediate antiviral activity. For remdesivir, the analysis included 1000 and 6000 simulated adult and pediatric participants, respectively. The proposed pediatric dosing strategy supported weight-normalized dosing for participants weighing less than 60 kg. Geometric mean-simulated plasma area under the time curve 0 to infinity values among children within different developmental age-groups (4315-5027 ng × h/mL) were similar to adults (4398 ng × h/mL). Conclusions and Relevance: This analysis provides pediatric-specific dosing suggestions for hydroxychloroquine and remdesivir and raises concerns regarding hydroxychloroquine use for COVID-19 treatment because concentrations were less than those needed to mediate an antiviral effect.

positive: Is a "Cytokine Storm" Relevant to COVID-19?

positive: Coronavirus (COVID-19) infection in children at a specialist centre: outcome and implications of underlying high-risk comorbidities in a paediatric population Background: There is evolving evidence of significant differences in severity and outcomes of coronavirus disease 2019 (COVID-19) in children compared to adults. Underlying medical conditions associated with increased risk of severe disease are based on adult data, but have been applied across all ages resulting in large numbers of families undertaking social shielding (vulnerable group). We conducted a retrospective analysis of children with suspected COVID-19 at a Specialist Childrens Hospital to determine outcomes based on COVID-19 testing status and underlying health vulnerabilities. Methods: Routine clinical data were extracted retrospectively from the Institutions Electronic Health Record system and Digital Research Environment for patients with suspected and confirmed COVID-19 diagnoses. Data were compared between Sars-CoV-2 positive and negative patients (CoVPos / CoVNeg respectively), and in relation to presence of underlying health vulnerabilities based on Public Health England guidance. Findings: Between 1st March and 15th May 2020, 166 children (<18 years of age) presented to a specialist childrens hospital with clinical features of possible COVID-19 infection. 65 patients (39.2%) tested positive for SARS-CoV-2 virus. CoVPos patients were older (median 9 [0.9-14] years vs median 1 [0.1-5.7.5] years respectively, p<0.001). There was a significantly reduced proportion of vulnerable cases (47.7% vs 72.3%, p=0.002), but no difference in proportion of vulnerable patients requiring ventilation (61% vs 64.3%, p = 0.84) between CoVPos and CoVNeg groups. However, a significantly lower proportion of CoVPos patients required mechanical ventilation support compared to CoVNeg patients (27.7 vs 57.4%, p<0.001). Mortality was not significantly different between CoVPos and CoVNeg groups (1.5 vs 4% respectively, p=0.67) although there were no direct COVID-19 related deaths in this highly preselected paediatric population. Interpretation: COVID-19 infection may be associated with severe disease in childhood presenting to a specialist hospital, but does not appear significantly different in severity to other causes of similar clinical presentations. In children presenting with pre-existing COVID-19 vulnerable medical conditions at a specialist centre, there does not appear to be significantly increased risk of either contracting COVID-19 or severe complications, apart from those undergoing chemotherapy, who are over-represented.

positive: Coronavirus Disease 2019 (COVID-19) in Children - What We Know So Far and What We Do Not Pediatric coronavirus disease-19 (COVID-19) infection is relatively mild when compared to adults, and children are reported to have a better prognosis. Mortality in children appears rare. Clinical features of COVID-19 in children include fever and cough, but a large proportion of infected children appears to be asymptomatic and may contribute to transmission. It remains unclear why children and young adults are less severely affected than older individuals, but this might involve differences in immune system function in the elderly and/or differences in the expression/function of the cellular receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)- Angiotensin converting enzyme 2 (ACE2). Laboratory findings and chest imaging may not be specific in children with COVID-19. Diagnosis is by Reverse transcriptase-Polymerase chain reaction (RT-PCR) testing of upper or lower respiratory tract secretions. This review additionally considers COVID-19 in immunosuppressed children, and also suggests a management algorithm for the few children who appear to present with life threatening infection, including the potential use of antiviral and immunomodulatory treatment. The most significant threat to global child health from SARS-CoV-2 is unlikely to be related to COVID 19 in children, but rather the socio-economic consequences of a prolonged pandemic.

positive: Shedding of infectious SARS-CoV-2 in symptomatic neonates, children and adolescents Children are underrepresented in COVID-19 case numbers, with most pediatric cases exhibiting limited severity, and do not seem to be major drivers of transmission, unlike for other respiratory viruses. That said, SARS-CoV-2 infects children across all age groups, and despite the high proportion of mild or asymptomatic infections, it would be naive not to consider them as transmitters. To address this point we used cell culture to systematically assess the presence of cultivable SARS-CoV-2 in the upper respiratory tract in a cohort of our institution first 23 symptomatic neonates, children and teenagers with COVID-19 diagnosed by RT-PCR (See Appendix). Median age was 12.0 years (interquartile range [IQR 3.8-14.5], range 7 days-15.9 yrs). Most patients had an upper respiratory tract infection (n=13), followed by fever without source and pneumonia (each, n=2). Samples were collected at a median of 2 days (IQR 1-3) after symptom onset. Median viral load (VL) at time of diagnosis was 3.0x106 copies/ml (mean 4,4x108, IQR 6.9x103-4.4x108) from a nasopharyngeal swab (NPS). SARS-CoV-2 virus isolation was successful in 12/23 (52%) children after inoculating VeroE6 cells with a NPS specimen. SARS-CoV-2 isolation was determined by the presence of a typical cytopathic effect (CPE) and increased viral RNA in the supernatant. SARS-CoV-2 replication in all positive isolates (12/12) was confirmed by a second passage using new VeroE6 cells. Virus isolation was successful from NPS from all age groups, with a median initial VL of 1.7x108 copies/ml (mean 7.9x108, IQR 4.7x106-1.0x109) (Figure 1). The youngest patient that SARS-CoV-2 was isolated from was a 7-day old neonate. No correlation between disease presentation and success of virus isolation was observed. Our data show that initial VLs at diagnosis in symptomatic children is comparable to those in adults, and that symptomatic children of all ages shed infectious virus in early acute illness. Infectious virus isolation success was largely comparable to that of adults, although two specimens yielded an isolate at a lower VL (1.2x104 and 1.4x105 copies/ml) than what was observed in adults. SARS-CoV-2 shedding patterns of culture competent virus in symptomatic children resemble those observed in adults. Therefore, transmission of SARS-CoV-2 from children is plausible. Considering the relatively low frequency of infected children at this time, biological or other unknown factors could reduce transmission in this population. Both large serological investigations and systematic surveillance of acute respiratory diseases are needed to understand the role of children in this new pandemic.

positive: Antibody responses to SARS-CoV2 are distinct in children with MIS-C compared to adults with COVID-19 Clinical manifestations of COVID-19 caused by the novel coronavirus SARS-CoV-2 are associated with age. While children are largely spared from severe respiratory disease, they can present with a SARS-CoV-2-associated multisystem inflammatory syndrome (MIS-C) similar to Kawasaki's disease. Here, we show distinct antibody (Ab) responses in children with MIS-C compared to adults with severe COVID-19 causing acute respiratory distress syndrome (ARDS), and those who recovered from mild disease. There was a reduced breadth and specificity of anti-SARS-CoV-2-specific antibodies in MIS-C patients compared to the COVID patient groups; MIS-C predominantly generated IgG Abs specific for the Spike (S) protein but not for the nucleocapsid (N) protein, while both COVID-19 cohorts had anti-S IgG, IgM and IgA Abs, as well as anti-N IgG Abs. Moreover, MIS-C patients had reduced neutralizing activity compared to COVID-19 cohorts, indicating a reduced protective serological response. These results suggest a distinct infection course and immune response in children and adults who develop severe disease, with implications for optimizing treatments based on symptom and age.

positive: The impact of influenza-like illness in young children on their parents: a quality of life survey BACKGROUND: Influenza-like illness can cause excess paediatric morbidity and burden on parents. OBJECTIVES: We determined the quality of life (QoL) impact of children’s influenza-like illness (ILI) on their parents. METHODS: We conducted a prospective cohort study in childcare centres and a general practice in Sydney, Australia. Using PAR-ENT-QoL, we measured QoL of parents of children aged 6 months–3 years before the 2010 influenza season, then again for parents of children with ILI (ILI group) using SF-12v2 Acute Form and PAR-ENT-QoL, and contemporaneously for parents of aged-matched children without ILI (non-ILI group). RESULTS: Of 381 children enrolled from 90 childcare centres, 105 developed ILI. PAR-ENT-QoL scores of the ILI group were significantly lower in the post-ILI follow-up interviews than at baseline (60.99 vs. 79.77, p < 0.001), and those of non-ILI group at follow-up interviews (60.99 vs. 84.05, p < 0.001). SF-12v2 scores of the ILI group were also significantly lower than those of non-ILI group: physical component summary (50.66 vs. 53.16, p = 0.011) and mental component summary (45.67 vs. 53.66, p < 0.001). Two factors were significantly associated with parental QoL: total time spent caring child during ILI and whether the child had severe ILI or not. Correlations between PAR-ENT-QoL and SF-12v2 scores were satisfactory. CONCLUSIONS: Parents had significantly lower QoL while their child had ILI, compared with before ILI and with parents of children without ILI. The public health impact of ILI in children on the QoL in families is far from negligible. QoL measurement can complement economic evaluation of ILI disease burden and provide a more complete picture of impact.

positive: [Retracted: Clinical and epidemiological characteristics of 34 children with 2019 novel coronavirus infection in Shenzhen] Objective: To describe the characteristics of clinical manifestations and epidemiology of children with 2019 novel coronavirus (2019-nCoV) infection. Methods: All 34 children with laboratory-confirmed 2019-nCoV infection by quantitative real-time reverse transcription-PCR through nasopharyngeal swab specimens were admitted to the Third People's Hospital of Shenzhen from January 19 to Febuary 7, 2020. Clinical data and epidemiological history of these patients were retrospectively collected and analyzed. Results: Among the 34 cases, 14 were males, and 20 were females. The median age was 8 years and 11 months. No patients had underlying diseases. There were 28 children (82%) related with a family cluster outbreak. There were 26 children (76%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 22 (65%) common cases, 9 (26%) mild cases and 3 (8.8%) asymptomatic cases. No severe or critical cases were identified. The most common symptoms were fever (17 cases, 50%) and cough (13 cases, 38% ). In the 34 cases, the white blood cell counts of 28 cases (82%) were normal. Five cases had white blood cell counts more than 10×10(9)/L. One case had white blood cell counts less than 4×10(9)/L. Neutropenia and lymphopenia was found in one case, respectively. C-reactive protein levels and erythrocyte sedimentation rates were elevated in 1 and 5 case, respectively. Elevated procalcitonin was found in 1 case and D-Dimer in 3 cases. The levels of lactic dehydrogenase (LDH) were more than 400 U/L in 10 cases. The CT images of these patients showed bilateral multiple patchy or nodular ground-glass opacities and/or infiltrating shadows in middle and outer zone of the lung or under the pleura. Twenty patients were treated with lopinavir and ritonavir. Glucocorticoids and immunoglobulin were not used in any cases. All the cases improved and were discharged from hospital. Further following up was need. Conclusions: The clinical manifestations in children with 2019-nCoV infection are non-specific and are milder than that in adults. Chest CT scanning is heplful for early diagnosis. Children's infection is mainly caused by family cluster outbreak and imported cases. Family daily prevention is the main way to prevent 2019-nCoV infection.

positive: High-Resolution Computed Tomography Manifestations of 5 Pediatric Patients With 2019 Novel Coronavirus We present clinical and chest computed tomography (CT) features of 5 cases of pediatric patients with 2019 novel coronavirus. Two patients had fever and dry cough, whereas the rest of 3 patients were asymptomatic. Three patients had unilateral ground glass opacities with or without consolidation in the subpleural region on high-resolution chest CT, 1 patient had bilateral ground glass opacities, and 1 patient was negative for CT. We note that up to 66.7% asymptomatic patients had pulmonary lesions, so the asymptomatic children with Wuhan contact are recommended to do a 2019 novel coronavirus real-time fluorescence polymerase chain reaction screening. Unlike adult patients, only a small amount of patients had multilobes affected, so we speculate that the pediatric patients generally have milder CT findings than adults.

positive: Coronavirus disease (COVID‐19) and neonate: What neonatologist need to know Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) cause china epidemics with high morbidity and mortality, the infection has been transmitted to other countries. About three neonates and more than 230 children cases are reported. The disease condition of the main children was mild. There is currently no evidence that SARS‐CoV‐2 can be transmitted transplacentally from mother to the newborn. The treatment strategy for children with Coronavirus disease (COVID‐19) is based on adult experience. Thus far, no deaths have been reported in the pediatric age group. This review describes the current understanding of COVID‐19 infection in newborns and children.

positive: Novel coronavirus infection (COVID-19) in children younger than one year: A systematic review of symptoms, management and outcomes AIM: The aim of this systematic review was to evaluate the clinical characteristics of COVID-19 in neonates and children under one year of age. METHODS: A systematic literature review of the MEDLINE, PubMed, CINAHL, Embase and EBSCO databases was carried out for studies from January 1, 2020, to April 7, 2020. We included all papers that addressed clinical manifestations, laboratory results, imaging findings and outcomes in infants and neonates. RESULTS: Our search identified 77 peer-reviewed papers, and 18 papers covering 160 infants were reviewed. One paper was from Vietnam, and the other 17 were from China: eight were cross-sectional studies, eight were case reports, one was a case series, and one was a prospective cohort study. The most common clinical symptoms were fever (54%) and cough (33%). Most infants were treated symptomatically, with frequent use of various empirical medications. Infants and neonates tended to have more severe COVID-19 disease than older children: 11 (7%) were admitted to intensive care and one infant died. The mortality rate was 0.006%, with favourable outcomes in most cases. CONCLUSION: Infants and neonates were more vulnerable to more severe COVID-19 disease than older children, but morbidity and mortality were low.

positive: Strengthening Health Systems and Improving the Capacity of Pediatric Care Centers to Respond to Epidemics Such as COVID-19 in Resource-limited Settings

positive: COVID-19 in children: an epidemiology study from China

positive: COVID-19 virus and children: What do we know?

positive: Understanding the age divide in COVID-19: why are children overwhelmingly spared? The rapid emergence and subsequent global dissemination of SARS-CoV-2 disease (COVID-19) has resulted in over 4 million cases worldwide. The disease has a marked predilection for adults, and children are relatively spared. Understanding the age-based differences in pathophysiological pathways and processes relevant to the onset and progression of disease both in the clinical course and in experimental disease models may hold the key to the identification of therapeutic targets. The differences in the clinical course are highlighted by the lack of progression of the SARS-CoV-2 infection beyond mild symptoms in a majority of children, whereas in adults the disease progresses to acute lung injury and an acute respiratory distress syndrome (ARDS)-like phenotype with high mortality. The pathophysiological mechanisms leading to decreased lung injury in children may involve the decreased expression of the mediators necessary for viral entry into the respiratory epithelium and differences in the immune system responses in children. Specifically, decreased expression of proteins, including angiotensin-converting enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) in the airway epithelium in children may prevent viral entry. The immune system differences may include a relative preponderance of CD4+ T cells, decreased neutrophil infiltration, decreased production of proinflammatory cytokines, and increased production of immunomodulatory cytokines in children compared with adults. Notably, the developing lung in children may have a greater capacity to recover and repair after viral infection. Understanding the relative contributions of the above processes to the protective phenotype in the developing lung can guide the trial of the appropriate therapies in adults.

positive: Neurotropic mechanisms in COVID-19 and their potential influence on neuropsychological outcomes in children Children have shown more physical resilience to COVID-19 than adults, but there is a cohort of vulnerable infants and young children who may experience disease burden, both in the acute phase and chronically. Children may have had early undocumented exposure to COVID-19. Even when the risk of exposure was known, developmental variables may have made the avoidance of physical proximity difficult for children. Preliminary hypotheses concerning neurotropic factors have been documented by researchers. Children with COVID-19 and comorbid physical or mental disorders may be vulnerable to exacerbations of neurotropic factors and comorbidities, the neural impact of which has been documented for other coronaviruses. Researchers are investigating COVID-19 symptom descriptions, neurotropic mechanisms at the genomic and transcriptomatic levels, neurological manifestations, and the impact of comorbid health complications. Neuropsychologists need information concerning the likely impact of COVID-19 on children. With a view toward that goal, this article provides recommendations for some initial updates in neuropsychology practice.

positive: Editorial Perspective: Perils and promise for child and adolescent sleep and associated psychopathology during the COVID-19 pandemic It is anticipated that the novel coronavirus disease 2019 (COVID-19) pandemic and associated societal response will have wide-ranging impacts on youth development and mental health. Sleep is crucial for child and adolescent health and well-being, and the potential for sleep problems to emerge or worsen during and following the pandemic is high. This may be particularly true for children and adolescents who are at heightened risk for the onset of sleep and mental health disturbances and for those whom developmental changes impacting sleep are rapidly occurring. Youth with preexisting psychopathologies (including anxiety and depression) and neurodevelopmental conditions (including attention-deficit/hyperactivity disorder and autism spectrum disorder) could be especially vulnerable to disturbed sleep during this period of change and uncertainty. It is thus imperative that sleep considerations be part of research and clinical initiatives aimed at understanding and mitigating the impact of the COVID-19 pandemic in children and adolescents. This article considers ways in which the pandemic may impact sleep, including research and clinical implications.

positive: COVID-19 in children: More than meets the eye

positive: The new coronavirus and the risk to children's health

positive: COVID-19 in Children, Pregnancy and Neonates: A Review of Epidemiologic and Clinical Features. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has spread rapidly across the globe. In contrast to initial reports, recent studies suggest that children are just as likely as adults to become infected with the virus but have fewer symptoms and less severe disease. In this review, we summarize the epidemiologic and clinical features of children infected with SARS-CoV-2 reported in pediatric case series to date. We also summarize the perinatal outcomes of neonates born to women infected with SARS-CoV-2 in pregnancy. We found 11 case series including a total of 333 infants and children. Overall, 83% of the children had a positive contact history, mostly with family members. The incubation period varied between 2 and 25 days with a mean of 7 days. The virus could be isolated from nasopharyngeal secretions for up to 22 days and from stool for more than 30 days. Co-infections were reported in up to 79% of children (mainly mycoplasma and influenza). Up to 35% of children were asymptomatic. The most common symptoms were cough (48%; range 19%-100%), fever (42%; 11%-100%) and pharyngitis (30%; 11%-100%). Further symptoms were nasal congestion, rhinorrhea, tachypnoea, wheezing, diarrhea, vomiting, headache and fatigue. Laboratory test parameters were only minimally altered. Radiologic findings were unspecific and included unilateral or bilateral infiltrates with, in some cases, ground-glass opacities or consolidation with a surrounding halo sign. Children rarely needed admission to intensive care units (3%), and to date, only a small number of deaths have been reported in children globally. Nine case series and 2 case reports described outcomes of maternal SARS-CoV-2 infection during pregnancy in 65 women and 67 neonates. Two mothers (3%) were admitted to intensive care unit. Fetal distress was reported in 30% of pregnancies. Thirty-seven percent of women delivered preterm. Neonatal complications included respiratory distress or pneumonia (18%), disseminated intravascular coagulation (3%), asphyxia (2%) and 2 perinatal deaths. Four neonates (3 with pneumonia) have been reported to be SARS-CoV-2 positive despite strict infection control and prevention procedures during delivery and separation of mother and neonates, meaning vertical transmission could not be excluded.

positive: [Pediatric impact of COVID-19] Children infected with SARS-CoV-2 are underrepresented during the current COVID-19 outbreak Unlike other respiratory viruses, SARS-CoV-2 rather infects adults who subsequently infect their children From recent Chinese and Italian data, children commonly present mild to moderate disease, a large proportion of them being asymptomatic In particular, children present significantly less fever, cough and pneumonia compared to adults However, more cases of pneumonia were reported from children infected with SARS-CoV-2 compared to those infected with H1N1 No vertical transmission of SARS-CoV-2 has been described so far

positive: SARS-CoV-2: Is it the newest spark in the TORCH? Abstract Amid the rapidly evolving global coronavirus disease 2019 (COVID-19) pandemic that has already had profound effects on public health and medical infrastructure globally, many questions remain about its impact on child health. The unique needs of neonates and children, and their role in the spread of the virus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) should be included in preparedness and response plans. Fetuses and newborn infants may be uniquely vulnerable to the damaging consequences of congenitally- or perinatally-acquired SARS-CoV-2 infection, but data are limited about outcomes of COVID-19 disease during pregnancy. Therefore, information on illnesses associated with other highly pathogenic coronaviruses (i.e., severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome [MERS]), as well as comparisons to common congenital infections, such as cytomegalovirus (CMV), are warranted. Research regarding the potential routes of acquisition of SARS-CoV-2 infection in the prenatal and perinatal setting is of a high public health priority. Vaccines targeting women of reproductive age, and in particular pregnant patients, should be evaluated in clinical trials and should include the endpoints of neonatal infection and disease.

positive: Findings in children severely infected with a novel influenza A virus of swine origin: pulmonary imaging BACKGROUND: This article reviews the chest radiography of children with severe infection caused by a novel influenza A (H1N1) virus of swine origin (S-OIV). We analyzed the role of their pulmonary images in predicting the severity and diagnosis of the disease. METHODS: Among 97 patients with confirmed novel H1N1 infection, 42 patients treated with mechanical ventilation formed group 1, and the remaining 55 patients constituted group 2. The initial and subsequent radiograhic findings in groups 1 and 2 were compared with respect to the pattern, distribution, and extent of the abnormality. RESULTS: In group 1, 24 patients presented with three or more lung zone diseases, whereas only 5 patients in group 2 demonstrated these findings (P<0.001). A pneumomediastinum or pneumothorax was observed in 24/42 patients in group 1 and in 18/55 patients in group 2 (P=0.019). Twelve patients in group 1 and 5 in group 2 developed a ground-glass opacity cyst with a honeycomb appearance (P=0.007). CONCLUSIONS: The most common radiographic and computed tomography findings in children who were severely infected with S-OIV included unilateral or bilateral ground-glass opacities with or without associated focal or multifocal areas of consolidation. Children with bilateral involvement or with greater opacity on the chest radiographs were more likely to worsen and require the mechanical ventilation.

positive: Smoking Is Associated With COVID-19 Progression: A Meta-analysis INTRODUCTION: Smoking depresses pulmonary immune function and is a risk factor contracting other infectious diseases and more serious outcomes among people who become infected. This paper presents a meta-analysis of the association between smoking and progression of the infectious disease COVID-19. METHODS: PubMed was searched on April 28, 2020, with search terms “smoking”, “smoker*”, “characteristics”, “risk factors”, “outcomes”, and “COVID-19”, “COVID”, “coronavirus”, “sar cov-2”, “sar cov 2”. Studies reporting smoking behavior of COVID-19 patients and progression of disease were selected for the final analysis. The study outcome was progression of COVID-19 among people who already had the disease. A random effects meta-analysis was applied. RESULTS: We identified 19 peer-reviewed papers with a total of 11,590 COVID-19 patients, 2,133 (18.4%) with severe disease and 731 (6.3%) with a history of smoking. A total of 218 patients with a history of smoking (29.8%) experienced disease progression, compared with 17.6% of non-smoking patients. The meta-analysis showed a significant association between smoking and progression of COVID-19 (OR 1.91, 95% confidence interval [CI] 1.42-2.59, p = 0.001). Limitations in the 19 papers suggest that the actual risk of smoking may be higher. CONCLUSIONS: Smoking is a risk factor for progression of COVID-19, with smokers having higher odds of COVID-19 progression than never smokers. IMPLICATIONS: Physicians and public health professionals should collect data on smoking as part of clinical management and add smoking cessation to the list of practices to blunt the COVID-19 pandemic.

positive: COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study BACKGROUND: To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. METHODS: This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network—the Paediatric Tuberculosis Network European Trials Group (ptbnet)—that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. FINDINGS: 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5–12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2–11, range 1–34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5·06, 95% CI 1·72–14·87; p=0·0035), male sex (2·12, 1·06–4·21; p=0·033), pre-existing medical conditions (3·27, 1·67–6·42; p=0·0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10·46, 5·16–21·23; p<0·0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 [7%] patients), followed by remdesivir (17 [3%] patients), lopinavir–ritonavir (six [1%] patients), and oseltamivir (three [1%] patients). Immunomodulatory medication used included corticosteroids (22 [4%] patients), intravenous immunoglobulin (seven [1%] patients), tocilizumab (four [1%] patients), anakinra (three [1%] patients), and siltuximab (one [<1%] patient). Four children died (case-fatality rate 0·69%, 95% CI 0·20–1·82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support. INTERPRETATION: COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed. FUNDING: ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit.

positive: Complete Heart Block, Severe Ventricular Dysfunction and Myocardial Inflammation in a Child with COVID-19 Infection Abstract A young child presented with severe ventricular dysfunction and troponin leak in the setting of Coronavirus-19 disease (COVID-19). He developed intermittent, self-resolving, and hemodynamically insignificant episodes of complete heart block (CHB), which were diagnosed on telemetry and managed conservatively. This report is the first description of COVID-19 induced transient CHB in a child.

positive: Human and novel coronavirus infections in children: a review Coronaviruses, seven of which are known to infect humans, can cause a spectrum of clinical presentations ranging from asymptomatic infection to severe illness and death. Four human coronaviruses (hCoVs)-229E, HKU1, NL63 and OC43-circulate globally, commonly infect children and typically cause mild upper respiratory tract infections. Three novel coronaviruses of zoonotic origin have emerged during the past two decades: severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV) and the recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. These novel coronaviruses are known to cause severe illness and death predominantly in older adults and those with underlying comorbidities. Consistent with what has been observed during the outbreaks of SARS and MERS, children with COVID-19 are more likely to be asymptomatic or to have mild-to-moderate illness, with few deaths reported in children globally thus far. Clinical symptoms and laboratory and radiological abnormalities in children have been similar to those reported in adults but are generally less severe. A rare multisystem inflammatory syndrome in children (MIS-C) which has resulted in critical illness and some deaths has recently been described. Clinical trials for therapeutics and vaccine development should include paediatric considerations. Children may play an important role in the transmission of infection and outbreak dynamics and could be a key target population for effective measures to control outbreaks. The unintended consequences of the unprecedented scale and duration of pandemic control measures for children and families around the world should be carefully examined. ABBREVIATIONS: 2019-nCoV, 2019 novel coronavirus; ADEM, acute demyelinating encephalomyelitis; AAP, American Academy of Pediatrics; ACE-2, angiotensin-converting enzyme 2; ARDS, acute respiratory distress syndrome; BCG, bacillus Calmette-Guérin; BNP, brain natriuretic peptide; CDC, Centers for Disease Control and Prevention; CRP, C-reactive protein; CSF, cerebrospinal fluid; COVID-19, coronavirus disease 2019; CT, computed tomography; CXR, chest X-ray; DOL, day of life; hCoV, human coronavirus; ICU, intensive care unit; IL, interleukin; IVIG, intravenous immunoglobulin; KD, Kawasaki disease; LDH, lactate dehydrogenase; MERS, Middle East respiratory syndrome; MERS-CoV, Middle East respiratory syndrome coronavirus; MEURI, monitored emergency use of unregistered and experimental interventions; MIS-C, multi-system inflammatory syndrome in children; PCR, polymerase chain reaction; PICU, paediatric intensive care unit; RNA, ribonucleic acid; RCT, randomised-controlled trial; RSV, respiratory syncytial virus; SARS, severe acute respiratory syndrome; SARS-CoV-1, severe acute respiratory syndrome coronavirus 1; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNF-alpha, tumour necrosis factor alpha; UK United Kingdom; UNICEF, United Nations Children's Fund; USA, United States of America; WHO, World Health Organization.

positive: Clinical Characteristics of COVID-19 Infection in Newborns and Pediatrics: A Systematic Review INTRODUCTION: World Health Organization has declared COVID-19 a pandemic and a global health emergency. Thus, it is necessary to clearly characterize clinical manifestations and management of COVID-19 infection in children to provide accurate information for healthcare workers. Accordingly, the present study was designed to review articles published on clinical manifestations and characteristics of children and infants with COVID-19. METHODS: In this systematic review, medical databases including Cochrane Library, Web of Science, Embase, Scopus, SID, Medline, WHO and LitCovid were searched using English and Persian keywords including COVID-19, Pediatrics, Newborn, Coronavirus 2019, 2019-nCoV, SARS-CoV-2. Finally, data of 14 related articles were included in the study. RESULTS: A total of 2228 children, newborns and infants were studied. Clinical manifestation in children may be mild (72%), moderate (22%) or severe (6%), and the most common symptoms include dry cough (91%) and fever (96%). According to the included articles, two children had died, one of which was a 14-year-old boy and his exposure history and underlying disease were unclear, and the other was a male newborn with gestational age of 35 weeks and 5 days, birth weight of 2200, Apgar score of 8, 8 (1 min and 5 min) and his first symptom was increased heart rate. No differences were found between male and female children regarding infection with COVID-19. CONCLUSION: Most pediatrics were infected with COVID-19 due to family cluster or history of close contact. Infected children have relatively milder clinical symptoms compared to infected adults. We should pay special attention to early diagnosis and early treatment in children infected with COVID-19.

positive: Clinical features of covid-19 in children In early December, pneumonia cases of unknown origin started to appear and, on the 7thof January 2020, these cases were declared to be caused by a novel beta-coronavirus according to viral genome sequencing on the 11thof February, 2020. Coronaviruses are enveloped, single strand RNA viruses that have been known to have the ability to mutate rapidly, alter tissue tropism and adjust to different epidemiological situations. As of the end of April 2020, 122,392 laboratory-confirmed cases of COVID-19 had been detected in Turkey, of whom 3,258 died. From the beginning of the COVID-19 epidemic, children seem to be less affected than adults. Therefore, there are limited data regarding the clinical features of COVID-19 in children. The majority of children with confirmed COVID-19 had a history of household contact. The most common symptoms were fever and cough. Previous data suggest that nearly half of patients are afebrile at the onset of the disease. Hospitalization and PICU admission rates for children were lower than for adults. However, PICU admission can be necessitated in children with severe disease. Infants, particularly under the age of 12 months, were more likely to develop severe disease. In children, milder and asymptomatic cases can be challenging and can play a role in transmission. In particular, clinicians should test those children who have a history of family cluster even though they are asymptomatic or present with mild symptoms.

positive: Clinical and Immune Features of Hospitalized Pediatric Patients With Coronavirus Disease 2019 (COVID-19) in Wuhan, China Importance: The epidemiologic and clinical characteristics of pediatric patients with coronavirus disease 2019 (COVID-19) have been reported, but information on immune features associated with disease severity is scarce. Objective: To delineate and compare the immunologic features of mild and moderate COVID-19 in pediatric patients. Design, Setting, and Participants: This single-center case series included 157 pediatric patients admitted to Wuhan Children's Hospital with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data were collected from January 25 to April 18, 2020. Exposures: Documented SARS-CoV-2 infection. Main Outcomes and Measures: Clinical and immunologic characteristics were collected and analyzed. Outcomes were observed until April 18, 2020. Results: Of the 157 pediatric patients with COVID-19, 60 (38.2%) had mild clinical type with pneumonia, 88 (56.1%) had moderate cases, 6 (3.8%) had severe cases, and 3 (1.9%) were critically ill. The 148 children with mild or moderate disease had a median (interquartile range [IQR]) age of 84 (18-123) months, and 88 (59.5%) were girls. The most common laboratory abnormalities were increased levels of alanine aminotransferase (ALT) (median [IQR], 16.0 [12.0-26.0] U/L), aspartate aminotransferase (AST) (median [IQR], 30.0 [23.0-41.8] U/L), creatine kinase MB (CK-MB) activity (median [IQR], 24.0 [18.0-34.0] U/L), and lactate dehydrogenase (LDH) (median [IQR], 243.0 [203.0-297.0] U/L), which are associated with liver and myocardial injury. Compared with mild cases, levels of inflammatory cytokines including interleukin 6, tumor necrosis factor α, and interferon Î³ were unchanged, whereas the level of immune suppressive interleukin 10 was markedly increased in moderate cases compared with mild cases (median [IQR], 3.96 [3.34-5.29] pg/mL vs 3.58 [3.10-4.36] pg/mL; P = .048). There was no statistically significant difference in absolute number of lymphocytes (including T cells and B cells) between mild and moderate cases, but moderate cases were associated with a decrease in neutrophil levels compared with mild cases (median [IQR], 2310/µL [1680/µL-3510/µL] vs 3120/µL [2040/µL-4170/µL]; P = .01). Immunoglobin G and the neutrophil to lymphocyte ratio were negatively associated with biochemical indices related to liver and myocardial injury (immunoglobulin G, ALT: r, -0.3579; AST: r, -0.5280; CK-MB activity: r, -0.4786; LDH: r, -0.4984; and neutrophil to lymphocyte ratio, ALT: r, -0.1893; AST: r, -0.3912; CK-MB activity: r, -0.3428; LDH: r, -0.3234), while counts of lymphocytes, CD4+ T cells, and interleukin 10 showed positive associations (lymphocytes, ALT: r, 0.2055; AST: r, 0.3615; CK-MB activity: r, 0.338; LDH: r, 0.3309; CD4+ T cells, AST: r, 0.4701; CK-MB activity: r, 0.4151; LDH: r, 0.4418; interleukin 10, ALT: r, 0.2595; AST: r, 0.3386; CK-MB activity: r, 0.3948; LDH: r, 0.3794). Conclusions and Relevance: In this case series, systemic inflammation rarely occurred in pediatric patients with COVID-19, in contrast with the lymphopenia and aggravated inflammatory responses frequently observed in adults with COVID-19. Gaining a deeper understanding of the role of neutrophils, CD4+ T cells, and B cells in the pathogenesis of SARS-CoV-2 infection could be important for the clinical management of COVID-19.

positive: Characteristics of Hospitalized Pediatric COVID-19 Cases - Chicago, Illinois, March - April 2020 BACKGROUND: To date, no report on COVID-19 pediatric patients in a large urban center with data on underlying comorbidities and co-infection for hospitalized cases has been published. METHODS: Case series of Chicago COVID-19 patients aged 0-17 years reported to Chicago Department of Public Health (CDPH) from 3/5/20-4/8/20. Enhanced case investigation performed. Chi-square and Wilcoxon two-sample tests to compare characteristics among hospitalized and non-hospitalized cases. RESULTS: During March 5-April 8, 2020, 6369 lab-confirmed cases of COVID-19 were reported to CDPH; 64 (1.0%) were among children 0-17 years. Ten patients (16%) were hospitalized, seven (70%) required intensive care (ICU); median length of hospitalization 4 days (range: 1-14). Reported fever and dyspnea were significantly higher in hospitalized patients compared to non-hospitalized patients (9/10 vs. 28/54, p = 0.04 and 7/10 vs. 10/54, p = 0.002, respectively). Hospitalized patients were significantly younger than non-hospitalized patients (median, 3.5 years vs. 12 years; p = 0.03) and all either had an underlying comorbidity or co-infection. Among the 34 unique households with multiple laboratory-confirmed infections, median number of laboratory-confirmed infections was 2 (range: 2-5), and 31 (91%) households had at least one COVID-19 infected adult. For 15 households with available data to assess transmission, 11 (73%) were adult-to-child, 2 (13%) child-to-child, and 2 (13%) child-to-adult. CONCLUSIONS: Enhanced case investigation of hospitalized patients revealed that underlying comorbidities and co-infection might have contributed to severe disease. Given frequency of household transmission, healthcare providers should consider alternative dispositional planning for affected families of children living with comorbidities.

positive: Clinical Features and Outcome of SARS-CoV-2 Infection in Children: A Systematic Review and Meta-analysis BACKGROUND AND OBJECTIVE: Knowledge about COVID-19 in children is limited due to the paucity of reported data. The pediatric age group comprises only less than 5% of total COVID-19 worldwide, therefore, large studies in this population are unlikely in the immediate future. Hence, we planned to synthesize the current data that will help in a better understanding of COVID-19 in children. METHODS: Four different electronic databases (MEDLINE, EMBASE, Web of Science, and CENTRAL) were searched for articles related to COVID-19 in the pediatric population. We included studies reporting disease characteristics and outcomes of COVID-19 in patients aged less than 19 years. We performed a random-effect meta-analysis to provide pooled estimates of various disease characteristics. RESULTS: 27 studies (4857 patients) fulfilling the eligibility criteria were included in this systematic review, from a total of 883 records. About half of the patients had each of fever and cough, 11% (6-17%) had fast breathing, and 6-13% had gastrointestinal manifestations. Most of the patients had mild to moderate disease, and only 4% had a severe or critical illness. Leukopenia was the commonest reported laboratory abnormality. CONCLUSION: Even among the symptomatic COVID-19 cases, severe manifestations are seen in very few children. Though fever and respiratory symptoms are most common, many children also have gastrointestinal manifestations.

positive: Clinical Analysis of 25 COVID-19 Infections in Children BACKGROUND: To describe the characteristics of clinical manifestations of children with 2019 novel coronavirus (2019-nCoV) infection in Chongqing. METHODS: All 25 children with laboratory-confirmed 2019-nCoV infection by real-time reverse transcription-PCR (RNA-PCR) were admitted from the 4 designated treatment hospitals of 2019-nCoV in Chongqing from January 19 to March 12, 2020. Clinical data and epidemiologic history of these patients were retrospectively collected and analyzed. RESULTS: The diagnosis was confirmed through RNA-PCR testing. Among the 25 cases, 14 were males and 11 were females. The median age was 11.0 (6.3-14.5) years (range 0.6-17.0 years). All children were related to a family cluster outbreak, and 7 children (28%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 8 (32%) asymptomatic, 4 (16%) very mild cases and 13 (52%) common cases. No severe or critical cases were identified. The most common symptoms were cough (13 cases, 52%) and fever (6 cases, 24%). The duration time of clinical symptoms was 13.0 (8.0-25.0) days. In the 25 cases, on admission, 21 cases (84%) had normal white blood cell counts, while only 2 cases (8%) more than 10 × 10/L and 2 cases (8%) less than 4 × 10/L, respectively; 22 cases(88%) had normal CD4+ T lymphocyte counts, while in the remaining 3 cases(8%) this increased mildly; 23 cases had normal CD8+ T lymphocyte counts, while in the remaining 2 cases (8%) CD8+ T lymphocyte counts were mildly increased as well. All Lymphocyte counts were normal. There were no statistical differences of lab results between the groups of asymptomatic cases, mild cases and common cases. There were only 13 cases with abnormal CT imaging, most of which were located in the subpleural area of the bottom of the lung. All patients were treated with interferon, 6 cases combined with Ribavirin, and 12 cases combined with lopinavir or ritonavir. The days from onset to RNA turning negative was 15.20 ± 6.54 days. There was no significant difference of RNA turning negative between the groups of interferon, interferon plus ribavirin and interferon plus lopinavir or ritonavir treatment. All the cases recovered and were discharged from hospital. CONCLUSIONS: The morbidity of 2019-nCoV infection in children is lower than in adults and the clinical manifestations and inflammatory biomarkers in children are nonspecific and milder than that in adults. RNA-PCR test is still the most reliable diagnostic method, especially for asymptomatic patients.

positive: Vitamin D Insufficiency is Prevalent in Severe COVID-19 Background: COVID-19 is a major pandemic that has killed more than 196,000 people. The COVID-19 disease course is strikingly divergent. Approximately 80-85% of patients experience mild or no symptoms, while the remainder develop severe disease. The mechanisms underlying these divergent outcomes are unclear. Emerging health disparities data regarding African American and homeless populations suggest that vitamin D insufficiency (VDI) may be an underlying driver of COVID-19 severity. To better define the VDI-COVID-19 link, we determined the prevalence of VDI among our COVID-19 intensive care unit (ICU) patients. Methods: In an Institutional Review Board approved study performed at a single, tertiary care academic medical center, the medical records of COVID-19 patients were retrospectively reviewed. Subjects were included for whom serum 25-hydroxycholecalcifoerol (25OHD) levels were determined. COVID-19-relevant data were compiled and analyzed. We determined the frequency of VDI among COVID-19 patients to evaluate the likelihood of a VDI-COVID-19 relationship. Results: Twenty COVID-19 patients with serum 25OHD levels were identified; 65.0% required ICU admission.The VDI prevalence in ICU patients was 84.6%, vs. 57.1% in floor patients. Strikingly, 100% of ICU patients less than 75 years old had VDI. Coagulopathy was present in 62.5% of ICU COVID-19 patients, and 92.3% were lymphocytopenic. Conclusions: VDI is highly prevalent in severe COVID-19 patients. VDI and severe COVID-19 share numerous associations including hypertension, obesity, male sex, advanced age, concentration in northern climates, coagulopathy, and immune dysfunction. Thus, we suggest that prospective, randomized controlled studies of VDI in COVID-19 patients are warranted.

positive: Spectrum of COVID‐19 in Children The prevalence of coronavirus disease 2019 (COVID‐19) is lower in children compared to adults. Children contribute to 1‐5% of all COVID‐19 cases (1) . A recent study from China reported that 171(12.3%) of 1391 children with suspected disease had confirmed COVID‐19 infection (2) . As of May 15, 2020, there are 33,241 children with COVID‐19 in the United States (3) . The most common symptoms in children with confirmed and suspected COVID‐19 include fever and cough followed by diarrhea, and abdominal pain.

positive: Chilblain-like lesions in children following suspected COVID-19 infection During the COVID-19 pandemic, chilblain-like lesions have been reported in mildly symptomatic children and adolescents. We present four children investigated for suspected COVID-19 infection who presented with acral skin findings and mild systemic symptoms. Histology from one case showed signs of vasculitis with evident fibrin thrombus.

positive: A COVID-19 Transmission within a family cluster by presymptomatic infectors in China We report a COVID-19 family cluster caused by a presymptomatic case. There were 9 family members, including 8 laboratory-confirmed with COVID-19, and a 6-year-old child had no evidence of infection. Amongst the 8 patients, one adult and one 13-month-old infant were asymptomatic, one adult was diagnosed as having severe pneumonia.

positive: Children in Coronaviruses’ Wonderland: What Clinicians Need to Know Human coronaviruses (HCoVs) commonly cause mild upper-respiratory tract illnesses but can lead to more severe and diffusive diseases. A variety of signs and symptoms may be present, and infections can range in severity from the common cold and sore throat to more serious laryngeal or tracheal infections, bronchitis, and pneumonia. Among the seven coronaviruses that affect humans (SARS)-CoV, the Middle East respiratory syndrome (MERS)-CoV, and the most recent coronavirus disease 2019 (COVID-19) represent potential life-threatening diseases worldwide. In adults, they may cause severe pneumonia that evolves in respiratory distress syndrome and multiorgan failure with a high mortality rate. Children appear to be less susceptible to develop severe clinical disease and present usually with mild and aspecific symptoms similar to other respiratory infections typical of childhood. However, some children, such as infants, adolescents, or those with underlying diseases may be more at-risk categories and require greater caution from clinicians. Available data on pediatric coronavirus infections are rare and scattered in the literature. The purpose of this review is to provide to clinicians a complete and updated panel useful to recognize and characterize the broad spectrum of clinical manifestations of coronavirus infections in the pediatric age.

positive: One size does not fit all – Patterns of vulnerability and resilience in the COVID-19 pandemic and why heterogeneity of disease matters

positive: COVID-19 epidemic: Disease characteristics in children In mid-December 2019, a disease caused by infection with severe acute respiratory syndrome coronavirus-2, which began in Wuhan, China, has spread throughout the country and many countries around the world. The number of children with coronavirus disease-2019 (COVID-19) has also increased significantly. Although information regarding the epidemiology of COVID-19 in children has accumulated, relevant comprehensive reports are lacking. The present article reviews the epidemiological characteristics of COVID-19 in children.

positive: Characteristics and Outcomes of Coronavirus Infection in Children: The Role of Viral Factors and an Immunocompromised State BACKGROUND: Immunocompromised children might be predisposed to serious infections from human coronaviruses (HCoVs), including strains OC43, NL63, HKU1, and 229E; however, the virologic and clinical features of HCoV infection in immunocompromised children have not been compared to those in nonimmunocompromised children. METHODS: We retrospectively analyzed a cohort of children who presented to Seattle Children’s Hospital and in whom HCoV was detected by a multiplex respiratory polymerase chain reaction assay of a nasal sample between October 2012 and March 2016. Lower respiratory tract disease (LRTD) was defined as possible or definite infiltrate seen in chest imaging, need for oxygen, or abnormal lung examination in conjunction with a physician diagnosis of LRTD. We used logistic regression modeling to evaluate risk factors for LRTD and LRTD that necessitated oxygen use (severe LRTD), including an immunocompromised state, in children with HCoV infection. RESULTS: The median ages of 85 immunocompromised and 1152 nonimmunocompromised children with HCoV infection were 6.3 and 1.6 years, respectively. The prevalence of LRTD and of severe LRTD did not differ greatly between the immunocompromised and nonimmunocompromised patients (22% vs 26% [LRTD] and 15% vs 11% [severe LRTD], respectively); however, in a multivariable model, an immunocompromised state was associated with an increased likelihood of severe LRTD (adjusted odds ratio, 2.5 [95% confidence interval, 1.2–4.9]; P = .01). Younger age, having an underlying pulmonary disorder, and the presence of respiratory syncytial virus were also associated with LRTD or severe LRTD in multivariable models. The risks of LRTD or severe LRTD did not differ among the children with different HCoV strains. CONCLUSIONS: The presence of a copathogen and host factors, including an immunocompromised state, were associated with increased risk for severe LRTD. Recognizing risk factors for severe respiratory illness might assist in risk stratification.

positive: Concurrent chilblains and retinal vasculitis in a child with COVID-19 Reports on COVID-19 in children are limited. Despite new data emerging, and understanding of the disease improves rapidly, there are as yet several features and complications related to the disease that remain unknown. Herein, we report the first case of a child with chilblains and retinal vasculitis related to COVID-19.

positive: Acute myocarditis and multisystem inflammatory emerging disease following SARS-CoV-2 infection in critically ill children BACKGROUND: A recent increase in children admitted with hypotensive shock and fever in the context of the COVID-19 outbreak requires an urgent characterization and assessment of the involvement of SARS-CoV-2 infection. This is a case series performed at 4 academic tertiary care centers in Paris of all the children admitted to the pediatric intensive care unit (PICU) with shock, fever and suspected SARS-CoV-2 infection between April 15th and April 27th, 2020. RESULTS: 20 critically ill children admitted for shock had an acute myocarditis (left ventricular ejection fraction, 35% (25–55); troponin, 269 ng/mL (31–4607)), and arterial hypotension with mainly vasoplegic clinical presentation. The first symptoms before PICU admission were intense abdominal pain and fever for 6 days (1–10). All children had highly elevated C-reactive protein (> 94 mg/L) and procalcitonin (> 1.6 ng/mL) without microbial cause. At least one feature of Kawasaki disease was found in all children (fever, n = 20, skin rash, n = 10; conjunctivitis, n = 6; cheilitis, n = 5; adenitis, n = 2), but none had the typical form. SARS-CoV-2 PCR and serology were positive for 10 and 15 children, respectively. One child had both negative SARS-CoV-2 PCR and serology, but had a typical SARS-CoV-2 chest tomography scan. All children but one needed an inotropic/vasoactive drug support (epinephrine, n = 12; milrinone, n = 10; dobutamine, n = 6, norepinephrine, n = 4) and 8 were intubated. All children received intravenous immunoglobulin (2 g per kilogram) with adjuvant corticosteroids (n = 2), IL 1 receptor antagonist (n = 1) or a monoclonal antibody against IL-6 receptor (n = 1). All children survived and were afebrile with a full left ventricular function recovery at PICU discharge. CONCLUSIONS: Acute myocarditis with intense systemic inflammation and atypical Kawasaki disease is an emerging severe pediatric disease following SARS-CoV-2 infection. Early recognition of this disease is needed and referral to an expert center is recommended. A delayed and inappropriate host immunological response is suspected. While underlying mechanisms remain unclear, further investigations are required to target an optimal treatment.

positive: SARS-CoV-2 testing and outcomes in the first 30 days after the first case of COVID-19 at an Australian children's hospital OBJECTIVE: International studies describing COVID-19 in children have shown low proportions of paediatric cases and generally a mild clinical course. We aimed to present early data on children tested for SARS-CoV-2 at a large Australian tertiary children's hospital according to the state health department guidelines, which varied over time. METHODS: We conducted a retrospective cohort study at The Royal Children's Hospital, Melbourne, Australia. It included all paediatric patients (aged 0-18 years) who presented to the ED or the Respiratory Infection Clinic (RIC) and were tested for SARS-CoV-2. The 30-day study period commenced after the first confirmed positive case was detected at the hospital on 21 March 2020, until 19 April 2020. We recorded epidemiological and clinical data. RESULTS: There were 433 patients in whom SARS-CoV-2 testing was performed in ED (331 [76%]) or RIC (102 [24%]). There were four (0.9%) who had positive SARS-CoV-2 detected, none of whom were admitted to hospital or developed severe disease. Of these SARS-CoV-2 positive patients, 1/4 (25%) had a comorbidity, which was asthma. Of the SARS-CoV-2 negative patients, 196/429 (46%) had comorbidities. Risk factors for COVID-19 were identified in 4/4 SARS-CoV-2 positive patients and 47/429 (11%) SARS-CoV-2 negative patients. CONCLUSION: Our study identified a very low rate of SARS-CoV-2 positive cases in children presenting to a tertiary ED or RIC, none of whom were admitted to hospital. A high proportion of patients who were SARS-CoV-2 negative had comorbidities.

positive: Coronavirus disease 2019 in children: Current status Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged from China in December 2019. The outbreak further exploded in Europe and America in mid-March 2020 to become a global health emergency. We reviewed recent published articles and on-line open messages on SARS-CoV-2-positive infants and children younger than 20 years of age. Symptoms are usually less severe in children than in adults. Twelve critically or mortally ill children were found in the published or news reports before April 6, 2020. Vertical transmission from the mother to her fetus or neonate has not been proven definitively. However, six early-onset (<7 days) and 3 late-onset neonatal SARS-CoV-2 infections were found in the literature. We also summarized the presentations and contact information of 24 SARS-CoV-2-positive children announced by the Taiwan Centers for Disease Control. Early identification and isolation, adequate management, prevention, and vaccine development are the keys to controlling the disease spread. Clinical physicians should be alert to asymptomatic children with COVID-19. Multidirectional investigations are crucial in the global fight against COVID-19.

positive: COVID-19 in children: Epidemiology, presentation, diagnosis and management The new pandemic coronavirus disease (COVID-19) has affected children, including neonates, who mostly comprise of approximately 2% of total confirmed cases. Most children are asymptomatic or have mild disease and much lower mortality compared to adults for yet unknown reasons. Recovery from illness has largely been universal and <2% have severe disease requiring intensive care. Standardised guidelines from initial studies are now available for diagnosis, treatment, and prevention. Treatment is mostly supportive with no recommendations for any specific drugs so far. As the pandemic evolves, it is expected that more children will be diagnosed and treated with evolving newer regimens. Research should now focus on early diagnosis, better drugs for children, intensive care modalities, and a universal vaccine. New developments will help in better prevention asides from the other precautionary measures already being practiced.

positive: Preliminary Estimates of the Prevalence of Selected Underlying Health Conditions Among Patients with Coronavirus Disease 2019 — United States, February 12–March 28, 2020 On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic (1). As of March 28, 2020, a total of 571,678 confirmed COVID-19 cases and 26,494 deaths have been reported worldwide (2). Reports from China and Italy suggest that risk factors for severe disease include older age and the presence of at least one of several underlying health conditions (3,4). U.S. older adults, including those aged ≥65 years and particularly those aged ≥85 years, also appear to be at higher risk for severe COVID-19-associated outcomes; however, data describing underlying health conditions among U.S. COVID-19 patients have not yet been reported (5). As of March 28, 2020, U.S. states and territories have reported 122,653 U.S. COVID-19 cases to CDC, including 7,162 (5.8%) for whom data on underlying health conditions and other known risk factors for severe outcomes from respiratory infections were reported. Among these 7,162 cases, 2,692 (37.6%) patients had one or more underlying health condition or risk factor, and 4,470 (62.4%) had none of these conditions reported. The percentage of COVID-19 patients with at least one underlying health condition or risk factor was higher among those requiring intensive care unit (ICU) admission (358 of 457, 78%) and those requiring hospitalization without ICU admission (732 of 1,037, 71%) than that among those who were not hospitalized (1,388 of 5,143, 27%). The most commonly reported conditions were diabetes mellitus, chronic lung disease, and cardiovascular disease. These preliminary findings suggest that in the United States, persons with underlying health conditions or other recognized risk factors for severe outcomes from respiratory infections appear to be at a higher risk for severe disease from COVID-19 than are persons without these conditions.

positive: Favourable outcome of coronavirus disease 2019 in a 1‐year‐old girl with acute myeloid leukaemia and severe treatment‐induced immunosuppression Since the beginning of coronavirus disease 2019 (COVID-19) pandemic outbreak, it has emerged that the clinical course and outcome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is definitely more favourable in children than in adults.1 Few cases of infection in children with cancer are described; also in these patients, except for one reported case,2 the disease was largely asymptomatic.3 Nevertheless, the management of COVID-19 in young patients with comorbidities, particularly cancer, remains a challenge for the clinician; further data are required to optimize the clinical approach to these cases.

positive: Managing COVID-19 disease in pediatric patients Children are less likely to be infected with SARS-CoV-2 than adults and often have a milder course of COVID-19 disease and a lower case fatality rate. Children account for an estimated 1% to 5% of those diagnosed with COVID-19. Even so, preschool-aged children, infants, and children with underlying health conditions may still be at risk for severe disease and complications. Unique aspects of COVID-19 presentation and disease course in children and possible vertical transmission to newborns from COVID-19-positive mothers are discussed.

positive: Lessons from COVID-19 in children: Key hypotheses to guide preventative and therapeutic strategies The current pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), reveals a peculiar trend of milder disease and lower case fatality in children compared to adults. Consistent epidemiologic evidence of reduced severity of infection in children across different populations and countries suggests there are underlying biologic differences between children and adults that mediate differential disease pathogenesis. This presents a unique opportunity to learn about disease modifying host factors from pediatric populations. Our review summarizes the current knowledge of pediatric clinical disease, role in transmission, risks for severe disease, protective immunity, as well as novel therapies and vaccine trials for children. We then define key hypotheses and areas for future research that can use the pediatric model of disease, transmission, and immunity to develop preventive and therapeutic strategies for people of all age groups.

positive: Pediatric COVID-19: Systematic review of the literature. OBJECTIVES There is limited data regarding the demographics and clinical features of SARS-CoV-2 infection in children. This information is especially important as pneumonia is the single leading cause of death in children worldwide. This Systematic Review aims to elucidate a better understanding of the global impact of COVID-19 on the pediatric population. METHODS A systematic review of the literature was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to gain insight into pediatric COVID-19 epidemiology. Specifically, Pubmed and Google Scholar databases were searched to identify any relevant article with a focus on Pediatric Covid 19, Pediatric Covid-19, Pediatric SARS-COV-2, and Pediatric Coronavirus 19. References within the included articles were reviewed. All articles that met criteria where analyzed for demographics, clinical, laboratory, radiographic, treatment and outcomes data. RESULTS Ten studies including two case series and 8 retrospective chart reviews, altogether describing a total of 2914 pediatric patients with COVID-19 were included in this systematic review. Of the patients whose data was available, 56% were male, the age range was 1 day to 17 years, 79% were reported to have no comorbidities, and of the 21% with comorbidities, the most common were asthma, immunosupression, and cardiovascular disease. Of pediatric patients that were tested and positive for an infection with SARS-CoV-2, patients were asymptomatic, 14.9% of the time. Patients presented with cough (48%), fever (47%) and sore throat/pharyngitis (28.6%), more commonly than with upper respiratory symptoms/rhinorrhea/sneezing/nasal congestion (13.7%), vomiting/nausea (7.8%) and diarrhea (10.1%). Median lab values including those for WBC, lymphocyte count and CRP, were within the reference ranges with the exception of procalcitonin levels, which were slightly elevated in children with COVID-19 (median procalcitonin levels ranged from 0.07 to 0.5 ng/mL. Computed tomography (CT) results suggest that unilateral CT imaging findings are present 36% of cases while 64% of pediatric patients with COVID-19 had bilateral findings. Of the studies with age specific hospitalization data available, 27.0% of patients hospitalized were infants under 1 year of age. Various treatment regimens including interferon, antivirals, and hydroxychloroquine therapies have been trialed on the pediatric population but there are currently no studies showing efficacy of one regimen over the other. The mortality rate of children that were hospitalized with COVID-19 was 0.0018%. CONCLUSION In contrast to adults, most infected children appear to have a milder course and have better outcomes overall. Additional care may be needed for children with comorbidities and younger children. This review also suggests that unilateral CT chest imaging findings were seen in 36.4% pediatric COVID-19 patients. This is particularly concerning as the work-up of pediatric patients with cough may warrant a bronchoscopy to evaluate for airway foreign bodies. Extra precautions need to be taken with personal protective equipment for these cases, as aerosolizing procedures may be a method of viral transmission. LEVEL OF EVIDENCE 4 (Systematic Review).

positive: [Clinical features of coronavirus disease 2019 in children aged <18 years in Jiangxi, China: an analysis of 23 cases] OBJECTIVE: To study the clinical features of coronavirus disease 2019 (COVID-19) in children aged <18 years. METHODS: A retrospective analysis was performed from the medical data of 23 children, aged from 3 months to 17 years and 8 months, who were diagnosed with COVID-19 in Jiangxi, China from January 21 to February 29, 2020. RESULTS: Of the 23 children with COVID-19, 17 had family aggregation. Three children (13%) had asymptomatic infection, 6 (26%) had mild type, and 14 (61%) had common type. Among these 23 children, 16 (70%) had fever, 11 (48%) had cough, 8 (35%) had fever and cough, and 8 (35%) had wet rales in the lungs. The period from disease onset or the first nucleic acid-positive detection of SARS-CoV-2 to the virus nucleic acid negative conversion was 6-24 days (median 12 days). Of the 23 children, 3 had a reduction in total leukocyte count, 2 had a reduction in lymphocytes, 2 had an increase in C-reactive protein, and 2 had an increase in D-dimer. Abnormal pulmonary CT findings were observed in 12 children, among whom 9 had patchy ground-glass opacities in both lungs. All 23 children received antiviral therapy and were recovered. CONCLUSIONS: COVID-19 in children aged <18 years often occurs with family aggregation, with no specific clinical manifestation and laboratory examination results. Most of these children have mild symptoms and a good prognosis. Epidemiological history is of particular importance in the diagnosis of COVID-19 in children aged <18 years.

positive: Coronavirus disease (COVID-19) and neonate: What neonatologist need to know Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause china epidemics with high morbidity and mortality, the infection has been transmitted to other countries. About three neonates and more than 230 children cases are reported. The disease condition of the main children was mild. There is currently no evidence that SARS-CoV-2 can be transmitted transplacentally from mother to the newborn. The treatment strategy for children with Coronavirus disease (COVID-19) is based on adult experience. Thus far, no deaths have been reported in the pediatric age group. This review describes the current understanding of COVID-19 infection in newborns and children.

positive: COVID-19 disease in children: not as mild as we have been led to believe

positive: Epidemiology, Clinical Features, and Disease Severity in Patients With Coronavirus Disease 2019 (COVID-19) in a Children's Hospital in New York City, New York. Importance Descriptions of the coronavirus disease 2019 (COVID-19) experience in pediatrics will help inform clinical practices and infection prevention and control for pediatric facilities. Objective To describe the epidemiology, clinical, and laboratory features of patients with COVID-19 hospitalized at a children's hospital and to compare these parameters between patients hospitalized with and without severe disease. Design, Setting, and Participants This retrospective review of electronic medical records from a tertiary care academically affiliated children's hospital in New York City, New York, included hospitalized children and adolescents (≤21 years) who were tested based on suspicion for COVID-19 between March 1 to April 15, 2020, and had positive results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Exposures Detection of SARS-CoV-2 from a nasopharyngeal specimen using a reverse transcription-polymerase chain reaction assay. Main Outcomes and Measures Severe disease as defined by the requirement for mechanical ventilation. Results Among 50 patients, 27 (54%) were boys and 25 (50%) were Hispanic. The median days from onset of symptoms to admission was 2 days (interquartile range, 1-5 days). Most patients (40 [80%]) had fever or respiratory symptoms (32 [64%]), but 3 patients (6%) with only gastrointestinal tract presentations were identified. Obesity (11 [22%]) was the most prevalent comorbidity. Respiratory support was required for 16 patients (32%), including 9 patients (18%) who required mechanical ventilation. One patient (2%) died. None of 14 infants and 1 of 8 immunocompromised patients had severe disease. Obesity was significantly associated with mechanical ventilation in children 2 years or older (6 of 9 [67%] vs 5 of 25 [20%]; P = .03). Lymphopenia was commonly observed at admission (36 [72%]) but did not differ significantly between those with and without severe disease. Those with severe disease had significantly higher C-reactive protein (median, 8.978 mg/dL [to convert to milligrams per liter, multiply by 10] vs 0.64 mg/dL) and procalcitonin levels (median, 0.31 ng/mL vs 0.17 ng/mL) at admission (P < .001), as well as elevated peak interleukin 6, ferritin, and D-dimer levels during hospitalization. Hydroxychloroquine was administered to 15 patients (30%) but could not be completed for 3. Prolonged test positivity (maximum of 27 days) was observed in 4 patients (8%). Conclusions and Relevance In this case series study of children and adolescents hospitalized with COVID-19, the disease had diverse manifestations. Infants and immunocompromised patients were not at increased risk of severe disease. Obesity was significantly associated with disease severity. Elevated inflammatory markers were seen in those with severe disease.

positive: A single-center, retrospective study of COVID-19 features in children: a descriptive investigation BACKGROUND: Compared to adults, there are relatively few studies on COVID-19 infection in children, and even less focusing on the unique features of COVID-19 in children in terms of laboratory findings, locations of computerized tomography (CT) lesions, and the role of CT in evaluating clinical recovery. The objective of this study is to report the results from patients at Wuhan Children's Hospital, located within the initial center of the outbreak. METHODS: Clinical, imaging, and laboratory data of 76 children were collected retrospectively and analyzed with the Fisher exact test and Cox regression statistical methods. RESULTS: Among 50 children with a positive COVID-19 real-time reverse-transcriptase polymerase chain reaction (PCR), five had negative PCR results initially but showed positive results in subsequent tests. Eight (16%) patients had lymphopenia, seven (14%) with thrombocytopenia, four (8%) with lymphocytosis, two (4%) with thrombocytosis, ten (20%) with elevated C-reactive protein, four (8%) with hemoglobin above, and six (12%) with below standard reference values. Seven (14%) of the 50 had no radiologic evidence of disease on chest CT. For the 43 patients who had abnormal CT findings, in addition to previously reported patterns of ground-glass opacity (67%), local patchy shadowing (37%), local bilateral patchy shadowing (21%), and lesion location of lower lobes (65%), other CT features include that an overwhelming number of pediatric patients had lesions in the subpleural area (95%) and 22 of the 28 lower lobe lesions were in the posterior segment (78%). Lesions in most of the 15 patients (67%) who received chest CT at discharge were not completely absorbed, and 26% of these pediatric patients had CT lesions that were either unchanged or worse. CONCLUSIONS: There were a few differences between COVID-19 children and COVID-19 adults in terms of laboratory findings and CT characteristics. CT is a powerful tool to detect and characterize COVID-19 pneumonia but has little utility in evaluating clinical recovery for children. These results oppose current COVID-19 hospital discharge criteria in China, as one requirement is that pulmonary imaging must show significant lesion absorption prior to discharge. These differences between pediatric and adult cases of COVID-19 may necessitate pediatric-specific discharge criteria.

positive: Clinical features of pediatric patients with coronavirus disease (COVID-19) Abstract Background Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has spread around the world, and reports of children with COVID-19 are increasing. Objectives To assess clinical profiles of pediatric COVID-19. Study design A retrospective analysis was undertaken using clinical data of sixteen children (11 months-14 years) diagnosed with COVID-19 between January 1, 2020 and March 17, 2020 at Xiangyang Central Hospital, Hubei province, China. Results All children had positive epidemiologic histories, 12 (12/16, 75 %) involving family units. The illnesses were either mild (5/16, 31.3 %) or ordinary (11/16, 68.8 %), presenting as follows: asymptomatic (8/16, 50 %), fever and/or cough (8/16, 50 %). Four asymptomatic patients (4/16, 25 %) in ordinary cases had chest computed tomography (CT) abnormalities. Leukocyte counts were normal in 14 cases(88 %), but 2 patients (12.5 %) had leukopenia, and 1 (6.3 %) was lymphopenic. There were 11 patients with chest CT abnormalities, some nodular, others small patchy and others ground-glass opacities. In asymptomatic children, the median time to SRAS-CoV-2 nucleic acid test(NAT) positivity once exposed to a family member with confirmed infection was 15.5 days (range, 10–26 days). The median time to first NAT-negative conversion was 5.5 days (range, 1–23 days). Conclusions COVID-19 in children of Xiangyang city is often family acquired and not serious, with favorable outcomes. Asymptomatic children can be diagnosed as pneumonia because of chest CT abnormalities. It is essential to actively screen this segment of the population.

positive: Paediatric COVID‐19 admissions in a region with open schools during the two first months of the pandemic According to the United Nations Educational, Science and Cultural Organization, 194 countries had implemented country‐wide school closures by April 1(st) 2020 in an effort to combat the COVID‐19 pandemic. It’s estimated that those closures affected 91.3% of students across the globe. However, Sweden adopted a different approach to the strict lockdowns imposed elsewhere and day care centres and schools for children up to 15 years of age remained open. The strategy decision to shift schools to distance learning only for children aged 16 years and older was influenced by multiple factors, including the potential impact on school closures on the availability of the healthcare work force, the increasing evidence of mainly mild infections among children and the potential negative consequences of school closures for younger children.

positive: COVID‐19 in pregnancy: risk of adverse neonatal outcomes We read with great interest the study by Siyu Chen and colleagues. The authors evaluated the clinical features and outcomes of five pregnant patients with COVID‐19 at term, whose delivery was uneventful and led to favorable perinatal outcomes for both mother and neonate. We would like to draw attention to a growing body of evidence that now points towards an under‐addressed association between preterm maternal SARS‐CoV‐2 infection, preterm delivery and adverse neonatal outcomes, which is not reflected in Chen et al.'s small cohort. We also stress that vertical transmission, which was not tested for by Chen et al., should not be excluded as a potential mechanism for viral spread. Centers should therefore be meticulous in their approach to a SARS‐CoV‐2+ pregnancy to optimize clinical outcomes for both mother and child. This article is protected by copyright. All rights reserved.

positive: A wake-up call: COVID-19 and its impact on children's health and wellbeing

positive: Children are unlikely to be the main drivers of the COVID‐19 pandemic – a systematic review AIM: Many countries have closed schools and kindergartens to minimise COVID‐19, but the role that children play in disease transmission is unclear. METHODS: A systematic literature review of the MEDLINE and EMBASE databases and medRxiv/bioRxiv preprint servers to 11 May 2020 identified published and unpublished papers on COVID‐19 transmission by children. RESULTS: We identified 700 scientific papers and letters and 47 full texts were studied in detail. Children accounted for a small fraction of COVID‐19 cases and mostly had social contacts with peers or parents, rather than older people at risk of severe disease. Data on viral loads were scarce, but indicated that children may have lower levels than adults, partly because they often have fewer symptoms, and this should decrease the transmission risk. Household transmission studies showed that children were rarely the index case and case studies suggested that children with COVID‐19 seldom caused outbreaks. However, it is highly likely that children can transmit the SARS‐COV‐2 virus, which causes COVID‐19, and even asymptomatic children can have viral loads. CONCLUSION: Children are unlikely to be the main drivers of the pandemic. Opening up schools and kindergartens is unlikely to impact COVID‐19 mortality rates in older people.

positive: Chest CT imaging characteristics of COVID-19 pneumonia in preschool children: a retrospective study BACKGROUND: Recently, the World Health Organization has declared the coronavirus disease 2019 (COVID-19) outbreak a public health emergency of international concern. So far, however, limited data are available for children. Therefore, we aimed to investigate the clinical and chest CT imaging characteristics of COVID-19 in preschool children. METHODS: From January 26, 2020 to February 20, 2020, the clinical and initial chest CT imaging data of eight preschool children with laboratory-confirmed COVID-19 from two hospitals were retrospectively collected. The chest CT imaging characteristics, including the distribution, shape, and density of lesions, and the pleural effusion, pleural changes, and enlarged lymph nodes were evaluated. RESULTS: Two cases (25%) were classified as mild type, and they showed no obvious abnormal CT findings or minimal pleural thickening on the right side. Five cases (62.5%) were classified as moderate type. Among these patients, one case showed consolidation located in the subpleural region of the right upper lobe, with thickening in the adjacent pleura; one case showed multiple consolidation and ground-glass opacities with blurry margins; one case displayed bronchial pneumonia-like changes in the left upper lobe; and two cases displayed asthmatic bronchitis-like changes. One case (12.5%) was classified as critical type and showed bronchial pneumonia-like changes in the bilateral lungs, presenting blurred and messy bilateral lung markings and multiple patchy shadows scattered along the lung markings with blurry margins. CONCLUSIONS: The chest CT findings of COVID-19 in preschool children are atypical and various. Accurate diagnosis requires a comprehensive evaluation of epidemiological, clinical, laboratory and CT imaging data.

positive: Children and SARS-CoV-2 infection: innocent bystanders…until proven otherwise In this commentary, we focus our attention on what is known about SARS-CoV-2 infection in the pediatric population. We report literature and National data. The possible and different explanations for understanding why the infection seems to be more benign and less frequent in children are discussed. The possible role of children in the COVID-19 viral disease pandemic is also commented. Finally, our work suggests to search for future evidence and containment strategies to manage virus spread.

positive: Covid-19 in children: A brief overview after three months experience. Severe Acute Respiratory Syndrome - Coronavirus - 2 (SARS-CoV-2) and its related Coronavirus Disease - 19 (COVID-19) has become a health emergency worldwide. The medical community has been concerned since the beginning of the outbreak about the potential impact of COVID-19 in children, especially in those with underlying chronic diseases. Fortunately, COVID-19 has been reported to be less severe in children than in adults. However, epidemiologic and clinical data are scarce. Children show unique features of SARS-CoV-2 involvement that may account for the low rate of infection and death in this age group. The purpose of this review is to summarize the most relevant evidence of COVID-19 in children highlighting similarities and differences with adults.

positive: Safeguarding children with long-term conditions from COVID-19. Professor Alan Glasper, from the University of Southampton, discusses strategies to protect children with long-term health conditions from acquiring the disease caused by the SARS-CoV-2 virus.

positive: Clinical manifestations of children with COVID‐19: A systematic review BACKGROUND: The coronavirus disease 2019 (COVID‐19) outbreak is an unprecedented global public health challenge, leading to thousands of deaths every day worldwide. Despite the epidemiological importance, clinical patterns of children with COVID‐19 remain unclear. The aim of this study was to describe the clinical, laboratorial, and radiological characteristics of children with COVID‐19. METHODS: The Medline database was searched between December 1st 2019 and April 6th 2020. No language restrictions were applied. Inclusion criteria were (a) studied patients younger than 18 years old; (b) presented original data from cases of COVID‐19 confirmed by reverse‐transcription polymerase chain reaction; and (c) contained descriptions of clinical manifestations, laboratory tests, or radiological examinations. RESULTS: A total of 38 studies (1124 cases) were included. From all the cases, 1117 had their severity classified: 14.2% were asymptomatic, 36.3% were mild, 46.0% were moderate, 2.1% were severe, and 1.2% were critical. The most prevalent symptom was fever (47.5%), followed by cough (41.5%), nasal symptoms (11.2%), diarrhea (8.1%), and nausea/vomiting (7.1%). One hundred forty‐five (36.9%) children were diagnosed with pneumonia and 43 (10.9%) upper airway infections were reported. Reduced lymphocyte count was reported in 12.9% of cases. Abnormalities in computed tomography were reported in 63.0% of cases. The most prevalent abnormalities reported were ground‐glass opacities, patchy shadows, and consolidations. Only one death was reported. CONCLUSIONS: Clinical manifestations of children with COVID‐19 differ widely from adult cases. Fever and respiratory symptoms should not be considered a hallmark of COVID‐19 in children.

positive: New spectrum of COVID-19 manifestations in children: Kawasaki-like syndrome and hyperinflammatory response Since late April 2020, data regarding Kawasaki-like syndrome and hyperinflammatory response in children associated with COVID-19 has rapidly emerged. Much remains unknown about the risk factors, pathogenesis, prognosis, and specific therapy for this emerging manifestation of COVID-19 known as Multisystem Inflammatory Syndrome in Children (MIS-C). MIS-C is rare and early recognition is crucial though no standardized treatment guideline have been established. Worldwide collaboration will be important as more cases are recognized going forward.

positive: Multisystem Inflammatory Syndrome in U.S. Children and Adolescents BACKGROUND: Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome. METHODS: We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms. RESULTS: We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki’s disease–like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%). CONCLUSIONS: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.)

positive: First Case of an Infant with COVID-19 in the Middle East The novel coronavirus (COVID-19) has been declared a worldwide pandemic. It was initially thought to spare children and adolescents as significantly smaller number of cases have been reported in the pediatric population in comparison to adults. Here, we report the case of a 16-month-old female infant from Lebanon who presented with fever and severe diarrhea and tested positive for COVID-19. Her symptoms started six days prior to presentation with no cough, rhinorrhea, or other respiratory manifestations reported. Chest radiography showed lobar consolidation and bronchial infiltrates. Blood culture was positive for Streptococcus pneumoniae. Stool and urine cultures were negative. She was treated with ceftriaxone and metronidazole. Her RT-PCR test was negative after five days of treatment, suggesting that children can clear the virus faster than adults. The patient likely contracted the virus from her parents, who because of the fear of social stigma hide recent history of respiratory illness. These findings serve as a practical reference for the clinical diagnosis and medical treatment of children with COVID-19.

positive: Cardiac MRI of Children with Multisystem Inflammatory Syndrome (MIS-C) Associated with COVID-19: Case Series This case series examines cardiac MRI findings in four children and adolescents admitted to intensive care in April 2020 for multisystem inflammatory syndrome and Kawasaki disease-like features related to COVID-19. Acute myocarditis occurred less than 1 week after onset of fever and gastrointestinal symptoms. Physical examination showed rash and cheilitis/conjunctivitis. All patients recovered after intravenous immunoglobulin therapy. SARS-CoV-2 RT-PCR was negative on nasopharyngeal, stool, and respiratory samples and was positive on serology. Cardiac MRI showed diffuse myocardial edema on T2-STIR sequences and native-T1 mapping, with no evidence of late gadolinium enhancement suggestive of replacement fibrosis or focal necrosis. These findings favor post-infectious myocarditis in children and adolescents with COVID-19.

positive: Human and novel coronavirus infections in children: a review. Coronaviruses, seven of which are known to infect humans, can cause a spectrum of clinical presentations ranging from asymptomatic infection to severe illness and death. Four human coronaviruses (hCoVs)-229E, HKU1, NL63 and OC43-circulate globally, commonly infect children and typically cause mild upper respiratory tract infections. Three novel coronaviruses of zoonotic origin have emerged during the past two decades: severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV) and the recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. These novel coronaviruses are known to cause severe illness and death predominantly in older adults and those with underlying comorbidities. Consistent with what has been observed during the outbreaks of SARS and MERS, children with COVID-19 are more likely to be asymptomatic or to have mild-to-moderate illness, with few deaths reported in children globally thus far. Clinical symptoms and laboratory and radiological abnormalities in children have been similar to those reported in adults but are generally less severe. A rare multisystem inflammatory syndrome in children (MIS-C) which has resulted in critical illness and some deaths has recently been described. Clinical trials for therapeutics and vaccine development should include paediatric considerations. Children may play an important role in the transmission of infection and outbreak dynamics and could be a key target population for effective measures to control outbreaks. The unintended consequences of the unprecedented scale and duration of pandemic control measures for children and families around the world should be carefully examined. ABBREVIATIONS 2019-nCoV, 2019 novel coronavirus; ADEM, acute demyelinating encephalomyelitis; AAP, American Academy of Pediatrics; ACE-2, angiotensin-converting enzyme 2; ARDS, acute respiratory distress syndrome; BCG, bacillus Calmette-Guérin; BNP, brain natriuretic peptide; CDC, Centers for Disease Control and Prevention; CRP, C-reactive protein; CSF, cerebrospinal fluid; COVID-19, coronavirus disease 2019; CT, computed tomography; CXR, chest X-ray; DOL, day of life; hCoV, human coronavirus; ICU, intensive care unit; IL, interleukin; IVIG, intravenous immunoglobulin; KD, Kawasaki disease; LDH, lactate dehydrogenase; MERS, Middle East respiratory syndrome; MERS-CoV, Middle East respiratory syndrome coronavirus; MEURI, monitored emergency use of unregistered and experimental interventions; MIS-C, multi-system inflammatory syndrome in children; PCR, polymerase chain reaction; PICU, paediatric intensive care unit; RNA, ribonucleic acid; RCT, randomised-controlled trial; RSV, respiratory syncytial virus; SARS, severe acute respiratory syndrome; SARS-CoV-1, severe acute respiratory syndrome coronavirus 1; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNF-alpha, tumour necrosis factor alpha; UK United Kingdom; UNICEF, United Nations Children's Fund; USA, United States of America; WHO, World Health Organization.

positive: Epidemiology and Clinical Features of Coronavirus Disease 2019 in Moroccan Children OBJECTIVES: This study aims to analyze the epidemiological and clinical features of coronavirus disease 19 (COVID-19) in a Moroccan pediatric population METHODS: A retrospective study of a cohort of 74 children with RT-PCR confirmed COVID-19 We collected information on clinical and laboratory features of all children (age <18 years) admitted between 2 March, 2020 and 1 April, 2020 RESULTS: The mean (SD) age of the 74 children (40 girls) was 7 (1 5) years The mean (SD) time from illness onset to diagnosis was 2 (1) days 54 children were asymptomatic, while eight had fever, and five cases had cough Recovery was after a mean (SD) of 12 (1) days CONCLUSION: COVID-19 was mostly mild in the pediatric population in Morocco

positive: Will Children Reveal their Secret? The Coronavirus Dilemma A recent ERJ editorial cited ACE2 upregulation as a key reason for the better outcomes of COVID-19 seen in paediatric patients. However, there is significant conflicting literature on the topic, and many questions about ACE2 physiology still unanswered

positive: Coronavirus Disease 2019 (COVID-19) in Children: Vulnerable or Spared? A Systematic Review The ongoing pandemic of coronavirus disease 2019 (COVID-19) has affected people from all cultures, religions, gender, and age groups around the world. In the last few months, several studies have been conducted on various aspects of COVID-19. Our goal was to see if the pediatric population is vulnerable to this infection. In this review, we conducted extensive research mainly by using the PubMed database. We used Medical Subject Headings (MeSH) and associated keywords to engage in an extensive search focussing on COVID-19 in the pediatric population. We discovered that most of the studies were from China, and some of them were in the Chinese language. However, English translations of many of the studies were available. For accessing the relevant statistical data, we relied on the World Health Organization (WHO) resources and the official website of the Ontario Government (ontario.ca). Most of the studies showed that the virus has affected the pediatric population. However, we found some differences among these studies regarding the severity of symptoms in children affected by COVID-19. While a few studies stated that the virus has presented with milder symptoms in the pediatric population, some studies have presented data of children who have suffered life-threatening complications due to COVID-19. Although the data is limited, we have been able to conclude from the studies we reviewed that COVID-19 does indeed affect children the same way as any other age group. Moreover, children can act as carriers of the virus and can endanger the lives of other individuals. Besides, neonates and infants can easily acquire the infection from family members without having any exposure to the outside world. Hence, utmost care should be taken while handling this population. More trials and studies should be conducted to analyze the impact of early diagnosis of infection in children and its management.

positive: Characteristic of COVID-19 infection in pediatric patients: early findings from two Italian Pediatric Research Networks Detailed data on clinical presentations and outcomes of children with COVID-19 in Europe are still lacking. In this descriptive study, we report on 130 children with confirmed COVID-19 diagnosed by 28 centers (mostly hospitals), in 10 regions in Italy, during the first months of the pandemic. Among these, 67 (51.5%) had a relative with COVID-19 while 34 (26.2%) had comorbidities, with the most frequent being respiratory, cardiac, or neuromuscular chronic diseases. Overall, 98 (75.4%) had an asymptomatic or mild disease, 11 (8.5%) had moderate disease, 11 (8.5%) had a severe disease, and 9 (6.9%) had a critical presentation with infants below 6 months having significantly increased risk of critical disease severity (OR 5.6, 95% CI 1.3 to 29.1). Seventy-five (57.7%) children were hospitalized, 15 (11.5%) needed some respiratory support, and nine (6.9%) were treated in an intensive care unit. All recovered. Conclusion:This descriptive case series of children with COVID-19, mostly encompassing of cases enrolled at hospital level, suggest that COVID-19 may have a non-negligible rate of severe presentations in selected pediatric populations with a relatively high rates of comorbidities. More studies are needed to further understand the presentation and outcomes of children with COVID-19 in children with special needs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00431-020-03683-8) contains supplementary material, which is available to authorized users.

positive: Epidemiology, Clinical Features, and Disease Severity in Patients With Coronavirus Disease 2019 (COVID-19) in a Children's Hospital in New York City, New York Importance: Descriptions of the coronavirus disease 2019 (COVID-19) experience in pediatrics will help inform clinical practices and infection prevention and control for pediatric facilities. Objective: To describe the epidemiology, clinical, and laboratory features of patients with COVID-19 hospitalized at a children's hospital and to compare these parameters between patients hospitalized with and without severe disease. Design, Setting, and Participants: This retrospective review of electronic medical records from a tertiary care academically affiliated children's hospital in New York City, New York, included hospitalized children and adolescents (≤21 years) who were tested based on suspicion for COVID-19 between March 1 to April 15, 2020, and had positive results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Exposures: Detection of SARS-CoV-2 from a nasopharyngeal specimen using a reverse transcription-polymerase chain reaction assay. Main Outcomes and Measures: Severe disease as defined by the requirement for mechanical ventilation. Results: Among 50 patients, 27 (54%) were boys and 25 (50%) were Hispanic. The median days from onset of symptoms to admission was 2 days (interquartile range, 1-5 days). Most patients (40 [80%]) had fever or respiratory symptoms (32 [64%]), but 3 patients (6%) with only gastrointestinal tract presentations were identified. Obesity (11 [22%]) was the most prevalent comorbidity. Respiratory support was required for 16 patients (32%), including 9 patients (18%) who required mechanical ventilation. One patient (2%) died. None of 14 infants and 1 of 8 immunocompromised patients had severe disease. Obesity was significantly associated with mechanical ventilation in children 2 years or older (6 of 9 [67%] vs 5 of 25 [20%]; P = .03). Lymphopenia was commonly observed at admission (36 [72%]) but did not differ significantly between those with and without severe disease. Those with severe disease had significantly higher C-reactive protein (median, 8.978 mg/dL [to convert to milligrams per liter, multiply by 10] vs 0.64 mg/dL) and procalcitonin levels (median, 0.31 ng/mL vs 0.17 ng/mL) at admission (P < .001), as well as elevated peak interleukin 6, ferritin, and D-dimer levels during hospitalization. Hydroxychloroquine was administered to 15 patients (30%) but could not be completed for 3. Prolonged test positivity (maximum of 27 days) was observed in 4 patients (8%). Conclusions and Relevance: In this case series study of children and adolescents hospitalized with COVID-19, the disease had diverse manifestations. Infants and immunocompromised patients were not at increased risk of severe disease. Obesity was significantly associated with disease severity. Elevated inflammatory markers were seen in those with severe disease.

positive: Features of COVID-19 post-infectious cytokine release syndrome in children presenting to the emergency department The 2019 coronavirus disease (COVID-19) has not appeared to affect children as severely as adults. However, approximately 1 month after the COVID-19 peak in New York City in April 2020, cases of children with prolonged fevers abruptly developing inflammatory shock-like states have been reported in Western Europe and the United States. This case series describes four previously healthy children with COVID-19 infection confirmed by serologic antibody testing, but negative by nasopharyngeal RT-PCR swab, presenting to the Pediatric Emergency Department (PED) with prolonged fever (5 or more days) and abrupt onset of hemodynamic instability with elevated serologic inflammatory markers and cytokine levels (IL-6, IL-8 and TNF-α). Emergency physicians must maintain a high clinical suspicion for this COVID-19 associated post-infectious cytokine release syndrome, with features that overlap with Kawasaki Disease (KD) and Toxic Shock Syndrome (TSS) in children with recent or current COVID-19 infection, as patients can decompensate quickly.

positive: SARS-COV-2 infection in children and newborns: a systematic review A recent outbreak of a novel Coronavirus responsible for a Severe Acute Respiratory Syndrome (SARS-CoV-2) is spreading globally. The aim of this study was to systematically review main clinical characteristics and outcomes of SARS-CoV-2 infections in pediatric age. An electronic search was conducted in PubMed database. Papers published between 1 January and 1 May 2020 including children aged 0–18 years were selected. Sixty-two studies and three reviews were included, with a total sample size of 7480 children (2428/4660 males, 52.1%; weighted mean age 7.6 years). Patients showed mainly mild (608/1432, 42.5%) and moderate (567/1432, 39.6%) signs of the infection. About 2% of children were admitted to the pediatric intensive care unit. The most commonly described symptoms were fever (51.6%) and cough (47.3%). Laboratory findings were often unremarkable. Children underwent a chest CT scan in 73.9% of all cases, and 32.7% resulted normal. Overall, the estimated mortality was 0.08%. A higher proportion of newborns was severely ill (12%) and dyspnea was the most common reported sign (40%). Conclusion: SARS-CoV-2 affects children less severely than adults. Laboratory and radiology findings are mainly nonspecific. Larger epidemiological and clinical cohort studies are needed to better understand possible implications of COVID-19 infection in children. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00431-020-03684-7) contains supplementary material, which is available to authorized users.

positive: COVID-19 and children. From Luis Sepulveda to Madam Mim

positive: COVID-19 in Children in the United States: Intensive Care Admissions, Estimated Total Infected, and Projected Numbers of Severe Pediatric Cases in 2020 IMPORTANCE: A surge in severe cases of COVID-19 (coronavirus disease 2019) in children would present unique challenges for hospitals and public health preparedness efforts in the United States. OBJECTIVE: To provide evidence-based estimates of children infected with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and projected cumulative numbers of severely ill pediatric COVID-19 cases requiring hospitalization during the US 2020 pandemic. DESIGN: Empirical case projection study. MAIN OUTCOMES AND MEASURES: Adjusted pediatric severity proportions and adjusted pediatric criticality proportions were derived from clinical and spatiotemporal modeling studies of the COVID-19 epidemic in China for the period January-February 2020. Estimates of total children infected with SARS-CoV-2 in the United States through April 6, 2020, were calculated using US pediatric intensive care unit (PICU) cases and the adjusted pediatric criticality proportion. Projected numbers of severely and critically ill children with COVID-19 were derived by applying the adjusted severity and criticality proportions to US population data, under several scenarios of cumulative pediatric infection proportion (CPIP). RESULTS: By April 6, 2020, there were 74 children who had been reported admitted to PICUs in 19 states, reflecting an estimated 176 190 children nationwide infected with SARS-CoV-2 (52 381 infants and toddlers younger than 2 years, 42 857 children aged 2-11 years, and 80 952 children aged 12-17 years). Under a CPIP scenario of 5%, there would be 3.7 million children infected with SARS-CoV-2, 9907 severely ill children requiring hospitalization, and 1086 critically ill children requiring PICU admission. Under a CPIP scenario of 50%, 10 865 children would require PICU admission, 99 073 would require hospitalization for severe pneumonia, and 37.0 million would be infected with SARS-CoV-2. CONCLUSIONS AND RELEVANCE: Because there are 74.0 million children 0 to 17 years old in the United States, the projected numbers of severe cases could overextend available pediatric hospital care resources under several moderate CPIP scenarios for 2020 despite lower severity of COVID-19 in children than in adults.

positive: Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units Importance: The recent and ongoing coronavirus disease 2019 (COVID-19) pandemic has taken an unprecedented toll on adults critically ill with COVID-19 infection. While there is evidence that the burden of COVID-19 infection in hospitalized children is lesser than in their adult counterparts, to date, there are only limited reports describing COVID-19 in pediatric intensive care units (PICUs). Objective: To provide an early description and characterization of COVID-19 infection in North American PICUs, focusing on mode of presentation, presence of comorbidities, severity of disease, therapeutic interventions, clinical trajectory, and early outcomes. Design, Setting, and Participants: This cross-sectional study included children positive for COVID-19 admitted to 46 North American PICUs between March 14 and April 3, 2020. with follow-up to April 10, 2020. Main Outcomes and Measures: Prehospital characteristics, clinical trajectory, and hospital outcomes of children admitted to PICUs with confirmed COVID-19 infection. Results: Of the 48 children with COVID-19 admitted to participating PICUs, 25 (52%) were male, and the median (range) age was 13 (4.2-16.6) years. Forty patients (83%) had significant preexisting comorbidities; 35 (73%) presented with respiratory symptoms and 18 (38%) required invasive ventilation. Eleven patients (23%) had failure of 2 or more organ systems. Extracorporeal membrane oxygenation was required for 1 patient (2%). Targeted therapies were used in 28 patients (61%), with hydroxychloroquine being the most commonly used agent either alone (11 patients) or in combination (10 patients). At the completion of the follow-up period, 2 patients (4%) had died and 15 (31%) were still hospitalized, with 3 still requiring ventilatory support and 1 receiving extracorporeal membrane oxygenation. The median (range) PICU and hospital lengths of stay for those who had been discharged were 5 (3-9) days and 7 (4-13) days, respectively. Conclusions and Relevance: This early report describes the burden of COVID-19 infection in North American PICUs and confirms that severe illness in children is significant but far less frequent than in adults. Prehospital comorbidities appear to be an important factor in children. These preliminary observations provide an important platform for larger and more extensive studies of children with COVID-19 infection.

positive: Coronavirus disease (COVID‐19): Characteristics in children and considerations for dentists providing their care The emergence of the novel virus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has caused a global pandemic called coronavirus disease (COVID‐19) and has become one of the most significant challenges to the healthcare profession. Dental practices are focal points for cross‐infection, and care must be taken to minimise the risk of infection to, from, or between dental care professionals and patients. The COVID‐19 epidemiological and clinical characteristics are still being collated but children's symptoms seem to be milder than those that adults experience. It is unknown whether certain groups, for example children with comorbidities, might be at a higher risk of more severe illness. Emerging data on disease spread in children, affected by COVID‐19, have not been presented in detail. The purpose of this article was to report current data on the paediatric population affected with COVID‐19 and highlight considerations for dentists providing care for children during this pandemic. All members of the dental team have a professional responsibility to keep themselves informed of current guidance and be vigilant in updating themselves as recommendations are changing so quickly.

positive: The clinical and immunological features of pediatric COVID-19 patients in China Abstract In December 2019, the corona virus disease 2019 (COVID-19) caused by novel coronavirus (SARS-CoV-2) emerged in Wuhan, China and rapidly spread worldwide. Few information on clinical features and immunological profile of COVID-19 in paediatrics. The clinical features and treatment outcomes of twelve paediatric patients confirmed as COVID-19 were analyzed. The immunological features of children patients was investigated and compared with twenty adult patients. The median age was 14.5-years (range from 0.64 to 17), and six of the patients were male. The average incubation period was 8 days. Clinically, cough (9/12, 75%) and fever (7/12, 58.3%) were the most common symptoms. Four patients (33.3%) had diarrhea during the disease. As to the immune profile, children had higher amount of total T cell, CD8+ T cell and B cell but lower CRP levels than adults (P < 0.05). Ground-glass opacity (GGO) and local patchy shadowing were the typical radiological findings on chest CT scan. All patients received antiviral and symptomatic treatment and the symptom relieved in 3–4 days after admitted to hospital. The paediatric patients showed mild symptom but with longer incubation period. Children infected with SARS-CoV-2 had different immune profile with higher T cell amount and low inflammatory factors level, which might ascribed to the mild clinical symptom. We advise that nucleic acid test or examination of serum IgM/IgG antibodies against SARS-CoV-2 should be taken for children with exposure history regardless of clinical symptom.

positive: Additional hypotheses about why COVID‐19 is milder in children than adults We read with great interest the editorial by Brodin discussing why COVID-19 appears to be so mild in children (1). In particular, the author discussed the potential theories that could explain why children have a lower incidence and milder clinical manifestations than adults. However, we feel it is important to present some other additional hypotheses in order to address all the potential theories.

positive: Challenges in Neonatal COVID-19 Infection

positive: Clinical Features and Outcome of SARS-CoV-2 Infection in Children: A Systematic Review and Meta-analysis. BACKGROUND AND OBJECTIVE Knowledge about COVID-19 in children is limited due to the paucity of reported data. The pediatric age group comprises only less than 5% of total COVID-19 worldwide, therefore, large studies in this population are unlikely in the immediate future. Hence, we planned to synthesize the current data that will help in a better understanding of COVID-19 in children. METHODS Four different electronic databases (MEDLINE, EMBASE, Web of Science, and CENTRAL) were searched for articles related to COVID-19 in the pediatric population. We included studies reporting disease characteristics and outcomes of COVID-19 in patients aged less than 19 years. We performed a random-effect meta-analysis to provide pooled estimates of various disease characteristics. RESULTS 27 studies (4857 patients) fulfilling the eligibility criteria were included in this systematic review, from a total of 883 records. About half of the patients had each of fever and cough, 11% (6-17%) had fast breathing, and 6-13% had gastrointestinal manifestations. Most of the patients had mild to moderate disease, and only 4% had a severe or critical illness. Leukopenia was the commonest reported laboratory abnormality. CONCLUSION Even among the symptomatic COVID-19 cases, severe manifestations are seen in very few children. Though fever and respiratory symptoms are most common, many children also have gastrointestinal manifestations.

positive: COVID- 19 Infection in Children: Estimating Pediatric Morbidity and Mortality BACKGROUND: Estimates of pediatric morbidity and mortality from COVID-19 are vital for planning optimal use of human and material resources throughout this pandemic. METHODS: Government websites from countries with minimum 1000 cases in adults and children on April 13, 2020 were searched to find the number of cases confirmed in children, the age range, and the number leading to hospitalization, intensive care unit (ICU) admission or death. A systematic literature search was performed April 13, 2020 to find additional data from cases series. RESULTS: Data on pediatric cases were available from government websites for 23 of the 70 countries with minimum 1000 cases by April 13, 2020. Of 424 978 cases in these 23 countries, 8113 (1.9%) occurred in children. Nine publications provided data from 4251 cases in 4 additional countries. Combining data from the websites and the publications, 330 of 2361 cases required admission (14%). The ICU admission rate was 2.2 % of confirmed cases (44 of 2031) and 7.2% of admitted children (23 of 318). Death was reported for 15 cases. CONCLUSION: Children accounted for 1.9% of confirmed cases. The true incidence of pediatric infection and disease will only be known once testing is expanded to individuals with less severe or no symptoms. Admission rates vary from 0.3 to 10% of confirmed cases (presumably varying with the threshold for testing) with about 7% of admitted children requiring ICU care. Death is rare in middle and high income countries.

positive: A case series of children with Coronavirus Disease 2019: what have we learned?

positive: Managing Children with Renal Diseases during COVID-19 Pandemic The coronavirus outbreak is a rapidly evolving pandemic, placing unprecedented strain on health-care systems COVID-19 presents challenges for management of children with renal diseases especially those receiving long-term immunosuppressive medications, including renal transplant recipients and those with chronic kidney disease and acute kidney injury requiring dialysis Our preparedness for managing this vulnerable group of children is the need of the hour The purpose of this article is to provide guidance to caregivers and health care personnel involved in management of children with renal diseases and to ensure patient well-being, while protecting staff from infection

positive: Clinical and epidemiological characteristics of 34 children with 2019 novel coronavirus infection in Shenzhen/ 中华儿科杂志 Objective@#To describe the characteristics of clinical manifestations and epidemiology of children with 2019 novel coronavirus (2019-nCoV) infection.@*Methods@#All 34 children with laboratory-confirmed 2019-nCoV infection by quantitative real-time reverse transcription-PCR through nasopharyngeal swab specimens were admitted to the Third People’s Hospital of Shenzhen from January 19 to Febuary 7, 2020. Clinical data and epidemiological history of these patients were retrospectively collected and analyzed.@*Results@#Among the 34 cases, 14 were males, and 20 were females. The median age was 8 years and 11 months. No patients had underlying diseases. There were 28 children (82%) related with a family cluster outbreak. There were 26 children (76%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 22 (65%) common cases, 9 (26%) mild cases and 3 (8.8%) asymptomatic cases. No severe or critical cases were identified. The most common symptoms were fever (17 cases, 50%) and cough (13 cases, 38% ). In the 34 cases, the white blood cell counts of 28 cases (82%) were normal. Five cases had white blood cell counts more than 10×109/L. One case had white blood cell counts less than 4×109/L. Neutropenia and lymphopenia was found in one case, respectively. C-reactive protein levels and erythrocyte sedimentation rates were elevated in 1 and 5 case, respectively. Elevated procalcitonin was found in 1 case and D-Dimer in 3 cases. The levels of lactic dehydrogenase (LDH) were more than 400 U/L in 10 cases. The CT images of these patients showed bilateral multiple patchy or nodular ground-glass opacities and/or infiltrating shadows in middle and outer zone of the lung or under the pleura. Twenty patients were treated with lopinavir and ritonavir. Glucocorticoids and immunoglobulin were not used in any cases. All the cases improved and were discharged from hospital. Further following up was need.@*Conclusions@#The clinical manifestations in children with 2019-nCoV infection are non-specific and are milder than that in adults. Chest CT scanning is heplful for early diagnosis. Children's infection is mainly caused by family cluster outbreak and imported cases. Family daily prevention is the main way to prevent 2019-nCoV infection.

positive: Paediatric aspects of COVID-19: an update

positive: Pathophysiology of COVID-19: Why Children Fare Better than Adults? The world is facing Coronavirus Disease-2019 (COVID-19) pandemic, which is causing a large number of deaths and burden on intensive care facilities. It is caused by Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) originating in Wuhan, China. It has been seen that fewer children contract COVID-19 and among infected, children have less severe disease. Insights in pathophysiological mechanisms of less severity in children could be important for devising therapeutics for high-risk adults and elderly. Early closing of schools and day-care centers led to less frequent exposure and hence, lower infection rate in children. The expression of primary target receptor for SARS-CoV-2, i.e. angiotensin converting enzyme-2 (ACE-2), decreases with age. ACE-2 has lung protective effects by limiting angiotensin-2 mediated pulmonary capillary leak and inflammation. Severe COVID-19 disease is associated with high and persistent viral loads in adults. Children have strong innate immune response due to trained immunity (secondary to live-vaccines and frequent viral infections), leading to probably early control of infection at the site of entry. Adult patients show suppressed adaptive immunity and dysfunctional over-active innate immune response in severe infections, which is not seen in children. These could be related to immune-senescence in elderly. Excellent regeneration capacity of pediatric alveolar epithelium may be contributing to early recovery from COVID-19. Children, less frequently, have risk factors such as co-morbidities, smoking, and obesity. But young infants and children with pre-existing illnesses could be high risk groups and need careful monitoring. Studies describing immune-pathogenesis in COVID-19 are lacking in children and need urgent attention.

positive: The curious case of COVID-19 in children

positive: Financial Burden of Hospitalization of Children with Coronavirus Disease 2019 under the National Health Insurance Service in Korea Coronavirus disease 2019 (COVID-19) has resulted in an ongoing pandemic; however, the socioeconomic burden of COVID-19 treatment in the pediatric population remains unclear. Thus, the aim of this study was to determine the hospitalization periods and medical costs among children with COVID-19. In total, 145 billing statements for pediatric patients receiving healthcare services because of COVID-19 from February 1, 2020 to March 31, 2020 were used. The study showed that individual treatment costs for children with COVID-19 are approximately USD 2,192 under the Korean National Health Insurance Service System. This study revealed the differences in cost among age groups, determined by the type of hospital wherein admission occurred, as a trend of increasing age, increasing hospitalization time, and increasing cost was observed. Tailored COVID-19 treatment strategies by age group may lower costs and increase the effectiveness of resource allocation.

positive: COVID-19: Four Paediatric Cases in Malaysia OBJECTIVE: This is a brief report of 4 paediatric cases of COVID-19 infection in Malaysia BACKGROUND: COVID-19, a coronavirus, first detected in Wuhan, China has now spread rapidly to over 60 countries and territories around the world, infecting more than 85000 individuals. As the case count amongst children is low, there is need to report COVID-19 in children to better understand the virus and the disease. CASES: In Malaysia, until end of February 2020, there were four COVID-19 paediatric cases with ages ranging from 20 months to 11 years. All four cases were likely to have contracted the virus in China. The children had no symptoms or mild flu-like illness. The cases were managed symptomatically. None required antiviral therapy. DISCUSSION: There were 2 major issues regarding the care of infected children. Firstly, the quarantine of an infected child with a parent who tested negative was an ethical dilemma. Secondly, oropharyngeal and nasal swabs in children were at risk of false negative results. These issues have implications for infection control. Consequently, there is a need for clearer guidelines for child quarantine and testing methods in the management of COVID-19 in children.

positive: Neurologic and Radiographic Findings Associated With COVID-19 Infection in Children Importance: Neurological manifestations have been reported in adults with coronavirus disease 2019 (COVID-19), which is caused by the highly pathogenic virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objective: To report the neurological manifestations of children with COVID-19. Design, Setting, and Participants: In this case-series study, patients younger than 18 years who presented with SARS-CoV-2 infection and neurological symptoms to Great Ormond Street Hospital for Children (London, UK) between March 1, 2020, and May 8, 2020, were included after infection was confirmed by either a quantitative reverse transcription-polymerase chain reaction assay by nasopharyngeal swab or a positive test result for IgG antibodies against SARS-CoV-2 in serum. Main Outcomes and Measures: Clinical and paraclinical features were retrieved from electronic patient records. Results: Of the 27 children with COVID-19 pediatric multisystem inflammatory syndrome, 4 patients (14.8%) who were previously healthy had new-onset neurological symptoms. Symptoms included encephalopathy, headaches, brainstem and cerebellar signs, muscle weakness, and reduced reflexes. All 4 patients required intensive care unit admission for the treatment of COVID-19 pediatric multisystem inflammatory syndrome. Splenium signal changes were seen in all 4 patients on magnetic resonance imaging of the brain. In the 2 patients whose cerebrospinal fluid was tested, samples were acellular, with no evidence of infection on polymerase chain reaction or culture (including negative SARS-CoV-2 polymerase chain reaction results) and negative oligoclonal band test results. In all 3 patients who underwent electroencephalography, a mild excess of slow activity was found. Tests for N-methyl-d-aspartate receptor, myelin oligodendrocyte glycoprotein, and aquaporin-4 autoantibodies had negative results in all patients. In all 3 patients who underwent nerve conduction studies and electromyography, mild myopathic and neuropathic changes were seen. Neurological improvement was seen in all patients, with 2 making a complete recovery by the end of the study. Conclusions and Relevance: In this case-series study, children with COVID-19 presented with new neurological symptoms involving both the central and peripheral nervous systems and splenial changes on imaging, in the absence of respiratory symptoms. Additional research is needed to assess the association of neurological symptoms with immune-mediated changes among children with COVID-19.

positive: Novel coronavirus disease (COVID-19) in children Coronavirus disease (COVID-19) was firstly reported at the end of 2019. The disease rapidly spread all around the world in a few months and was declared a worldwide pandemic by WHO in March 2020. By April 9, there were 1,436,198 confirmed COVID-19 cases in the world, nearly with 6% mortality rate. This novel infectious disease causes respiratory tract illness that may generally occur as mild upper respiratory tract disease or pneumonia. In older patients and/or patients with underlying conditions, it may result in acute respiratory distress syndrome, multi organ failure and even death. According to the current literature, children account approximately for 1%–5% of diagnosed COVID-19 cases. Generally, COVID-19 seems to be a less severe disease for children than adults. Approximately 90% of pediatric patients are diagnosed as asymptomatic, mild, or moderate disease. However, up to 6.7% of cases may be severe. Severe illness is generally seen in patients smaller than 1 year of age and patients who have underlying disesases. The epidemiological and clinical patterns of COVID-19 and treatment approaches in pediatric patients still remain unclear although many pediatric reports are published. This review aims to summarize the current epidemics, clinical presentations, diagnosis, and treatment of COVID-19 in pediatric patients.

positive: The intriguing features of COVID-19 in children and its impact on the pandemic

positive: Age specificity of cases and attack rate of novel coronavirus disease (COVID-19) Age distribution of the cases with novel coronavirus disease (COVID-19) is rather different from that of influenza. We examined the age distribution of COVID-19 cases in Japan from January to March, 2020. Children are less likely to be diagnosed as cases, and moreover, the risk of disease given exposure among children appears to be low. Both the overall risk and the conditional risk of disease given exposure are likely to be the highest among adults aged from 50-69 years. The most plausible explanation that we believe is immune imprinting to a similar virus among adults.

positive: Risks to children during the covid-19 pandemic: some essential epidemiology.

positive: Coronavirus Disease 2019 in Children — United States, February 12–April 2, 2020 As of April 2, 2020, the coronavirus disease 2019 (COVID-19) pandemic has resulted in >890,000 cases and >45,000 deaths worldwide, including 239,279 cases and 5,443 deaths in the United States (1,2). In the United States, 22% of the population is made up of infants, children, and adolescents aged <18 years (children) (3). Data from China suggest that pediatric COVID-19 cases might be less severe than cases in adults and that children might experience different symptoms than do adults (4,5); however, disease characteristics among pediatric patients in the United States have not been described. Data from 149,760 laboratory-confirmed COVID-19 cases in the United States occurring during February 12-April 2, 2020 were analyzed. Among 149,082 (99.6%) reported cases for which age was known, 2,572 (1.7%) were among children aged <18 years. Data were available for a small proportion of patients on many important variables, including symptoms (9.4%), underlying conditions (13%), and hospitalization status (33%). Among those with available information, 73% of pediatric patients had symptoms of fever, cough, or shortness of breath compared with 93% of adults aged 18-64 years during the same period; 5.7% of all pediatric patients, or 20% of those for whom hospitalization status was known, were hospitalized, lower than the percentages hospitalized among all adults aged 18-64 years (10%) or those with known hospitalization status (33%). Three deaths were reported among the pediatric cases included in this analysis. These data support previous findings that children with COVID-19 might not have reported fever or cough as often as do adults (4). Whereas most COVID-19 cases in children are not severe, serious COVID-19 illness resulting in hospitalization still occurs in this age group. Social distancing and everyday preventive behaviors remain important for all age groups as patients with less serious illness and those without symptoms likely play an important role in disease transmission (6,7).

positive: Concurrent chilblains and retinal vasculitis in a child with COVID‐19 Reports on COVID‐19 in children are limited. Despite new data emerging, and understanding of the disease improves rapidly, there are as yet several features and complications related to the disease that remain unknown. Herein, we report the first case of a child with chilblains and retinal vasculitis related to COVID‐19.

positive: Clinical and Epidemiological Characteristics of Pandemic Influenza A/(H1N1) in Hospitalized Pediatric Patients at a University Hospital, Istanbul, Turkey Background: The aim of this study was to describe the clinical and epidemiological characteristics of pandemic influenza in hospitalized children. Methods: A total of 114 patients with suspected H1N1 virus infection were hospitalized, and nasal swabs were sent to National Influenza Reference Laboratory for confirmation of pandemic influenza A (H1N1) virus infection by rRT–PCR assay. Results: Forty-six female and 68 male patients were included in the study. Age of the patients ranged from 40 days to 16 years. Clinical and/or radiological pneumonia were detected in 96% of all. Sixteen patients required mechanical ventilation due to hypoxemia. Previously healthy children required mechanical ventilation and oxygen therapy more than patients with chronic diseases. Elevated levels of CRP and LDH in patients with respiratory distress and patients who required mechanical ventilation were statistically significant. Conclusion: Our study showed that progress of pandemic influenza infection in previously healthy children is as severe as their counterparts with chronic underlying diseases.

positive: Clinical Features of Critical Coronavirus Disease 2019 in Children We sought to describe the presentation, course, and outcomes of hospitalized pediatric coronavirus disease 2019 patients, with detailed description of those requiring mechanical ventilation, and comparisons between critically ill and noncritical hospitalized pediatric patients. DESIGN: Observational cohort study. SETTING: Riley Hospital for Children at Indiana University Health in Indianapolis in the early weeks of the coronavirus disease 2019 pandemic. PATIENTS: All hospitalized pediatric patients with confirmed coronavirus disease 2019 as of May 4, 2020, were included. INTERVENTIONS: Patients received therapies including hydroxychloroquine, remdesivir, tocilizumab, and convalescent serum and were managed according to an institutional algorithm based on evidence available at the time of presentation. MEASUREMENTS AND MAIN RESULTS: Of 407 children tested for severe acute respiratory syndrome-coronavirus 2 at our hospital, 24 were positive, and 19 required hospitalization. Seven (36.8%) were critically ill in ICU, and four (21%) required mechanical ventilation. Hospitalized children were predominantly male (14, 74%) and African-American or Hispanic (14, 74%), with a bimodal distribution of ages among young children less than or equal to 2 years old (8, 42%) and older adolescents ages 15–18 (6, 32%). Five of seven (71.4%) of critically ill patients were African-American (n = 3) or Hispanic (n = 2). Critical illness was associated with older age (p = 0.017), longer duration of symptoms (p = 0.036), and lower oxygen saturation on presentation (p = 0.016); with more thrombocytopenia (p = 0.015); higher C-reactive protein (p = 0.031); and lower WBC count (p = 0.039). Duration of mechanical ventilation averaged 14.1 days. One patient died. CONCLUSIONS: Severe, protracted coronavirus disease 2019 is seen in pediatric patients, including those without significant comorbidities. We observed a greater proportion of hospitalized children requiring mechanical ventilation than has been reported to date. Older children, African-American or Hispanic children, and males may be at risk for severe coronavirus disease 2019 requiring hospitalization. Hypoxia, thrombocytopenia, and elevated C-reactive protein may be useful markers of critical illness. Data regarding optimal management and therapies for pediatric coronavirus disease 2019 are urgently needed.

positive: Coronavirus disease 2019 (COVID-19) in children and/or adolescents: a meta-analysis. BACKGROUND To assess the overall prevalence of clinical signs, symptoms, and radiological findings in children and/or adolescents with COVID-19. METHODS We systematically researched in PubMed, Scopus and Web of Science databases observational studies describing COVID-19 in children and/or adolescents until April 11, 2020. Data regarding clinical and radiological features were extracted from eligible studies and meta-analysis was performed using random-effects modeling. RESULTS We examined 19 eligible studies for a total of 2855 children and/or adolescents with COVID-19. Approximately 47% of subjects had fever (95% confidence interval [CI] 22-72%; I2 = 98.6%), 37% cough (95%CI 15-63%; I2 = 98.6%), 4% diarrhea (95%CI 0-12%; I2 = 92.2%), 2% nasal congestion (95%CI 0-7%; I2 = 87.7%), 1% dyspnea (95%CI 0-7%; I2 = 91.5%) and 0% abdominal pain (95%CI 0-1%; I2 = 76.3%). Subjects presented mild symptoms in 79% (95%CI 65-91%; I2 = 93.5%) of cases, whereas only 4% (95%CI 1-9%; I2 = 76.4%) were critical. Among those with pneumonia on computed tomography, 26.4% (95%CI 13-41%; I2 = 80.8%) presented a unilateral involvement, 16% (95%CI 5-29%, I2 = 81.2%) had bilateral involvement and 9% (95%CI 0-24%; I2 = 88.7%) had interstitial pneumonia. CONCLUSIONS Children and/or adolescents tend to have a mild COVID-19 course with a good prognosis. IMPACT Compared to adults, children and/or adolescents tend to have a mild COVID-19 course with a good prognosis. This study provides new and consistence information on the clinical and radiological characteristics of COVID-19 in pediatrics. This study may help to fight COVID-19 in pediatric population.

positive: COVID-19 in Children: An Ample Review The aim of this review was to describe the current knowledge about coronavirus disease 2019 (COVID-19, which is caused by severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) in children, from epidemiological, clinical, and laboratory perspectives, including knowledge on the disease course, treatment, and prognosis. An extensive literature search was performed to identify papers on COVID-19 (SARS-CoV-2 infection) in children, published between January 1, 2020 and April 1, 2020. There were 44 relevant papers on COVID-19 in children. The results showed that COVID-19 occurs in 0.39–12.3% of children. Clinical signs and symptoms are comparable to those in adults, but milder forms and a large percentage of asymptomatic carriers are found among children. Elevated inflammatory markers are associated with complications and linked to various co-infections. Chest computed tomography (CT) scans in children revealed structural changes similar to those found in adults, with consolidations surrounded by halos being somewhat specific for children with COVID-19. The recommended treatment includes providing symptomatic therapy, with no specific drug recommendations for children. The prognosis is much better for children compared to adults. This review highlights that COVID-19 in children is similar to the disease in the adult population, but with particularities regarding clinical manifestations, laboratory test results, chest imaging, and treatment. The prognosis is much better for children compared to adults, but with the progression of the pandemic; the cases in children might change in the future.

positive: A 3-month-old child with COVID-19: A case report INTRODUCTION: Coronavirus disease 2019 (COVID-19) is pandemic and is a medical issue. However, children account for a small portion of those with the disease, and there are few published reports of COVID-19 in children. The patient reported in this case report is the youngest case reported in Chengdu, China to date. PATIENT CONCERNS: A 3-month-old male infant presented with cough and rhinorrhea. DIAGNOSIS: Family members from Wuhan, the epicenter of the epidemic came to stay in the patient's home 16 days before the onset of his disease, and his mother had been diagnosed with COVID-19. He was diagnosed with COVID-19 based on a history of exposure and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), detected using reverse transcription polymerase chain reaction (RT-PCR). INTERVENTIONS: The patient was admitted to hospital and treated symptomatically with oral medication. OUTCOMES: The patient recovered completely and was discharged after one month of hospitalization. He tested negative for SARS-CoV-2 using RT-PCR and a chest CT performed 4 weeks after admission showed marked improvement prior to discharge. CONCLUSION: Clinicians must be aware of the presentation of COVID-19 in children because it differs from that in adults.

positive: Pediatric coronavirus disease 2019 (COVID-19): An insight from west of Iran OBJECTIVE: To study the clinical, laboratory, and radiological characteristics of the pediatric patients infected with the new emerging 2019 coronavirus virus (SARS-CoV-2) in Hamadan and Sanandaj, west of Iran. METHODS: A descriptive study was conducted in Hamadan and Kurdistan province between March 1 to April 15, 2020. Medical records of the children diagnosed as probable or confirmed cases of COVID-19 disease were extracted and analyzed in this study. We followed the WHO Guideline for the case definition of the patients. RESULTS: Thirty patients admitted to the wards specified for COVID-19 diseases. Nineteen (63%) patients categorized as confirmed by Real-Time Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) and 11 (37%) patients as probable according to Computed Tomography (CT) findings of the chest. Sixteen (53.3%) cases were female, the youngest patient was one day old, and the oldest patient was 15 years old. 11 (36.7%) cases had a definite history of close contact. The most common symptoms were fever, cough, and dyspnea, and the most common sign was tachypnea. None of our patients presented with a runny nose. Lymphopenia and marked elevation of the C-reactive Protein observed in four (13.3%) and 12 (40%) cases, respectively. There were 10 (33.3%) cases with normal chest X-rays. Ground-Glass Opacities (GGOs) were the most common CT findings (19, 73.1%). All but one of the patients discharged without sequala. An 11-yrs-old girl expired with a fulminant pneumonia. CONCLUSION: COVID-19 is not uncommon in children and could have different presentations. Concomitant use of RT-PCR and chest CT scans in symptomatic cases recommended as a modality of choice to diagnose the disease. Routine laboratory tests, like many other viral infections, may not show significant or specific changes. The superimposed bacterial infection seems not the determinant of clinical outcomes as most patients had a negative evaluation by specific laboratory tests for bacterial infections; got improved dramatically with a short or no antibiotic therapy.

positive: Distinct systems serology features in children, elderly and COVID patients SARS-CoV-2, the pandemic coronavirus that causes COVID-19, has infected millions worldwide, causing unparalleled social and economic disruptions. COVID-19 results in higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive coronavirus immunological responses, induced by circulating human coronaviruses, is critical to understand such divergent clinical outcomes. The cross-reactivity of coronavirus antibody responses of healthy children (n=89), adults (n=98), elderly (n=57), and COVID-19 patients (n=19) were analysed by systems serology. While moderate levels of cross-reactive SARS-CoV-2 IgG, IgM, and IgA were detected in healthy individuals, we identified serological signatures associated with SARS-CoV-2 antigen-specific Fc{gamma} receptor binding, which accurately distinguished COVID-19 patients from healthy individuals and suggested that SARS-CoV-2 induces qualitative changes to antibody Fc upon infection, enhancing Fc{gamma} receptor engagement. Vastly different serological signatures were observed between healthy children and elderly, with markedly higher cross-reactive SARS-CoV-2 IgA and IgG observed in elderly, whereas children displayed elevated SARS-CoV-2 IgM, including receptor binding domain-specific IgM with higher avidity. These results suggest that less-experienced humoral immunity associated with higher IgM, as observed in children, may have the potential to induce more potent antibodies upon SARS-CoV-2 infection. These key insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.

positive: Clinical characteristics of COVID‐19 in children: Are they similar to those of SARS? Although the number of SARS‐CoV‐2 infections has been rising amid the current pandemic of COVID‐19, the low infection rate of SARS‐CoV‐2 in children has been low. By examining the clinical data available in the public domain, the present work clarifies the clinical presentations in children with COVID‐19 in China. Statistical significance tests and adjusted odds ratios estimation were performed on the children (age below 18) and adults (age 18 or above) cohorts in China. SARS‐CoV and SARS‐CoV‐2 shared similar clinical features. Lower respiratory tract infection was less prominent in children as evidenced by the relatively low prevalence in chest pain/discomfort and dyspnea. Similar to SARS, younger children had a less aggressive clinical course, compared with adolescents. While fewer symptoms were observed in children compared to adults, there is not yet sufficient evidence to conclude shorter hospital stay in children.

positive: Coronavirus Disease 2019: Understanding Immunopathogenesis Is the “Holy Grail” to Explain Why Children Have Less Severe Acute Disease

positive: The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19 SARS-CoV2 infection is typically very mild and often asymptomatic in children. A complication is the rare Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever and organ dysfunction and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. We apply systems-level analyses of blood immune cells, cytokines and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV2 and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, is more similar to Kawasaki disease, but also differ from this with respect to T-cell subsets, IL-17A and biomarkers associated with arterial damage. Finally, autoantibody profiling suggests endoglin, an endothelial glycoprotein as one of several candidate targets of autoantibodies in MIS-C.

positive: Impact of COVID-19 on pediatric asthma: practice adjustments and disease burden. Abstract Background It is unclear whether asthma may affect susceptibility or severity of the Coronavirus Disease 2019 (COVID-19) in children and how pediatric asthma services worldwide have responded to the pandemic. Objective To describe the impact of the COVID-19 pandemic on pediatric asthma services and on disease burden in their patients. Methods An online survey was sent to members of the Pediatric Asthma in Real Life (PeARL) think-tank and the World Allergy Organization Pediatric Asthma Committee. It included questions on service provision, disease burden and on the clinical course of confirmed cases of COVID-19 infection among children with asthma. Results Ninety-one respondents, caring for an estimated population of >133,000 children with asthma, completed the survey. COVID-19 significantly impacted pediatric asthma services: 39% ceased physical appointments, 47% stopped accepting new patients, 75% limited patients visits. Consultations were almost halved to a median of 20 (IQR: 10-25) patients per week. Virtual clinics and helplines were launched in most centers. Better than expected disease control was reported in 20% (10-40%) of patients, while control was negatively affected in only 10% (7.5-12.5%). Adherence also appeared to increase. Only 15 confirmed cases of COVID-19 were reported among the population; the estimated incidence is not apparently different from the reports of general pediatric cohorts. Conclusion Children with asthma do not appear to be disproportionately affected by COVID-19. Outcomes may even have improved, possibly through increased adherence and/or reduced exposures. Clinical services have rapidly responded to the pandemic by limiting and replacing physical appointments with virtual encounters.

positive: Kawasaki-like disease: emerging complication during the COVID-19 pandemic

positive: Current Scenario of COVID-19 in Pediatric Age Group and Physiology of Immune and Thymus response Abstract COVID-19 pandemic caused by SARS-CoV-2, continues to manifest with severe acute respiratory syndrome among the adults, however, it offers a convincing indication of less severity and fatality in pediatric age group (0-18 years). The current trend suggests that children may get infected but are less symptomatic with less fatality, which is concordant to earlier epidemic outbreaks of SARS-CoV and MERS-CoV, in 2002 and 2012, respectively. According to the available data, children appear to be at lower risk for COVID-19, as adults constitute for maximum number of the confirmed cases (308,592) and deaths (13,069) as on 22nd March ( https://www.worldometers.info/coronavirus ). However, rapid publications and information of the adult patients with COVID-19 is in progress and published, on the contrary, almost no comprehensive data or discussion about the COVID-19 in children is available. Therefore, in this review, we outline the epidemiology, clinical symptoms, diagnosis, treatment, prevention, possible immune response and role of thymus in children to combat the COVID-19 outbreak.

positive: Clinical characteristics of 19 neonates born to mothers with COVID-19 The aim of this study was to investigate the clinical characteristics of neonates born to SARS-CoV-2 infected mothers and increase the current knowledge on the perinatal consequences of COVID-19. Nineteen neonates were admitted to Tongji Hospital from January 31 to February 29, 2020. Their mothers were clinically diagnosed or laboratory-confirmed with COVID-19. We prospectively collected and analyzed data of mothers and infants. There are 19 neonates included in the research. Among them, 10 mothers were confirmed COVID-19 by positive SARS-CoV-2 RT-PCR in throat swab, and 9 mothers were clinically diagnosed with COVID-19. Delivery occurred in an isolation room and neonates were immediately separated from the mothers and isolated for at least 14 days. No fetal distress was found. Gestational age of the neonates was 38.6 ± 1.5 weeks, and average birth weight was 3293 ± 425 g. SARS-CoV-2 RT-PCR in throat swab, urine, and feces of all neonates were negative. SARS-CoV-2 RT-PCR in breast milk and amniotic fluid was negative too. None of the neonates developed clinical, radiologic, hematologic, or biochemical evidence of COVID-19. No vertical transmission of SARS-CoV-2 and no perinatal complications in the third trimester were found in our study. The delivery should occur in isolation and neonates should be separated from the infected mothers and care givers.

positive: COVID-19 in Great Britain: epidemiological and clinical characteristics of the first few hundred (FF100) cases: a descriptive case series and case control analysis Objectives: Following detection of the first virologically-confirmed cases of COVID-19 in Great Britain, an enhanced surveillance study was initiated by Public Health England to describe the clinical presentation, course of disease and identify risk factors for infection of the first few hundred cases. Methods: Information was collected on the first COVID-19 cases according to the First Few X WHO protocol. Case-control analyses of the sensitivity, specificity and predictive value of symptoms and risk factors for infection were conducted. Point prevalences of underlying health conditions among the UK general population were presented. Findings: The majority of FF100 cases were imported (51.4%), of which the majority had recent travel to Italy (71.4%). 24.7% were secondary cases acquired mainly through household contact (40.4%). Children had lower odds of COVID-19 infection compared with the general population. The clinical presentation of cases was dominated by cough, fever and fatigue. Non-linear relationships with age were observed for fever, and sensitivity and specificity of symptoms varied by age. Conditions associated with higher odds of COVID-19 infection (after adjusting for age and sex) were chronic heart disease, immunosuppression and multimorbidity. Conclusion: This study presents the first epidemiological and clinical summary of COVID-19 cases in Great Britain. The FFX study design enabled systematic data collection. The study was able to characterize the risk factors for infection with population prevalence estimates setting these relative risks into a public health context. It also provides important evidence for generating case definitions to support public health risk assessment, clinical triage and diagnostic algorithms.

positive: Why the SARS‐Cov‐2 has prolonged spreading time in children?

positive: Herd Immunity and Vaccination of children for COVID19

positive: SARS-CoV-2 (COVID-19): What do we know about children? A systematic review BACKGROUND: Few paediatric cases of COVID-19 have been reported and we know little about the epidemiology in children, though more is known about other coronaviruses. We aimed to understand the infection rate, clinical presentation, clinical outcomes and transmission dynamics for SARS-CoV-2, in order to inform clinical and public health measures. METHODS: We undertook a rapid systematic review and narrative synthesis of all literature relating to SARS-CoV-2 in paediatric populations. The search terms also included SARS-CoV and MERS-CoV. We searched three databases and the COVID-19 resource centres of eleven major journals and publishers. English abstracts of Chinese language papers were included. Data were extracted and narrative syntheses conducted. RESULTS: 24 studies relating to COVID-19 were included in the review. Children appear to be less affected by COVID-19 than adults by observed rate of cases in large epidemiological studies. Limited data on attack rate indicate that children are just as susceptible to infection. Data on clinical outcomes are scarce but include several reports of asymptomatic infection and a milder course of disease in young children, though radiological abnormalities are noted. Severe cases are not reported in detail and there are little data relating to transmission. CONCLUSIONS: Children appear to have a low observed case rate of COVID-19 but may have similar rates to adults of infection with SARS-CoV-2. This discrepancy may be because children are asymptomatic or too mildly infected to draw medical attention, be tested and counted in observed cases of COVID-19.

positive: COVID-19 and Neonatal Respiratory Care: Current Evidence and Practical Approach The novel coronavirus disease 2019 (COVID-19) pandemic has urged the development and implementation of guidelines and protocols on diagnosis, management, infection control strategies, and discharge planning. However, very little is currently known about neonatal COVID-19 and severe acute respiratory syndrome–coronavirus-2 (SARS-CoV-2) infections. Thus, many questions arise with regard to respiratory care after birth, necessary protection to health care workers (HCW) in the delivery room and neonatal intensive care unit (NICU), and safety of bag and mask ventilation, noninvasive respiratory support, deep suctioning, endotracheal intubation, and mechanical ventilation. Indeed, these questions have created tremendous confusion amongst neonatal HCW. In this manuscript, we comprehensively reviewed the current evidence regarding COVID-19 perinatal transmission, respiratory outcomes of neonates born to mothers with COVID-19 and infants with documented SARS-CoV-2 infection, and the evidence for using different respiratory support modalities and aerosol-generating procedures in this specific population. The results demonstrated that to date, neonatal COVID-19 infection is uncommon, generally acquired postnatally, and associated with favorable respiratory outcomes. The reason why infants display a milder spectrum of disease remains unclear. Nonetheless, the risk of severe or critical illness in young patients exists. Currently, the recommended respiratory approach for infants with suspected or confirmed infection is not evidence based but should include all routinely used types of support, with the addition of viral filters, proper personal protective equipment, and placement of infants in isolation rooms, ideally with negative pressure. As information is changing rapidly, clinicians should frequently watch out for updates on the subject. Key Points: Novel coronavirus disease 2019 (COVID-19) pandemic urged development of guidelines. Neonatal COVID-19 disease is uncommon. Respiratory outcomes in neonates seems favorable. Current neonatal respiratory care should continue. Clinicians should watch frequently for updates.

positive: Children Hospitalized With Severe COVID-19 in Wuhan BACKGROUND: Novel coronavirus disease (COVID-19) is spreading globally. Little is known about the risk factors for the clinical outcomes of COVID-19 in children. METHODS: A retrospective case-control study was taken in children with severe acute respiratory syndrome coronary virus-2 infection in Wuhan Children's Hospital. Risk factors associated with the development of COVID-19 and progression were collected and analyzed. RESULTS: Eight of 260 children diagnosed with severe COVID-19 pneumonia were included in the study. Thirty-five children with COVID-19 infection matched for age, sex and date of admission, and who classified as non-severe type, were randomly selected from the hospital admissions. For cases with severe pneumonia caused by COVID-19, the most common symptoms were dyspnea (87.5%), fever (62.5%) and cough (62.5%). In laboratory, white blood cells count was significantly higher in severe children than non-severe children. Levels of inflammation bio-makers such as hsCRP, IL-6, IL-10 and D-dimer elevated in severe children compared with non-severe children on admission. The level of total bilirubin and uric acid clearly elevated in severe children compared with non-severe children on admission. All of severe children displayed the lesions on chest CT, more lung segments were involved in severe children than in non-severe children, which was only risk factor associated with severe COVID-19 pneumonia in multivariable analysis. CONCLUSIONS: More than 3 lung segments involved were associated with greater risk of development of severe COVID-19 in children. Moreover, the possible risk of the elevation of IL-6, high total bilirubin and D-dimer with univariable analysis could identify patients to be severe earlier.

positive: Flash Survey on SARS-CoV-2 Infections in Pediatric Patients on anti-Cancer Treatment Abstract Introduction Since the beginning of COVID-19 pandemics, it is known that the severe course of the disease occurs mostly among elderly, whereas it is rare among children and young adults. Comorbidities, in particular diabetes and hypertension, clearly associated with age, besides obesity and smoke are strongly associated with the need of intensive treatment and a dismal outcome. A weaker immunity of the elderly has been proposed as a possible explanation of this uneven age distribution. Along the same line, anecdotal information from Wuhan, China mentioned a severe course of COVID-19 in a child treated for leukemia. Aim and methods We made a flash survey on COVID19 incidence and severity among children on anticancer treatment. Respondents were asked by email to fill in a short web based survey. Results We received reports from 25 countries, where approximately 10,000 patients at risk are followed. At the time of the survey, over 200 of these children were tested, nine of whom were positive for COVID-19. Eight of the nine cases had asymptomatic to mild disease and one was just diagnosed with COVID-19. We also discuss preventive measures that are in place or should be taken as well as treatment options in immunocompromised children with COVID-19. Conclusion Thus, even children receiving anti-cancer chemotherapy may have a mild or asymptomatic course of COVID-19. While we should not underestimate the risk of developing a more severe course of COVID-19 than observed here, the intensity of preventive measures should not cause delays or obstructions in oncological treatment.

positive: Coronavirus Disease 2019 (COVID-19) in adolescents: An update on current clinical and diagnostic characteristics The current outbreak of infections with SARS-CoV-2 is defined as Coronavirus Disease 2019 (COVID-19). The clinical symptoms of COVID-19 include fever, fatigue, cough, breathing difficulty that may lead to respiratory distress; a small population of patients may have diarrhea, nausea or vomiting. The highest infection rate occurs in adults; however, neonates, children, and adolescents can also be infected. As the outbreak continues to spread worldwide, attention has switched toward determinants of clinical manifes- tations and disease severity. The situation surrounding the outbreak is rapidly evolving and the information and recommendations are changing as new information becomes available. This paper summarises the cur- rent findings (April 3,2020) from a systematic literature review on the current knowledge of COVID-19 in adolescents (10-19 years according to the WHO definition) and reports the preliminary epidemiological data stated by the Italian National Institute of Health.

positive: Pay attention to SARS-CoV-2 infection in children

positive: Detectable SARS‐CoV‐2 viral RNA in feces of three children during recovery period of COVID‐19 pneumonia Coronavirus Disease 2019 (COVID‐19) is a newly emerging infectious disease caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). After its first occurrence in Wuhan of China from December 2019, COVID‐19 rapidly spread around the world. According to the World Health Organization statement on 13 March 2020, there had been over 132 500 confirmed cases globally. Nevertheless, the case reports of children are rare, which results in the lack of evidence for preventing and controlling of children's infection. Here, we report three cases of SARS‐CoV‐2 infected children diagnosed from 3 February to 17 February 2020 in Tianjin, China. All of these three cases experienced mild illness and recovered soon after the treatment, with the nucleic acid of throat swab turning negative within 14, 11, and 7 days after diagnosis, respectively. However, after been discharged, all three cases were tested SARS‐CoV‐2 positive in the stool samples within 10 days, in spite of their remained negative nucleic acid in throat swab specimens. Therefore, it is necessary to be aware of the possibility of fecal‐oral transmission of SARS‐CoV‐2 infection, especially for children cases.

positive: Is the use of ACE inb/ARBs associated with higher in-hospital mortality in Covid-19 pneumonia patients? INTRODUCTION The present research aimed to determine the relation between the use of angiotensin-converting enzyme inhibitors (ACE inh) and angiotensinogen receptor blockers (ARBs) and in-hospital mortality of hypertensive patients diagnosed with Covid-19 pneumonia. MATERIAL AND METHOD In this retrospective study, we included 113 consecutive hypertensive patients admitted due to Covid-19 infection. In all patients, Covid-19 infection was confirmed with using reverse-transcription polymerase chain reaction. All patients were on ACE inh/ARBs or other antihypertensive therapy unless no contraindication was present. The primary outcome of the study was the in-hospital all-cause mortality. RESULTS In total, 113 hypertensive Covid-19 patients were included, of them 74 patients were using ACE inh/ARBs. During in-hospital follow up, 30.9% [n = 35 patients] of patients died. The frequency of admission to the ICU and endotracheal intubation were significantly higher in patients using ACE inh/ARBs. In a multivariable analysis, the use of ACE inh/ARBs was an independent predictor of in-hospital mortality (OR: 3.66; 95%CI: 1.11-18.18; p= .032). Kaplan-Meir curve analysis displayed that patients on ACE inh/ARBs therapy had higher incidence of in-hospital death than those who were not. CONCLUSION The present study has found that the use of ACE inh/ARBs therapy might be associated with an increased in-hospital mortality in patients who were diagnosed with Covid-19 pneumonia. It is likely that ACE inh/ARBs therapy might not be beneficial in the subgroup of hypertensive Covid-19 patients despite the fact that there might be the possibility of some unmeasured residual confounders to affect the results of the study.

positive: COVID-19 Disease in Children: Clinical Course, Diagnosis and Treatment Overview and Literature Data Compilation The novel Coronavirus is named as SARS-CoV-2 is a highly contagious infection agent compared to the previous human coronaviruses Each previous outbreak had distinctive danger The high potential of infectiousness is the primary danger of novel coronavirus While MERS-CoV infection is known to have higher mortality rate, SARS-CoV-2 has spread to many people all over the world in a concise time SARS-CoV-2 (like SARS-CoV and MERS) infects fewer children and results in milder clinical symptoms than in adults The primary pathogenesis of it is not known;the difference in children's immunities, less likelihood of exposure to the agent may be the reasons Nevertheless, along with being mostly asymptomatic, the child population is a potential source for infection spread

positive: SARS-CoV-2: The Path of Prevention and Control The 2019 coronavirus pandemic (COVID-19) continues to expand worldwide. Although the number of cases and the death rate among children and adolescents are reported to be low compared to adults, limited data have been reported. We urgently need to find treatment and vaccine to stop the epidemic. Vaccine development is in progress, but any approved and effective vaccine for COVID-19 is at least 12 to 18 months. The World Health Organization (WHO), the Center for Disease Control and Prevention (CDC), and the Food and Agriculture Organization (FAO) have issued instructions and strategies for containing COVID-19 outbreak to the general public, physicians, travelers and injured patients to follow so that the transmission to a healthy population can be prevented. In this review, we summarize demographic data, clinical characteristics, complications and outcomes and finally prevention and control of this serious pandemic.

positive: The clinical and immunological features of pediatric COVID-19 patients in China In December 2019, the corona virus disease 2019 (COVID-19) caused by novel coronavirus (SARS-CoV-2) emerged in Wuhan, China and rapidly spread worldwide. Few information on clinical features and immunological profile of COVID-19 in paediatrics. The clinical features and treatment outcomes of twelve paediatric patients confirmed as COVID-19 were analyzed. The immunological features of children patients was investigated and compared with twenty adult patients. The median age was 14.5-years (range from 0.64 to 17), and six of the patients were male. The average incubation period was 8 days. Clinically, cough (9/12, 75%) and fever (7/12, 58.3%) were the most common symptoms. Four patients (33.3%) had diarrhea during the disease. As to the immune profile, children had higher amount of total T cell, CD8+ T cell and B cell but lower CRP levels than adults (P < 0.05). Ground-glass opacity (GGO) and local patchy shadowing were the typical radiological findings on chest CT scan. All patients received antiviral and symptomatic treatment and the symptom relieved in 3-4 days after admitted to hospital. The paediatric patients showed mild symptom but with longer incubation period. Children infected with SARS-CoV-2 had different immune profile with higher T cell amount and low inflammatory factors level, which might ascribed to the mild clinical symptom. We advise that nucleic acid test or examination of serum IgM/IgG antibodies against SARS-CoV-2 should be taken for children with exposure history regardless of clinical symptom.

positive: Children Infected With SARS-CoV-2 From Family Clusters Background: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is ongoing globally. Limited data are available for children with SARS-CoV-2 infection. Methods: A retrospective case study was conducted in one designated hospital for children with SARS-CoV-2 infection in Wuhan. Results: Out of the 74 children with laboratory-confirmed SARS-CoV-2 infection, the median age was 5.8 years, with no notable variation based on gender. All of the children had had direct exposure to at least one family member with confirmed SARS-CoV-2 infection. The most common symptoms were cough in 41 (55.4%) and fever in 38 (51.4%). Typical CT patterns of viral pneumonia were exhibited in 40 (54.1%) children, including ground-glass opacity and interstitial abnormalities. However, 17 (23.0%) children were classified as asymptomatic carriers, with neither symptoms nor radiological findings. Also, 68 (91.9%) children recovered fully and showed negative results on RT-PCR assay by nasopharyngeal swabs during our observation period. In contrast to the negative result for nasopharyngeal swab, 34% of the anal swabs showed a continued positive result. The mean hospitalization days of the children discharged after full recovery was 10.0 days. Conclusion: Within family clusters that had SARS-CoV-2 infection, children had mild or even asymptomatic illness. Although CT is highly sensitive, it should be avoided in follow-up of the disease in consideration of the radiological hazards and limited clinical benefits for mild illness in children. Furthermore, it is advocated that both nasopharyngeal and anal swabs should be confirmed negative for viral load prior to declaring full recovery so as to avoid oral-fecal transmission. Asymptomatic children with family clusters are potentially a little-known source of COVID-19. This therefore warrants an urgent reassessment of the transmission dynamics of the current outbreak.

positive: COVID-19 pandemic: Impact on children, families and the future

positive: COVID-19: lessons to date from China The pandemic due to a novel coronavirus has been sweeping across different regions of the globe since January 2020. Early reports of this infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) consisted of mostly adult patients. As the outbreak spreads rapidly beyond the epicentre of Wuhan, it becomes clear that infants and children of all ages are susceptible to this infection. In China, there have been more than 1200 paediatric cases. Most paediatric patients acquire the infection through household contact with infected adults. The disease in children is usually self-limiting and most infected children will recover uneventfully within 7-10 days. Other than symptoms of the respiratory tract, many children may present with gastrointestinal symptoms. Older children are more likely to have asymptomatic infection. Although deaths related to SARS-CoV-2 are rarely reported in the paediatric age group, young children and those with underlying medical conditions are more likely to develop severe illness. Only a small fraction of neonates born to infected mother would acquire the virus by vertical transmission. Because a large proportion of children and adolescents may have asymptomatic or mildly symptomatic infection, children are likely to play an important role in community transmission of this infection. Screening of children who have a definitive contact history will facilitate early diagnosis and isolation of all infected children. This review summarises the lessons learned in China with regard to the current understanding of SARS-CoV-2 infection in the paediatric population.

positive: Children's heart and COVID-19: Up-to-date evidence in the form of a systematic review The new coronavirus disease outbreak in 2019 (COVID-19) represents a dramatic challenge for healthcare systems worldwide. As to viral tropism, lungs are not the only COVID-19 target but also the heart may be involved in a not negligible percentage of the infected patients. Myocarditis-related cardiac dysfunction and potentially life-threatening arrhythmias are the main aftermaths. A few studies showed that myocardial injury in adult patients is often linked with a fatal outcome. Conversely, scientific evidence in children is sparse, although several reports were published with the description of a cardiac involvement in COVID-19 paediatric patients. In these young subjects, a background of surgically treated congenital heart disease seems to be a predisposing factor.Conclusion: This systematic review is aimed at summarizing all COVID-19 cases with a cardiac involvement published in paediatric age and trying to explain the underlying mechanisms responsible for COVID-19-related myocardial damage.What is Known:â¢ Coronaviruses proved to be able to jump from animals to humans.â¢ The outbreak of COVID-19 started from China (Dec 2019) and became pandemic.What is New:â¢ Even in childhood, COVID-19 is not without the risk of cardiac involvement.â¢ Myocarditis, heart failure, and arrhythmias are among the possible manifestations.

positive: African American children are at higher risk for COVID‐19 infection Infection by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the viral etiology of the novel coronavirus disease 2019 (COVID‐19), was first reported in Wuhan, China in late 2019. Peculiarly, the virus has not caused significant impact on pediatric populations, unlike other coronaviruses (1). Children comprise only 1.7% of COVID‐19 positive cases in the United States (2). Furthermore, children are noted to have a milder disease course (3, 4). However, much is unknown about the age, gender and race risk factors of COVID‐19 among children. There has been recent evidence suggestive of higher rates of COVID‐19 and related fatality rates in African American adult communities around the United States(5). However, there is limited data, to our knowledge, whether any race or ethnicity group is at higher risk for COVID‐19 infection in children.

positive: From SARS to COVID-19: What we have learned about children infected with COVID-19 Abstract Coronaviruses, both SARS-CoV and SARS-CoV-2 were firstly appeared in China. They have certain similarities in biological, epidemiological and pathological. To data, the researches have shown that their gene exhibit 79% of identical sequence and the receptor-binding domain structure is also very similar. There have been extensive research performed on SARS, however, the understanding of pathophysiology impact of Corona Virus Disease 2019(COVID-19) is still limited. In the review, we draw upon the lessons learnt from SARS in the epidemiology, clinical characteristics and pathogenesis for further understand the features of COVID-19. By comparing these two diseases, we found, COVID-19 has quicker and wider transmission, obvious family agglomeration, higher morbidity and mortality. Newborns, asymptomatic children and normal chest imaging cases were emerged in COVID-19. Children started with gastrointestinal symptoms may progress to severe condition and newborn whose mother was infected with COVID-19 could have severe complications. The laboratory test data showed, the percentage of neutrophils and the level of LDH is higher, otherwise the number of CD4+ and CD8+T cells is decreased in children's COVID-19 cases. Based on these early observations, as pediatrician, we put forward some thoughts on children's COVID-19 and give some recommendations to contain the disease.

positive: Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 2020 Data on features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents are scarce. We report preliminary results of an Italian multicentre study comprising 168 laboratory-confirmed paediatric cases (median: 2.3 years, range: 1 day–17.7 years, 55.9% males), of which 67.9% were hospitalised and 19.6% had comorbidities. Fever was the most common symptom, gastrointestinal manifestations were frequent; two children required intensive care, five had seizures, 49 received experimental treatments and all recovered.

positive: Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units. Importance The recent and ongoing coronavirus disease 2019 (COVID-19) pandemic has taken an unprecedented toll on adults critically ill with COVID-19 infection. While there is evidence that the burden of COVID-19 infection in hospitalized children is lesser than in their adult counterparts, to date, there are only limited reports describing COVID-19 in pediatric intensive care units (PICUs). Objective To provide an early description and characterization of COVID-19 infection in North American PICUs, focusing on mode of presentation, presence of comorbidities, severity of disease, therapeutic interventions, clinical trajectory, and early outcomes. Design, Setting, and Participants This cross-sectional study included children positive for COVID-19 admitted to 46 North American PICUs between March 14 and April 3, 2020. with follow-up to April 10, 2020. Main Outcomes and Measures Prehospital characteristics, clinical trajectory, and hospital outcomes of children admitted to PICUs with confirmed COVID-19 infection. Results Of the 48 children with COVID-19 admitted to participating PICUs, 25 (52%) were male, and the median (range) age was 13 (4.2-16.6) years. Forty patients (83%) had significant preexisting comorbidities; 35 (73%) presented with respiratory symptoms and 18 (38%) required invasive ventilation. Eleven patients (23%) had failure of 2 or more organ systems. Extracorporeal membrane oxygenation was required for 1 patient (2%). Targeted therapies were used in 28 patients (61%), with hydroxychloroquine being the most commonly used agent either alone (11 patients) or in combination (10 patients). At the completion of the follow-up period, 2 patients (4%) had died and 15 (31%) were still hospitalized, with 3 still requiring ventilatory support and 1 receiving extracorporeal membrane oxygenation. The median (range) PICU and hospital lengths of stay for those who had been discharged were 5 (3-9) days and 7 (4-13) days, respectively. Conclusions and Relevance This early report describes the burden of COVID-19 infection in North American PICUs and confirms that severe illness in children is significant but far less frequent than in adults. Prehospital comorbidities appear to be an important factor in children. These preliminary observations provide an important platform for larger and more extensive studies of children with COVID-19 infection.

positive: Correspondence regarding recently published editorial: ‘Will children reveal their secret? The coronavirus dilemma’ When individuals without prior immunity are considered, case fatality ratios are typically higher in adults than in children for most infectious diseases, with few exceptions.

positive: Why is SARS-CoV-2 infection milder among children?

positive: Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort BACKGROUND: Current data suggest that COVID-19 is less frequent in children, with a milder course. However, over the past weeks, an increase in the number of children presenting to hospitals in the greater Paris region with a phenotype resembling Kawasaki disease (KD) has led to an alert by the French national health authorities. METHODS: Multicentre compilation of patients with KD in Paris region since April 2020, associated with the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (‘Kawa-COVID-19’). A historical cohort of ‘classical’ KD served as a comparator. RESULTS: Sixteen patients were included (sex ratio=1, median age 10 years IQR (4·7 to 12.5)). SARS-CoV-2 was detected in 11 cases (69%), while a further five cases had documented recent contact with a quantitative PCR-positive individual (31%). Cardiac involvement included myocarditis in 44% (n=7). Factors prognostic for the development of severe disease (ie, requiring intensive care, n=7) were age over 5 years and ferritinaemia >1400 µg/L. Only five patients (31%) were successfully treated with a single intravenous immunoglobulin (IVIg) infusion, while 10 patients (62%) required a second line of treatment. The Kawa-COVID-19 cohort differed from a comparator group of ‘classical’ KD by older age at onset 10 vs 2 years (p<0.0001), lower platelet count (188 vs 383 G/L (p<0.0001)), a higher rate of myocarditis 7/16 vs 3/220 (p=0.0001) and resistance to first IVIg treatment 10/16 vs 45/220 (p=0.004). CONCLUSION: Kawa-COVID-19 likely represents a new systemic inflammatory syndrome temporally associated with SARS-CoV-2 infection in children. Further prospective international studies are necessary to confirm these findings and better understand the pathophysiology of Kawa-COVID-19. Trial registration number NCT02377245

positive: COVID-19 in Children: Clinical Approach and Management COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health crisis threatening humanity at this point in time. Transmission of the infection occurs by inhalation of infected droplets or direct contact with soiled surfaces and fomites. It should be suspected in all symptomatic children who have undertaken international travel in the last 14 d, all hospitalized children with severe acute respiratory illness, and asymptomatic direct and high-risk contacts of a confirmed case. Clinical symptoms are similar to any acute respiratory viral infection with less pronounced nasal symptoms. Disease seems to be milder in children, but situation appears to be changing. Infants and young children had relatively more severe illness than older children. The case fatality rate is low in children. Diagnosis can be confirmed by Reverse transcriptase – Polymerase chain reaction (RT-PCR) on respiratory specimen (commonly nasopharyngeal and oropharyngeal swab). Rapid progress is being made to develop rapid diagnostic tests, which will help ramp up the capacity to test and also reduce the time to getting test results. Management is mainly supportive care. In severe pneumonia and critically ill children, trial of hydroxychloroquine or lopinavir/ritonavir should be considered. As per current policy, children with mild disease also need to be hospitalized; if this is not feasible, these children may be managed on ambulatory basis with strict home isolation. Pneumonia, severe disease and critical illness require admission and aggressive management for acute lung injury and shock and/or multiorgan dysfunction, if present. An early intubation is preferred over non-invasive ventilation or heated, humidified, high flow nasal cannula oxygen, as these may generate aerosols increasing the risk of infection in health care personnel. To prevent post discharge dissemination of infection, home isolation for 1–2 wk may be advised. As of now, no vaccine or specific chemotherapeutic agents are approved for children.

positive: Is macrophages heterogeneity important in determining COVID-19 lethality? COVID-19 (coronavirus disease 2019) pandemic due to infection with SARS-CoV-2 has led to the death of thousands of adults worldwide. It is now clear that the hyper-inflammatory response triggered by SARS-CoV-2 plays a major role in disease severity and lethality of the infection. Macrophages are innate immune cells that sense and respond to infections by producing a plethora of inflammatory molecules and by interacting with other inflammatory cells. Therefore, macrophages may be diriment on eliminating pathogens and promoting organ repair. However, macrophages can be a major player of the so called cytokine storm and may be damaging to the tissues. It is believed that macrophage activation syndrome is induced by SARS-CoV to be lethal. Surprisingly and fortunately few children die from COVID-19. For instance, in Italy, out of more than 30.000 deaths for COVID-19, three are children. Therefore, we must wonder why? Are macrophages different in children compared to adults? In my opinion they are different. It has been demonstrated that macrophages populate the lung in three “developmental waves”, and it has been suggested that similar waves may be observed in other important organs, such as the heart and kidney. It is most likely that macrophages heterogeneity is involved in determining the severity. There are no doubts that macrophages are important in determining life or death in these patients. Comparing macrophages of children with those of adults with different degrees of disease severity is, therefore, mandatory.

positive: Novel coronavirus infection and children. BACKGROUND AND AIM Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its outbreak in many states of the world, forced the World Health Organization (WHO) to declare a pandemic. Currently, COVID-19 has infected 1 991 562 patients causing 130 885 deaths globally as of 16 April 2020. The aim of this review is to underline the epidemiological, clinical and management characteristics in children affected by COVID-19. METHODS We searched Pubmed, from January to April 2020, for the following search terms: "COVID-19", "children", "SARS-COV2", "complications", "epidemiology", "clinical features", focusing our attention mostly on epidemiology and symptoms of COVID-19 in children. RESULTS Usually, infants and children present milder symptoms of the disease with a better outcome than adults. Consequently, children may be considered an infection reservoir that may play a role as spreader of the infection in community.

positive: Clinical and epidemiological characteristics of children with COVID-19.

positive: Physiological advantages of children against COVID‐19 We read the editorial by Dr. Brodin with great interest, which is discussing why COVID-19 appears to be so mild in children(1). The author discussed the potential theories that could explain why children have a lower incidence and milder clinical manifestations than adults. Additionally to the theories mentioned by the author; we would like to emphasize the differences between the child and adult respiratory systems that potentially protect children from severe COVID-19 disease.

positive: Health-education to prevent COVID-19 in schoolchildren: a call to action BACKGROUND: There is currently considerable international debate around school closures/openings and the role of children in the transmission of coronavirus disease 2019 (COVID-19). Whilst evidence suggests that children are not impacted by COVID-19 as severely as adults, little is still known about their transmission potential, and with a lot of asymptomatic cases they may be silent transmitters (i.e. infectious without showing clinical signs of disease), albeit at a lower level than adults. In relation to this, it is somewhat concerning that in many countries children are cared for, or are often in close contact with, older individuals such as grandparents â the age group most at risk of acquiring serious respiratory complications resulting in death. MAIN TEXT: We emphasise that in the absence of a vaccine or an effective therapeutic drug, preventive measures such as good hygiene practices â hand washing, cough etiquette, disinfection of surfaces and social distancing represent the major (in fact only) weapons that we have against COVID-19. Accordingly, we stress that there is a pressing need to develop specific COVID-19 prevention messages for schoolchildren. CONCLUSION: An entertainment education intervention for schoolchildren systematically implemented in schools would be highly effective and fill this need. With such measures in place there would be greater confidence around the opening of schools.

positive: [Clinical features of asymptomatic or subclinical COVID-19 in children] OBJECTIVE: To study the clinical features of asymptomatic or subclinical coronavirus disease 2019 (COVID-19) in children METHODS: A retrospective analysis was performed for the clinical data of 53 children who were confirmed with asymptomatic or subclinical COVID-19, including epidemiological history, clinical typing, co-infection, time to clearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid in nasopharyngeal swabs, laboratory examination results, length of hospital stay, and treatment outcome RESULTS: The children with asymptomatic or subclinical COVID-19 accounted for 30 5% (53/174) in children with COVID-19 hospitalized in the COVID-19 ward of Wuhan Children's Hospital All cases occurred with familial aggregation Among the 53 children, 35 (66%) had asymptomatic infection and 18 (34%) had subclinical infection Mycoplasma infection was found in 17 children (32%) For the 53 children, the mean time to clearance of SARS-CoV-2 nucleic acid in nasopharyngeal swabs was 9+/-4 days Most laboratory markers were maintained within the normal range The mean hospital stay was 11+/-4 days Lung CT of 18 children with subclinical COVID-19 showed ground-glass opacities, linear opacities, and patchy opacities, with relatively limited lesions CONCLUSIONS: There is a high proportion of children with asymptomatic or subclinical COVID-19 among the children with COVID-19 hospitalized in the COVID-19 ward The transmission risk of asymptomatic or subclinical COVID-19 should be taken seriously

positive: COVID-19 in children: patiently and critically evaluate the scientific evidence

positive: ACE2 (Angiotensin-Converting Enzyme 2), COVID-19, and ACE Inhibitor and Ang II (Angiotensin II) Receptor Blocker Use During the Pandemic: The Pediatric Perspective Potential but unconfirmed risk factors for coronavirus disease 2019 (COVID-19) in adults and children may include hypertension, cardiovascular disease, and chronic kidney disease, as well as the medications commonly prescribed for these conditions, ACE (angiotensin-converting enzyme) inhibitors, and Ang II (angiotensin II) receptor blockers. Coronavirus binding to ACE2 (angiotensin-converting enzyme 2), a crucial component of the renin-angiotensin-aldosterone system, underlies much of this concern. Children are uniquely impacted by the coronavirus, but the reasons are unclear. This review will highlight the relationship of COVID-19 with hypertension, use of ACE inhibitors and Ang II receptor blockers, and lifetime risk of cardiovascular disease from the pediatric perspective. We briefly summarize the renin-angiotensin-aldosterone system and comprehensively review the literature pertaining to the ACE 2/Ang-(1-7) pathway in children and the clinical evidence for how ACE inhibitors and Ang II receptor blockers affect this important pathway. Given the importance of the ACE 2/Ang-(1-7) pathway and the potential differences between adults and children, it is crucial that children are included in coronavirus-related research, as this may shed light on potential mechanisms for why children are at decreased risk of severe COVID-19.

positive: [Viral respiratory infections in children].

positive: Coronavirus Infection Among Children and Adolescents Coronavirus infection is a global emergency. Over the past few months, there is a rapid increase in the number of cases and deaths due to coronavirus infection. It has been observed that elderly individuals and those with medical co-morbidities are maximally affected. In children and adolescents, coronavirus infection has low mortality as well as the severity of symptoms are less. Children and adolescents with immunocompromised state, malnutrition, medical co-morbidities and poor hygiene are at higher risk of contracting coronavirus infection. Minimizing this risk factors and adopting appropriate prevention measures will be helpful in limiting the spread of infection as there is no specific treatment and immunization available to date to address this serious issue. This chapter highlights the issues and challenges of coronavirus infection in children and adolescents.

positive: Children’s heart and COVID-19: Up-to-date evidence in the form of a systematic review The new coronavirus disease outbreak in 2019 (COVID-19) represents a dramatic challenge for healthcare systems worldwide. As to viral tropism, lungs are not the only COVID-19 target but also the heart may be involved in a not negligible percentage of the infected patients. Myocarditis-related cardiac dysfunction and potentially life-threatening arrhythmias are the main aftermaths. A few studies showed that myocardial injury in adult patients is often linked with a fatal outcome. Conversely, scientific evidence in children is sparse, although several reports were published with the description of a cardiac involvement in COVID-19 paediatric patients. In these young subjects, a background of surgically treated congenital heart disease seems to be a predisposing factor. Conclusion: This systematic review is aimed at summarizing all COVID-19 cases with a cardiac involvement published in paediatric age and trying to explain the underlying mechanisms responsible for COVID-19-related myocardial damage.

positive: How is immunosuppressive status affecting children and adults in SARS-CoV-2 infection? A systematic review OBJECTIVES: SARS-CoV-2 infection has now a global resonance. Data on how COVID-19 is affecting immunocompromised patients are however few. With our study we aimed to systematically review the current knowledge on SARS-CoV-2 cases in children and adults with immunosuppression, to evaluate outcomes in this special population. METHODS: A systematic review of literature was carried out to identify relevant articles, searching the EMBASE, Medline, and Google Scholar databases. Studies reporting data on pre-defined outcomes and related to immunosuppressed adults and children with SARS-CoV-2 were included. RESULTS: Sixteen relevant articles were identified with 110 immunosuppressed patients, mostly presenting cancer, along with transplantation and immunodeficiency. Cancer was more often associated with a more severe course, but not necessarily with a bad prognosis. Our data show that both children and adults with immunosuppression seem to have a favorable disease course, as compared to the general population. CONCLUSION: Immunosuppressed patients with COVID-19 seem to be few in relation to the overall figures, and to present a favorable outcome as compared to other comorbidities. This might be explained by a hypothetical protective role of a weaker immune response, determining a milder disease presentation and thus underdiagnosis. Nevertheless, surveillance on this special population should be encouraged.

positive: Understanding Covid and the associated post- infectious hyper-inflammatory inflammatory state (PIMS-TS) in children Summary When SARS-CoV2 infection was first reported from China, very few children had severe lung or systemic disease. Approximately six weeks after the first adult cases were reported in the United Kingdom, a small subgroup of children of largely non-white backgrounds, presented with severe hyper-inflammatory disease, most likely associated with Covid. The possible reasons for this ethnic predilection are explored.

positive: Human Leukocyte Transcriptional Response to SARS-CoV-2 Infection

positive: Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study Summary Background Since December, 2019, an outbreak of coronavirus disease 2019 (COVID-19) has spread globally. Little is known about the epidemiological and clinical features of paediatric patients with COVID-19. Methods We retrospectively retrieved data for paediatric patients (aged 0–16 years) with confirmed COVID-19 from electronic medical records in three hospitals in Zhejiang, China. We recorded patients' epidemiological and clinical features. Findings From Jan 17 to March 1, 2020, 36 children (mean age 8·3 [SD 3·5] years) were identified to be infected with severe acute respiratory syndrome coronavirus 2. The route of transmission was by close contact with family members (32 [89%]) or a history of exposure to the epidemic area (12 [33%]); eight (22%) patients had both exposures. 19 (53%) patients had moderate clinical type with pneumonia; 17 (47%) had mild clinical type and either were asymptomatic (ten [28%]) or had acute upper respiratory symptoms (seven [19%]). Common symptoms on admission were fever (13 [36%]) and dry cough (seven [19%]). Of those with fever, four (11%) had a body temperature of 38·5°C or higher, and nine (25%) had a body temperature of 37·5–38·5°C. Typical abnormal laboratory findings were elevated creatine kinase MB (11 [31%]), decreased lymphocytes (11 [31%]), leucopenia (seven [19%]), and elevated procalcitonin (six [17%]). Besides radiographic presentations, variables that were associated significantly with severity of COVID-19 were decreased lymphocytes, elevated body temperature, and high levels of procalcitonin, D-dimer, and creatine kinase MB. All children received interferon alfa by aerosolisation twice a day, 14 (39%) received lopinavir–ritonavir syrup twice a day, and six (17%) needed oxygen inhalation. Mean time in hospital was 14 (SD 3) days. By Feb 28, 2020, all patients were cured. Interpretation Although all paediatric patients in our cohort had mild or moderate type of COVID-19, the large proportion of asymptomatic children indicates the difficulty in identifying paediatric patients who do not have clear epidemiological information, leading to a dangerous situation in community-acquired infections. Funding Ningbo Clinical Research Center for Children's Health and Diseases, Ningbo Reproductive Medicine Centre, and Key Scientific and Technological Innovation Projects of Wenzhou.

positive: Clinical and CT features in pediatric patients with COVID‐19 infection: Different points from adults PURPOSE: To discuss the different characteristics of clinical, laboratory, and chest computed tomography (CT) in pediatric patients from adults with 2019 novel coronavirus (COVID‐19) infection. METHODS: The clinical, laboratory, and chest CT features of 20 pediatric inpatients with COVID‐19 infection confirmed by pharyngeal swab COVID‐19 nucleic acid test were retrospectively analyzed during 23 January and 8 February 2020. The clinical and laboratory information was obtained from inpatient records. All the patients were undergone chest CT in our hospital. RESULTS: Thirteen pediatric patients (13/20, 65%) had an identified history of close contact with COVID‐19 diagnosed family members. Fever (12/20, 60%) and cough (13/20, 65%) were the most common symptoms. For laboratory findings, procalcitonin elevation (16/20, 80%) should be pay attention to, which is not common in adults. Coinfection (8/20, 40%) is common in pediatric patients. A total of 6 patients presented with unilateral pulmonary lesions (6/20, 30%), 10 with bilateral pulmonary lesions (10/20, 50%), and 4 cases showed no abnormality on chest CT (4/20, 20%). Consolidation with surrounding halo sign was observed in 10 patients (10/20, 50%), ground‐glass opacities were observed in 12 patients (12/20, 60%), fine mesh shadow was observed in 4 patients (4/20, 20%), and tiny nodules were observed in 3 patients (3/20, 15%). CONCLUSION: Procalcitonin elevation and consolidation with surrounding halo signs were common in pediatric patients which were different from adults. It is suggested that underlying coinfection may be more common in pediatrics, and the consolidation with surrounding halo sign which is considered as a typical sign in pediatric patients.

positive: Guillain-Barre Syndrome Associated with SARS-CoV-2 Detection and a COVID-19 Infection in a Child Coronavirus disease (COVID-19) is caused by SARS-CoV-2. Physicians in China reported what is believed to be the first adult case of a SARS-CoV-2 infection associated with acute Guillain-Barré syndrome (GBS), followed by five adult Italian patients and another case in the United States of America. In the current report we present one of the first descriptions of an association of GBS and SARS-CoV-2 infection within a child. In our facility, and eleven year old boy presented with typical features of GBS and after five days a morbilliform skin rash over the palms of both hands. Three weeks before the start of the neurological symptoms, the boy had experienced an episode of mild febrile illness with mild respiratory manifestations and a persisting cough. The diagnosis of the SARS-CoV-2 infection was confirmed by oropharyngeal swab on reverse transcription polymerase chain reaction assay. The disease course of our patient strongly suggests a possible relationship between the development of GBS and SARS-CoV-2 infection. The case is discussed in view of the previous case reports with the association of GBS and Covid-19.

positive: COVID‐19 epidemic: Disease characteristics in children In mid‐December 2019, a disease caused by infection with severe acute respiratory syndrome coronavirus‐2, which began in Wuhan, China, has spread throughout the country and many countries around the world. The number of children with coronavirus disease‐2019 (COVID‐19) has also increased significantly. Although information regarding the epidemiology of COVID‐19 in children has accumulated, relevant comprehensive reports are lacking. The present article reviews the epidemiological characteristics of COVID‐19 in children.

positive: COVID-19 affects healthy pediatricians more than pediatric patients

positive: COVID-19 multisystem inflammatory syndrome in three teenagers with confirmed SARS-CoV-2 infection Coronavirus disease 2019 (COVID-19) is generally a relatively mild illness in children. An emerging disease entity coined as pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) has been reported recently, but is very rare and only affects a very small minority of children. Here we describe the clinical presentations and outcomes of three teenagers with serologically-confirmed SARS-CoV-2 infection admitted to a pediatric intensive care unit for PIMS-TS. Although their initial presentations were very similar, their COVID-19-related disease varied in severity.

positive: Perspectives of Immune Therapy in Coronavirus Disease 2019 The global fight against coronavirus disease 2019 (COVID-19) is largely based on strategies to boost immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent its severe course and complications. The human defence may include antibodies which interact with SARS-CoV-2 and neutralize its aggressive actions on multiple organ systems. Protective cross-reactivity of antibodies against measles and other known viral infections has been postulated, primarily as a result of the initial observations of asymptomatic and mild COVID-19 in children. Uncontrolled case series have demonstrated virus-neutralizing effect of convalescent plasma, supporting its efficiency at early stages of contracting SARS-CoV-2. Given the variability of the virus structure, the utility of convalescent plasma is limited to the geographic area of its preparation, and for a short period of time. Intravenous immunoglobulin may also be protective in view of its nonspecific antiviral and immunomodulatory effects. Finally, human monoclonal antibodies may interact with some SARS-CoV-2 proteins, inhibiting the virus-receptor interaction and prevent tissue injury. The improved understanding of the host antiviral responses may help develop safe and effective immunotherapeutic strategies against COVID-19 in the foreseeable future.

positive: SARS-CoV-2 infection in children - Understanding the immune responses and controlling the pandemic. In December 2019, a cluster of patients with severe pneumonia caused by a novel coronavirus (SARS-CoV-2) emerged in the city of Wuhan, China. The disease is now termed coronavirus disease 2019 (COVID-19). In the early reports, the patients were mainly middle-aged and elderly men, and children appeared to be less susceptible to this infection. With modern and efficient transportation, the disease quickly spread to almost all corners of the world and the mortality far exceeds those caused by severe acute respiratory syndrome coronavirus (SARS) or Middle East respiratory syndrome coronavirus (MERS). As the number of children with COVID-19 gradually increases, the disease has been documented in premature babies, infants, children and adolescents. Severe and fatal cases in children are relatively rare. The burden of disease in children has been relatively low, but the high proportions of asymptomatic or mildly symptomatic infections in children deserve careful attention. Clear understanding of the immune responses to the virus in children and the transmission potential of asymptomatic children are of paramount importance for the development of specific treatments and vaccine in order to effectively control the ongoing pandemic.

positive: Coronavirus Disease 2019 in Children Cared for at Texas Children’s Hospital: Initial Clinical Characteristics and Outcomes We describe the clinical course of 57 children with coronavirus disease 2019 (COVID-19) cared for through a single hospital system. Most children were mildly symptomatic, and only a few patients with underlying medical conditions required hospitalization. Systemwide patient evaluation processes allowed for prompt identification and management of patients with COVID-19.

positive: Mechanisms and evidence of vertical transmission of infections in pregnancy including SARS-CoV-2 There remain unanswered questions concerning mother-to-child-transmission (MTCT) of SARS-CoV-2. Despite reports of neonatal COVID-19, SARS-CoV-2 has not been consistently isolated in perinatal samples thus, definitive proof of transplacental infection is still lacking. To address these questions, we assessed investigative tools used to confirm maternal-fetal infection and known protective mechanisms of the placental barrier that prevent transplacental pathogen migration. Forty studies of COVID-19 pregnancies reviewed suggest a lack of consensus on diagnostic strategy for congenital infection. While RT-PCR of neonatal swabs was universally performed, a wide range of clinical samples was screened including vaginal secretions (22.5%), amniotic fluid (35%), breast milk (22.5%) and umbilical cord blood. Neonatal COVID-19 was reported in eight studies, two of which were based on the detection of SARS-CoV-2 IgM in neonatal blood. Histological examination demonstrated sparse viral particles, vascular malperfusion and inflammation in the placenta from pregnant women with COVID-19. The paucity of placental co-expression of ACE-2 and TMPRSS2, two receptors involved in cytoplasmic entry of SARS-CoV-2, may explain its relative insensitivity to transplacental infection. Viral interactions may utilise membrane receptors other than ACE-2 thus, tissue susceptibility may be broader than currently known. Further spatial-temporal studies are needed to determine the true potential for transplacental migration. This article is protected by copyright. All rights reserved.

positive: Covid-19 and pregnancy Guideline: Coronavirus (COVID-19) Infection in pregnancyPublished by the Royal College of Obstetricians and Gynaecologists (RCOG), with input from the Royal College of Midwives, the Royal College of Paediatrics and Child Health (RCPH), the Royal College of Anaesthetists, and the Obstetric Anaesthetists' Association.This summary is based on version 8 of the guideline, published on 17 April 2020 (https://www.rcog.org.uk/globalassets/documents/guidelines/2020-04-17-coronavirus-covid-19-infection-in-pregnancy.pdf).

positive: Major cluster of pediatric “ true ” primary chilblains during the COVID‐19 pandemic: a consequence of lifestyle changes due to lockdown BACKGROUND: Over the last months, during the COVID‐19 pandemic, a growing number of chilblain‐like lesions was reported mainly in children, rarely in young adults. The relationship with SARS‐CoV‐2 infection was postulated, often without any laboratory, instrumental or clinical confirmation. The disclosure of information about chilblain‐like lesions as a COVID‐19 manifestation in social media has created concern in children’s families and pediatricians OBJECTIVES: to verify whether the chilblain‐like lesions were caused by SARS‐CoV‐2 infection. METHODS: prospective study on a case series including children who presented with acral lesions at the Pediatric Dermatology Outpatient and Pediatric Emergency Unit of the University of Bologna, from April 1 to April 30, 2020. We reported demographical, laboratory and clinical features, history of close contact with COVID‐19 patients, presence of similar skin lesions in other family members, precipitating and risk factors for chilblain onset. RESULTS: We evaluated 8 patients (5 females, 3 males) aged between 11 and 15 years. We excluded acute or previous SARS‐CoV‐2 infection with RT‐PCR nasopharyngeal swab, serum antibody levels using chemiluminescent immunoassays. Other acute infections causing purpuric lesions at the extremities were negative in all patients. Skin lesion biopsy for histological and immunohistochemical evaluation was made in two cases and was consistent with chilblain. PCR‐assay on skin lesion biopsy for Parvovirus B19, Mycoplasma pneumoniae and SARS‐CoV‐2 was performed in a patient and resulted negative. We identified common precipitating and risk factors: physical (cold and wet extremities, low BMI), cold and wet indoor and outdoor environment, behaviors, habits, lifestyle. We therefore reached a diagnosis of primary chilblains. CONCLUSIONS: During the COVID‐19 pandemic, a “cluster” of primary chilblains developed in predisposed subjects, mainly teenagers, due to to cold exposure in the lockdown period. Laboratory findings support our hypothesis, although it is also possible that an unknown infectious trigger may have contributed to the pathogenesis.

positive: Psychosocial and Behavioral Impact of COVID-19 in Autism Spectrum Disorder: An Online Parent Survey. The 2019 coronavirus disease (COVID-19) outbreak could result in higher levels of psychological distress, especially among people suffering from pre-existing mental health conditions. Young individuals with autism spectrum disorders (ASD) are particularly at risk due to their vulnerability to unpredictable and complex changes. This study aimed to investigate the impact of the COVID-19 pandemic on ASD individuals, whether any pre-pandemic sociodemographic or clinical characteristics would predict a negative outcome, and to narratively characterize their needs. Parents and guardians of ASD individuals filled out an online survey consisting of 40 questions investigating socio-demographic and clinical characteristics of their children, impact of the COVID-19 outbreak on their wellbeing and needs to deal with the emergency. Data were available on 527 survey participants. The COVID-19 emergency resulted in a challenging period for 93.9% of families, increased difficulties in managing daily activities, especially free time (78.1%) and structured activities (75.7%), and, respectively, 35.5% and 41.5% of children presenting with more intense and more frequent behavior problems. Behavior problems predating the COVID-19 outbreak predicted a higher risk of more intense (odds ratio (OR) = 2.16, 95% confidence interval (CI) 1.42-3.29) and more frequent (OR = 1.67, 95% CI 1.13-2.48) disruptive behavior. Even though ASD children were receiving different types of support, also requiring specialist (19.1%) or emergency (1.5%) interventions in a relatively low proportion of cases, a number of needs emerged, including receiving more healthcare support (47.4%), especially in-home support (29.9%), as well as interventions to tackle a potentially disruptive quarantine (16.8%). The COVID-19 outbreak has undoubtedly resulted in increased difficulties among ASD individuals.

positive: A Comparison of Mortality-related Risk Factors of COVID-19, SARS, and MERS: A Systematic Review and Meta-analysis Objective: Coronavirus Disease 2019 (COVID-19) is a pandemic. This systematic review compares mortality risk factors including clinical, demographic and laboratory features of COVID-19, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The aim is to provide new strategies for COVID-19 prevention and treatment. Methods: We performed a systematic review with meta-analysis, using five databases to compare the predictors of death for COVID-19, SARS and MERS. A random-effects model meta-analysis calculated odds ratios (OR) and 95% confidence intervals (95% CI). Results: 845 articles up through 11/4/2020 were retrieved, but only 28 studies were included in this meta-analysis. The results showed that males had a higher likelihood of death than females (OR = 1.82, 95% CI 1.56-2.13). Age (OR = 7.86, 95% CI 5.46-11.29), diabetes comorbidity (OR = 3.73, 95% CI 2.35-5.90), chronic lung disease (OR = 3.43, 95% CI 1.80-6.52) and hypertension (OR = 3.38, 95% CI 2.45-4.67) were the mortality risk factors. The laboratory indicators lactic dehydrogenase (OR = 37.52, 95% CI 24.68-57.03), C-reactive protein (OR = 12.11, 95% CI 5.24-27.98), and neutrophils (OR = 17.56, 95% CI 10.67-28.90) had stronger correlations with COVID-19 mortality than with SARS or MERS mortality. Consolidation and ground-glass opacity imaging features were similar among COVID-19, SARS, and MERS patients. Conclusions: COVID-19’s mortality factors are similar to those of SARS and MERS. Age and laboratory indicators could be effective predictors of COVID-19 mortality outcomes.

positive: Presenting symptoms of COVID-19 in children: a meta-analysis of published studies

positive: SARS-CoV-2 infection in infants under 1 year of age in Wuhan City, China BACKGROUND: The clinical characteristics and outcome of COVID-19 in children are different from those in adults. We aimed to describe the characteristics of infants under 1 year of age (excluding newborns) with COVID-19. METHODS: We retrospectively retrieved data of 36 infants with SARS-CoV-2 infection in Wuhan Children's Hospital from January 26 to March 22, 2020. Clinical features, chest imaging findings, laboratory tests results, treatments and clinical outcomes were analyzed. RESULTS: The mean age of the infected infants was 6.43 months, with a range of 2-12 months. 61.11% of the patients were males and 38.89% females. 86.11% of the infants were infected due to family clustering. Cough (77.78%) and fever (47.22%) were the most common clinical manifestations. Chest CT scan revealed 61.11% bilateral pneumonia and 36.11% unilateral pneumonia. 47.22% of the infants developed complications. Increased leucocytes, neutrophils, lymphocytes, and thrombocytes were observed in 11.11, 8.33, 36.11 and 44.44% of infants, respectively. Decreased leucocytes, neutrophils, thrombocyte and hemoglobin were observed in 8.33, 19.44, 2.78 and 36.11% of infants, respectively. Increased C-reactive protein, procalcitonin, lactate dehydrogenase, alanine aminotransferase, creatine kinase and D-dimer were observed in 19.44, 67.74, 47.22, 19.44, 22.22 and 20.69% of infants, respectively. Only one infant had a high level of creatinine. Co-infections with other respiratory pathogens were observed in 62.86% of infants. CD3 (20.69%), CD4 (68.97%), CD19 (31.03%) and Th/Ts (44.83%) were elevated; CD8 (6.9%) and CD16+CD56 (48.28%) was reduced. IL-4 (7.69%), IL-6 (19.23%), IL-10 (50%), TNF-α (11.54%) and IFN-Î³ (19.23%) were elevated. Up to March 22, 97.22% of infants recovered, while a critical ill infant died. When the infant's condition deteriorates rapidly, lymphocytopenia was discovered. Meanwhile, C-reactive protein, D-dimer, alanine aminotransferase, creatine kinase, creatinine, IL-6 and IL-10 increased significantly. CONCLUSIONS: In the cohort, we discovered that lymphocytosis, elevated CD4 and IL-10, and co-infections were common in infants with COVID-19, which were different from adults with COVID-19. Most infants with COVID-19 have mild clinical symptoms and good prognosis.

positive: Laboratory Abnormalities in Children with Mild and Severe Coronavirus Disease 2019 (COVID-19): a pooled analysis and review Limited data exists to-date on the laboratory findings in children with COVID-19, warranting the conduction of this study, in which we pool the currently available literature data on the laboratory findings seen in children with mild and severe COVID-19. Following an extensive literature search, we identified 24 eligible studies, including a total of 624 pediatric cases with laboratory-confirmed COVID-19, which report data on 27 different biomarkers. We then performed a meta-analysis to calculate the pooled prevalence estimates (PPE) for these laboratory abnormalities in mild COVID-19. As data was too limited for children with severe COVID-19 to allow pooling, results were presented descriptively in a summary of findings table. Our data show an inconsistent pattern of change in the leukocyte index of mild and severe cases of COVID-19 in children. Specifically, changes in leukocyte counts were only observed in 32% of the mild pediatric cases (PPE: 13% increase, 19% decrease). In mild disease, creatine kinase-MB (CK-MB) was frequently elevated, with a PPE of 33%. In severe disease, c-reactive protein (CRP), procalcitonin (PCT), and lactate dehydrogenase (LDH) were frequently elevated. Based on data obtained from early COVID-19 studies, leukocyte indices in children appear inconsistent, differing from those reported in adults that highlight specific leukocyte trends. This brings into question the utility and reliability of such parameters in monitoring disease severity in the pediatric population. Instead, we suggest physicians to serially monitor CRP, PCT, and LDH to track the course of illness in hospitalized children. Finally, elevated CK-MB in mild pediatric COVID-19 cases is indicative of possible cardiac injury. This highlights the importance of monitoring cardiac biomarkers in hospitalized patients and the need for further investigation of markers such as cardiac troponin in future studies.

positive: Spectrum of COVID-19 in Children The prevalence of coronavirus disease 2019 (COVID-19) is lower in children compared to adults. Children contribute to 1-5% of all COVID-19 cases (1) . A recent study from China reported that 171(12.3%) of 1391 children with suspected disease had confirmed COVID-19 infection (2) . As of May 15, 2020, there are 33,241 children with COVID-19 in the United States (3) . The most common symptoms in children with confirmed and suspected COVID-19 include fever and cough followed by diarrhea, and abdominal pain.

positive: 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 104 studies with 5694 patients were included. Using 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, 0.11-1.00). 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.

positive: Outcomes of COVID-19: disparities in obesity and by ethnicity/race

positive: Novel coronavirus disease (COVID-19) in children Coronavirus disease (COVID-19) was firstly reported at the end of 2019. The disease rapidly spread all around the world in a few months and was declared a worldwide pandemic by WHO in March 2020. By April 9, there were 1,436,198 confirmed COVID-19 cases in the world, nearly with 6% mortality rate. This novel infectious disease causes respiratory tract illness that may generally occur as mild upper respiratory tract disease or pneumonia. In older patients and/or patients with underlying conditions, it may result in acute respiratory distress syndrome, multi organ failure and even death. According to the current literature, children account approximately for 1%5% of diagnosed COVID-19 cases. Generally, COVID-19 seems to be a less severe disease for children than adults. Approximately 90% of pediatric patients are diagnosed as asymptomatic, mild, or moderate disease. However, up to 6.7% of cases may be severe. Severe illness is generally seen in patients smaller than 1 year of age and patients who have underlying disesases. The epidemiological and clinical patterns of COVID-19 and treatment approaches in pediatric patients still remain unclear although many pediatric reports are published. This review aims to summarize the current epidemics, clinical presentations, diagnosis, and treatment of COVID-19 in pediatric patients.

positive: Coronavirus Disease 2019 in Children Cared for at Texas Children's Hospital: Initial Clinical Characteristics and Outcomes We describe the clinical course of 57 children with coronavirus disease 2019 (COVID-19) cared for through a single hospital system. Most children were mildly symptomatic, and only a few patients with underlying medical conditions required hospitalization. System-wide patient evaluation processes allowed for prompt identification and management of COVID-19 patients.

positive: COVID-19 and newborn health: systematic review OBJECTIVE. To describe perinatal and neonatal outcomes in newborns exposed to SARS-CoV-2. METHODS. A systematic review was conducted by searching PubMed Central, LILACS, and Google Scholar using the keywords ‘covid ’ AND ‘newborn’ OR ‘child’ OR ‘infant,’ on 18 March 2020, and again on 17 April 2020. One researcher conducted the search and extracted data on demographics, maternal outcomes, diagnostic tests, imaging, and neonatal outcomes. RESULTS. Of 256 publications identified, 20 met inclusion criteria and comprised neonatal outcome data for 222 newborns whose mothers were suspected or confirmed to be SARS-CoV-2 positive perinatally (17 studies) or of newborns referred to hospital with infection/pneumonia (3 studies). Most (12 studies) were case-series reports; all were from China, except three (Australia, Iran, and Spain). Of the 222 newborns, 13 were reported as positive for SARS-CoV-2; most of the studies reported no or mild symptoms and no adverse perinatal outcomes. Two papers among those from newborns who tested positive reported moderate or severe clinical characteristics. Five studies using data on umbilical cord blood, placenta, and/or amniotic fluid reported no positive results. Nine studies reported radiographic imaging, including 5 with images of pneumonia, increased lung marking, thickened texture, or high-density nodular shadow. Minor, non-specific changes in biochemical variables were reported. Studies that tested breast milk reported negative SARS-CoV-2 results. CONCLUSIONS. Given the paucity of studies at this time, vertical transmission cannot be confirmed or denied. Current literature does not support abstaining from breastfeeding nor separating mothers and newborns. Further evidence and data collection networks, particularly in the Americas, are needed for establishing definitive guidelines and recommendations.

positive: Clinical characteristics and outcome of SARS-CoV-2 infection in Italian pediatric oncology patients: a study from the Infectious Diseases Working Group of the AIEOP BACKGROUND: Little is known as yet about the outcome of SARS-CoV-2 infection in children being treated for cancer. METHODS: We collected information on the clinical characteristics and outcomes of a cohort of 29 children (16 females and 13 males, median age 7 years, range [0-16]) diagnosed with SARS-CoV-2 infection while on chemotherapy/immunotherapy (N=26), or after stem cell transplantation (N=3) during the peak of the epidemic in Italy. These patients suffered from leukemia (N=16), lymphoma (N=3), solid tumors (N=10), and Langerhans cell histiocytosis (N=1). RESULTS: The course of the disease was mild in all cases, with only 12 children developing symptoms (pneumonia in 3 cases), and none needing intensive care. Fifteen patients were hospitalized, including 7 asymptomatic patients. Nine patients (including 5 with no symptoms) were given hydroxychloroquine, and 3 of them were also given lopinavir/ritonavir. CONCLUSIONS: SARS-CoV-2 infection seems to take a milder clinical course in children than in adults with cancer. Specific SARS-CoV-2 treatment seems unnecessary for most children. In the light of our findings, and albeit with the necessary caution, we suggest avoiding major changes to planned anticancer treatments in pediatric patients acquiring COVID-19.

positive: A Mini Review on Current Clinical and Research Findings for Children Suffering from COVID-19 Background: As the novel coronavirus triggering COVID-19 has broken out in Wuhan, China and spread rapidly worldwide, it threatens the lives of thousands of people and poses a global threat on the economies of the entire world. However, infection with COVID-19 is currently rare in children. Objective To discuss the latest findings and research focus on the basis of characteristics of children confirmed with COVID-19, and provide an insight into the future treatment and research direction. Methods: We searched the terms "COVID-19 OR coronavirus OR SARS-CoV-2" AND "Pediatric OR children" on PubMed, Embase, Cochrane library, NIH, CDC, and CNKI. The authors also reviewed the guidelines published on Chinese CDC and Chinese NHC. Results: We included 25 published literature references related to the epidemiology, clinical manifestation, accessary examination, treatment, and prognosis of pediatric patients with COVID-19. Conclusion: The numbers of children with COVID-19 pneumonia infection are small, and most of them come from family aggregation. Symptoms are mainly mild or even asymptomatic, which allow children to be a risk factor for transmission. Thus, strict epidemiological history screening is needed for early diagnosis and segregation. This holds especially for infants, who are more susceptible to infection than other age groups in pediatric age, but have most likely subtle and unspecific symptoms. They need to be paid more attention to. CT examination is a necessity for screening the suspected cases, because most of the pediatric patients are mild cases, and plain chest X-ray do not usually show the lesions or the detailed features. Therefore, early chest CT examination combined with pathogenic detection is a recommended clinical diagnosis scheme in children. The risk factors which may suggest severe or critical progress for children are: Fast respiratory rate and/or; lethargy and drowsiness mental state and/or; lactate progressively increasing and/or; imaging showed bilateral or multi lobed infiltration, pleural effusion or rapidly expending of lesions in a short period of time and/or; less than 3 months old or those who underly diseases. For those critical pediatric patients with positive SARS-CoV-2 diagnosis, polypnea may be the most common symptom. For treatment, the elevated PCT seen in children in contrast to adults suggests that the underlying coinfection/secondary infection may be more common in pediatric patients and appropriate antibacterial treatment should be considered. Once cytokine storm is found in these patients, anti-autoimmune or blood-purifying therapy should be given in time. Furthermore, effective isolation measures and appropriate psychological comfort need to be provided timely.

positive: The different clinical characteristics of corona virus disease cases between children and their families in China - the character of children with COVID-19 This study aims to analyze the different clinical characteristics between children and their families infected with severe acute respiratory syndrome coronavirus 2. Clinical data from nine children and their 14 families were collected, including general status, clinical, laboratory test, and imaging characteristics. All the children were detected positive result after their families onset. Three children had fever (22.2%) or cough (11.2%) symptoms and six (66.7%) children had no symptom. Among the 14 adult patients, the major symptoms included fever (57.1%), cough (35.7%), chest tightness/pain (21.4%), fatigue (21.4%) and sore throat (7.1%). Nearly 70% of the patients had normal (71.4%) or decreased (28.6%) white blood cell counts, and 50% (7/14) had lymphocytopenia. There were 10 adults (71.4%) showed abnormal imaging. The main manifestations were pulmonary consolidation (70%), nodular shadow (50%), and ground glass opacity (50%). Five discharged children were admitted again because their stool showed positive result in SARS-CoV-2 PCR. COVID-19 in children is mainly caused by family transmission, and their symptoms are mild and prognosis is better than adult. However, their PCR result in stool showed longer time than their families. Because of the mild or asymptomatic clinical process, it is difficult to recognize early for pediatrician and public health staff.

positive: SARS‐CoV‐2 Testing and Outcomes in the First 30 Days after the First Case of COVID‐19 at an Australian Children’s Hospital OBJECTIVE: International studies describing COVID‐19 in children have shown low proportions of paediatric cases and generally a mild clinical course. We aimed to present early data on children tested for SARS‐CoV‐2 at a large Australian tertiary children’s hospital according to the state health department guidelines, which varied over time. METHODS: We conducted a retrospective cohort study at The Royal Children’s Hospital, Melbourne, Australia. It included all paediatric patients (aged 0–18 years) who presented to the Emergency Department (ED) or the Respiratory Infection Clinic (RIC) and were tested for SARS‐CoV‐2. The 30‐day study period commenced after the first confirmed positive case was detected at the hospital on 21(st) March 2020, until 19(th) April 2020. We recorded epidemiological and clinical data. RESULTS: There were 433 patients in whom SARS‐CoV‐2 testing was performed in ED (331 (76%)) or RIC (102 (24%)). There were 4 (0.9%) who had positive SARS‐CoV‐2 detected, none of whom were admitted to hospital or developed severe disease. Of these SARS‐CoV‐2 positive patients, 1/4 (25%) had a comorbidity, which was asthma. Of the SARS‐CoV‐2 negative patients, 196/429 (46%) had comorbidities. Risk factors for COVID‐19 were identified in 4/4 SARS‐CoV‐2 positive patients and 47/429 (11%) SARS‐CoV‐2 negative patients. CONCLUSIONS: Our study identified a very low rate of SARS‐CoV‐2 positive cases in children presenting to a tertiary ED or RIC, none of whom were admitted to hospital. A high proportion of patients who were SARS‐CoV‐2 negative had comorbidities.

positive: Clinical Characteristics of Children with COVID-19 BACKGROUND: In December 2019, the infection caused by 2019 novel coronavirus (COVID-19) led to an outbreak in Wuhan, situated in the Hubei Province of China. Following this, there has been a rapid increase in the number of cases. On 12th March 2020, there were over 100,000 confirmed cases and almost 4,300 deaths worldwide. The clinical profile of children with COVID-19 is unknown due to the few number of cases reported. Currently, available data suggest they may have a milder form of illness. METHODS: A review of the literature published from June 2019 to March 2020 was undertaken to evaluate the clinical presentation, management and outcomes of COVID-19 in in children. Data sources included EMBASE, MEDLINE, Cochrane library, ISI Web of Knowledge and references within identified articles. RESULTS: We identified 303 potential studies, and 295 were excluded for reasons including duplicates, experimental studies and case reports. Eight studies were eligible for inclusion, including a total of 820 paediatric cases of COVID-19. Asymptomatic cases represented 14.3% (n = 117) of the total number of cases identified, and thus the remaining 85.7% (n = 703) experienced symptoms. Fever was the commonest symptom in 53.9% (n = 48) of cases, followed by cough in 39.3% (n = 35) of cases, and rhinorrhoea or pharyngeal congestion in 13.5% (n = 12) of cases. Diarrhoea and sore throats were less common symptoms, 7.9% (n = 7) and 9.0% (n = 8) respectively. Other symptoms, including fatigue, headache and dizziness were rare. CONCLUSION: Children are disproportionately affected by COVID-19 and are more likely to run a milder cause of illness following this infection compared to adults. This outbreak only started 3 months ago, therefore, further population wide studies are needed to validate these findings.

positive: Clinical characteristics of COVID-19 in children compared with adults in Shandong Province, China AIMS AND BACKGROUND: The COVID-19 outbreak spread in China and is a threat to the world. We reported on the epidemiological, clinical, laboratory, and radiological characteristics of children cases to help health workers better understand and provide timely diagnosis and treatment. METHODS: Retrospectively, two research centers' case series of 67 consecutive hospitalized cases including 53 adult and 14 children cases with COVID-19 between 23 Jan 2020 and 15 Feb 2020 from Jinan and Rizhao were enrolled in this study. Epidemiological, clinical, laboratory, and radiological characteristics of children and adults were analyzed and compared. RESULTS: Most cases in children were mild (21.4%) and conventional cases (78.6%), with mild clinical signs and symptoms, and all cases were of family clusters. Fever (35.7%) and dry cough (21.4%) were described as clinical manifestations in children cases. Dry cough and phlegm were not the most common symptoms in children compared with adults (p = 0.03). In the early stages of the disease, lymphocyte counts did not significantly decline but neutrophils count did in children compared with adults (p = 0.02). There was a lower level of CRP (p = 0.00) in children compared with adults. There were 8 (57.1%) asymptomatic cases and 6 (42.9%) symptomatic cases among the 14 children cases. The age of asymptomatic patients was younger than that of symptomatic patients (p = 0.03). Even among asymptomatic patients, 5 (62.5%) cases had lung injuries including 3 (60%) cases with bilateral involvement, which was not different compared with that of symptomatic cases (p = 0.58, p = 0.74). CONCLUSIONS: The clinical symptoms of children are mild, there is substantial lung injury even among children, but that there is less clinical disease, perhaps because of a less pronounced inflammatory response, and that the occurrence of this pattern appears to inversely correlate with age.

positive: Potential influence of COVID-19/ACE2 on the female reproductive system The 2019 novel coronavirus (2019-nCoV) appeared in December 2019 and then spread throughout the world rapidly. The virus invades the target cell by binding to angiotensin-converting enzyme (ACE) 2 and modulates the expression of ACE2 in host cells. ACE2, a pivotal component of the renin-angiotensin system, exerts its physiological functions by modulating the levels of angiotensin II (Ang II) and Ang-(1-7). We reviewed the literature that reported the distribution and function of ACE2 in the female reproductive system, hoping to clarify the potential harm of 2019-nCoV to female fertility. The available evidence suggests that ACE2 is widely expressed in the ovary, uterus, vagina and placenta. Therefore, we believe that apart from droplets and contact transmission, the possibility of mother-to-child and sexual transmission also exists. Ang II, ACE2 and Ang-(1-7) regulate follicle development and ovulation, modulate luteal angiogenesis and degeneration, and also influence the regular changes in endometrial tissue and embryo development. Taking these functions into account, 2019-nCoV may disturb the female reproductive functions through regulating ACE2.

positive: Children with Coronavirus Disease 2019 (COVID-19): A Review of Demographic, Clinical, Laboratory and Imaging Features in 2,597 Pediatric Patients An epidemic of coronavirus disease 2019 (COVID-19) has been spreading worldwide. With the rapid increase in the number of infections, children with COVID-19 appear to be rising. Most research findings regarding adult cases, which are not always transferrable to children. Evidence-based studies are still expected to formulate clinical decisions for pediatric patients. In this review, we evaluated the demographic, clinical, laboratory and imaging features from 2,597 pediatric patients of COVID-19 that reported recently. We found that even lymphopenia was the most common lab finding in adults, it infrequently occurred in children (9.8%). Moreover, elevated creatine kinase MB isoenzyme (CK-MB) was much more commonly observed in children (27.0%) than that in adults, suggesting that heart injury would be more likely to happen in pediatric patients. Our analysis may contribute to determine the spectrum of disease in children, as well as to develop strategies to control the disease transmission. This article is protected by copyright. All rights reserved.

positive: Pediatric COVID-19: Systematic review of the literature OBJECTIVES: There is limited data regarding the demographics and clinical features of SARS-CoV-2 infection in children. This information is especially important as pneumonia is the single leading cause of death in children worldwide. This Systematic Review aims to elucidate a better understanding of the global impact of COVID-19 on the pediatric population. METHODS: A systematic review of the literature was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to gain insight into pediatric COVID-19 epidemiology. Specifically, Pubmed and Google Scholar databases were searched to identify any relevant article with a focus on Pediatric Covid 19, Pediatric Covid-19, Pediatric SARS-COV-2, and Pediatric Coronavirus 19. References within the included articles were reviewed. All articles that met criteria where analyzed for demographics, clinical, laboratory, radiographic, treatment and outcomes data. RESULTS: Ten studies including two case series and 8 retrospective chart reviews, altogether describing a total of 2914 pediatric patients with COVID-19 were included in this systematic review. Of the patients whose data was available, 56% were male, the age range was 1â¯day to 17â¯years, 79% were reported to have no comorbidities, and of the 21% with comorbidities, the most common were asthma, immunosupression, and cardiovascular disease. Of pediatric patients that were tested and positive for an infection with SARS-CoV-2, patients were asymptomatic, 14.9% of the time. Patients presented with cough (48%), fever (47%) and sore throat/pharyngitis (28.6%), more commonly than with upper respiratory symptoms/rhinorrhea/sneezing/nasal congestion (13.7%), vomiting/nausea (7.8%) and diarrhea (10.1%). Median lab values including those for WBC, lymphocyte count and CRP, were within the reference ranges with the exception of procalcitonin levels, which were slightly elevated in children with COVID-19 (median procalcitonin levels ranged from 0.07 to 0.5â¯ng/mL. Computed tomography (CT) results suggest that unilateral CT imaging findings are present 36% of cases while 64% of pediatric patients with COVID-19 had bilateral findings. Of the studies with age specific hospitalization data available, 27.0% of patients hospitalized were infants under 1â¯year of age. Various treatment regimens including interferon, antivirals, and hydroxychloroquine therapies have been trialed on the pediatric population but there are currently no studies showing efficacy of one regimen over the other. The mortality rate of children that were hospitalized with COVID-19 was 0.0018%. CONCLUSION: In contrast to adults, most infected children appear to have a milder course and have better outcomes overall. Additional care may be needed for children with comorbidities and younger children. This review also suggests that unilateral CT chest imaging findings were seen in 36.4% pediatric COVID-19 patients. This is particularly concerning as the work-up of pediatric patients with cough may warrant a bronchoscopy to evaluate for airway foreign bodies. Extra precautions need to be taken with personal protective equipment for these cases, as aerosolizing procedures may be a method of viral transmission. LEVEL OF EVIDENCE: 4 (Systematic Review).

positive: Intensive care admissions of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the UK: a multicentre observational study BACKGROUND: In April, 2020, clinicians in the UK observed a cluster of children with unexplained inflammation requiring admission to paediatric intensive care units (PICUs). We aimed to describe the clinical characteristics, course, management, and outcomes of patients admitted to PICUs with this condition, which is now known as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). METHODS: We did a multicentre observational study of children (aged <18 years), admitted to PICUs in the UK between April 1 and May 10, 2020, fulfilling the case definition of PIMS-TS published by the Royal College of Paediatrics and Child Health. We analysed routinely collected, de-identified data, including demographic details, presenting clinical features, underlying comorbidities, laboratory markers, echocardiographic findings, interventions, treatments, and outcomes; serology information was collected if available. PICU admission rates of PIMS-TS were compared with historical trends of PICU admissions for four similar inflammatory conditions (Kawasaki disease, toxic shock syndrome, haemophagocytic lymphohistiocytosis, and macrophage activation syndrome). FINDINGS: 78 cases of PIMS-TS were reported by 21 of 23 PICUs in the UK. Historical data for similar inflammatory conditions showed a mean of one (95% CI 0·85–1·22) admission per week, compared to an average of 14 admissions per week for PIMS-TS and a peak of 32 admissions per week during the study period. The median age of patients was 11 years (IQR 8–14). Male patients (52 [67%] of 78) and those from ethnic minority backgrounds (61 [78%] of 78) were over-represented. Fever (78 [100%] patients), shock (68 [87%]), abdominal pain (48 [62%]), vomiting (49 [63%]), and diarrhoea (50 [64%]) were common presenting features. Longitudinal data over the first 4 days of admission showed a serial reduction in C-reactive protein (from a median of 264 mg/L on day 1 to 96 mg/L on day 4), D-dimer (4030 μg/L to 1659 μg/L), and ferritin (1042 μg/L to 757 μg/L), whereas the lymphocyte count increased to more than 1·0 × 10(9) cells per L by day 3 and troponin increased over the 4 days (from a median of 157 ng/mL to 358 ng/mL). 36 (46%) of 78 patients were invasively ventilated and 65 (83%) needed vasoactive infusions; 57 (73%) received steroids, 59 (76%) received intravenous immunoglobulin, and 17 (22%) received biologic therapies. 28 (36%) had evidence of coronary artery abnormalities (18 aneurysms and ten echogenicity). Three children needed extracorporeal membrane oxygenation, and two children died. INTERPRETATION: During the study period, the rate of PICU admissions for PIMS-TS was at least 11-fold higher than historical trends for similar inflammatory conditions. Clinical presentations and treatments varied. Coronary artery aneurysms appear to be an important complication. Although immediate survival is high, the long-term outcomes of children with PIMS-TS are unknown. FUNDING: None.

positive: Pediatric Acute Lung Injury Epidemiology and Natural History study: Incidence and outcome of the acute respiratory distress syndrome in children. OBJECTIVES The incidence and outcome of the acute respiratory distress syndrome in children are not well-known, especially under current ventilatory practices. The goal of this study was to determine the incidence, etiology, and outcome of acute respiratory distress syndrome in the pediatric population in the setting of lung protective ventilation. DESIGN A 1-yr, prospective, multicenter, observational study in 12 geographical areas of Spain (serving a population of 3.77 million ≤ 15 yrs of age) covered by 21 pediatric intensive care units. SUBJECTS All consecutive pediatric patients receiving invasive mechanical ventilation and meeting American-European Consensus Criteria for acute respiratory distress syndrome. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Data on ventilatory management, gas exchange, hemodynamics, and organ dysfunction were collected. A total of 146 mechanically ventilated patients fulfilled the acute respiratory distress syndrome definition, representing a incidence of 3.9/100,000 population ≤ 15 yrs of age/yr. Pneumonia and sepsis were the most common causes of acute respiratory distress syndrome. At the time of meeting acute respiratory distress syndrome criteria, mean PaO2/FIO2 was 99 mm Hg ± 41 mm Hg, mean tidal volume was 7.6 mL/kg ± 1.8 mL/kg predicted body weight, mean plateau pressure was 27 cm H2O ± 6 cm H2O, and mean positive end-expiratory pressure was 8.9 cm ± 2.9 cm H2O. Overall pediatric intensive care unit and hospital mortality were 26% (95% confidence interval 19.6-33.7) and 27.4% (95% confidence interval 20.8-35.1), respectively. At 24 hrs, after the assessment of oxygenation under standard ventilatory settings, 118 (80.8%) patients continued to meet acute respiratory distress syndrome criteria (PaO2/FIO2 104 mm Hg ± 36 mm Hg; pediatric intensive care units mortality 30.5%), whereas 28 patients (19.2%) had a PaO2/FIO2 >200 mm Hg (pediatric intensive care units mortality 7.1%) (p = .014). CONCLUSIONS This is the largest study to estimate prospectively the pediatric population-based acute respiratory distress syndrome incidence and the first incidence study performed during the routine application of lung protective ventilation in children. Our findings support a lower acute respiratory distress syndrome incidence and mortality than those reported for adults. PaO2/FIO2 ratios at acute respiratory distress syndrome onset and at 24 hrs after onset were helpful in defining groups at greater risk of dying (clinical trials registered with http://www.clinicaltrials.gov; NCT 01142544).

positive: Covid-19 in children: A brief overview after three months experience Severe Acute Respiratory Syndrome - Coronavirus - 2 (SARS-CoV-2) and its related Coronavirus Disease - 19 (COVID-19) has become a health emergency worldwide. The medical community has been concerned since the beginning of the outbreak about the potential impact of COVID-19 in children, especially in those with underlying chronic diseases. Fortunately, COVID-19 has been reported to be less severe in children than in adults. However, epidemiologic and clinical data are scarce. Children show unique features of SARS-CoV-2 involvement that may account for the low rate of infection and death in this age group. The purpose of this review is to summarize the most relevant evidence of COVID-19 in children highlighting similarities and differences with adults.

positive: Guidelines for coronavirus disease 2019 response in children and adolescents The Korean Society of Pediatric Infectious Diseases and the Korea Centers for Disease Control and Prevention issued the guidelines about coronavirus disease 2019 (COVID-19) for children and adolescents. Case definitions and management of COVID-19 in neonates, infants, children and adolescents are presented in this guideline. In addition, guidelines for caregiver management are also provided. In this review, we introduce the contents of the current guidelines for COVID-19 in children and adolescents in Korea.

positive: Promoting and supporting children’s health and healthcare during COVID-19 – International Paediatric Association Position Statement

positive: Olfactory and Gustatory Dysfunction as An Early Identifier of COVID-19 in Adults and Children: An International Multicenter Study Abstract Objective: Evaluate the prevalence and characteristics of olfactory or gustatory dysfunction in COVID-19 patients Study Design: Multicenter Case Series Setting: 5 tertiary care hospitals (3 in China, 1 in France, 1 in Germany) Subjects and Methods: 394 PCR confirmed COVID-19 positive patients were screened, and those with olfactory or gustatory dysfunction were included. Data including demographics, COVID-19 severity, patient outcome, and the incidence and degree of olfactory and/or gustatory dysfunction were collected and analyzed. The Questionnaire of Olfactory Disorders (QOD) and Visual Analogue Scale (VAS) were used to quantify olfactory and gustatory dysfunction respectively. All subjects at one hospital (Shanghai) without subjective olfactory complaints underwent objective testing. Results: Of 394 screened subjects, 161 (41%) reported olfactory and/or gustatory dysfunction and were included. Incidence of olfactory and/or gustatory disorders in Chinese (n=239), German (n=39) and French (n=116) cohorts were 32%, 69%, and 49% 138 respectively. The median age of included subjects was 39 years old, 92/161 (57%) were male, and 10/161 (6%) were children. Of included subjects, 10% had only olfactory or gustatory symptoms, and 19% had olfactory and/or gustatory complaints prior to any other COVID-19 symptom. Of subjects with objective olfactory testing, 10/90 demonstrated abnormal chemosensory function despite reporting normal subjective olfaction. 43% (44/102) of subjects with follow-up showed symptomatic improvement in olfaction or gustation. Conclusions: Olfactory and/or gustatory disorders may represent early or isolated symptoms of SARS-CoV-2 infection. They may serve as a useful additional screening criterion, particularly for the identification of patients in the early stages of infection.

positive: The Epidemiological and Clinical Characteristics of 81 Children with COVID-19 in a Pandemic Hospital in Turkey: an Observational Cohort Study BACKGROUND: Coronavirus disease-2019 (COVID-19) pandemic has affected millions of people throughout the world since December 2019. However, there is a limited amount of data about pediatric patients infected with the disease agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: The epidemiological, laboratory, radiological, and treatment features of the pediatric patients who were positive for SARS-CoV-2 based on the reverse-transcription polymerase chain reaction (RT-PCR) test, were investigated retrospectively. RESULTS: The median age of 81 children included in the study was 9.50 years (0–17.75 years). The most frequent symptoms at the time of admission were fever (58%), cough (52%), and fatigue or myalgia (19%). The abnormal laboratory findings in these cases were decreased lymphocytes (2.5%, n = 2), leucopenia (5%, n = 4), and increased lactate dehydrogenase (17.2%, n = 14), C-reactive protein (16%, n = 13), procalcitonin (3.7%, n = 3), and D-dimer (12.3%, n = 10). Three (4%) patients had consolidation in chest computed tomography, and three (4%) had ground-glass opacities. None of the patients needed intensive care except for the newborns. The median time to turn SARS-CoV-2 negative in the RT-PCR test was 5 (3–10) days. The median length of hospital stay was 5 (4–10) days. The time to turn SARS-CoV-2 negative in the RT-PCR test and the length of hospital stay were significantly longer for those aged five years or younger than others (P = 0.037, P = 0.01). CONCLUSION: Compared to adults, COVID-19 is milder and more distinctive in children. As a result, more conservative approaches might be preferred in children for the diagnostic, clinical, and even therapeutic applications.

positive: The role of children in the transmission of mild SARS-CoV-2 infection

positive: Are children less susceptible to COVID-19?

positive: Development of child immunity in the context of COVID-19 pandemic Children, because of having an immature immune system, are usually more prone than the adults to the microbial infections and have more severe symptoms, which is especially true for the newborns, and very young children. However, the review of clinical data from the current COVID-19 pandemic indicates otherwise. We discuss here what are the main features and components of children's immune system, the role of maternal transmission of immunity, and what are the possible explanations for the seemingly lower infection rate and severity of COVI-19 in children.

positive: SARS-CoV-2: Is it the newest spark in the TORCH? Amid the rapidly evolving global coronavirus disease 2019 (COVID-19) pandemic that has already had profound effects on public health and medical infrastructure globally, many questions remain about its impact on child health. The unique needs of neonates and children, and their role in the spread of the virus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) should be included in preparedness and response plans. Fetuses and newborn infants may be uniquely vulnerable to the damaging consequences of congenitally- or perinatally-acquired SARS-CoV-2 infection, but data are limited about outcomes of COVID-19 disease during pregnancy. Therefore, information on illnesses associated with other highly pathogenic coronaviruses (i.e., severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome [MERS]), as well as comparisons to common congenital infections, such as cytomegalovirus (CMV), are warranted. Research regarding the potential routes of acquisition of SARS-CoV-2 infection in the prenatal and perinatal setting is of a high public health priority. Vaccines targeting women of reproductive age, and in particular pregnant patients, should be evaluated in clinical trials and should include the endpoints of neonatal infection and disease.

positive: Children of COVID-19: pawns, pathfinders or partners? Countries throughout the world are counting the health and socioeconomic costs of the COVID-19 pandemic, including the strategies necessary to contain it. Profound consequences from social isolation are beginning to emerge, and there is an urgency about charting a path to recovery, albeit to a ‘new normal’ that mitigates them. Children have not suffered as much from the direct effects of COVID-19 infection as older adults. Still, there is mounting evidence that their health and welfare are being adversely affected. Closure of schools has been a critical component of social isolation but has a far broader impact than the diminution of educational opportunities, as important as these are. Reopening of schools is therefore essential to recovery, with some countries already tentatively implementing it. Children’s interests are vital considerations in any recovery plan, but the question remains as to how to address them within the context of how society views children; should they be regarded as pawns, pathfinders or partners in this enterprise?

positive: Clinical characteristics of 182 pediatric COVID‐19 patients with different severities and allergic status BACKGROUND: The pandemic of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has made widespread impact recently. We aim to investigate the clinical characteristics of COVID‐19 children with different severities and allergic status. METHODS: Data extracted from the electronical medical records, including demographics, clinical manifestations, comorbidities, laboratory and immunological results and radiological images of 182 hospitalized COVID‐19 children were summarized and analyzed. RESULTS: The median age was 6 years old, ranging from 3 days to 15 years, and there were more boys (male‐female ratio about 2:1) within the studied 182 patients. Most of the children were infected by family members. Fever (43.4%) and dry cough (44.5%) were common symptoms, and gastrointestinal manifestations accounted for 11.0%, including diarrhea, abdominal discomfort and vomiting. 71.4% had abnormal chest computed tomography (CT) scan images, and typical signs of pneumonia were ground‐glass opacity and local patchy shadowing on admission. Laboratory results were mostly within normal ranges, and only a small ratio of lymphopenia (3.9%) and eosinopenia (29.5%) were observed. The majority (97.8%) of infected children were not severe, and 24 (13.2%) of them had asymptomatic infections. Compared to children without pneumonia(manifested as asymptomatic and acute upper respiratory infection), children with pneumonia were associated with higher percentages of the comorbidity history, symptoms of fever and cough, and increased levels of serum procalcitonin, alkaline phosphatase and serum interleukins (IL)‐2, IL‐4, IL‐6, IL‐10 and TNF‐α.There were no differences of treatments, duration of hospitalization, time from first positive to first negative nucleic acid testing and outcomes between children with mild pneumonia and without pneumonia. All the hospitalized COVID‐19 children had recovered except one death due to intussusception and sepsis. In 43 allergic children with COVID‐19, allergic rhinitis (83.7%) was the major disease, followed by drug allergy, atopic dermatitis, food allergy and asthma. Demographics and clinical features were not significantly different between allergic and non‐allergic groups. Allergic patients showed less increase in acute phase reactants, procalcitonin, D‐dimer and aspartate aminotransferase levels compared to all patients. Immunological profiles including circulating T, B and NK lymphocyte subsets, total immunoglobulin and complement levels and serum cytokines did not show any difference in allergic and pneumonia groups. Neither eosinophil counts nor serum total immunoglobulin E (IgE) levels showed a significant correlation with other immunological measures, such as other immunoglobulins, complements, lymphocyte subsets numbers and serum cytokine levels. CONCLUSION: Pediatric COVID‐19 patients tended to have a mild clinical course. Patients with pneumonia had higher proportion of fever and cough and increased inflammatory biomarkers than those without pneumonia. There was no difference between allergic and non‐allergic COVID‐19 children in disease incidence, clinical features, laboratory and immunological findings. Allergy was not a risk factor for developing and severity of SARS‐CoV‐2 infection and hardly influenced the disease course of COVID‐19 in children.

positive: Children in Critical Care Due to Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Experience in a Spanish Hospital Spain has been one of the countries most severely affected by the coronavirus disease 2019. This study aims to describe a series of children admitted to a PICU due to coronavirus disease 2019 infection. DESIGN: Prospective observational study. SETTING: Tertiary hospital in Madrid, Spain. PATIENTS: Children admitted to the PICU with severe acute respiratory syndrome coronavirus 2 (severe acute respiratory syndrome coronavirus 2) infection, from March 1, 2020, to April 15, 2020. INTERVENTIONS: Observational study. MEASUREMENTS AND MAIN RESULTS: Epidemiologic data, previous clinical characteristics, support therapy needed, imaging tests, laboratory observations on admission, and pharmacologic therapy. Eleven children were admitted to the PICU, with suspected coronavirus disease 2019; the polymerase chain reaction test was positive in seven. The median age was 100.7 months (range, 0.5–162). Five were admitted from the emergency department and two from the ward. The Pediatric Sequential Organ Failure Assessment score was 3 (range, 0–9), and Pediatric Risk of Mortality II score was 4 (range, 0–16). All children were previously healthy except one (allogeneic hematopoietic stem cell transplantation). Respiratory symptoms and fever were prevalent. A chest radiograph led to a pneumonia diagnosis. Not all patients presented with lymphopenia on admission. d-Dimer and ferritin were elevated. All patients needed oxygen therapy through a nasal cannula; five patients received high-flow nasal cannula therapy, which was later substituted with noninvasive ventilation in four. Mechanical ventilation was necessary in two patients on the first day of PICU admission. Two children required mechanical ventilation and inotropic support. Tocilizumab was applied in two intubated children. Also, four children received heparin. No patients died. CONCLUSIONS: On the whole, the children were previously healthy and are more than 1 year old. Respiratory symptoms were the leading cause of PICU admission, making respiratory support the principal therapy. Patients requiring mechanical ventilation showed deterioration on the first day of admission. These children seemed to require close monitoring, and multicenter studies are necessary.

positive: Longitudinal symptom dynamics of COVID-19 infection in primary care Importance: Data regarding the clinical characteristics of COVID-19 infection is rapidly accumulating. However, most studies thus far are based on hospitalized patients and lack longitudinal follow up. As the majority of COVID-19 cases are not hospitalized, prospective studies of symptoms in the population presenting to primary care are needed. Objective: To assess the longitudinal dynamic of clinical symptoms in non-hospitalized individuals prior to and throughout the diagnosis of SARS-CoV-2 infection. Design, Setting, and Participants: From 1/3/2020 to 07/06/2020, information on symptoms from either surveys or primary care visits was available for 206,377 individuals, including 2,471 who tested positive for COVID-19. Data were extracted from electronic health records (EHR) of the second largest Health Maintenance Organization in Israel, consisting of both results of PCR tests and symptoms recorded by primary care physicians, and linked longitudinal self reported symptoms. Exposures: Diagnosis of COVID-19 disease was made by PCR testing for SARS-CoV-2 from nasopharyngeal swabs. Main Outcomes and Measures: Longitudinal prevalence of clinical symptoms Results: In adults, the most prevalent symptoms recorded in EHR were cough (11.6%), fever (10.3%), and myalgia (7.7%) and the most prevalent self-reported symptoms were cough (21%), fatigue (19%) and rhinorrhea and/or nasal congestion (17%). In children, the most prevalent symptoms recorded in the EHR were fever (7%), cough (5.5%) and abdominal pain (2.4%). Emotional disturbances were documented in 15.9% of the positive adults and 4.2% of the children. Loss of taste and smell, either self-reported or documented by a physician, 3 weeks prior to testing, were the most discriminative symptoms in adults (OR =11.18 and OR=5.47 respectively). Additional symptoms included self reported confusion (OR =4.02), and fatigue (OR = 1.73) and a documentation of syncope, rhinorrhea (OR = 2.09 for both ) and fever (OR= 1.62 ) by a physician. Mean time to recovery was 23.5 +- 9.9 days. Children had a significantly shorter disease duration (21.7 +- 8.8 days, p-value=0.01). Several symptoms, including fatigue, myalgia, runny nose and shortness of breath were reported weeks after recovery. Conclusions and Relevance: As the COVID-19 pandemic progresses rapidly worldwide, obtaining accurate information on symptoms and their progression is of essence. Our study shed light on the full clinical spectrum of symptoms experienced by infected individuals in primary care, and may alert physicians for the possibility of COVID-19 infection.

positive: Coronavirus Disease 2019 (COVID-19) in adolescents: An update on current clinical and diagnostic characteristics. The current outbreak of infections with SARS-CoV-2 is defined as Coronavirus Disease 2019 (COVID-19). The clinical symptoms of COVID-19 include fever, fatigue, cough, breathing difficulty that may lead to respiratory distress; a small population of patients may have diarrhea, nausea or vomiting. The highest infection rate occurs in adults; however, neonates, children, and adolescents can also be infected. As the outbreak continues to spread worldwide, attention has switched toward determinants of clinical manifes- tations and disease severity. The situation surrounding the outbreak is rapidly evolving and the information and recommendations are changing as new information becomes available. This paper summarises the cur- rent findings (April 3,2020) from a systematic literature review on the current knowledge of COVID-19 in adolescents (10-19 years according to the WHO definition) and reports the preliminary epidemiological data stated by the Italian National Institute of Health.

positive: Clinical characteristics of a case series of children with coronavirus disease 2019 We reported the clinical characteristics of a case series of 10 patients with coronavirus disease 2019 (COVID‐19) aged from 1 year to 18 years. Seven patients had contact with confirmed COVID‐19 family members before onset. Fever (4 [40.0%]) and cough (3 [30.0%]) were the most common symptoms. No patient showed leucopenia and lymphopenia on admission. Pneumonia was observed in chest CT images in 5 (50.0%) patients. Five (50.0%) patients received antiviral treatment. No patient had severe complications or developed a severe illness in our study. Our study indicated that COVID‐19 children present less severe symptoms and have better outcomes.

positive: Fatal respiratory distress syndrome due to coronavirus infection in a child with severe combined immunodeficiency Please cite this paper as: Szczawinska‐Poplonyk et al. (2012) Fatal respiratory distress syndrome due to coronavirus infection in a child with severe combined immunodeficiency. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12059. Coronaviruses have been demonstrated to contribute substantially to respiratory tract infections among the child population. Though infected children commonly present mild upper airway symptoms, in high‐risk patients with underlying conditions, particularly in immunocompromised children these pathogens may lead to severe lung infection and extrapulmonary disorders. In this paper, we provide the first report of the case of a 15‐month‐old child with severe combined immunodeficiency and coronavirus HKU1‐related pneumonia with fatal respiratory distress syndrome.

positive: Coronavirus disease 2019 in children: Surprising findings in the midst of a global pandemic. Question Coronavirus disease 2019 (COVID-19) is affecting millions of people worldwide. It seems that it affects mostly adults older than 40 years of age, and the death rate is highest for older individuals in the population. What should I tell parents worried about their children contracting the coronavirus (SARS-CoV-2) causing COVID-19, and what symptoms should I look for to determine if there is a need to test for the virus?Answer The COVID-19 global pandemic affects all ages. Severe respiratory manifestations have been the mainstay of illness in adults, with what seems to be rapid deterioration necessitating mechanical ventilation. Only 5% of those tested and found to have COVID-19 have been younger than 19 years, possibly owing to limited testing, as the symptoms in children are usually mild. Symptoms in children include fever, dry cough, rhinorrhea, sore throat, and fatigue, and in 10% diarrhea or vomiting. Rarely dyspnea or hypoxemia were also described. Blood tests and imaging have been shown to be of little value in children and should only be ordered for those in whom you would normally order these investigations for viral-like illness. No specific therapy is available and supportive care with rest, fluids, and antipyretics for children is the recommended approach. Ibuprofen or acetaminophen for fever and pain can be given. Antiviral and immunomodulatory treatment is not recommended at this time for otherwise healthy children, and corticosteroids should also not be used. Children with immunocompromised states should be isolated and avoid contact with others.

positive: Coronavirus disease-19: The First 7,755 Cases in the Republic of Korea We report the first 7,755 patients with confirmed COVID19 in Korea as of March 13, 2020. A total of 66 deaths were identified, resulting case fatality proportion of 0.9%. Older people, and those with coexisting medical conditions were at risk for fatal outcomes. The highest number of cases were from Daegu, followed by Gyeongbuk, with elevated age-stratified case fatality. This summary may help to understand the disease dynamics in the early phase of COVID19 outbreak, therefore, to guide future public health measures.

positive: A Case Report of Neonatal Acute Respiratory Failure Due to Severe Acute Respiratory Syndrome Coronavirus-2

positive: Clinical Characteristics of COVID-19 Infection in Newborns and Pediatrics: A Systematic Review Introduction: World Health Organization has declared COVID-19 a pandemic and a global health emergency Thus, it is necessary to clearly characterize clinical manifestations and management of COVID-19 infection in children to provide accurate information for healthcare workers Accordingly, the present study was designed to review articles published on clinical manifestations and characteristics of children and infants with COVID-19 Methods: In this systematic review, medical databases including Cochrane Library, Web of Science, Embase, Scopus, SID, Medline, WHO and LitCovid were searched using English and Persian keywords including COVID-19, Pediatrics, Newborn, Coronavirus 2019, 2019-nCoV, SARS-CoV-2 Finally, data of 14 related articles were included in the study Results: A total of 2228 children, newborns and infants were studied Clinical manifestation in children may be mild (72%), moderate (22%) or severe (6%), and the most common symptoms include dry cough (91%) and fever (96%) According to the included articles, two children had died, one of which was a 14-year-old boy and his exposure history and underlying disease were unclear, and the other was a male newborn with gestational age of 35 weeks and 5 days, birth weight of 2200, Apgar score of 8, 8 (1 min and 5 min) and his first symptom was increased heart rate No differences were found between male and female children regarding infection with COVID-19 Conclusion: Most pediatrics were infected with COVID-19 due to family cluster or history of close contact Infected children have relatively milder clinical symptoms compared to infected adults We should pay special attention to early diagnosis and early treatment in children infected with COVID-19

positive: Is the effect of COVID-19 on children underestimated in low- and middle- income countries? The COVID-19 pandemic has had a huge impact on health and society, worldwide. While most high income countries are felt to be reaching their COVID-19 peak, most low- and middle-income countries (LMICs), particularly sub-Saharan countries, are anticipating an exponential growth of cases.(1) Overall it has been documented that children are less affected.(2) However, in this commentary we describe how in Kenya, a LMIC in sub-Saharan Africa, COVID-19 is likely to have far-reaching direct and indirect implications on children.

positive: Clinical characteristics of acute respiratory syndrome with SARS‐CoV‐2 infection in children in South China BACKGROUND: A retrospective study was conducted to summarize the clinical information of childhood infections during the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) epidemic. METHODS: Children with SARS‐CoV‐2 infection in 11 hospitals from three provinces of South China were included in the study. Clinical information was collected and compared with children and adults infected by SARS‐CoV‐2 in Wuhan. RESULTS: In total, 52 children were enrolled, including 28 boys. The median age was 9 years (interquartile range [IQR], 4‐12); 44.2% cases were of clustered occurrences, 40.4% patients had fever, 48.1% had cough, and 46.2% had a high lymphocyte count. No abnormalities were found in the liver and kidney function. Also, 82.7% of patients received antiviral therapy, but such therapy did not shorten the time to virus negativity or hospital stay (P = .082). The time to virus negativity was 12.0 days (IQR, 8.0‐16.8) and hospital stay was 14.5 days (IQR, 10.3‐17.9). Compared with reports in Wuhan, there were more acute upper respiratory tract infection (AURTI) and fewer pneumonia cases (P = .000). Compared with the non‐ICU adult COVID‐19 in Wuhan, these children's diseases were relatively mild, with fewer complications. CONCLUSIONS: Children with SARS‐CoV‐2 infection had a mild fever, lymphocyte elevation was more common than reduction, and antiviral treatment had no obvious effect. The overall clinical manifestations were mild, and the prognosis was good.

positive: Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center's observational study BACKGROUND: An outbreak of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was first detected in Wuhan, Hubei, China. People of all ages are susceptible to SARS-CoV-2 infection. No information on severe pediatric patients with COVID-19 has been reported. We aimed to describe the clinical features of severe pediatric patients with COVID-19. METHODS: We included eight severe or critically ill patients with COVID-19 who were treated at the Intensive Care Unit (ICU), Wuhan Children's Hospital from January 24 to February 24. We collected information including demographic data, symptoms, imaging data, laboratory findings, treatments and clinical outcomes of the patients with severe COVID-19. RESULTS: The onset age of the eight patients ranged from 2 months to 15 years; six were boys. The most common symptoms were polypnea (8/8), followed by fever (6/8) and cough (6/8). Chest imaging showed multiple patch-like shadows in seven patients and ground-glass opacity in six. Laboratory findings revealed normal or increased whole blood counts (7/8), increased C-reactive protein, procalcitonin and lactate dehydrogenase (6/8), and abnormal liver function (4/8). Other findings included decreased CD16 + CD56 (4/8) and Th/Ts*(1/8), increased CD3 (2/8), CD4 (4/8) and CD8 (1/8), IL-6 (2/8), IL-10 (5/8) and IFN-Î³ (2/8). Treatment modalities were focused on symptomatic and respiratory support. Two critically ill patients underwent invasive mechanical ventilation. Up to February 24, 2020, three patients remained under treatment in ICU, the other five recovered and were discharged home. CONCLUSIONS: In this series of severe pediatric patients in Wuhan, polypnea was the most common symptom, followed by fever and cough. Common imaging changes included multiple patch-like shadows and ground-glass opacity; and a cytokine storm was found in these patients, which appeared more serious in critically ill patients.

positive: Epidemiology and Clinical Features of Coronavirus disease 2019 in Children Coronavirus disease-2019 (COVID-19), which started in Wuhan, China, in December 2019 and has been declared a worldwide pandemic in March 11, 2020, is a novel infectious disease that causes respiratory illness and death. Pediatric COVID-19 accounts for a small percentage of patients with outbreaks and is often milder than adults, but can progress to severe disease in some cases. Even neonates can suffer from COVID-19, and children may play a role as a spreader in the community. In this review, we summarize what is known about COVID-19 in children and adolescents until now.

positive: Addressing the Impact of the Coronavirus Disease (COVID-19) Pandemic on Hematopoietic Cell Transplantation: Learning Networks as a Means for Sharing Best Practices ABSTRACT The full impact of the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), on the field of hematopoietic cell transplantation (HCT) is unknown. This perspective paper reviews the following: current COVID-19 epidemiology, diagnosis, and potential therapies; care considerations unique to HCT recipients; and the concept of a learning network to assimilate emerging guidelines and best practices and to optimize patient outcomes through facilitating shared learning and experience across transplantation centers.

positive: Varying Presentations and Favourable Outcomes of COVID-19 Infection in Children and Young Adults with Sickle Cell Disease: An Additional Case Series with Comparisons to Published Cases Patients with sickle cell disease (SCD) are theoretically at greater risk for serious illness from COVID 19 due to the underlying pathophysiology of chronic inflammation with an increased risk of thrombosis, especially at the time of a vaso-occlusive event (1). Individuals living with SCD are also considered to be immunocompromised due to autoinfarction of their spleen or surgical splenectomy, often as a result of red cell splenic sequestration (2). In addition, patients with SCD often have comorbidities and secondary organ dysfunction that can put them at risk of significant morbidity and or mortality from the severe acute respiratory coronavirus 2 (SARS-CoV-2), and its subsequent disease COVID-19.

positive: COVID-19: A tale of two pandemics across the Asia Pacific region The widely diverse impacts of SAR-CoV-2 infection resulting in the COVID-19 pandemic cannot be held in more stark relief when contrasting the devastating impact upon China, Italy, Great Britain, America and Brazil with the considerably milder course in the geographically isolated countries of Australia and New Zealand and the densely populated Vietnam. Children in the Asia-Pacific region, as with children all over the world to date, have fared better than older adults. Other countries in the Asia-Pacific region, including Indonesia and India have struggled to deal with the pandemic because of a lack of health infrastructure, inability to provide sufficient testing and isolation and widespread poverty. This article will provide a snapshot of the impact of COVID-19 upon countries in the Asia-Pacific region in the six months since the first case of the novel zoonotic coronavirus infection appeared in China.

positive: Consecuencias maternas y neonatales de la infección por coronavirus COVID-19 durante el embarazo: una scoping review./ [Maternal and neonatal consequences of coronavirus COVID-19 infection during pregnancy: a scoping review] BACKGROUND: Coronavirus disease 2019 (COVID-19) is a new pathology, declared a public health emergency by the World Health Organization, which can have negative consequences for pregnant women and their newborns. The aim of this study was to explore the available knowledge on the consequences of developing COVI-19 in pregnant women and their neonates. METHODS: Scoping Review, in which the search for articles was conducted using DeCS ("pregnancy", "coronavirus", "health") and MeSH ("pregnan*", "pregnant women", "coronavirus"), linking the terms with the Boolean AND operator. Databases used were Web of Science, Scopus, BVS, Scielo and CUIDEN. In addition, the PRISMA methodology was applied. RESULTS: Ten studies were identified that assessed maternal and neonatal health after maternal COVID-19 infection. Pregnant women seem to had no serious symptoms. Neonates appeared to be affected to a greater extent. A death was reported in a premature newborn whose mother had COVID-19 pneumonia. There did not appear to be vertical transmission from mother to child. Nevertheless, this information was not conclusive. CONCLUSIONS: COVID-19 appears to be more benign with pregnant women than with their neonates.

positive: Coronavirus disease 2019 in children: Surprising findings in the midst of a global pandemic Question Coronavirus disease 2019 (COVID-19) is affecting millions of people worldwide. It seems that it affects mostly adults older than 40 years of age, and the death rate is highest for older individuals in the population. What should I tell parents worried about their children contracting the coronavirus (SARS-CoV-2) causing COVID-19, and what symptoms should I look for to determine if there is a need to test for the virus?Answer The COVID-19 global pandemic affects all ages. Severe respiratory manifestations have been the mainstay of illness in adults, with what seems to be rapid deterioration necessitating mechanical ventilation. Only 5% of those tested and found to have COVID-19 have been younger than 19 years, possibly owing to limited testing, as the symptoms in children are usually mild. Symptoms in children include fever, dry cough, rhinorrhea, sore throat, and fatigue, and in 10% diarrhea or vomiting. Rarely dyspnea or hypoxemia were also described. Blood tests and imaging have been shown to be of little value in children and should only be ordered for those in whom you would normally order these investigations for viral-like illness. No specific therapy is available and supportive care with rest, fluids, and antipyretics for children is the recommended approach. Ibuprofen or acetaminophen for fever and pain can be given. Antiviral and immunomodulatory treatment is not recommended at this time for otherwise healthy children, and corticosteroids should also not be used. Children with immunocompromised states should be isolated and avoid contact with others.

positive: COVID-19: Loss of bridging between innate and adaptive immunity? COVID-19 has spread to most countries in the world. However, there are some striking differences in how COVID-19 is behaving in different age groups. While data on COVID-19 is limited, children appear to be less susceptible to severe disease. These unique characteristics may be considered as a potential link to understanding the immune system and response in COVID-19 and lead to an effective cure to the disease. We suggest a possible role of loss of bridging between innate and adaptive immunity in COVID-19 and a potential treatment modality also discussed.

positive: Implications of COVID-19 in pediatric rheumatology COVID-19 (coronavirus disease 2019) pandemic caused by SARS-CoV-2, is a global public health issue threatening millions of lives worldwide. Although the infection is mild in most of the affected individuals, it may cause severe clinical manifestations such as acute respiratory distress syndrome or cytokine storm leading to death. Children are affected less, and most experience a milder disease. As rheumatologists, we deal with the uncontrolled response of the immune system, and most of the drugs we use are either immune modulators or immunosuppressants. Thus, the rheumatologists participate in the multidisciplinary management of COVID-19 patients. On the other hand, our patients with rheumatic diseases constitute a vulnerable group in this pandemic. In this review, a systematic literature search was conducted utilizing MEDLINE/PubMed and Scopus databases, and 231 COVID-19 patients with rheumatic diseases have been identified. Only one of these patients was a child. Among these, 9 (3.9%) died due to COVID-19. In light of the current data, the aspects of COVID-19 resembling rheumatic diseases, the possible reasons for why children are affected less severely, the hypothetic role of available vaccines in preventing COVID-19, the unique position of patients with rheumatic diseases in this pandemic, and the use of anti-rheumatic drugs in COVID-19 treatment are discussed.

positive: Coronavirus disease 2019 (COVID-19) in children and/or adolescents: a meta-analysis BACKGROUND: To assess the overall prevalence of clinical signs, symptoms, and radiological findings in children and/or adolescents with COVID-19. METHODS: We systematically researched in PubMed, Scopus and Web of Science databases observational studies describing COVID-19 in children and/or adolescents until April 11, 2020. Data regarding clinical and radiological features were extracted from eligible studies and meta-analysis was performed using random-effects modeling. RESULTS: We examined 19 eligible studies for a total of 2855 children and/or adolescents with COVID-19. Approximately 47% of subjects had fever (95% confidence interval [CI] 22-72%; I2 = 98.6%), 37% cough (95%CI 15-63%; I2 = 98.6%), 4% diarrhea (95%CI 0-12%; I2 = 92.2%), 2% nasal congestion (95%CI 0-7%; I2 = 87.7%), 1% dyspnea (95%CI 0-7%; I2 = 91.5%) and 0% abdominal pain (95%CI 0-1%; I2 = 76.3%). Subjects presented mild symptoms in 79% (95%CI 65-91%; I2 = 93.5%) of cases, whereas only 4% (95%CI 1-9%; I2 = 76.4%) were critical. Among those with pneumonia on computed tomography, 26.4% (95%CI 13-41%; I2 = 80.8%) presented a unilateral involvement, 16% (95%CI 5-29%, I2 = 81.2%) had bilateral involvement and 9% (95%CI 0-24%; I2 = 88.7%) had interstitial pneumonia. CONCLUSIONS: Children and/or adolescents tend to have a mild COVID-19 course with a good prognosis. IMPACT: Compared to adults, children and/or adolescents tend to have a mild COVID-19 course with a good prognosis.This study provides new and consistence information on the clinical and radiological characteristics of COVID-19 in pediatrics.This study may help to fight COVID-19 in pediatric population.

positive: Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study. OBJECTIVES To describe the characteristics of children and adolescents affected by an outbreak of Kawasaki-like multisystem inflammatory syndrome and to evaluate a potential temporal association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN Prospective observational study. SETTING General paediatric department of a university hospital in Paris, France. PARTICIPANTS 21 children and adolescents (aged ≤18 years) with features of Kawasaki disease who were admitted to hospital between 27 April and 11 May 2020 and followed up until discharge by 15 May 2020. MAIN OUTCOME MEASURES The primary outcomes were clinical and biological data, imaging and echocardiographic findings, treatment, and outcomes. Nasopharyngeal swabs were prospectively tested for SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR) and blood samples were tested for IgG antibodies to the virus. RESULTS 21 children and adolescents (median age 7.9 (range 3.7-16.6) years) were admitted with features of Kawasaki disease over a 15 day period, with 12 (57%) of African ancestry. 12 (57%) presented with Kawasaki disease shock syndrome and 16 (76%) with myocarditis. 17 (81%) required intensive care support. All 21 patients had noticeable gastrointestinal symptoms during the early stage of illness and high levels of inflammatory markers. 19 (90%) had evidence of recent SARS-CoV-2 infection (positive RT-PCR result in 8/21, positive IgG antibody detection in 19/21). All 21 patients received intravenous immunoglobulin and 10 (48%) also received corticosteroids. The clinical outcome was favourable in all patients. Moderate coronary artery dilations were detected in 5 (24%) of the patients during hospital stay. By 15 May 2020, after 8 (5-17) days of hospital stay, all patients were discharged home. CONCLUSIONS The ongoing outbreak of Kawasaki-like multisystem inflammatory syndrome among children and adolescents in the Paris area might be related to SARS-CoV-2. In this study an unusually high proportion of the affected children and adolescents had gastrointestinal symptoms, Kawasaki disease shock syndrome, and were of African ancestry.

positive: Everything old is new again: COVID-19 and public health

positive: Flash survey on severe acute respiratory syndrome coronavirus-2 infections in paediatric patients on anticancer treatment INTRODUCTION: Since the beginning of COVID-19 pandemic, it is known that the severe course of the disease occurs mostly among the elderly, whereas it is rare among children and young adults. Comorbidities, in particular, diabetes and hypertension, clearly associated with age, besides obesity and smoke, are strongly associated with the need for intensive treatment and a dismal outcome. A weaker immunity of the elderly has been proposed as a possible explanation of this uneven age distribution. Thus, there is concern that children treated for cancer may allso be at risk for an unfavourable course of infection. Along the same line, anecdotal information from Wuhan, China, mentioned a severe course of COVID-19 in a child treated for leukaemia. AIM AND METHODS: We made a flash survey on COVID-19 incidence and severity among children on anticancer treatment. Respondents were asked by email to fill in a short Web-based survey. RESULTS: We received reports from 25 countries, where approximately 10,000 patients at risk are followed up. At the time of the survey, more than 200 of these children were tested, nine of whom were positive for COVID-19. Eight of the nine cases had asymptomatic to mild disease, and one was just diagnosed with COVID-19. We also discuss preventive measures that are in place or should be taken and treatment options in immunocompromised children with COVID-19. CONCLUSION: Thus, even children receiving anticancer chemotherapy may have a mild or asymptomatic course of COVID-19. While we should not underestimate the risk of developing a more severe course of COVID-19 than that observed here, the intensity of preventive measures should not cause delays or obstructions in oncological treatment.

positive: Clinical Characteristics of Children with Coronavirus Disease 2019 in Hubei, China Since December 2019, COVID-19 has occurred unexpectedly and emerged as a health problem worldwide. Despite the rapidly increasing number of cases in subsequent weeks, the clinical characteristics of pediatric cases are rarely described. A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province. A total of 25 confirmed pediatric cases of COVID-19 were collected. The demographic data, epidemiological history, underlying diseases, clinical manifestations, laboratory and radiological data, treatments, and outcomes were analyzed. Of 25 hospitalized patients with COVID-19, the boy to girl ratio was 1.27:1. The median age was 3 years. COVID-19 cases in children aged <3 years, 3.6 years, and ≥6-years patients were 10 (40%), 6 (24%), and 9 (36%), respectively. The most common symptoms at onset of illness were fever (13 [52%]), and dry cough (11 [44%]). Chest CT images showed essential normal in 8 cases (33.3%), unilateral involvement of lungs in 5 cases (20.8%), and bilateral involvement in 11 cases (45.8%). Clinical diagnoses included upper respiratory tract infection (n=8), mild pneumonia (n=15), and critical cases (n=2). Two critical cases (8%) were given invasive mechanical ventilation, corticosteroids, and immunoglobulin. The symptoms in 24 (96%) of 25 patients were alleviated and one patient had been discharged. It was concluded that children were susceptible to COVID-19 like adults, while the clinical presentations and outcomes were more favorable in children. However, children less than 3 years old accounted for majority cases and critical cases lied in this age group, which demanded extra attentions during home caring and hospitalization treatment.

positive: COVID‐19 breakthroughs: separating fact from fiction The newly recognised coronavirus SARS‐CoV‐2, causative agent of COVID‐19, has caused a pandemic with huge ramifications for human interactions around the globe. As expected, research efforts to understand the virus and curtail the disease are moving at a frantic pace alongside the spread of rumours, speculations and falsehoods. In this article, we aim to clarify the current scientific view behind several claims or controversies related to COVID‐19. Starting with the origin of the virus, we then discuss the effect of ibuprofen and nicotine on the severity of the disease. We highlight the knowledge on fomites and SARS‐CoV‐2 and discuss the evidence and explications for a disproportionately stronger impact of COVID‐19 on ethnic minorities, including a potential protective role for vitamin D. We further review what is known about the effects of SARS‐CoV‐2 infection in children, including their role in transmission of the disease, and conclude with the science on different mortality rates between different countries and whether this hints at the existence of more pathogenic cohorts of SARS‐CoV‐2.

positive: Why is Coronavirus Disease 2019 not as severe in children?—A look at type 2 alveolar cells

positive: Coronavirus Disease 2019 (COVID-19) in Neonates and Children From China: A Review At the end of 2019, a novel coronavirus began to spread in Wuhan, Hubei Province, China. The confirmed cases increased nationwide rapidly, in part due to the increased population mobility during the Chinese Lunar New Year festival. The World Health Organization (WHO) subsequently named the novel coronavirus pneumonia Coronavirus Disease 2019 (COVID-19) and named the virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Soon, transmission from person to person was confirmed and the virus spread to many other countries. To date, many cases have been reported in the pediatric age group, most of which were from China. The management and treatment strategies have also been improved, which we believe would be helpful to pediatric series in other countries as well. However, the characteristics of neonatal and childhood infection still have not been evaluated in detail. This review summarizes the current understanding of SARS-CoV-2 infection in neonates and children from January 24 to May 1, as an experience from China.

positive: Preliminary epidemiological analysis on children and adolescents with novel coronavirus disease 2019 outside Hubei Province, China: an observational study utilizing crowdsourced data Background: The outbreak of coronavirus disease 2019 (COVID-19) continues to expand across the world. Though both the number of cases and mortality rate in children and adolescents is reported to be low in comparison to adults, limited data has been reported on the outbreak with respect to pediatric patients. To elucidate information, we utilized crowdsourced data to perform a preliminary epidemiologic analysis of pediatric patients with COVID-19 Methods: In this observational study, data was collected from two open-access, line list crowdsourced online databases. Pediatric cases of COVID-19 were defined as patients ≤19 years of age with a laboratory confirmed diagnosis. The primary outcomes were case counts and cumulative case counts. Secondary outcomes included days between symptoms onset and first medical care and days between first medical care and reporting. Tertiary outcomes were rate of travel to Wuhan, rate of infected family members and rates of symptoms. Results: A total of 82 patients were included. The median age was 10 [IQR: 5-15] years. Patients from mainland China (outside Hubei) accounted for 46.3% of cases, while the remaining 53.7% of cases were international. Males and females accounted for 52.4% and 32.9% of cases, respectively, with the remaining 14.6% being designated as unknown. A male skew persisted across subgroup analyses by age group (p=1.0) and location (inside/outside China) (p=0.22). While the number of reported international cases has been steadily increasing over the study period, the number of reported cases in China rapidly decreased from the start point. The median reporting delay was 3 [IQR: 2-4.8] days. The median delay between symptom onset and first seeking medical care was 1 [IQR: 0-3.25] day. In international cases, time to first seeking medical care was a median of 2.5 days longer than in China (p=0.04). When clinical features were reported, fever was the most common presentation (68.0%), followed by cough (36.0%). Conclusions: The number of reported international pediatric COVID-19 cases is rapidly increasing. COVID-19 infections are, to-date, more common in males than females in both the children and adolescent age groups. Additionally, this male predominance remains the case both inside and outside of China. Crowdsourced data enabled early analysis of epidemiologic variables in pediatric patients with COVID-19. Further data sharing is required to enable analyses that are required to understand the course of this infection in children.

positive: Radiographic and Clinical Features of Children With Coronavirus Disease (COVID-19) Pneumonia Objective: The purpose of this study was to investigate chest computed tomography (CT) findings in children with coronavirus disease-19 (COVID-19) pneumonia in our hospital. Methods: This study included 22 pediatric patients with confirmed COVID-19 from January to March, 2020. The chest CT images and clinical data were reviewed. Results: The most prevalent presenting symptoms were fever (64%) and cough (59%), and a mildly elevated mean (SD) C-reactive protein (CRP) level of 11.22(11.06) and erythrocyte sedimentation rateof 18.8(15.17) were detected. The major CT abnormalities observed were mixed ground-glass opacity and consolidation lesions (36%), consolidations (32%), and groundglass opacities (14%). Peripheral distribution (45%) of lung lesions was predominant. Most of the lesions were multilobar(68%), with an average of three lung segments involved. Conclusion: Children with COVID-19 had relatively milder symptoms and less severe lung inflammation than adults.Chest CT plays an important role in the management of children with COVID-19 pneumonia.

positive: SARS-CoV-2 Infections in Children — Multi-Center Surveillance, United States, January–March 2020 Previous reports of COVID-19 among US children have been based on health jurisdiction reporting. We performed SARS-CoV-2 testing on children enrolled in active, prospective, multi-center surveillance during January–March, 2020. Among 3187 children, only 4 (0.1%) SARS-CoV-2–positive cases were identified March 20–31 despite evidence of rising community circulation.

positive: Placental SARS-CoV-2 in a patient with mild COVID-19 disease Background: The full impact of COVID-19 on pregnancy remains uncharacterized. Current literature suggests minimal maternal, fetal, and neonatal morbidity and mortality,1 and COVID-19 manifestations appear similar between pregnant and non-pregnant women.2 We present a case of placental SARS-CoV-2 virus in a woman with an uncomplicated pregnancy and mild COVID-19 disease. Methods: A pregnant woman was evaluated at University of Missouri Women and Childrens Hospital. Institutional review board approval was obtained; information was obtained from medical records. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to detect SARS-CoV-2. A gynecological pathologist examined the placenta and performed histolopathology. Sections were formalin-fixed and paraffin-embedded; slides were cut and subjected to hematoxylin-and-eosin or immunohistochemistry (IHC) staining. IHC was performed with specific monoclonal antibodies to detect SARS-CoV-2 antigen or to identify trophoblasts. Findings: A 29 year-old multigravida presented at 40-4/7 weeks for labor induction. With myalgias two days prior, she tested positive for SARS-CoV-2. Her parents were in self-isolation for COVID-19 positivity; husband was asymptomatic and tested negative for COVID-19, but exposed to a workplace (meatpacking facility) outbreak. Prenatal course was uncomplicated, with no gestational hypertension. She was afebrile and asymptomatic with normal vital signs throughout hospitalization. Her myalgias improved prior to admission. A liveborn male infant was delivered vaginally. Newborn course was uneventful; he was appropriate for gestational age, physical was unremarkable, and he was discharged home at 36 hours. COVID-19 RT-PCR test was negative at 24 hours. At one-week follow-up, newborn was breastfeeding well, with no fevers or respiratory distress. Overall placental histology is consistent with acute uterine hypoxia (subchorionic laminar necrosis) superimposed on chronic uterine hypoxia (extra-villous trophoblasts and focal chronic villitis). IHC using SARS-CoV-2 nucleocapsid-specific monoclonal antibody demonstrated SARS-CoV-2 antigens throughout the placenta in chorionic villi endothelial cells, and rarely in CK7-expressing trophoblasts. Negative control placenta (November 2019 delivery) and ferret nasal turbinate tissues (not shown) were negative for SARS-CoV-2. Interpretation: In this report, SARS-CoV-2 was found in the placenta, but newborn was COVID-19 negative. Our case shows maternal vascular malperfusion, with no features of fetal vascular malperfusion. To our knowledge, this is the first report of placental COVID-19 despite mild COVID-19 disease in pregnancy (with no symptoms of COVID-19 aside from myalgias); specifically, this patient had no fever, cough, or shortness of breath, but only myalgias and sick contacts. Despite her having mild COVID-19 disease in pregnancy, we demonstrate placental vasculopathy and presence of SARS-CoV-2 virus across the placenta. Evidence of placental COVID-19 raises concern for possible placental vasculopathy (potentially leading to fetal growth restriction, pre-eclampsia, and other pregnancy complications) as well as for potential vertical transmission -- especially for pregnant women who may be exposed to COVID-19 in early pregnancy. Further studies are urgently needed, to determine whether women with mild, pre-symptomatic, or asymptomatic COVID-19 may have SARS-CoV-2 virus that can cross the placenta, cause fetal vascular malperfusion, and possibly affect the fetus. This raises important public health and public policy questions of whether future pregnancy guidance should include stricter pandemic precautions, such as screening for a wider array of COVID-19 symptoms, increased antenatal surveillance, and possibly routine COVID-19 testing on a regular basis throughout pregnancy.

positive: ENT management of children with adenotonsillar disease during COVID-19 pandemic. Ready to start again? Clinical manifestations of COVID-19 in children are milder, but the real burden of disease is unknown. After the lockdown, in our Region Lombardia we have been requested to progressively resume medical services including outpatient assessment and priority surgery. Therefore, we screened surgical waiting lists with identification of 47 children candidates to priority surgery (among 358). No homogeneous national health surveillance/screening programs are ongoing or have been conceived to test susceptible population among children/healthcare workers in preparation of coming down to routinely daily activities, and diagnostic strategies are not completely accurate in children. So, restoring medical services now might be untimely.

positive: COVID-19 and what pediatric rheumatologists should know: a review from a highly affected country On March 11th, 2020 the World Health Organization declared COVID-19 a global pandemic. The infection, transmitted by 2019 novel coronavirus (2019-nCov), was first discovered in December 2019, in Wuhan, Hubei Province, and then rapidly spread worldwide. Italy was early and severely involved, with a critical spread of the infection and a very high number of victims. Person-to-person spread mainly occurs via respiratory droplets and contact. The median incubation period is 5 days. The spectrum of respiratory symptoms may range from mild to severe, strictly depending on the age of the patient and the underlying comorbidities.In children COVID-19 related disease is less frequent and less aggressive. In Italy 1% of positive cases are under 18 years of age, and no deaths have been recorded before 29 years of age. For patients affected by rheumatic disease, despite the concerns related to the imbalance of their immune response and the effect of immunosuppressive treatments, there are still few data to understand the real consequences of this infection. Major scientific societies have issued recommendations to help rheumatologists in caring their patients. Interestingly, some of the drugs mostly used by rheumatologists appear to be promising in critical COVID-19 infected patients, where the hyperinflammation and cytokine storm seem to drive to the multiorgan failure.Pediatric rheumatologists are expected to play a supporting role in this new front of COVID-19 pandemic, both as general pediatricians treating infected children, and as rheumatologists taking care of their rheumatic patients, as well as offering their experience in the possible alternative use of immunomodulatory drugs.

positive: The psycho‐physical impact that COVID‐19 has on children must not be underestimated Italy has been one of the European countries that has been most affected by the COVID‐19 pandemic. By 16 April 2020, 159,107 Italian residents had tested positive for COVID‐19 and these included 1,123 children, up to nine years of age (0.7%) and 1,804 adolescents, aged between 10 and 19 years old (1.1%) (1). These data were in line with the case studies reported for the Chinese population, where the respective percentage (proportion) was 0.9% and 1.2% respectively (2). A five‐year‐old Italian child, who had been affected by many previous and unspecified pathologies, died after testing positive for COVID‐19 infection (1). The lower vulnerability of the paediatric population to COVID‐19 seems evident.

positive: Endemic human coronaviruses induce distinct antibody repertoires in adults and children Four endemic human coronaviruses (HCoVs) are commonly associated with acute respiratory infection in humans but immune responses to these “common cold” viruses remain incompletely understood. Moreover, there is evidence emerging from independent studies which suggests that endemic HCoVs can induce broadly cross-reactive T cell responses and may thereby affect clinical outcomes of acute infections with the phylogenetically related epidemic viruses, namely MERS-CoV and SARS-CoV-2. Here we report a comprehensive retrospective analysis of CoV-specific antibody specificities in a large number of samples from children and adults using Phage-Immunoprecipitation Sequencing (PhIP-Seq). We estimate the seroprevalence for endemic HCoVs to range from ~4% to ~27% depending on species and cohort. Most importantly, we identified a large number of novel linear B cell epitopes of HCoV proteins and demonstrate that antibody repertoires against endemic HCoVs are qualitatively different in children in comparison to the general adult population and healthy adult blood bank donors. We show that anti-HCoV IgG specificities more frequently found among children target functionally important and structurally conserved regions of the HCoV spike and nucleocapsid proteins and some antibody specificities are broadly cross-reactive with peptides of epidemic human and non-human coronavirus isolates. Our findings shed light on the humoral immune responses to natural infection with endemic HCoVs and may have important implications for understanding of the highly variable clinical outcomes of human coronavirus infections, for the development of prophylactic or therapeutic monoclonal antibodies and vaccine design.

positive: Risks to Children under-five in India from COVID-19 Objective: The novel coronavirus, COVID-19, has rapidly emerged to become a global pandemic and is known to cause a high risk to patients over the age of 70 and those with co-morbidities, such as hypertension and diabetes. Though children are at comparatively lower risk compared to adults, the Indian population has a large young demographic that is likely to be at higher risk due to exposure to pollution, malnutrition and poor access to medical care. We aimed to quantify the potential impact of COVID-19 on Indias child population. Methods: We combined district family household survey data with data from the COVID-19 outbreak in China to analyze the potential impact of COVID-19 on children under the age of 5, under three different scenarios; each of which assumed the prevalence of infection to be 0.5%, 1%, or 5%. Results: We find that in the lowest prevalence scenario, across the most populous 18 Indian states, asymptomatic, non-hospitalized symptomatic and hospitalized symptomatic cases could reach 87,200, 412,900 and 31,900, respectively. In a moderate prevalence scenario, these figures reach 174,500, 825,800, and 63,800, and in the worst case, high prevalence scenario these cases could climb as high as 872,200, 4,128,900 and 319,700. Conclusion: These estimates show COVID-19 has the potential to pose a substantial threat to Indias large population of children, particularly those suffering from malnutrition and exposure to indoor air pollution, who may have limited access to health services.

positive: Maternal transmission of SARS‐COV‐2 to the neonate, and possible routes for such transmission: A systematic review and critical analysis BACKGROUND: Early reports of COVID‐19 in pregnancy described management by caesarean, strict isolation of the neonate and formula feeding, is this practise justified? OBJECTIVE: To estimate the risk of the neonate becoming infected with SARS‐COV‐2 by mode of delivery, type of infant feeding and mother‐infant interaction SEARCH STRATEGY: Two biomedical databases were searched between September 2019 ‐ June 2020. SELECTION CRITERIA: Case reports or case series of pregnant women with confirmed COVID‐19, where neonatal outcomes were reported. DATA COLLECTION AND ANALYSIS: Data was extracted on mode of delivery, infant infection status, infant feeding and mother‐infant interaction. For reported infant infection a critical analysis was performed to evaluate the likelihood of vertical transmission. MAIN RESULTS: We included 49 studies which included 666 neonates and 655 women where information was provided on the mode of delivery and the infant’s infection status. 28/666 (4%) neonates had confirmed COVID‐19 infection postnatally. Of the 291 women who delivered vaginally, 8/292 (2.7%) neonates were positive. Of the 364 women who had a Caesarean birth, 20/374 (5.3%) neonates were positive. Of the 28 neonates with confirmed COVID‐19 infection, 7 were breast fed, 3 formula fed, 1 was given expressed breast milk and in 17 neonates the method of infant feeding was not reported. CONCLUSIONS: Neonatal COVID‐19 infection is uncommon, uncommonly symptomatic, and the rate of infection is no greater when the baby is born vaginally, breastfed or allowed contact with the mother.

positive: Clinical Characteristics of Children with COVID-19: A Rapid Review and Meta-Analysis Abstract 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 1667 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.

positive: Epidemiology and clinical features of coronavirus disease 2019 in children Coronavirus disease-2019 (COVID-19), which started in Wuhan, China, in December 2019 and declared a worldwide pandemic on March 11, 2020, is a novel infectious disease that causes respiratory illness and death. Pediatric COVID-19 accounts for a small percentage of patients and is often milder than that in adults; however, it can progress to severe disease in some cases. Even neonates can suffer from COVID-19, and children may spread the disease in the community. This review summarizes what is currently known about COVID-19 in children and adolescents.

positive: 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 odds ratio [OR] 0.84, 95% confidence interval [CI] 0.47-1.51, P = 0.56) and improvement in MERS-CoV RNA clearance (adjusted hazard ratio [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.

positive: Nasal Swab as Preferred Clinical Specimen for Covid-19 Testing in Children The first pediatric study demonstrating significantly higher positivity rate of nasal (mid-turbinate) swab testing over oropharyngeal swab testing in detecting SARS-CoV-2 (Fisher exact test 0.046, Cohen K 0.43, confidence interval 95%, 0.014-0.855). Benefits might include lower collection-related hazard for healthcare workers. We recommend it as preferred choice for swab-based SARS-CoV-2 testing in children.

positive: Characterisation of COVID-19 Pandemic in Paediatric Age Group: A Systematic Review Abstract Background Coronavirus disease 2019 (COVID-19) is a pandemic first originated in Wuhan the capital of Hubei province, China in December 2019 and then spread globally. It is caused by SARS-CoV-2. Until 1 April 2020, the number of cases worldwide was recorded to be 823,626 with 40,598 deaths. Most of the reported cases were adults with few cases described in children and neonates. Objectives We performed a systematic review to analyse the disease characterisation in paediatric age group including the possibility of vertical transmission to the neonates. Methods Articles published up to the 2nd April 2020 in PubMed and google Scholar were considered for this study. Findings The most frequently reported symptoms were cough 49% (95% CI: 42 – 55%) and fever 47% (95% CI: 41- 53%). Lymphopenia and increased Procalcitonin were recorded in (21%, 95% CI:12 – 30%) and (28%, 95% CI:18 – 37%) respectively. No sex difference for COVID-19 in paediatric age group (p = 0.7). Case fatality rate was 0%. Four out of 58 neonates (6.8%) born to COVID-19 confirmed mothers tested positive for the disease. Conclusion The disease trajectory in Paediatric patients has good prognosis compared to adults. Intensive care unit and death are rare. Vertical transmission and virus shedding in breast milk are yet to be established.

positive: Serial Computed Tomography Manifestations in a Child with Coronavirus Disease (COVID-19) Pneumonia Computed tomography (CT) manifestations and treatment of children with COVID-19 are still unclear We report serial CT findings of a child with COVID-19 pneumonia who recovered without any sequelae

positive: Challenges of COVID-19 in children in low- and middle-income countries As the coronavirus pandemic extends to low and middle income countries (LMICs), there are growing concerns about the risk of coronavirus disease (COVID-19) in populations with high prevalence of comorbidities, the impact on health and economies more broadly and the capacity of existing health systems to manage the additional burden of COVID-19. The direct effects of COVID are less of a concern in children, who seem to be largely asymptomatic or to develop mild illness as occurs in high income countries; however children in LMICs constitute a high proportion of the population and may have a high prevalence of risk factors for severe lower respiratory infection such as HIV or malnutrition. Further diversion of resources from child health to address the pandemic among adults may further impact on care for children. Poor living conditions in LMICs including lack of sanitation, running water and overcrowding may facilitate transmission of SARS-CoV-2. The indirect effects of the pandemic on child health are of considerable concern, including increasing poverty levels, disrupted schooling, lack of access to school feeding schemes, reduced access to health facilities and interruptions in vaccination and other child health programs. Further challenges in LMICs include the inability to implement effective public health measures such as social distancing, hand hygiene, timely identification of infected people with self-isolation and universal use of masks. Lack of adequate personal protective equipment, especially N95 masks is a key concern for health care worker protection. While continued schooling is crucial for children in LMICs, provision of safe environments is especially challenging in overcrowded resource constrained schools. The current crisis is a harsh reminder of the global inequity in health in LMICs. The pandemic highlights key challenges to the provision of health in LMICs, but also provides opportunities to strengthen child health broadly in such settings.

positive: COVID 19 in babies: Knowledge for neonatal care Infection is a leading cause of death worldwide in babies under one month of age who are more susceptible to sepsis due to immature host defence mechanisms. Usually, babies may become acutely unwell from infective pathogens due to specific differences in their respiratory and immune systems. However, with the Covid-19 virus, the focus of this paper, it appears that the neonatal population is not significantly affected in the same way as adults. That said, knowledge about this novel virus is rapidly emerging. Therefore, it is vital that neonatal nurses, midwives and other healthcare professionals are adequately informed and educated about the potential impact on neonatal practice. This review paper draws upon key findings and themes from a selection of recent literature to provide an overview of current knowledge on Covid-19 and the implications for care within the neonatal field. The discussion focuses on the nature of Covid-19, its pathophysiology and transmission relevant to maternal and neonatal care. This is followed by implications for practice; namely, maternal issues, the importance of human breast milk, neonatal care relating to parenting and specific management before a final review of the current World Health Organization guidance.

positive: Asthma and COVID‐19 in children – a systematic review and call for data RATIONALE: Whether asthma constitutes a risk factor for COVID‐19 is unclear. Here we aimed to assess whether asthma, the most common chronic disease in children, is associated with higher COVID‐19 risk or severity in pediatric populations. METHODS: We performed a systematic literature search in three stages: First, we reviewed PubMed, EMBASE and CINAHL for systematic reviews of SARS‐CoV‐2 and COVID‐19 in pediatric populations, and reviewed their primary articles; second, we searched PubMed for studies on COVID‐19 or SARS‐CoV‐2 and asthma/wheeze, and evaluated whether the resulting studies included pediatric populations; third, we repeated the second search in BioRxiv.org and MedRxiv.org to find pre‐prints that may have information on pediatric asthma. RESULTS: In the first search, eight systematic reviews were found, of which five were done in pediatric populations; none of the 67 primary studies included data on pediatric asthma as a comorbidity for COVID‐19. In the second search, we found 34 results in PubMed, of which five reported asthma in adults, but none included data on children. In the third search, 25 pre‐prints in MedRxiv included data on asthma, but none on children. We found one report by the U.S. CDC stating that 40/345 (~11.5%) children with data on chronic conditions had “chronic lung diseases including asthma”, and one from a tertiary hospital in New York that reported asthma in 11/46 (~23.9%) children hospitalized for COVID‐19. CONCLUSION: There is scarcely any data on whether childhood asthma (or other pediatric respiratory diseases) constitute risk factors for SARS‐CoV‐2 infection or COVID‐19 severity. Studies are needed that go beyond counting the number of cases in the pediatric age range. This article is protected by copyright. All rights reserved.

positive: Asymptomatic COVID-19 infection in a child with nasal foreign body While children, particularly infants, are susceptible to severe and critical COVID-19 disease, over 55% of pediatric cases are present in asymptomatic or mildly symptomatic children. Aerosolized SARS-CoV-2 viral particles remain viable for up to 3 hours, raising concern about risk to healthcare workers during aerosol generating procedures (APGs) in the airway and nasopharynx. Herein we describe the first case of a nasal foreign body in an asymptomatic child with SARS-CoV-2 infection. We discuss management of this child and highlight the importance of considering asymptomatic infection and preoperative testing when planning procedures of the airway in the COVID-19 era.

positive: SARS-CoV-2 infection in infants under 1 year of age in Wuhan City, China BACKGROUND: The clinical characteristics and outcome of COVID-19 in children are different from those in adults. We aimed to describe the characteristics of infants under 1 year of age (excluding newborns) with COVID-19. METHODS: We retrospectively retrieved data of 36 infants with SARS-CoV-2 infection in Wuhan Children’s Hospital from January 26 to March 22, 2020. Clinical features, chest imaging findings, laboratory tests results, treatments and clinical outcomes were analyzed. RESULTS: The mean age of the infected infants was 6.43 months, with a range of 2–12 months. 61.11% of the patients were males and 38.89% females. 86.11% of the infants were infected due to family clustering. Cough (77.78%) and fever (47.22%) were the most common clinical manifestations. Chest CT scan revealed 61.11% bilateral pneumonia and 36.11% unilateral pneumonia. 47.22% of the infants developed complications. Increased leucocytes, neutrophils, lymphocytes, and thrombocytes were observed in 11.11, 8.33, 36.11 and 44.44% of infants, respectively. Decreased leucocytes, neutrophils, thrombocyte and hemoglobin were observed in 8.33, 19.44, 2.78 and 36.11% of infants, respectively. Increased C-reactive protein, procalcitonin, lactate dehydrogenase, alanine aminotransferase, creatine kinase and D-dimer were observed in 19.44, 67.74, 47.22, 19.44, 22.22 and 20.69% of infants, respectively. Only one infant had a high level of creatinine. Co-infections with other respiratory pathogens were observed in 62.86% of infants. CD3 (20.69%), CD4 (68.97%), CD19 (31.03%) and Th/Ts (44.83%) were elevated; CD8 (6.9%) and CD16+CD56 (48.28%) was reduced. IL-4 (7.69%), IL-6 (19.23%), IL-10 (50%), TNF-α (11.54%) and IFN-γ (19.23%) were elevated. Up to March 22, 97.22% of infants recovered, while a critical ill infant died. When the infant’s condition deteriorates rapidly, lymphocytopenia was discovered. Meanwhile, C-reactive protein, D-dimer, alanine aminotransferase, creatine kinase, creatinine, IL-6 and IL-10 increased significantly. CONCLUSIONS: In the cohort, we discovered that lymphocytosis, elevated CD4 and IL-10, and co-infections were common in infants with COVID-19, which were different from adults with COVID-19. Most infants with COVID-19 have mild clinical symptoms and good prognosis.

positive: Neonatal Resuscitation and Postresuscitation Care of Infants Born to Mothers with Suspected or Confirmed SARS-CoV-2 Infection The first case of novel coronavirus disease of 2019 (COVID-19) caused by severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) was reported in November2019. The rapid progression to a global pandemic of COVID-19 has had profound medical, social, and economic consequences. Pregnant women and newborns represent a vulnerable population. However, the precise impact of this novel virus on the fetus and neonate remains uncertain. Appropriate protection of health care workers and newly born infants during and after delivery by a COVID-19 mother is essential. There is some disagreement among expert organizations on an optimal approach based on resource availability, surge volume, and potential risk of transmission. The manuscript outlines the precautions and steps to be taken before, during, and after resuscitation of a newborn born to a COVID-19 mother, including three optional variations of current standards involving shared-decision making with parents for perinatal management, resuscitation of the newborn, disposition, nutrition, and postdischarge care. The availability of resources may also drive the application of these guidelines. More evidence and research are needed to assess the risk of vertical and horizontal transmission of SARS-CoV-2 and its impact on fetal and neonatal outcomes. Key Points: The risk of vertical transmission is unclear; transmission from family members/providers to neonates is possible. Optimal personal-protective-equipment (airborne vs. droplet/contact precautions) for providers is crucial to prevent transmission. Parents should be engaged in shared decision-making with options for rooming in, skin-to-skin contact, and breastfeeding.

positive: What can we learn from neonates with COVID-19?

positive: The Risk of Children Hospitalized With Severe COVID-19 in Wuhan. BACKGROUND Novel coronavirus disease (COVID-19) is spreading globally. Little is known about the risk factors for the clinical outcomes of COVID-19 in children. METHODS A retrospective case-control study was taken in children with severe acute respiratory syndrome coronary virus-2 infection in Wuhan Children's Hospital. Risk factors associated with the development of COVID-19 and progression were collected and analyzed. RESULTS Eight out of 260 children diagnosed with severe COVID-19 pneumonia were included in the study. Thirty-five children with COVID-19 infection matched for age, sex and date of admission, and who classified as non-severe type, were randomly selected from the hospital admissions. For cases with severe pneumonia caused by COVID-19, the most common symptoms were dyspnea (87.5%), fever (62.5%) and cough (62.5%). In laboratory, white blood cells count was significantly higher in severe children than non-severe children. Levels of inflammation bio-makers such as hsCRP, IL-6, IL-10 and D-dimer elevated in severe children compared with non-severe children on admission. The level of total bilirubin and uric acid clearly elevated in severe children compared with non-severe children on admission. All of severe children displayed the lesions on chest CT, more lung segments were involved in severe children than in non-severe children, which was only risk factor associated with severe COVID-19 pneumonia in multivariable analysis. CONCLUSIONS More than 3 lung segments involved were associated with greater risk of development of severe COVID-19 in children. Moreover, the possible risk of the elevation of IL-6, high total bilirubin and D-dimer with univariable analysis could identify patients to be severe earlier.

positive: Neurotropic mechanisms in COVID-19 and their potential influence on neuropsychological outcomes in children. Children have shown more physical resilience to COVID-19 than adults, but there is a cohort of vulnerable infants and young children who may experience disease burden, both in the acute phase and chronically. Children may have had early undocumented exposure to COVID-19. Even when the risk of exposure was known, developmental variables may have made the avoidance of physical proximity difficult for children. Preliminary hypotheses concerning neurotropic factors have been documented by researchers. Children with COVID-19 and comorbid physical or mental disorders may be vulnerable to exacerbations of neurotropic factors and comorbidities, the neural impact of which has been documented for other coronaviruses. Researchers are investigating COVID-19 symptom descriptions, neurotropic mechanisms at the genomic and transcriptomatic levels, neurological manifestations, and the impact of comorbid health complications. Neuropsychologists need information concerning the likely impact of COVID-19 on children. With a view toward that goal, this article provides recommendations for relevant for some initial updates in neuropsychology practice.

positive: Understanding COVID-19 in children may provide clues to protect at-risk populations

positive: Covid-19 and pregnancy. Guideline: Coronavirus (COVID-19) Infection in pregnancyPublished by the Royal College of Obstetricians and Gynaecologists (RCOG), with input from the Royal College of Midwives, the Royal College of Paediatrics and Child Health (RCPH), the Royal College of Anaesthetists, and the Obstetric Anaesthetists' Association.This summary is based on version 8 of the guideline, published on 17 April 2020 (https://www.rcog.org.uk/globalassets/documents/guidelines/2020-04-17-coronavirus-covid-19-infection-in-pregnancy.pdf).

positive: Outbreak of Kawasaki disease in children during COVID-19 pandemic: a prospective observational study in Paris, France Background: Acute clinical manifestations of SARS-CoV-2 infection are less frequent and less severe in children than in adults. However, recent observations raised concerns about potential post-viral severe inflammatory reactions in children infected with SARS-CoV-2. Methods: We describe an outbreak of cases of Kawasaki disease (KD) admitted between April 27 and May 7, 2020, in the general paediatrics department of a university hospital in Paris, France. All children prospectively underwent nasopharyngeal swabs for SARS-CoV-2 RT-PCR, SARS-CoV-2 IgG serology testing, and echocardiography. The number of admissions for KD during the study period was compared to that observed since January 1, 2018, based on discharge codes, using Poisson regression. Results: A total of 17 children were admitted for KD over an 11-day period, in contrast with a mean of 1.0 case per 2-week period over 2018-2019 (Poisson incidence rate ratio: 13.2 [95% confidence interval: 7.3-24.1], p <0.001). Their median age was 7.5 (range, 3.7-16.6) years, and 59% of patients originated from sub-Saharan Africa or Caribbean islands. Eleven patients presented with KD shock syndrome (KDSS) requiring intensive care support, and 12 had myocarditis. All children had marked gastrointestinal symptoms at the early stage of illness and high levels of inflammatory markers. Fourteen patients (82%) had evidence of recent SARS-CoV-2 infection (positive RT-PCR 7/17, positive IgG antibody detection 14/16). All patients received immunoglobulins and some received corticosteroids (5/17). The clinical outcome was favourable in all patients. Moderate coronary artery dilations were detected in 5 cases (29%) during hospitalisation. Conclusions: The ongoing outbreak of KD in the Paris might be related to SARS-CoV2, and shows an unusually high proportion of children with gastrointestinal involvement, KDSS and African ancestry.

positive: [Pediatric impact of COVID-19]. Children infected with SARS-CoV-2 are underrepresented during the current COVID-19 outbreak. Unlike other respiratory viruses, SARS-CoV-2 rather infects adults who subsequently infect their children. From recent Chinese and Italian data, children commonly present mild to moderate disease, a large proportion of them being asymptomatic. In particular, children present significantly less fever, cough and pneumonia compared to adults. However, more cases of pneumonia were reported from children infected with SARS-CoV-2 compared to those infected with H1N1. No vertical transmission of SARS-CoV-2 has been described so far.

positive: Children with COVID-19 at a specialist centre: initial experience and outcome

positive: Modelling transmission and control of the COVID-19 pandemic in Australia We develop an agent-based model for a fine-grained computational simulation of the ongoing COVID-19 pandemic in Australia. This model is calibrated to reproduce key characteristics of COVID-19 transmission. An important calibration outcome is the age-dependent fraction of symptomatic cases, with this fraction for children found to be one-fifth of such fraction for adults. We apply the model to compare several intervention strategies, including restrictions on international air travel, case isolation, home quarantine, social distancing with varying levels of compliance, and school closures. School closures are not found to bring decisive benefits, unless coupled with high level of social distancing compliance. We report several trade-offs, and an important transition across the levels of social distancing compliance, in the range between 70% and 80% levels, with compliance at the 90% level found to control the disease within 13--14 weeks, when coupled with effective case isolation and international travel restrictions.

positive: Clinical characteristics of 182 pediatric COVID-19 patients with different severities and allergic status BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has made widespread impact recently. We aim to investigate the clinical characteristics of COVID-19 children with different severities and allergic status. METHODS: Data extracted from the electronical medical records, including demographics, clinical manifestations, comorbidities, laboratory and immunological results and radiological images of 182 hospitalized COVID-19 children were summarized and analyzed. RESULTS: The median age was 6 years old, ranging from 3 days to 15 years, and there were more boys (male-female ratio about 2:1) within the studied 182 patients. Most of the children were infected by family members. Fever (43.4%) and dry cough (44.5%) were common symptoms, and gastrointestinal manifestations accounted for 11.0%, including diarrhea, abdominal discomfort and vomiting. 71.4% had abnormal chest computed tomography (CT) scan images, and typical signs of pneumonia were ground-glass opacity and local patchy shadowing on admission. Laboratory results were mostly within normal ranges, and only a small ratio of lymphopenia (3.9%) and eosinopenia (29.5%) were observed. The majority (97.8%) of infected children were not severe, and 24 (13.2%) of them had asymptomatic infections. Compared to children without pneumonia(manifested as asymptomatic and acute upper respiratory infection), children with pneumonia were associated with higher percentages of the comorbidity history, symptoms of fever and cough, and increased levels of serum procalcitonin, alkaline phosphatase and serum interleukins (IL)-2, IL-4, IL-6, IL-10 and TNF-α.There were no differences of treatments, duration of hospitalization, time from first positive to first negative nucleic acid testing and outcomes between children with mild pneumonia and without pneumonia. All the hospitalized COVID-19 children had recovered except one death due to intussusception and sepsis. In 43 allergic children with COVID-19, allergic rhinitis (83.7%) was the major disease, followed by drug allergy, atopic dermatitis, food allergy and asthma. Demographics and clinical features were not significantly different between allergic and non-allergic groups. Allergic patients showed less increase in acute phase reactants, procalcitonin, D-dimer and aspartate aminotransferase levels compared to all patients. Immunological profiles including circulating T, B and NK lymphocyte subsets, total immunoglobulin and complement levels and serum cytokines did not show any difference in allergic and pneumonia groups. Neither eosinophil counts nor serum total immunoglobulin E (IgE) levels showed a significant correlation with other immunological measures, such as other immunoglobulins, complements, lymphocyte subsets numbers and serum cytokine levels. CONCLUSION: Pediatric COVID-19 patients tended to have a mild clinical course. Patients with pneumonia had higher proportion of fever and cough and increased inflammatory biomarkers than those without pneumonia. There was no difference between allergic and non-allergic COVID-19 children in disease incidence, clinical features, laboratory and immunological findings. Allergy was not a risk factor for developing and severity of SARS-CoV-2 infection and hardly influenced the disease course of COVID-19 in children.

positive: The different clinical characteristics of corona virus disease cases between children and their families in China – the character of children with COVID-19 This study aims to analyze the different clinical characteristics between children and their families infected with severe acute respiratory syndrome coronavirus 2. Clinical data from nine children and their 14 families were collected, including general status, clinical, laboratory test, and imaging characteristics. All the children were detected positive result after their families onset. Three children had fever (22.2%) or cough (11.2%) symptoms and six (66.7%) children had no symptom. Among the 14 adult patients, the major symptoms included fever (57.1%), cough (35.7%), chest tightness/pain (21.4%), fatigue (21.4%) and sore throat (7.1%). Nearly 70% of the patients had normal (71.4%) or decreased (28.6%) white blood cell counts, and 50% (7/14) had lymphocytopenia. There were 10 adults (71.4%) showed abnormal imaging. The main manifestations were pulmonary consolidation (70%), nodular shadow (50%), and ground glass opacity (50%). Five discharged children were admitted again because their stool showed positive result in SARS-CoV-2 PCR. COVID-19 in children is mainly caused by family transmission, and their symptoms are mild and prognosis is better than adult. However, their PCR result in stool showed longer time than their families. Because of the mild or asymptomatic clinical process, it is difficult to recognize early for pediatrician and public health staff.

positive: Anaesthesia and infection control in cesarean section of pregnant women with coronavirus disease 2019 (COVID-19) Background The coronavirus disease 2019 (COVID-19) first emerged in Wuhan, China, and soon caused an ongoing pandemic globally. In this study we conducted a retrospective study to evaluate the safety and efficacy of combined spinal-epidural anaesthesia (CSEA) and infection control measures on perinatal care quality of 30 pregnant women with confirmed and suspected COVID-19. Methods Individual demographic data, clinical outcomes, laboratory investigations of pregnant women and their newborns were collected from electronic medical records of the Maternal and Children Health Hospital of Hubei Province, during January 24 to February 29, 2020. Anaesthesia and surgery results were compared between pregnant women with confirmed and suspected COVID-19 infection. Results Using CSEA in cesarean section was effective and safe for pregnant women with confirmed and suspected COVID-19 infection. Administration of dezocine and morphine was effective as postoperative analgesia, and well tolerated in COVID-19 patients. The assessment of surgery outcomes also showed similar results in both confirmed and suspected cases. No respiratory failure nor distress were found in the mothers with confirmed COVID-19 infection and their neonates. None of these patients experienced severe obstetric complications related to anaesthesia and surgeries. No COVID-19 infection was reported in the neonates born to the mothers with confirmed COVID-19 infection and healthcare workers in these operations. Conclusions In cesarean section for pregnant women with COVID-19 infection, CSEA was safe and efficient in achieving satisfactory obstetrical anaesthesia and postoperative analgesia. No cross-infection occurred in the HCWs working in these operations.

positive: Clinical and Immune Features of Hospitalized Pediatric Patients With Coronavirus Disease 2019 (COVID-19) in Wuhan, China IMPORTANCE: The epidemiologic and clinical characteristics of pediatric patients with coronavirus disease 2019 (COVID-19) have been reported, but information on immune features associated with disease severity is scarce. OBJECTIVE: To delineate and compare the immunologic features of mild and moderate COVID-19 in pediatric patients. DESIGN, SETTING, AND PARTICIPANTS: This single-center case series included 157 pediatric patients admitted to Wuhan Children’s Hospital with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data were collected from January 25 to April 18, 2020. EXPOSURES: Documented SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES: Clinical and immunologic characteristics were collected and analyzed. Outcomes were observed until April 18, 2020. RESULTS: Of the 157 pediatric patients with COVID-19, 60 (38.2%) had mild clinical type with pneumonia, 88 (56.1%) had moderate cases, 6 (3.8%) had severe cases, and 3 (1.9%) were critically ill. The 148 children with mild or moderate disease had a median (interquartile range [IQR]) age of 84 (18-123) months, and 88 (59.5%) were girls. The most common laboratory abnormalities were increased levels of alanine aminotransferase (ALT) (median [IQR], 16.0 [12.0-26.0] U/L), aspartate aminotransferase (AST) (median [IQR], 30.0 [23.0-41.8] U/L), creatine kinase MB (CK-MB) activity (median [IQR], 24.0 [18.0-34.0] U/L), and lactate dehydrogenase (LDH) (median [IQR], 243.0 [203.0-297.0] U/L), which are associated with liver and myocardial injury. Compared with mild cases, levels of inflammatory cytokines including interleukin 6, tumor necrosis factor α, and interferon γ were unchanged, whereas the level of immune suppressive interleukin 10 was markedly increased in moderate cases compared with mild cases (median [IQR], 3.96 [3.34-5.29] pg/mL vs 3.58 [3.10-4.36] pg/mL; P = .048). There was no statistically significant difference in absolute number of lymphocytes (including T cells and B cells) between mild and moderate cases, but moderate cases were associated with a decrease in neutrophil levels compared with mild cases (median [IQR], 2310/μL [1680/μL-3510/μL] vs 3120/μL [2040/μL-4170/μL]; P = .01). Immunoglobin G and the neutrophil to lymphocyte ratio were negatively associated with biochemical indices related to liver and myocardial injury (immunoglobulin G, ALT: r, −0.3579; AST: r, −0.5280; CK-MB activity: r, −0.4786; LDH: r, −0.4984; and neutrophil to lymphocyte ratio, ALT: r, −0.1893; AST: r, −0.3912; CK-MB activity: r, −0.3428; LDH: r, −0.3234), while counts of lymphocytes, CD4(+) T cells, and interleukin 10 showed positive associations (lymphocytes, ALT: r, 0.2055; AST: r, 0.3615; CK-MB activity: r, 0.338; LDH: r, 0.3309; CD4(+) T cells, AST: r, 0.4701; CK-MB activity: r, 0.4151; LDH: r, 0.4418; interleukin 10, ALT: r, 0.2595; AST: r, 0.3386; CK-MB activity: r, 0.3948; LDH: r, 0.3794). CONCLUSIONS AND RELEVANCE: In this case series, systemic inflammation rarely occurred in pediatric patients with COVID-19, in contrast with the lymphopenia and aggravated inflammatory responses frequently observed in adults with COVID-19. Gaining a deeper understanding of the role of neutrophils, CD4(+) T cells, and B cells in the pathogenesis of SARS-CoV-2 infection could be important for the clinical management of COVID-19.

positive: The immune system of children: the key to understanding SARS-CoV-2 susceptibility?

positive: B5/133 – Longer-term follow up of aerobic capacity in children affected by Severe Acute Respiratory Syndrome (SARS)

positive: Type 2 and interferon inflammation strongly regulate SARS-CoV-2 related gene expression in the airway epithelium Coronavirus disease 2019 (COVID-19) outcomes vary from asymptomatic infection to death. This disparity may reflect different airway levels of the SARS-CoV-2 receptor, ACE2, and the spike protein activator, TMPRSS2. Here we explore the role of genetics and co-expression networks in regulating these genes in the airway, through the analysis of nasal airway transcriptome data from 695 children. We identify expression quantitative trait loci (eQTL) for both ACE2 and TMPRSS2, that vary in frequency across world populations. Importantly, we find TMPRSS2 is part of a mucus secretory network, highly upregulated by T2 inflammation through the action of interleukin-13, and that interferon response to respiratory viruses highly upregulates ACE2 expression. Finally, we define airway responses to coronavirus infections in children, finding that these infections upregulate IL6 while also stimulating a more pronounced cytotoxic immune response relative to other respiratory viruses. Our results reveal mechanisms likely influencing SARS-CoV-2 infectivity and COVID-19 clinical outcomes.

positive: Age-Related Morbidity and Mortality among Patients with COVID-19 On March 11, 2020, the World Health Organization declared coronavirus disease (COVID-19), caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a pandemic. During the COVID-19 pandemic, an age-associated vulnerability in the burden of disease has been uncovered. Understanding the spectrum of illness and the pathogenic mechanism of the disease in a vulnerable population is critical, especially during the pandemic. Herein, we reviewed published COVID-19 epidemiology data from several countries to identify any consistent trends in the relationship between age and COVID-19-associated morbidity or mortality. We also reviewed the literature for studies explaining the difference in the host response to SARS-CoV-2 infection according to age. The insights from these data will be useful in determining the treatment policies and preventive measures of COVID-19.

positive: Breastfeeding during the COVID-19 pandemic: suggestions on behalf of Woman Study Group of AMD Abstract SARS-Cov2 infection has recently spread to Italy with important consequences on pregnancy management, mother and child health and mother-child contact. Breastfeeding improves the health of mother and child and reduces risk of neonatal infection with other pathogens that are likely to cause serious illness. To date no evidence confirmed COVID-19 vertical transmission from infected pregnant mother to their fetus. However it is well known that an infected mother can transmit the COVID-19 virus through respiratory droplets during breastfeeding or intimate contact. Thus, the mothers with known or suspected COVID-19 should adhere to standard and contact precautions during breastfeeding. Woman Study Group of AMD, after reviewing current knowledge about COVID-19 vertical transmission and the compatibility of breastfeeding in COVID-19 mother, the available recommendations from Health Care Organizations and main experts opinions, issued the following suggestions on breastfeeding during the COVID-19 pandemic, addressed both to mothers with and without diabetes It should be considered that following suggestions may change in the future when more evidence is acquired regarding SARS-Cov2 infection.

positive: COVID-19 PICU guidelines: for high- and limited-resource settings Fewer children than adults have been affected by the COVID-19 pandemic, and the clinical manifestations are distinct from those of adults. Some children particularly those with acute or chronic comorbidities are likely to develop critical illness. Recently, a Multisystem Inflammatory Syndrome (MIS-C) has been described in children with these patients often requiring care in the Pediatric ICU. An international collaboration was formed to review the available evidence and develop evidence-based guidelines for the care of critically ill children with SARS-CoV-2 infection. Where the evidence was lacking, those gaps were replaced with consensus-based guidelines. This process has generated 44 recommendations related to pediatric COVID-19 patients presenting with respiratory distress or failure, sepsis or septic shock, cardiopulmonary arrest, MIS-C, or those requiring adjuvant therapies, or ECMO. Evidence to explain the milder disease patterns in children and the potential to use repurposed antiviral drugs, anti-inflammatory or antithrombotic therapies are also described. Brief summaries of pediatric SARS-CoV-2 infection in different regions of the world are included since few registries are capturing these data globally. These guidelines seek to harmonize the standards and strategies for intensive care that critically ill children with COVID-19 receive across the world. IMPACT: At the time of publication, this is the latest evidence for managing critically ill children infected with SARS-CoV-2.Referring to these guidelines can decrease the morbidity and potentially the mortality of children effected by COVID-19 and its sequalae.These guidelines can be adapted to both high- and limited-resource settings.

positive: Ethnicity and COVID-19 in children with comorbidities

positive: Clinical characteristics and radiological features of children infected with the 2019 novel coronavirus AIM: To identify and summarise the common findings from 2019 novel coronavirus (2019-nCoV) infections in children. MATERIALS AND METHODS: The clinical characteristics and radiological findings (chest radiography and chest computed tomography [CT]) of nine children infected with the 2019-nCoV were reviewed in this retrospective case series. RESULTS: Among the children, six had fever (including two children with cough), one had only cough, one had a stuffy nose when initially diagnosed, and one was an asymptomatic carrier. Chest radiographs seemed mostly normal in six cases whereas increased and/or disordered bilateral bronchovascular shadows and dense hilar shadows were seen in three cases. Chest CT exhibited no obvious abnormal signs in four cases. Typical CT findings included patchy, peripheral ground-grass opacities, subpleural lamellar dense shadows, and parenchymal bands. Pleural effusions, mediastinal lymphadenopathy, cavitation, and pleural thickening were absent. CONCLUSION: The clinical manifestations and radiological findings of the 2019-nCoV-infected children were mild and lacked a typical pattern.

positive: Why the SARS-Cov-2 has prolonged spreading time in children?

positive: Prolonged presence of SARS-CoV-2 in feces of pediatric patients during the convalescent phase Background: Severe acute respiratory coronavirus 2 (SARS-CoV-2) is a newly identified virus which mainly spreads from person-to-person. Fecal shedding of SARS-CoV-2 has been constantly reported in patients with coronavirus disease 2019 (COVID-19). Most published studies focus on adult populations, whereas data concerning pediatric patients is relatively scarce. Methods: From January 17, 2020 to March 6, 2020, three pediatric cases of COVID-19 were reported in Qingdao, Shandong Province, China. Epidemiological, clinical, laboratory, and radiological characteristics and treatment data of these children were collected. Real-time fluorescence reverse-transcriptase-polymerase-chain reaction (RT-PCR) was performed to detect SARS-CoV-2 RNA in throat swabs and fecal specimens. Results: All the three pediatric cases were household contacts of adults whose symptoms developed earlier. There has been no evidence showing the virus was transmitted from the children to others. Severity of disease of these children was mild to moderate and fever was the most consistent and predominant symptom at onset of illness (two cases had body temperature higher than 38.5 Celsius). All children showed increased lymphocytes (>4.4*109/L) with normal white blood cell counts on admission. One child had elevated serum levels of procalcitonin and C-reaction protein. Radiological changes were not typical for COVID-19. All children showed good response to supportive treatment. Clearance of SARS-CoV-2 in respiratory tract occurred within two weeks after abatement of fever, whereas persistent presence of viral RNA was found in stools of all children. One case had fecal SARS-CoV-2 turned negative 8 days after throat swabs showing negative, while that of another child lagged behind for 20 days. At the time of writing, one child still had positive results for RT-PCR analysis in stools after negative conversion of viral RNA in respiratory samples (over 19 days behind). Conclusions: Pediatric patients with COVID-19 are very different from adult patients in regards to epidemiological, clinical, laboratory, and radiological characteristics. Prolonged shedding of SARS-CoV-2 in stools of infected children indicates the potential for the virus to be transmitted through fecal excretion. Massive efforts should be made at all levels to prevent spreading of the infection among children after reopening of kindergartens and schools.

positive: 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.

positive: NASAL SWAB AS PREFERRED CLINICAL SPECIMEN FOR COVID-19 TESTING IN CHILDREN. The first pediatric study demonstrating significantly higher positivity rate of nasal (mid-turbinate) swab testing over oropharyngeal swab testing in detecting SARS-CoV-2 (Fisher exact test 0.046, Cohen K 0.43, confidence interval 95%, 0.014-0.855). Benefits might include lower collection-related hazard for healthcare workers. We recommend it as preferred choice for swab-based SARS-CoV-2 testing in children.

positive: Coronavirus Disease 2019 Case Surveillance - United States, January 22-May 30, 2020 The coronavirus disease 2019 (COVID-19) pandemic resulted in 5,817,385 reported cases and 362,705 deaths worldwide through May, 30, 2020, including 1,761,503 aggregated reported cases and 103,700 deaths in the United States.§ Previous analyses during February-early April 2020 indicated that age ≥65 years and underlying health conditions were associated with a higher risk for severe outcomes, which were less common among children aged <18 years (1-3). This report describes demographic characteristics, underlying health conditions, symptoms, and outcomes among 1,320,488 laboratory-confirmed COVID-19 cases individually reported to CDC during January 22-May 30, 2020. Cumulative incidence, 403.6 cases per 100,000 persons,¶ was similar among males (401.1) and females (406.0) and highest among persons aged ≥80 years (902.0). Among 599,636 (45%) cases with known information, 33% of persons were Hispanic or Latino of any race (Hispanic), 22% were non-Hispanic black (black), and 1.3% were non-Hispanic American Indian or Alaska Native (AI/AN). Among 287,320 (22%) cases with sufficient data on underlying health conditions, the most common were cardiovascular disease (32%), diabetes (30%), and chronic lung disease (18%). Overall, 184,673 (14%) patients were hospitalized, 29,837 (2%) were admitted to an intensive care unit (ICU), and 71,116 (5%) died. Hospitalizations were six times higher among patients with a reported underlying condition (45.4%) than those without reported underlying conditions (7.6%). Deaths were 12 times higher among patients with reported underlying conditions (19.5%) compared with those without reported underlying conditions (1.6%). The COVID-19 pandemic continues to be severe, particularly in certain population groups. These preliminary findings underscore the need to build on current efforts to collect and analyze case data, especially among those with underlying health conditions. These data are used to monitor trends in COVID-19 illness, identify and respond to localized incidence increase, and inform policies and practices designed to reduce transmission in the United States.

positive: Coping With COVID-19: Learning From Past Pandemics to Avoid Pitfalls and Panic It is imperative to concur on the main transmission routes of COVID-19 to explain risk and determine the most effective means to reduce illness and mortality. We must avoid generating irrational fear and maintain a broader perspective in the pandemic response, including assessing the possibility for substantial unintended consequences.

positive: Clinical characteristics of a case series of children with coronavirus disease 2019 We reported the clinical characteristics of a case series of 10 patients with coronavirus disease 2019 (COVID-19) aged from 1 year to 18 years. Seven patients had contact with confirmed COVID-19 family members before onset. Fever (4 [40.0%]) and cough (3 [30.0%]) were the most common symptoms. No patient showed leucopenia and lymphopenia on admission. Pneumonia was observed in chest CT images in 5 (50.0%) patients. Five (50.0%) patients received antiviral treatment. No patient had severe complications or developed a severe illness in our study. Our study indicated that COVID-19 children present less severe symptoms and have better outcomes.

positive: Novel coronavirus infection in children outside of Wuhan, China BACKGROUND: Since December 8, 2019, an epidemic of coronavirus disease 2019 (COVID-19) has spread rapidly, but information about children with COVID-19 is limited. METHODS: This retrospective and the single-center study were done at the Public Health Clinic Center of Changsha, Hunan, China. We identified all hospitalized children diagnosed with COVID-19 between January 8, 2019 and February 19, 2020, in Changsha. Epidemiological and clinical data of these children were collected and analyzed. Outcomes were followed until February 26th, 2020. RESULTS: By February 19, 2020, nine pediatric patients were identified as having 2019-nCoV infection in Changsha. Six children had a family exposure and could provide the exact dates of close contact with someone who was confirmed to have 2019-nCoV infection, among whom the median incubation period was 7.5 days. The initial symptoms of the nine children were mild, including fever (3/9), diarrhea (2/9), cough (1/9), and sore throat (1/9), two had no symptoms. Two of the enrolled patients showed small ground-glass opacity of chest computed tomography scan. As of February 26, six patients had a negative RT-PCR for 2019-nCoV and were discharged. The median time from exposure to a negative RT-PCR was 14 days. CONCLUSIONS: The clinical symptoms of the new coronavirus infection in children were not typical and showed a less aggressive clinical course than teenage and adult patients. Children who have a familial clustering or have a family member with a definite diagnosis should be reported to ensure a timely diagnosis.

positive: Serial Computed Tomography Findings in a Child with Coronavirus Disease (COVID-19) Pneumonia Computed tomography (CT) manifestations and treatment of children with COVID-19 are still unclear. We report serial CT findings of a child with COVID-19 pneumonia who recovered without any sequelae.

positive: SARS-CoV-2 entry related genes are comparably expressed in children's lung as adults To explore whether the expression levels of viral-entry associated genes might contribute to the milder symptoms in children, we analysed the expression of these genes in both children and adults' lung tissues by single cell RNA sequencing (scRNA-seq) and immunohistochemistry (IHC). Both scRNA-seq and IHC analyses showed comparable expression of the key genes for SARS-CoV-2 entry in children and adults, including ACE2, TMPRSS2 and FURIN, suggesting that instead of lower virus intrusion rate, other factors are more likely to be the key reasons for the milder symptoms of SARS-CoV-2 infected children.

positive: Clinical characteristics of COVID-19 in children compared with adults in Shandong Province, China AIMS AND BACKGROUND: The COVID-19 outbreak spread in China and is a threat to the world. We reported on the epidemiological, clinical, laboratory, and radiological characteristics of children cases to help health workers better understand and provide timely diagnosis and treatment. METHODS: Retrospectively, two research centers’ case series of 67 consecutive hospitalized cases including 53 adult and 14 children cases with COVID-19 between 23 Jan 2020 and 15 Feb 2020 from Jinan and Rizhao were enrolled in this study. Epidemiological, clinical, laboratory, and radiological characteristics of children and adults were analyzed and compared. RESULTS: Most cases in children were mild (21.4%) and conventional cases (78.6%), with mild clinical signs and symptoms, and all cases were of family clusters. Fever (35.7%) and dry cough (21.4%) were described as clinical manifestations in children cases. Dry cough and phlegm were not the most common symptoms in children compared with adults (p = 0.03). In the early stages of the disease, lymphocyte counts did not significantly decline but neutrophils count did in children compared with adults (p = 0.02). There was a lower level of CRP (p = 0.00) in children compared with adults. There were 8 (57.1%) asymptomatic cases and 6 (42.9%) symptomatic cases among the 14 children cases. The age of asymptomatic patients was younger than that of symptomatic patients (p = 0.03). Even among asymptomatic patients, 5 (62.5%) cases had lung injuries including 3 (60%) cases with bilateral involvement, which was not different compared with that of symptomatic cases (p = 0.58, p = 0.74). CONCLUSIONS: The clinical symptoms of children are mild, there is substantial lung injury even among children, but that there is less clinical disease, perhaps because of a less pronounced inflammatory response, and that the occurrence of this pattern appears to inversely correlate with age.

positive: COVID-19 in children: the link in the transmission chain

positive: Current Scenario of COVID-19 in Pediatric Age Group and Physiology of Immune and Thymus response COVID-19 pandemic caused by SARS-CoV-2, continues to manifest with severe acute respiratory syndrome among the adults, however, it offers a convincing indication of less severity and fatality in pediatric age group (0-18 years). The current trend suggests that children may get infected but are less symptomatic with less fatality, which is concordant to earlier epidemic outbreaks of SARS-CoV and MERS-CoV, in 2002 and 2012, respectively. According to the available data, children appear to be at lower risk for COVID-19, as adults constitute for maximum number of the confirmed cases (308,592) and deaths (13,069) as on 22nd March (https://www.worldometers.info/coronavirus). However, rapid publications and information of the adult patients with COVID-19 is in progress and published, on the contrary, almost no comprehensive data or discussion about the COVID-19 in children is available. Therefore, in this review, we outline the epidemiology, clinical symptoms, diagnosis, treatment, prevention, possible immune response and role of thymus in children to combat the COVID-19 outbreak.

positive: Age Related Morbidity and Mortality among Patients with COVID-19 On March 11, 2020, the World Health Organization declared coronavirus disease (COVID-19), caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a pandemic During the COVID-19 pandemic, an age-associated vulnerability in the burden of disease has been uncovered Understanding the spectrum of illness and the pathogenic mechanism of the disease in a vulnerable population is critical, especially during the pandemic Herein, we reviewed published COVID-19 epidemiology data from several countries to identify any consistent trends in the relationship between age and COVID-19-associated morbidity or mortality We also reviewed the literature for studies explaining the difference in the host response to SARS-CoV-2 infection according to age The insights from these data will be useful in determining the treatment policies and preventive measures of COVID-19

positive: Characteristics of Hospitalized Pediatric COVID-19 Cases - Chicago, Illinois, March - April 2020. BACKGROUND To date, no report on COVID-19 pediatric patients in a large urban center with data on underlying comorbidities and co-infection for hospitalized cases has been published. METHODS Case series of Chicago COVID-19 patients aged 0-17 years reported to Chicago Department of Public Health (CDPH) from 3/5/20-4/8/20. Enhanced case investigation performed. Chi-square and Wilcoxon two-sample tests to compare characteristics among hospitalized and non-hospitalized cases. RESULTS During March 5-April 8, 2020, 6369 lab-confirmed cases of COVID-19 were reported to CDPH; 64 (1.0%) were among children 0-17 years. Ten patients (16%) were hospitalized, seven (70%) required intensive care (ICU); median length of hospitalization 4 days (range: 1-14). Reported fever and dyspnea were significantly higher in hospitalized patients compared to non-hospitalized patients (9/10 vs. 28/54, p = 0.04 and 7/10 vs. 10/54, p = 0.002, respectively). Hospitalized patients were significantly younger than non-hospitalized patients (median, 3.5 years vs. 12 years; p = 0.03) and all either had an underlying comorbidity or co-infection. Among the 34 unique households with multiple laboratory-confirmed infections, median number of laboratory-confirmed infections was 2 (range: 2-5), and 31 (91%) households had at least one COVID-19 infected adult. For 15 households with available data to assess transmission, 11 (73%) were adult-to-child, 2 (13%) child-to-child, and 2 (13%) child-to-adult. CONCLUSIONS Enhanced case investigation of hospitalized patients revealed that underlying comorbidities and co-infection might have contributed to severe disease. Given frequency of household transmission, healthcare providers should consider alternative dispositional planning for affected families of children living with comorbidities.

positive: Clinical Analysis of 25 Novel Coronavirus Infections in Children BACKGROUND: To describe the characteristics of clinical manifestations of children with 2019 novel coronavirus (2019-nCoV) infection in Chongqing. METHODS: All 25 children with laboratory-confirmed 2019-nCoV infection by real-time reverse transcription-PCR (RNA-PCR) were admitted from the 4 designated treatment hospitals of 2019-nCoV in Chongqing from January 19 to March 12, 2020. Clinical data and epidemiological history of these patients were retrospectively collected and analyzed. RESULTS: The diagnosis was confirmed through RNA-PCR testing. Among the 25 cases, 14 were males and 11 were females. The median age was 11.0 (6.3-14.5) years (range 0.6-17.0 years). All children were related to a family cluster outbreak, and 7 children (28%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 8 (32%) asymptomatic, 4 (16%) very mild cases and 13 (52%) common cases. No severe or critical cases were identified. The most common symptoms were cough (13 cases, 52%) and fever (6 cases, 24%). The duration time of clinical symptoms was 13.0 (8.0-25.0) days. In the 25 cases, on admission, 21 cases (84%) had normal white blood cell counts, while only 2 cases (8%) more than 10 × 10/L and 2 cases (8%) less than 4 × 10/L, respectively; 22 cases(88%) had normal CD4+ T lymphocyte counts, while in the remaining 3 cases(8%) this increased mildly; 23 cases had normal CD8+ T lymphocyte counts, while in the remaining 2 cases (8%) CD8+ T lymphocyte counts were mildly increased as well. All Lymphocyte counts were normal. There were no statistical differences of lab results between the groups of asymptomatic cases, mild cases and common cases. There were only 13 cases with abnormal CT imaging, most of which were located in the subpleural area of the bottom of the lung. All patients were treated with interferon, 6 cases combined with Ribavirin, and 12 cases combined with lopinavir or ritonavir. The days from onset to RNA turning negative was 15.20 ± 6.54 days. There was no significant difference of RNA turning negative between the groups of interferon, interferon plus ribavirin and interferon plus lopinavir or ritonavir treatment. All the cases recovered and were discharged from hospital. CONCLUSIONS: The morbidity of 2019-nCoV infection in children is lower than in adults and the clinical manifestations and inflammatory biomarkers in children are nonspecific and milder than that in adults. RNA-PCR test is still the most reliable diagnostic method, especially for asymptomatic patients.

positive: The possible immunological pathways for the variable immunopathogenesis of COVID—19 infections among healthy adults, elderly and children Novel Coronavirus, COVID-19 discovered in December, 2019 in Wuhan, China started a world-wide epidemic. It is not clear till now what is the pathogenesis of this virus infection in human or the exact strategies of host immune response in combating this novel threat to human beings. However, morbidity and mortality of COVID-19 infections vary widely from asymptomatic, mild to deadly critical. Strangely, children were found to be protected from severe or deadly critical infections, while elderly and immunocompromised adults are most affected badly by this virus. It is necessary to disclose the possible viral and host interactions that lead to such variable morbid effects among patients of COVID-19 infections.

positive: What do differences in case fatality ratios between children and adults tell us about COVID-19?

positive: Epidemiologic and clinical characteristics of 10 children with coronavirus disease 2019 in Changsha, China Abstract Background The outbreak of a new coronavirus, first reported in Wuhan, China, is spreading around the world. Information on the characteristics of children with Coronavirus Disease 2019 (COVID-19) is limited. Methods In this retrospective study, we recruited 10 children infected with SARS-COV-2 from January 27 to March 10, 2020, in Changsha, China. We report the epidemiological, clinical, laboratory, and high-resolution CT findings for these children. Qualitative descriptive analysis was used to describe the key results. Results Ten children were included. Three were male and seven were female. Three were from Wuhan, Hubei Province, and seven were from Changsha. All had a history of close contact with adults with COVID-19 before the onset of disease. Clinical manifestations included fever in four cases, respiratory symptoms in three cases, febrile convulsions in one case, vomiting in one case, abdominal pain in one case, and asymptomatic infection in two cases. All the children tested positive for nucleic acid in throat swabs at admission. Stool swabs of three cases were positive for nucleic acid after several days of fever. In nine children, blood routine results were normal, whereas in one case the white blood cell count was elevated. In four cases, CT findings of the lungs showed light ground-glass opacities, one case showed changes similar to bronchopneumonia, and the remaining cases were normal. All were treated with symptomatic support without complications. Conclusion Our findings indicate that intrafamily transmission may be the main form of transmission of COVID-19 in children, and persistent intestinal excretion of virus is another characteristic among children. The results of stool swab tests should be considered for discharge and release from isolation.

positive: Clinical Characteristics of Children with Coronavirus Disease 2019 in Hubei, China Since December 2019, COVID-19 has occurred unexpectedly and emerged as a health problem worldwide. Despite the rapidly increasing number of cases in subsequent weeks, the clinical characteristics of pediatric cases are rarely described. A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province. A total of 25 confirmed pediatric cases of COVID-19 were collected. The demographic data, epidemiological history, underlying diseases, clinical manifestations, laboratory and radiological data, treatments, and outcomes were analyzed. Of 25 hospitalized patients with COVID-19, the boy to girl ratio was 1.27:1. The median age was 3 years. COVID-19 cases in children aged <3 years, 3.6 years, and ≥6-years patients were 10 (40%), 6 (24%), and 9 (36%), respectively. The most common symptoms at onset of illness were fever (13 [52%]), and dry cough (11 [44%]). Chest CT images showed essential normal in 8 cases (33.3%), unilateral involvement of lungs in 5 cases (20.8%), and bilateral involvement in 11 cases (45.8%). Clinical diagnoses included upper respiratory tract infection (n=8), mild pneumonia (n=15), and critical cases (n=2). Two critical cases (8%) were given invasive mechanical ventilation, corticosteroids, and immunoglobulin. The symptoms in 24 (96%) of 25 patients were alleviated and one patient had been discharged. It was concluded that children were susceptible to COVID-19 like adults, while the clinical presentations and outcomes were more favorable in children. However, children less than 3 years old accounted for majority cases and critical cases lied in this age group, which demanded extra attentions during home caring and hospitalization treatment.

positive: Coronavirus disease 2019 in children: Current status Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged from China in December 2019. The outbreak further exploded in Europe and America in mid-March 2020 to become a global health emergency. We reviewed recent published articles and on-line open messages on SARS-CoV-2–positive infants and children younger than 20 years of age. Symptoms are usually less severe in children than in adults. Twelve critically or mortally ill children were found in the published or news reports before April 6, 2020. Vertical transmission from the mother to her fetus or neonate has not been proven definitively. However, six early-onset (<7 days) and 3 late-onset neonatal SARS-CoV-2 infections were found in the literature. We also summarized the presentations and contact information of 24 SARS-CoV-2–positive children announced by the Taiwan Centers for Disease Control. Early identification and isolation, adequate management, prevention, and vaccine development are the keys to controlling the disease spread. Clinical physicians should be alert to asymptomatic children with COVID-19. Multidirectional investigations are crucial in the global fight against COVID-19.

positive: INCIDENCE OF ARRHYTHMIAS AND ELECTROCARDIOGRAPHIC ABNORMALITIES IN SYMPTOMATIC PEDIATRIC PATIENTS WITH PCR POSITIVE SARS-CoV-2 INFECTION INCLUDING DRUG INDUCED CHANGES IN THE CORRECTED QT INTERVAL (QTc). BACKGROUND: There is limited data regarding the electrophysiological abnormalities and arrhythmias in children with COVID-19, including those associated with treatment using potentially pro-arrhythmic Hydroxychloroquine (HCQ) and Azithromycin (AZN). OBJECTIVES: To describe the electrophysiologic findings and arrhythmias associated with pediatric COVID-19 and its treatment. METHODS: A single center retrospective chart review was undertaken and included all patients with 1) symptoms of COVID-19, and 2) PCR (+) nasopharyngeal swabs for SARS-CoV-2 who were placed on continuous telemetry for the duration of their hospitalization during March through May, 2020. RESULTS: Thirty-six patients were included in the study. Significant arrhythmias were found in 6 (non-sustained (ns) ventricular tachycardia in 5 and sustained atrial tachycardia in 1). All were self-resolving and half prompted prophylactic anti-arrhythmic therapy. Patients with significant arrhythmias were likely to have non-cardiac co-morbidities (4/6), but these were not more common than in patients without arrhythmias (20/30, p=1). The use of HCQ with or without AZN was associated with statistically significant QTc prolongation (411+19 msec vs 426+15 msec, p<0.0001). QTc was not statistically different in patients with and without arrhythmias (425+15 msec vs 425+15 msec, p=1). CONCLUSIONS: In pediatric patients with PCR positive active COVID-19 infection, significant arrhythmias are infrequent, but more common than expected in a general pediatric population. Comorbidities are not more common in patients with arrhythmias than in patients without arrhythmias. COVID-19 treatment using HCQ is associated with QTc prolongation, but was not associated with arrhythmias in pediatric patients.

positive: Guillain-Barre Syndrome Associated with SARS-CoV-2 Detection and a COVID-19 Infection in a Child. Coronavirus disease (COVID-19) is caused by SARS-CoV-2. Physicians in China reported what is believed to be the first adult case of a SARS-CoV-2 infection associated with acute Guillain-Barré syndrome (GBS), followed by five adult Italian patients and another case in the United States of America. In the current report we present one of the first descriptions of an association of GBS and SARS-CoV-2 infection within a child. In our facility, and eleven year old boy presented with typical features of GBS and after five days a morbilliform skin rash over the palms of both hands. Three weeks before the start of the neurological symptoms, the boy had experienced an episode of mild febrile illness with mild respiratory manifestations and a persisting cough. The diagnosis of the SARS-CoV-2 infection was confirmed by oropharyngeal swab on reverse transcription polymerase chain reaction assay. The disease course of our patient strongly suggests a possible relationship between the development of GBS and SARS-CoV-2 infection. The case is discussed in view of the previous case reports with the association of GBS and Covid-19.

positive: COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study BACKGROUND: To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. METHODS: This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network-the Paediatric Tuberculosis Network European Trials Group (ptbnet)-that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. FINDINGS: 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5-12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2-11, range 1-34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5·06, 95% CI 1·72-14·87; p=0·0035), male sex (2·12, 1·06-4·21; p=0·033), pre-existing medical conditions (3·27, 1·67-6·42; p=0·0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10·46, 5·16-21·23; p<0·0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 [7%] patients), followed by remdesivir (17 [3%] patients), lopinavir-ritonavir (six [1%] patients), and oseltamivir (three [1%] patients). Immunomodulatory medication used included corticosteroids (22 [4%] patients), intravenous immunoglobulin (seven [1%] patients), tocilizumab (four [1%] patients), anakinra (three [1%] patients), and siltuximab (one [<1%] patient). Four children died (case-fatality rate 0·69%, 95% CI 0·20-1·82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support. INTERPRETATION: COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed. FUNDING: ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit.

positive: A mild type of childhood Covid-19 - A case report This case is about a 9-year-old child diagnosed with COVID-19, with a history of epidemiology; SARS-CoV-2 nucleic acids testing was positive, while chest CT examination was negative. The clinical classification was light. Nonetheless, isolation measures should still be taken to avoid infecting others.

positive: [Clinical features of coronavirus disease 2019 in children aged <18 years in Jiangxi, China: an analysis of 23 cases]. OBJECTIVE To study the clinical features of coronavirus disease 2019 (COVID-19) in children aged <18 years. METHODS A retrospective analysis was performed from the medical data of 23 children, aged from 3 months to 17 years and 8 months, who were diagnosed with COVID-19 in Jiangxi, China from January 21 to February 29, 2020. RESULTS Of the 23 children with COVID-19, 17 had family aggregation. Three children (13%) had asymptomatic infection, 6 (26%) had mild type, and 14 (61%) had common type. Among these 23 children, 16 (70%) had fever, 11 (48%) had cough, 8 (35%) had fever and cough, and 8 (35%) had wet rales in the lungs. The period from disease onset or the first nucleic acid-positive detection of SARS-CoV-2 to the virus nucleic acid negative conversion was 6-24 days (median 12 days). Of the 23 children, 3 had a reduction in total leukocyte count, 2 had a reduction in lymphocytes, 2 had an increase in C-reactive protein, and 2 had an increase in D-dimer. Abnormal pulmonary CT findings were observed in 12 children, among whom 9 had patchy ground-glass opacities in both lungs. All 23 children received antiviral therapy and were recovered. CONCLUSIONS COVID-19 in children aged <18 years often occurs with family aggregation, with no specific clinical manifestation and laboratory examination results. Most of these children have mild symptoms and a good prognosis. Epidemiological history is of particular importance in the diagnosis of COVID-19 in children aged <18 years.

positive: A Comparison Between Chinese Children Infected with COVID-19 and with SARS OBJECTIVES: To compare the clinical and laboratory features of severe acute respiratory syndrome 2003 (SARS) and coronavirus disease 2019 (COVID-19) in two Chinese pediatric cohorts, given that the causative pathogens and are biologically similar., STUDY DESIGN: This is a cross-sectional study reviewing paediatric patients with SARS (n = 43) and COVID-19 (n=244) who were admitted to the Princess Margaret Hospital in Hong Kong and Wuhan Children’s Hospital in Wuhan, respectively. Demographics, hospital length of stay, clinical and laboratory features were compared RESULTS: Overall, 97.7% of patients with SARS and 85.2% of patients with COVID-19 had epidemiological associations with known cases. Significantly more patients with SARS developed fever, chills, myalgia, malaise, coryza, sore throat, sputum production, nausea, headache, and dizziness than patients COVID-19. No SARS patients were asymptomatic at the time of admission. 29.1% and 20.9% COVID-19 patients were asymptomatic on admission and throughout their hospital stay, respectively. More SARS patients required oxygen supplementation than COVID-19 patients (18.6 vs. 4.7%, P = 004). Only 1.6% COVID-19 and 2.3% SARS patients required mechanical ventilation. Leukopenia (37.2% vs. 18.6%, p=0.008), lymphopenia (95.4% versus 32.6%, p<0.01), and thrombocytopenia (41.9% vs 3.8%, p<0.001) were significantly more common in SARS than COVID-19 patients. The duration between positive and negative nasopharyngeal aspirate and the length in hospital stay were similar in COVID-19 patients regardless of whether they were asymptomatic or symptomatic, suggesting a similar duration of viral shedding. CONCLUSIONS: Children with COVID-19 were less symptomatic and had more favorable hematological findings than children with SARS.

positive: Cell-intrinsic differences between human airway epithelial cells from children and adults The airway epithelium is a key protective barrier whose integrity is preserved by the self-renewal and differentiation of basal progenitor cells. Epithelial cells are central to the pathogenesis of multiple lung diseases. In chronic diseases, increasing age is a principle risk factor. In acute diseases, such as COVID-19, children suffer less severe symptoms than adults and have a lower rate of mortality. Few studies have explored differences between airway epithelial cells in children and adults to explain this age dependent variation in diseases. Here, we perform bulk RNA sequencing studies in laser-capture microdissected whole epithelium, FACS-sorted basal cells and cultured basal cells, as well as in vitro cell proliferation experiments, to address the intrinsic molecular differences between paediatric and adult airway basal cells. We find that, while the cellular composition of the paediatric and adult tracheobronchial epithelium is broadly similar, in cell culture, paediatric airway epithelial cells displayed higher colony forming ability, better in vitro growth and outcompeted adult cells in competitive proliferation assays. In RNA sequencing experiments, we observed potentially important differences in airway epithelial gene expression between samples from children and adults. However, genes known to be associated with SARS-CoV-2 infection were not differentially expressed between children and adults. Our results chart cell-intrinsic differences in transcriptional profile and regenerative capacity between proximal airway epithelial cells of children and adults.

positive: Clinical and Transmission Dynamics Characteristics of 406 Children with Coronavirus Disease 2019 in China: A Review Abstract Objective Chinese pediatricians are working on the front line to fight COVID-19. They have published a great amount of first-hand clinical data. Collecting their data and forming a large sample for analysis is more conducive to the recognition, prevention and treatment of coronavirus disease 2019 in children. The epidemic prevention and control experience of Chinese pediatricians should be shared with the world. Methods By searching Chinese and English literature, the data of 406 children with COVID-19 in China were analyzed. Results It was found that the clustered incidence of children's families is a dynamic transmission feature; the incidence is low; asymptomatic infections and mild cases account for 44.8%, with only 7 cases of critical illness; laboratory examination of lymphocyte counts is not reduced, as it is for adults; chest CT findings are less severe than those for adults. These presentations are the clinical features of COVID-19 in children. Only 55 of the 406 cases were tested by anal swab for virus nucleic acid, 45 of which were positive, accounting for 81.8% of stool samples. Conclusion There are more children than adults with asymptomatic infections, milder conditions, faster recovery, and a better prognosis. Some concealed morbidity characteristics also bring difficulties to the early identification, prevention and control of COVID-19. COVID-19 screening is needed in the pediatric fever clinic, and respiratory and digestive tract nucleic acid tests should be performed. Efforts should be made to prevent children from becoming a hidden source of transmission in kindergartens, schools or families. Furthermore, China's experience in treating COVID-19 in children has led to faster recovery of sick children.

positive: Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths Abstract Since the emergence of coronavirus disease 2019 (COVID-19) (formerly known as the 2019 novel coronavirus [2019-nCoV]) in Wuhan, China in December 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more than 75,000 cases have been reported in 32 countries/regions, resulting in more than 2000 deaths worldwide. Despite the fact that most COVID-19 cases and mortalities were reported in China, the WHO has declared this outbreak as the sixth public health emergency of international concern. The COVID-19 can present as an asymptomatic carrier state, acute respiratory disease, and pneumonia. Adults represent the population with the highest infection rate; however, neonates, children, and elderly patients can also be infected by SARS-CoV-2. In addition, nosocomial infection of hospitalized patients and healthcare workers, and viral transmission from asymptomatic carriers are possible. The most common finding on chest imaging among patients with pneumonia was ground-glass opacity with bilateral involvement. Severe cases are more likely to be older patients with underlying comorbidities compared to mild cases. Indeed, age and disease severity may be correlated with the outcomes of COVID-19. To date, effective treatment is lacking; however, clinical trials investigating the efficacy of several agents, including remdesivir and chloroquine, are underway in China. Currently, effective infection control intervention is the only way to prevent the spread of SARS-CoV-2.

positive: Drugs being investigated for children with COVID‐19 We were interested to read the review paper on COVID‐19 by Ludvigsson in Acta Paediatrica (1). The author mentioned that COVID‐19 appeared to be milder in children than in adults but said there was a knowledge gap about antiviral treatment in severely ill patients. We would like to provide some comments about the experimental drugs that are being considered to treat children with the disease.

positive: Consensus statement of the Italian society of pediatric allergy and immunology for the pragmatic management of children and adolescents with allergic or immunological diseases during the COVID-19 pandemic The COVID-19 pandemic has surprised the entire population. The world has had to face an unprecedented pandemic. Only, Spanish flu had similar disastrous consequences. As a result, drastic measures (lockdown) have been adopted worldwide. Healthcare service has been overwhelmed by the extraordinary influx of patients, often requiring high intensity of care. Mortality has been associated with severe comorbidities, including chronic diseases. Patients with frailty were, therefore, the victim of the SARS-COV-2 infection. Allergy and asthma are the most prevalent chronic disorders in children and adolescents, so they need careful attention and, if necessary, an adaptation of their regular treatment plans. Fortunately, at present, young people are less suffering from COVID-19, both as incidence and severity. However, any age, including infancy, could be affected by the pandemic. Based on this background, the Italian Society of Pediatric Allergy and Immunology has felt it necessary to provide a Consensus Statement. This expert panel consensus document offers a rationale to help guide decision-making in the management of children and adolescents with allergic or immunologic diseases.

positive: Gastrointestinal involvement in COVID-19: a systematic review and meta-analysis BACKGROUND: Patients with COVID-19 usually manifest fever and respiratory symptoms. However, some patients also experience gastrointestinal (GI) symptoms such as diarrhea, vomiting and abdominal pain. In addition, SARS-CoV-2 RNA has been detected in feces of infected patients. Currently there is huge evolving research interest in this potentially lethal disease. We systematically reviewed and meta-analyzed the evidence suggesting involvement of the digestive system in COVID-19. METHODS: PubMed, Medline and Embase databases were searched up to 10 April 2020, using suitable keywords. Individual and pooled prevalence rates with 95% confidence intervals (CI) were calculated using the fixed- or random-effects model as appropriate. Heterogeneity between studies was calculated employing the Cochran Q test and I(2) values, whereas the possibility of publication bias was examined by constructing funnel plots. Additionally, subgroup and sensitivity analyses were performed. RESULTS: In adult COVID-19 patients, the prevalence rates (95%CI) for all GI symptoms, and separately for diarrhea, nausea/vomiting, and abdominal discomfort/pain were 9.8% (6.4-14.7), 10.4% (95%CI 7.7-13.9), 7.7% (95%CI 4.8-12.1), and 6.9% (95%CI 3.9-11.9) respectively. The prevalence rates for children were 9.6% (95%CI 6.3-14.3) for all symptoms, 9.6% (95%CI 6.3-14.3) for diarrhea, and 6.8% (95% CI 4.2-11) for nausea/vomiting. In 30.3% (95%CI 10.5-61.6) of the patients SARS-CoV-2 RNA was detected in feces. CONCLUSIONS: A percentage of patients with COVID-19 will manifest symptoms from the digestive system. The GI tract may be a target organ and potential transmission route of SARS-CoV-2, with important implications for disease management and transmission.

positive: COVID-19 in solid organ transplantation patients: A systematic review Coronavirus disease (COVID-19) rapidly progresses to severe acute respiratory syndrome. This review aimed at collating available data on COVID-19 infection in solid organ transplantation (SOT) patients. We performed a systematic review of SOT patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The MEDLINE and PubMed databases were electronically searched and updated until April 20, 2020. The MeSH terms used were “COVID-19” AND “Transplant.” Thirty-nine COVID-19 cases were reported among SOT patients. The median interval for developing SARS-CoV-2 infection was 4 years since transplantation, and the fatality rate was 25.64% (10/39). Sixteen cases were described in liver transplant (LT) patients, and the median interval since transplantation was 5 years. The fatality rate among LT patients was 37.5% (6/16), with death occurring more than 3 years after LT. The youngest patient who died was 59 years old; there were no deaths among children. Twenty-three cases were described in kidney transplant (KT) patients. The median interval since transplantation was 4 years, and the fatality rate was 17.4% (4/23). The youngest patient who died was 71 years old. Among all transplant patients, COVID-19 had the highest fatality rate in patients older than 60 years : LT, 62.5% vs 12.5% (p=0.006); KT 44.44% vs 0 (p=0.039); and SOT, 52.94% vs 4.54% (p=0.001). This study presents a novel description of COVID-19 in abdominal SOT recipients. Furthermore, we alert medical professionals to the higher fatality risk in patients older than 60 years. (PROSPERO, registration number=CRD42020181299)

positive: A child with household transmitted COVID-19 BACKGROUND: Although people of all ages are susceptible to the novel coronavirus infection, which is presently named "Coronavirus Disease 2019" (COVID-19), there has been relatively few cases reported among children. Therefore, it is necessary to understand the clinical characteristics of COVID-19 in children and the differences from adults. CASE PRESENTATION: We report one pediatric case of COVID-19. A 14-month-old boy was admitted to the hospital with a symptom of fever, and was diagnosed with a mild form of COVID-19. The child's mother and grandmother also tested positive for SARS-CoV-2 RNA. However, the lymphocyte counts were normal. The chest computed tomography (CT) revealed scattered ground glass opacities in the right lower lobe close to the pleura and resorption after the treatment. The patient continued to test positive for SARS-CoV-2 RNA in the nasopharyngeal swabs and stool at 17 days after the disappearance of symptoms. CONCLUSION: The present pediatric case of COVID-19 was acquired through household transmission, and the symptoms were mild. Lymphocyte counts did not significantly decrease. The RNA of SARS-CoV-2 in stool and nasopharyngeal swabs remained positive for an extended period of time after the disappearance of symptoms. This suggests that attention should be given to the potential contagiousness of pediatric COVID-19 cases after clinical recovery.

positive: Impact of COVID-19 on Pediatric Asthma: Practice Adjustments and Disease Burden BACKGROUND: It is unclear whether asthma may affect susceptibility or severity of coronavirus disease 2019 (COVID-19) in children and how pediatric asthma services worldwide have responded to the pandemic. OBJECTIVE: To describe the impact of the COVID-19 pandemic on pediatric asthma services and on disease burden in their patients. METHODS: An online survey was sent to members of the Pediatric Asthma in Real Life think tank and the World Allergy Organization Pediatric Asthma Committee. It included questions on service provision, disease burden, and the clinical course of confirmed cases of COVID-19 infection among children with asthma. RESULTS: Ninety-one respondents, caring for an estimated population of more than 133,000 children with asthma, completed the survey. COVID-19 significantly impacted pediatric asthma services: 39% ceased physical appointments, 47% stopped accepting new patients, and 75% limited patients' visits. Consultations were almost halved to a median of 20 (interquartile range, 10-25) patients per week. Virtual clinics and helplines were launched in most centers. Better than expected disease control was reported in 20% (10%-40%) of patients, whereas control was negatively affected in only 10% (7.5%-12.5%). Adherence also appeared to increase. Only 15 confirmed cases of COVID-19 were reported among the population; the estimated incidence is not apparently different from the reports of general pediatric cohorts. CONCLUSIONS: Children with asthma do not appear to be disproportionately affected by COVID-19. Outcomes may even have improved, possibly through increased adherence and/or reduced exposures. Clinical services have rapidly responded to the pandemic by limiting and replacing physical appointments with virtual encounters.

positive: Breastfeeding and coronavirus disease‐2019: Ad interim indications of the Italian Society of Neonatology endorsed by the Union of European Neonatal & Perinatal Societies The recent COVID‐19 pandemic has spread to Italy with heavy consequences on public health and economics. Besides the possible consequences of COVID‐19 infection on a pregnant woman and the fetus, a major concern is related to the potential effect on neonatal outcome, the appropriate management of the mother–newborn dyad, and finally the compatibility of maternal COVID‐19 infection with breastfeeding. The Italian Society on Neonatology (SIN) after reviewing the limited scientific knowledge on the compatibility of breastfeeding in the COVID‐19 mother and the available statements from Health Care Organizations has issued the following indications that have been endorsed by the Union of European Neonatal & Perinatal Societies (UENPS). If a mother previously identified as COVID‐19 positive or under investigation for COVID‐19 is asymptomatic or paucisymptomatic at delivery, rooming‐in is feasible, and direct breastfeeding is advisable, under strict measures of infection control. On the contrary, when a mother with COVID‐19 is too sick to care for the newborn, the neonate will be managed separately and fed fresh expressed breast milk, with no need to pasteurize it, as human milk is not believed to be a vehicle of COVID‐19. We recognize that this guidance might be subject to change in the future when further knowledge will be acquired about the COVID‐19 pandemic, the perinatal transmission of SARS‐CoV‐2, and clinical characteristics of cases of neonatal COVID‐19.

positive: Laboratory Findings of COVID-19 Infection are Conflicting in Different Age Groups and Pregnant Women: A Literature Review Abstract Coronavirus disease 2019 (COVID-19), a new type and rapidly spread viral pneumonia, is now producing an outbreak of pandemic proportions. The clinical features and laboratory results of different age groups are different due to the general susceptibility of the disease. The laboratory findings of COVID-19 in pregnant women are also conflicting. Para-clinical investigations including laboratory tests and radiologic findings play an important role in early diagnosis and treatment monitoring of COVID-19. The majority of previous reports on the COVID-19 laboratory results were based on data from the general population and limited information is available based on age difference and pregnancy status. This review aimed to describe the COVID-19 laboratory findings in neonates, children, adults, elderly and pregnant women altogether for the first time. The most attracting and reliable markers of COVID-19 in patients were: normal C-reactive protein (CRP) and very different and conflicting laboratory results regardless of clinical symptoms in neonates, normal or temporary elevated CRP, conflicting WBC count results and procalcitonin elevation in children, lymphopenia and elevated lactate dehydrogenase (LDH) in adult patients, lymphopenia and elevated CRP and LDH in the elderly people and high CRP, leukocytosis and elevated neutrophil ratio in pregnant women.

positive: No evidence of SARS‐Cov‐2 infection by PCR or serology in children with pseudochilblain Despite its aggressive clinical course, leading to 6.4% fatality rate as of May 25, 2020 (https://qap.ecdc.europa.eu/public/extensions/COVID-19/COVID-19.html), COVID‐19 turned out to be only marginally aggressive in children. In a report from Lombardy, 18/88 COVID‐19 hospitalized adults (20%) had developed cutaneous manifestations: erythematous rash, widespread urticarial, and chickenpox‐like vesicles. Trunk was the main involved region. Itching was low or absent and usually lesions healed in few days. An unexpected outbreak of acute pseudochilblain skin lesions is being reported from different countries and related to COVID‐19.

positive: Storm, typhoon, cyclone or hurricane in patients with COVID-19? Beware of the same storm that has a different origin Some of the articles being published during the severe acute respiratory syndrome–coronavirus (SARS-CoV)-2 pandemic highlight a link between severe forms of coronavirus disease 2019 (COVID-19) and the so-called cytokine storm, also with increased ferritin levels. However, this scenario is more complex than initially thought due to the heterogeneity of hyperinflammation. Some patients with coronavirus 2019 disease (COVID-19) develop a fully blown secondary haemophagocytic lymphohistiocytosis (sHLH), whereas others, despite a consistent release of pro-inflammatory cytokines, do not fulfil sHLH criteria but still show some features resembling the phenotype of the hyperferritinemic syndrome. Despite the final event (the cytokine storm) is shared by various conditions leading to sHLH, the aetiology, either infectious, autoimmune or neoplastic, accounts for the differences in the various phases of this process. Moreover, the evidence of a hyperinflammatory microenvironment provided the rationale to employ immunomodulating agents for therapeutic purposes in severe COVID-19. This viewpoint aims at discussing the pitfalls and issues to be considered with regard to the use of immunomodulating agents in COVID-19, such as timing of treatment based on the viral load and the extent of cytokine/ferritin overexpression. Furthermore, it encompasses recent findings in the paediatric field about a novel multisystem inflammatory disease resembling toxic shock syndrome and atypical Kawasaki disease observed in children with proven SARS-CoV2 infection. Finally, it includes arguments in favour of adding COVID-19 to the spectrum of the recently defined ‘hyperferritinemic syndrome’, which already includes adult-onset Still’s disease, macrophage activation syndrome, septic shock and catastrophic anti-phospholipid syndrome.

positive: Dealing with COVID-19 in a Pediatric Rheumatology Unit in Italy

positive: Determinants of Severity in Cancer Patients with COVID-19 Illness New York State had 180,458 cases of SARS-CoV-2 and 9385 reported deaths as of April 10th, 2020. Patients with cancer comprised 8.4% of deceased individuals1. Population-based studies from China and Italy suggested a higher COVID-19 death rate in patients with cancer2,3, although there is a knowledge gap as to which aspects of cancer and its treatment confer risk of severe COVID-19 disease4. This information is critical to balance the competing safety considerations of reducing SARS-CoV-2 exposure and cancer treatment continuation. Since March 10th, 2020 Memorial Sloan Kettering Cancer Center performed diagnostic testing for SARS-CoV-2 in symptomatic patients. Overall, 40% out of 423 patients with cancer were hospitalized for COVID-19 illness, 20% developed severe respiratory illness, including 9% that required mechanical ventilation, and 9% that died. On multivariate analysis, age [≥] 65 years and treatment with immune checkpoint inhibitors (ICI) within 90 days were predictors for hospitalization and severe disease, while receipt of chemotherapy within 30 days and major surgery were not. Overall, COVID-19 illness is associated with higher rates of hospitalization and severe outcomes in patients with cancer. Association between ICI and COVID-19 outcomes will need interrogation in tumor-specific cohorts.

positive: Clinical Manifestations of Children with COVID-19: a Systematic Review Context: The coronavirus disease 2019 (COVID-19) outbreak is an unprecedented global public health challenge, leading to thousands of deaths every day worldwide. Despite the epidemiological importance, clinical patterns of children with COVID-19 remain unclear. Objective: To describe the clinical, laboratorial and radiological characteristics of children with COVID-19. Data Sources: The Medline database was searched between December 1st 2019 and March 30th 2020. Study Selection: Inclusion criteria were: (1) studied patients younger than 18 years old; (2) presented original data from cases of COVID-19 confirmed by reverse-transcription polymerase chain reaction; and (3) contained descriptions of clinical manifestations, laboratory tests or radiological examinations. Data Extraction: Number of cases, gender, age, clinical manifestations, laboratory tests, radiological examinations and outcomes. Results: A total of 34 studies (1,118 cases) were included. From all the cases, 1,111 had their severity classified: 14.3% were asymptomatic, 36.4% were mild, 46.0% were moderate, 2.2% were severe and 1.2% were critical. The most prevalent symptom was fever (16.3%), followed by cough (14.4%), nasal symptoms (3.6%), diarrhea (2.7%) and nausea/vomiting (2.5%). One hundred forty-five (12.9%) children were diagnosed with pneumonia and 43 (3.8%) upper airway infections were reported. Reduced lymphocyte count were reported in 13.1% of cases. Abnormalities on computed tomography was reported in 62.7% of cases. The most prevalent abnormalities reported were ground glass opacities, patchy shadows and consolidations. Only one death was reported. Conclusions: Clinical manifestations of children with COVID-19 differ widely from adults cases. Fever and respiratory symptoms should not be considered a hallmark of COVID-19 in children.

positive: Wider collateral damage to children in the UK because of the social distancing measures designed to reduce the impact of COVID-19 in adults

positive: Novel Coronavirus disease (COVID-19) in newborns and infants: what we know so far Recently, an outbreak of viral pneumonitis in Wuhan, Hubei, China successively spread as a global pandemia, led to the identification of a novel betacoronavirus species, the 2019 novel coronavirus, successively designated 2019-nCoV then SARS-CoV-2). The SARS-CoV-2 causes a clinical syndrome designated coronavirus disease 2019 (COVID19) with a spectrum of manifestations ranging from mild upper respiratory tract infection to severe pneumonitis, acute respiratory distress syndrome (ARDS) and death. Few cases have been observed in children and adolescents who seem to have a more favorable clinical course than other age groups, and even fewer in newborn babies. This review provides an overview of the knowledge on SARS-CoV-2 epidemiology, transmission, the associated clinical presentation and outcomes in newborns and infants up to 6 months of life.

positive: Novel coronavirus infection and children BACKGROUND AND AIM: Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its outbreak in many states of the world, forced the World Health Organization (WHO) to declare a pandemic. Currently, COVID-19 has infected 1 991 562 patients causing 130 885 deaths globally as of 16 April 2020. The aim of this review is to underline the epidemiological, clinical and management characteristics in children affected by COVID-19. METHODS: We searched Pubmed, from January to April 2020, for the following search terms: "COVID-19", "children", "SARS-COV2", "complications", "epidemiology", "clinical features", focusing our attention mostly on epidemiology and symptoms of COVID-19 in children. RESULTS: Usually, infants and children present milder symptoms of the disease with a better outcome than adults. Consequently, children may be considered an infection reservoir that may play a role as spreader of the infection in community.

positive: Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic Background: Cardiac injury and myocarditis have been described in adults with COVID-19. SARS-CoV-2 infection in children is typically minimally symptomatic. We report a series of febrile pediatric patients with acute heart failure potentially associated with SARS-CoV-2 infection and the multisystem inflammatory syndrome in children (MIS-C) as defined by the US Centers for Disease Control. Methods: Over a two-month period contemporary with the SARS-CoV-2 pandemic in France and Switzerland, we retrospectively collected clinical, biological, therapeutic, and early outcomes data in children who were admitted to pediatric intensive care units in 14 centers for cardiogenic shock, left ventricular dysfunction and severe inflammatory state. Results: Thirty-five children were identified and included in the study. Median age at admission was 10 years (range 2-16 years). Co-morbidities were present in 28% including asthma and overweight. Gastrointestinal symptoms were prominent. Left ventricular ejection fraction was <30% in one third; 80% required inotropic support with 28% treated with ECMO. Inflammation markers were suggestive of cytokine storm (interleukin 6 median 135 pg/mL) and macrophage activation (D-dimer median 5284 ng/mL). Mean brain natriuretic peptide was elevated (5743 pg/mL). Thirty-one/35 (88%) patients tested positive for SARS-CoV-2 infection by PCR of nasopharyngeal swab or serology. All patients received intravenous immune globulin, with adjunctive steroid therapy used in one third. Left ventricular function was restored in the 25/35 of those discharged from the intensive care unit. No patient died, and all patients treated with ECMO were successfully weaned. Conclusion: Children may experience an acute cardiac decompensation due to severe inflammatory state following SARS-CoV-2 infection (multisystem inflammatory syndrome in children - MIS-C). Treatment with immune globulin appears to be associated with recovery of left ventricular systolic function.

positive: COVID-19 Disease in Children: What Dentists Should Know and Do to Prevent Viral Spread. The Italian Point of View Coronavirus disease 2019 (COVID-19) has spread rapidly across the globe, becoming a major public health challenge not for China only, but also for countries around the world. Despite worldwide efforts to contain viral spread, the outbreak has not been stopped yet. Among healthcare personnel, dentists seem to be at elevated risk of exposure to COVID-19. This risk is even more serious in pediatric dentistry, since affected children, frequently, present an asymptomatic, mild or moderate clinical viral infection and, therefore, they may play a major role in community-based COVID-19 transmission. To date, despite no universal guidelines are available for dental procedures in pediatric dentistry during COVID-19 outbreak, routine dental practice should be postponed and only severe dental emergencies must be treated. In the case of a dental emergency, involving a pediatric patient, dentists should be aware of which recommended management protocol can be adopted during the practice to protect patient health, to safeguard their-self and to prevent viral transmission. The aim of this paper is to provide clinical recommendations, presenting a needed tool for dentists to allow a valid and safe how-to-do protocol. Pediatric dentists should keep a high level of awareness to help patients, minimize risk and prevent viral spread.

positive: Clinical characteristics and outcome of SARS-CoV-2 infection in Italian pediatric oncology patients: a study from the Infectious Diseases Working Group of the AIEOP. BACKGROUND Little is known as yet about the outcome of SARS-CoV-2 infection in children being treated for cancer. METHODS We collected information on the clinical characteristics and outcomes of a cohort of 29 children (16 females and 13 males, median age 7 years, range [0-16]) diagnosed with SARS-CoV-2 infection while on chemotherapy/immunotherapy (N=26), or after stem cell transplantation (N=3) during the peak of the epidemic in Italy. These patients suffered from leukemia (N=16), lymphoma (N=3), solid tumors (N=10), and Langerhans cell histiocytosis (N=1). RESULTS The course of the disease was mild in all cases, with only 12 children developing symptoms (pneumonia in 3 cases), and none needing intensive care. Fifteen patients were hospitalized, including 7 asymptomatic patients. Nine patients (including 5 with no symptoms) were given hydroxychloroquine, and 3 of them were also given lopinavir/ritonavir. CONCLUSIONS SARS-CoV-2 infection seems to take a milder clinical course in children than in adults with cancer. Specific SARS-CoV-2 treatment seems unnecessary for most children. In the light of our findings, and albeit with the necessary caution, we suggest avoiding major changes to planned anticancer treatments in pediatric patients acquiring COVID-19.

positive: Neonatal Intensive Care Unit Preparedness for the Novel Coronavirus Disease-2019 Pandemic: A New York City Hospital Perspective In January 2020, China reported a cluster of cases of pneumonia associated with a novel pathogenic coronavirus provisionally named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2). Since then, Coronavirus Disease 2019 (COVID-19) has been reported in more than 180 countries with approximately 3 million known infections and more than 210,000 deaths attributed to this disease. The majority of confirmed COVID-19 cases have been reported in adults, especially older individuals with co-morbidities. Children have had a relatively lower rate and a less serious course of infection as reported in the literature to date. One of the most vulnerable pediatric patient populations is cared for in the neonatal intensive care unit. There is limited data on the effect of COVID-19 in fetal life, and among neonates after birth. Therefore there is an urgent need for proactive preparation, and planning to combat COVID-19, as well as to safeguard patients, their families, and healthcare personnel. This review article is based on the Centers for Disease Control and Prevention's (CDC) current recommendations for COVID-19 and its adaptation to our local resources. The aim of this article is to provide basic consolidated guidance and checklists to clinicians in the neonatal intensive care units in key aspects of preparation needed to counter exposure or infection with COVID-19. We anticipate that CDC will continue to update their guidelines regarding COVID-19 as the situation evolves, and we recommend monitoring CDC's updates for the most current information.

positive: Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic. Background: Cardiac injury and myocarditis have been described in adults with COVID-19. SARS-CoV-2 infection in children is typically minimally symptomatic. We report a series of febrile pediatric patients with acute heart failure potentially associated with SARS-CoV-2 infection and the multisystem inflammatory syndrome in children (MIS-C) as defined by the US Centers for Disease Control. Methods: Over a two-month period contemporary with the SARS-CoV-2 pandemic in France and Switzerland, we retrospectively collected clinical, biological, therapeutic, and early outcomes data in children who were admitted to pediatric intensive care units in 14 centers for cardiogenic shock, left ventricular dysfunction and severe inflammatory state. Results: Thirty-five children were identified and included in the study. Median age at admission was 10 years (range 2-16 years). Co-morbidities were present in 28% including asthma and overweight. Gastrointestinal symptoms were prominent. Left ventricular ejection fraction was <30% in one third; 80% required inotropic support with 28% treated with ECMO. Inflammation markers were suggestive of cytokine storm (interleukin 6 median 135 pg/mL) and macrophage activation (D-dimer median 5284 ng/mL). Mean brain natriuretic peptide was elevated (5743 pg/mL). Thirty-one/35 (88%) patients tested positive for SARS-CoV-2 infection by PCR of nasopharyngeal swab or serology. All patients received intravenous immune globulin, with adjunctive steroid therapy used in one third. Left ventricular function was restored in the 25/35 of those discharged from the intensive care unit. No patient died, and all patients treated with ECMO were successfully weaned. Conclusion: Children may experience an acute cardiac decompensation due to severe inflammatory state following SARS-CoV-2 infection (multisystem inflammatory syndrome in children - MIS-C). Treatment with immune globulin appears to be associated with recovery of left ventricular systolic function.

positive: Infection control practices in children during COVID-19 pandemic: differences from adults BACKGROUND: Limited studies have been published on practices and management of COVID-19 in children. Despite the fact that COVID-19 rarely caused any severe disease in children, the asymptomatic children might be playing an important role for spreading COVID-19 in healthcare facilities. This review aimed at sharing our experience of how to handle patients with COVID-19 in a pediatric referral and tertiary care hospital to prevent the possible transmissions to the healthcare workers (HCWs). METHODS: This review sought to identify infection control practices measures during COVID-19 pandemic comes from our daily practice combined with the most recent guidelines with the new experience and information. RESULTS: Prevention the transmission of COVID-19 to the HCWs, four primary themes should be taken into consideration; (1) ongoing education and importance of the organization of the healthcare facility, (2) proper clinical triage and isolation of the suspected or confirmed COVID-19 patients in the outpatient clinics and in the emergency departments, (3) necessity of the organization of the COVID-19 wards, and (4) utilization of personal protective equipment. CONCLUSIONS: Infection control precautions to prevent the possible transmissions to HCWs as well as the other patients and their caregivers from children with COVID-19 are very critical. If sufficient precautions are not taken, healthcare settings may serve as additional source of transmission and spread of COVID-19 in the society.

positive: Coronavirus disease 2019 (COVID-19) in children: a systematic review of imaging findings BACKGROUND: COVID-19 is a novel coronavirus infection that can cause a severe respiratory illness and has been declared a pandemic by the World Health Organization (WHO). Because children appear to be less severely affected than adults, their imaging appearances have not been extensively reported. OBJECTIVE: To systematically review available literature regarding imaging findings in paediatric cases of COVID-19. MATERIALS AND METHODS: We searched four databases (Medline, Embase, Cochrane, Google Scholar) for articles describing imaging findings in children with COVID-19. We included all modalities, age <18 years, and foreign language articles, using descriptive statistics to identify patterns and locations of imaging findings, and their association with outcomes. RESULTS: Twenty-two articles were included, reporting chest imaging findings in 431 children, of whom 421 (97.7%) underwent CT. Criteria for imaging were lacking. At diagnosis, 143/421 (34.0%) had a normal CT. Abnormalities were more common in the lower lobes and were predominantly unilateral. The most common imaging pattern was ground-glass opacification (159/255, 62.4%). None of the studies described lymphadenopathy, while pleural effusions were rare (three cases). Improvement at follow-up CT imaging (3-15 days later) was seen in 29/100 (29%), remained normal in 25/100 (25%) and progressed in 9/100 (9%). CONCLUSION: CT chest findings in children with COVID-19 are frequently normal or mild. Lower lobes are predominantly affected by patchy ground-glass opacification. Appearances at follow-up remain normal or improve in the majority of children. Chest CT imaging adds little to the further management of the patient and should be reserved for severe cases or for identifying alternative diagnoses.

positive: COVID-19 – Considerations for the paediatric rheumatologist Abstract The novel coronavirus SARS-CoV2 is a threat to the health and well-being of millions of lifes across the globe. A significant proportion of adult patients require hospitalisation and may develop severe life-threatening complications. Children, on the other hand, can carry and transmit the virus, but usually do not develop severe disease. Mortality in the paediatric age-group is relatively low. Differences in virus containment and clearance, as well as reduced inflammation-related tissue and organ damage may be caused by age-specific environmental and host factors. Since severe complications in adults are frequently caused by uncontrolled immune responses and a resulting “cytokine storm” that may be controlled by targeted blockade of cytokines, previously established treatment with immunosuppressive treatments may indeed protect children from complications.

positive: Systematic review of COVID‐19 in children shows milder cases and a better prognosis than adults AIM: The coronavirus disease 2019 (COVID‐19) pandemic has affected hundreds of thousands of people. Data on symptoms and prognosis in children are rare. METHODS: A systematic literature review was carried out to identify papers on COVID‐19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), using the MEDLINE and Embase databases between January 1 and March 18, 2020. RESULTS: The search identified 45 relevant scientific papers and letters. The review showed that children have so far accounted for 1%‐5% of diagnosed COVID‐19 cases, they often have milder disease than adults and deaths have been extremely rare. Diagnostic findings have been similar to adults, with fever and respiratory symptoms being prevalent, but fewer children seem to have developed severe pneumonia. Elevated inflammatory markers were less common in children, and lymphocytopenia seemed rare. Newborn infants have developed symptomatic COVID‐19, but evidence of vertical intrauterine transmission was scarce. Suggested treatment included providing oxygen, inhalations, nutritional support and maintaining fluids and electrolyte balances. CONCLUSIONS: The coronavirus disease 2019 has occurred in children, but they seemed to have a milder disease course and better prognosis than adults. Deaths were extremely rare.

positive: Diagnosis of COVID‐19 infection in children: less nasopharyngeal swabs, more saliva We read with great interest the article by Jonas F. Ludvigsson on COVID‐19 infection in Children (1). He conducted a systematic literature review to identify papers on COVID‐19. The conclusion was that COVID‐19 infection can occur in children, but they seemed to have a lower incidence as well as a milder disease course and better prognosis than adults.

positive: The Unexpected Risks of COVID-19 on Asthma Control in Children Abstract Much is being learned about clinical outcomes for adult COVID-19 patients with underlying chronic conditions, however, there is less coverage on how the COVID-19 pandemic impacts the management of chronic medical conditions in children and youth, such as asthma. Asthma is a common chronic medical condition in children that is uniquely susceptible to changes brought upon by COVID-19. Sudden dramatic changes in the environment, medical practice, and medication use have altered the asthma management landscape with potential impacts on asthma outcomes. In this paper, we review how changes in transportation and travel patterns, school attendance, physical activity, and time spent indoors, along with changes in healthcare delivery since the start of the pandemic all play a contributing role in asthma control in children. We review potentially important influences of asthma control in children during the COVID-19 pandemic worthy of further study.

positive: Differences in Clinical and Imaging Presentation of Pediatric Patients with COVID-19 in Comparison with Adults BACKGROUND: Although Coronavirus Disease 2019 (COVID-19) affects patients from all age groups, clinical and radiological features of COVID- 19 have been mainly described in adults. OBJECTIVE: To characterize and compare the initial clinical and imaging features of COVID-19 in pediatric and adult patients undergoing chest computed tomography (CT). MATERIALS AND METHODS: A total of 61 patients, consisting of 47 adults (18 years old or older) and 14 pediatric patients (younger than 18 years old) with laboratory-confirmed COVID-19 by real-time reverse transcriptase polymerase chain reaction (RT-PCR) between January 25, 2020 and February 15, 2020 were enrolled in this study. All patients underwent chest CT within 3 days after the initial RT-PCR. The clinical presentation, serum markers, and CT findings were assessed and compared between the adult and pediatric patients. RESULTS: Fever was less common in pediatric patients than in adults (6/14, 42.9% vs 39/47, 83%; p = 0.008). Leukopenia or normal, lymphopenia or normal, and increased or normal C-reactive protein were common in both groups with no difference (p > 0.05). Compared with the adults, pediatric patients had a lower rate of positive CT findings and a milder clinical grade (p = 0.004, p = 0.001 respectively). On chest CT, the number of pulmonary lobes involved was reduced in pediatric patients when compared to adults (p = 0.012). Subpleural distribution of lung opacities was a dominant feature in both groups, whereas bronchial distribution was more common in the pediatric group (p = 0.048). Among the CT features in adults, ground-glass opacities (GGO) were the most common finding (24/43, 53.5%), followed by GGO with consolidation (14/43, 27.9%). In pediatric patients, GGOs accounted for 42.9% (3/7), bronchial wall thickening occurred in 28.6% (2/7), and GGOs with consolidations and nodular opacities in 14.3% (1/7). However, these CT features did not differ in two groups, except for bronchial wall thickening, which was more commonly found in pediatric patients (p=0.048). Additionally, the semi-quantitative scores of lung involvement were higher in adults than in pediatric patients (8.89 ± 4.54 vs 1.86 ± 2.41, p < 0.001). CONCLUSIONS: Compared to adults, pediatric patients with COVID-19 showed distinctive clinical and CT. Pediatric patients tend to have milder clinical symptoms, fewer positive CTs, and less extensive involvement on imaging. Bronchial wall thickening was relatively more frequent on CT images from pediatric patients with COVID-19 in comparison with adults.

positive: Coronavirus disease 2019 in children: Characteristics, antimicrobial treatment, and outcomes BACKGROUND: At present, coronavirus disease 2019 (COVID-19) has spread in many countries. We conducted this study to help pediatricians understand the conditions of COVID-19 in children. METHODS: We retrospectively summarized the characteristics, treatment and outcomes of pediatric cases in Wuhan Children's Hospital which was the only designated hospital for children with COVID-19 in Hubei Province. A Cox proportional hazards regression analysis was used to evaluate factors associated with clinical outcomes. RESULTS: As of February 29, 75 children had been discharged, of which only one was has severe pneumonia and one was critical cases. Children younger than 2 years were more susceptible to COVID-19. All patients have received interferon-α nebulization, and eight cases including the severe and critical cases were co-administrated ribavirin. Five patients with mild pneumonia were given arbidol. Twenty-three patients were given traditional Chinese medicine (TCM). The average length of stay (LOS) and the time of SARS-CoV-2 clearance were 10.57 and 6.39 days, respectively. None of the factors was associated with LOS or time of SARS-CoV-2 clearance. CONCLUSIONS: The severity of COVID-19 in pediatric cases were milder than adults. The efficacy of the antiviral therapy in children with COVID-19 remains to be evaluated.

positive: Is the effect of COVID‐19 on children underestimated in low‐ and middle‐ income countries? The COVID‐19 pandemic has had a huge impact on health and society, worldwide. While most high income countries are felt to be reaching their COVID‐19 peak, most low‐ and middle‐income countries (LMICs), particularly sub‐Saharan countries, are anticipating an exponential growth of cases.(1) Overall it has been documented that children are less affected.(2) However, in this commentary we describe how in Kenya, a LMIC in sub‐Saharan Africa, COVID‐19 is likely to have far‐reaching direct and indirect implications on children.

positive: Clinical Characteristics and Outcomes of Hospitalized and Critically Ill Children and Adolescents with Coronavirus Disease 2019 (COVID-19) at a Tertiary Care Medical Center in New York City OBJECTIVE: To describe the clinical profiles and risk factors for critical illness in hospitalized children and adolescents with COVID-19. STUDY DESIGN: Children 1 month to 21 years with COVID-19 from a single tertiary care children's hospital between March 15-April 13, 2020 were included. Demographic and clinical data were collected. RESULTS: 67 children tested positive for COVID-19; 21 (31.3%) were managed as outpatients. Of 46 admitted patients, 33 (72%) were admitted to the general pediatric medical unit and 13 (28%) to the pediatric intensive care unit (PICU). Obesity and asthma were highly prevalent but not significantly associated with PICU admission (p=0.99). Admission to the PICU was significantly associated with higher C-reactive protein, procalcitonin, and pro-B type natriuretic peptide levels and platelet counts (p<0.05 for all). Patients in the PICU were more likely to require high-flow nasal cannula (p=0.0001) and were more likely to have received Remdesivir through compassionate release (p<0.05). Severe sepsis and septic shock syndromes were observed in 7 (53.8%) PICU patients. Acute respiratory distress syndrome (ARDS) was observed in 10 (77%) PICU patients, 6 of whom (46.2%) required invasive mechanical ventilation for a median of 9 days. Of the 13 patients in the PICU, 8 (61.5%) were discharged home, and 4 (30.7%) patients remain hospitalized on ventilatory support at day 14. One patient died after withdrawal of life-sustaining therapy because of metastatic cancer. CONCLUSIONS: We describe a higher than previously recognized rate of severe disease requiring PICU admission in pediatric patients admitted to the hospital with COVID-19.

positive: Reduced Physical Activity During COVID-19 Pandemic in Children With Congenital Heart Disease Children with congenital heart disease (CHD) are at risk for both COVID-19 and secondary cardiovascular outcomes. Their increased cardiovascular risk may be mitigated through physical activity, but public health measures implemented for COVID-19 can make physical activity challenging. We objectively measured the impact of the COVID-19 pandemic on physical activity, continuously measured by Fitbit step counts, in children with CHD. Step counts were markedly lower in late March and early April 2020, compared with 2019 and early March 2020. It is vital to understand how precautions for COVID-19 will affect the health of children with CHD, especially if they persist long term.

positive: Neonatal Coronavirus 2019 (COVID-19) Infection: A Case Report and Review of Literature Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global pandemic affecting 213 countries as of April 26, 2020. Although this disease is affecting all age groups, infants and children seem to be at a lower risk of severe infection, for reasons unknown at this time. We report a case of neonatal infection in New York, United States, and provide a review of the published cases. A 22-day-old, previously healthy, full-term neonate was hospitalized after presenting with a one-day history of fever and poor feeding. Routine neonatal sepsis evaluation was negative. SARS-CoV-2 polymerase chain reaction (PCR) testing was obtained, given rampant community transmission, which returned positive. There were no other laboratory or radiographic abnormalities. The infant recovered completely and was discharged home in two days once his feeding improved. The family was advised to self-quarantine to prevent the transmission of COVID-19. We believe that the mode of transmission was horizontal spread from his caregivers. This case highlights the milder presentation of COVID-19 in otherwise healthy, full-term neonates. COVID-19 must be considered in the evaluation of a febrile infant. Infants and children may play an important role in the transmission of COVID-19 in the community. Hence, with an understanding of the transmission patterns, parents and caregivers would be better equipped to limit the spread of the virus and protect the more vulnerable population.

positive: SARS-CoV-2 infection in children - Understanding the immune responses and controlling the pandemic In December 2019, a cluster of patients with severe pneumonia caused by a novel coronavirus (SARS-CoV-2) emerged in the city of Wuhan, China. The disease is now termed coronavirus disease 2019 (COVID-19). In the early reports, the patients were mainly middle-aged and elderly men, and children appeared to be less susceptible to this infection. With modern and efficient transportation, the disease quickly spread to almost all corners of the world and the mortality far exceeds that caused by severe acute respiratory syndrome (SARS) coronavirus or Middle East respiratory syndrome (MERS) coronavirus. As the number of children with COVID-19 gradually increases, the disease has been documented in premature babies, infants, children, and adolescents. Severe and fatal cases in children are relatively rare. The burden of disease in children has been relatively low, but the high proportions of asymptomatic or mildly symptomatic infections in children deserve careful attention. A clear understanding of the immune responses to the virus in children and the transmission potential of asymptomatic children is of paramount importance for the development of specific treatments and vaccine in order to effectively control the ongoing pandemic.

positive: Reduced Physical Activity During COVID-19 Pandemic in Children with Congenital Heart Disease Abstract Children with congenital heart disease (CHD) are at-risk for both COVID-19 and secondary cardiovascular outcomes. Their increased cardiovascular risk may be mitigated through physical activity, but public health measures implemented for COVID-19 can make physical activity challenging. We objectively measured the impact of the COVID-19 pandemic on physical activity, continuously measured by FitbitTM step-counts, in children with CHD. Step-counts were markedly lower in late March and early April 2020, compared to 2019 and to early March 2020. It is vital to understand how precautions for COVID-19 will impact the health of children with CHD, especially if they persist long-term.

positive: [Clinical analysis of 31 cases of 2019 novel coronavirus infection in children from six provinces (autonomous region) of northern China]. Objective: To analyze the epidemiological history, clinical manifestations, treatment and the short-term prognosis of 31 cases of 2019 novel coronavirus(2019-nCoV) infection in children from six provinces (autonomous region) in northern China. Methods: A retrospective analysis of the epidemiological history, clinical symptoms, signs, laboratory examinations, chest imaging, treatment and the short-term prognosis of 31 cases of 2019-nCoV was conducted. The patients were diagnosed between January 25th, 2020 and February 21st, 2020 in 21 hospitals in 17 cities of six provinces(autonomous region) of Shaanxi, Gansu, Ningxia, Hebei, Henan and Shandong. Results: The age of the 31 children with 2019-nCoV infection was 7 years and 1 month (6 months -17 years). Nine cases (29%) were imported cases. Other 21 cases (68%) had contact with confirmed infected adults. One case (3%) had contact with asymptomatic returnees from Wuhan. Among the 31 children, 28 patients (90%) were family cluster cases. The clinical types were asymptomatic type in 4 cases (13%), mild type in 13 cases (42%), and common type in 14 cases (45%). No severe or critical type existed. The most common symptom was fever (n=20, 65%), including 1 case of high fever, 9 cases of moderate fever, 10 cases of low fever. Fever lasted from 1 day to 9 days. The fever of fifteen cases lasted for ≤3 d, while in other 5 cases lasted > 3 d. Other symptoms included cough (n=14, 45%), fatigue (n=3, 10%) and diarrhea (n=3, 9%). Pharyngalgia, runny nose, dizziness, headache and vomiting were rare. In the early stage, the total leukocytes count in peripheral blood decreased in 2 cases (6%), the lymphocytes count decreased in 2 cases (6%), and the platelet count increased in 2 cases (6%).Elevation of C-reactive protein (10%, 3/30), erythrocyte sedimentation rate(19%,4/21), procalcitonin(4%,1/28), liver enzyme(22%, 6/27) and muscle enzyme (15%, 4/27) occurred in different proportions. Renal function and blood glucose were normal. There were abnormal chest CT changes in 14 cases, including 9 cases with patchy ground glass opacities and nodules, mostly located in the lower lobe of both lungs near the pleural area. After receiving supportive treatment, the viral nucleic acid turned negative in 25 cases within 7-23 days. Among them, 24 children (77%) recovered and were discharged from hospital. No death occurred. Conclusions: In this case series, 2019-nCoV infections in children from six provinces (autonomous region) in northern China are mainly caused by close family contact. Clinical types are asymptomatic, mild and common types. Clinical manifestations and laboratory examination results are nonspecific. Close contact history of epidemiology, nucleic acid detection and chest imaging are important bases for diagnosis. After general treatment, the short-term prognosis is good.

positive: SARS-CoV-2 infection in ambulatory and hospitalised Spanish children.

positive: Children are unlikely to be the main drivers of the COVID-19 pandemic - A systematic review AIM: Many countries have closed schools and kindergartens to minimise COVID-19, but the role that children play in disease transmission is unclear. METHODS: A systematic literature review of the MEDLINE and EMBASE databases and medRxiv/bioRxiv preprint servers to 11 May 2020 identified published and unpublished papers on COVID-19 transmission by children. RESULTS: We identified 700 scientific papers and letters and 47 full texts were studied in detail. Children accounted for a small fraction of COVID-19 cases and mostly had social contacts with peers or parents, rather than older people at risk of severe disease. Data on viral loads were scarce, but indicated that children may have lower levels than adults, partly because they often have fewer symptoms, and this should decrease the transmission risk. Household transmission studies showed that children were rarely the index case and case studies suggested that children with COVID-19 seldom caused outbreaks. However, it is highly likely that children can transmit the SARS-COV-2 virus, which causes COVID-19, and even asymptomatic children can have viral loads. CONCLUSION: Children are unlikely to be the main drivers of the pandemic. Opening up schools and kindergartens is unlikely to impact COVID-19 mortality rates in older people.

positive: Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center’s observational study BACKGROUND: An outbreak of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was first detected in Wuhan, Hubei, China. People of all ages are susceptible to SARS-CoV-2 infection. No information on severe pediatric patients with COVID-19 has been reported. We aimed to describe the clinical features of severe pediatric patients with COVID-19. METHODS: We included eight severe or critically ill patients with COVID-19 who were treated at the Intensive Care Unit (ICU), Wuhan Children’s Hospital from January 24 to February 24. We collected information including demographic data, symptoms, imaging data, laboratory findings, treatments and clinical outcomes of the patients with severe COVID-19. RESULTS: The onset age of the eight patients ranged from 2 months to 15 years; six were boys. The most common symptoms were polypnea (8/8), followed by fever (6/8) and cough (6/8). Chest imaging showed multiple patch-like shadows in seven patients and ground-glass opacity in six. Laboratory findings revealed normal or increased whole blood counts (7/8), increased C-reactive protein, procalcitonin and lactate dehydrogenase (6/8), and abnormal liver function (4/8). Other findings included decreased CD16 + CD56 (4/8) and Th/Ts*(1/8), increased CD3 (2/8), CD4 (4/8) and CD8 (1/8), IL-6 (2/8), IL-10 (5/8) and IFN-γ (2/8). Treatment modalities were focused on symptomatic and respiratory support. Two critically ill patients underwent invasive mechanical ventilation. Up to February 24, 2020, three patients remained under treatment in ICU, the other five recovered and were discharged home. CONCLUSIONS: In this series of severe pediatric patients in Wuhan, polypnea was the most common symptom, followed by fever and cough. Common imaging changes included multiple patch-like shadows and ground-glass opacity; and a cytokine storm was found in these patients, which appeared more serious in critically ill patients.

positive: Age-dependent effects in the transmission and control of COVID-19 epidemics. The COVID-19 pandemic has shown a markedly low proportion of cases among children1-4. Age disparities in observed cases could be explained by children having lower susceptibility to infection, lower propensity to show clinical symptoms or both. We evaluate these possibilities by fitting an age-structured mathematical model to epidemic data from China, Italy, Japan, Singapore, Canada and South Korea. We estimate that susceptibility to infection in individuals under 20 years of age is approximately half that of adults aged over 20 years, and that clinical symptoms manifest in 21% (95% credible interval: 12-31%) of infections in 10- to 19-year-olds, rising to 69% (57-82%) of infections in people aged over 70 years. Accordingly, we find that interventions aimed at children might have a relatively small impact on reducing SARS-CoV-2 transmission, particularly if the transmissibility of subclinical infections is low. Our age-specific clinical fraction and susceptibility estimates have implications for the expected global burden of COVID-19, as a result of demographic differences across settings. In countries with younger population structures-such as many low-income countries-the expected per capita incidence of clinical cases would be lower than in countries with older population structures, although it is likely that comorbidities in low-income countries will also influence disease severity. Without effective control measures, regions with relatively older populations could see disproportionally more cases of COVID-19, particularly in the later stages of an unmitigated epidemic.

positive: Lung Ultrasound in Children with COVID-19: Preliminary Findings Abstract— Recent evidence indicates the usefulness of lung ultrasound (LUS) in detecting coronavirus disease 19 (COVID-19) pneumonia. However, no data are available on the use of LUS in children with COVID-19 pneumonia. In this report, we describe LUS features of 10 consecutively admitted children with COVID-19 in two tertiary-level pediatric hospitals in Rome. LUS revealed signs of lung involvement during COVID-19 infection. In particular, vertical artifacts (70%), pleural irregularities (60%), areas of white lung (10%) and subpleural consolidations (10%) were the main findings in patients with COVID-19. No cases of pleural effusions were found. According to our experience, the routine use of LUS in the evaluation of children with suspected or confirmed COVID-19, when performed by clinicians with documented experience in LUS, was useful in diagnosing and monitoring pediatric COVID-19 pneumonia, reducing unnecessary radiation/sedation in children and exposure of health care workers to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

positive: A child with household transmitted COVID-19 BACKGROUND: Although people of all ages are susceptible to the novel coronavirus infection, which is presently named “Coronavirus Disease 2019” (COVID-19), there has been relatively few cases reported among children. Therefore, it is necessary to understand the clinical characteristics of COVID-19 in children and the differences from adults. CASE PRESENTATION: We report one pediatric case of COVID-19. A 14-month-old boy was admitted to the hospital with a symptom of fever, and was diagnosed with a mild form of COVID-19. The child’s mother and grandmother also tested positive for SARS-CoV-2 RNA. However, the lymphocyte counts were normal. The chest computed tomography (CT) revealed scattered ground glass opacities in the right lower lobe close to the pleura and resorption after the treatment. The patient continued to test positive for SARS-CoV-2 RNA in the nasopharyngeal swabs and stool at 17 days after the disappearance of symptoms. CONCLUSION: The present pediatric case of COVID-19 was acquired through household transmission, and the symptoms were mild. Lymphocyte counts did not significantly decrease. The RNA of SARS-CoV-2 in stool and nasopharyngeal swabs remained positive for an extended period of time after the disappearance of symptoms. This suggests that attention should be given to the potential contagiousness of pediatric COVID-19 cases after clinical recovery.

positive: Novel coronavirus infection in children outside of Wuhan, China BACKGROUND: Since December 8, 2019, an epidemic of coronavirus disease 2019 (COVID‐19) has spread rapidly, but information about children with COVID‐19 is limited. METHODS: This retrospective and the single‐center study were done at the Public Health Clinic Center of Changsha, Hunan, China. We identified all hospitalized children diagnosed with COVID‐19 between January 8, 2019 and February 19, 2020, in Changsha. Epidemiological and clinical data of these children were collected and analyzed. Outcomes were followed until February 26th, 2020. RESULTS: By February 19, 2020, nine pediatric patients were identified as having 2019‐nCoV infection in Changsha. Six children had a family exposure and could provide the exact dates of close contact with someone who was confirmed to have 2019‐nCoV infection, among whom the median incubation period was 7.5 days. The initial symptoms of the nine children were mild, including fever (3/9), diarrhea (2/9), cough (1/9), and sore throat (1/9), two had no symptoms. Two of the enrolled patients showed small ground‐glass opacity of chest computed tomography scan. As of February 26, six patients had a negative RT‐PCR for 2019‐nCoV and were discharged. The median time from exposure to a negative RT‐PCR was 14 days. CONCLUSIONS: The clinical symptoms of the new coronavirus infection in children were not typical and showed a less aggressive clinical course than teenage and adult patients. Children who have a familial clustering or have a family member with a definite diagnosis should be reported to ensure a timely diagnosis.

positive: A retrospective study of the clinical characteristics of COVID-19 infection in 26 children Background: The outbreak of novel coronavirus pneumonia in China began in December 2019. Studies on novel coronavirus disease (COVID-19) were less based on pediatric patients. This study aimed to reveal the clinical characteristics of COVID-19 in children. Method: This study retrospectively analyzed the clinical symptoms, laboratory results, chest CT, and treatment of children with laboratory-confirmed COVID-19(ie, with samples that were positive for 2019 novel coronavirus[2019-nCoV]) who were admitted to Shenzhen Center of National Infectious Disease Clinical Medical Research from January 16 to February 8, 2020. Result: Nine patients had no obvious clinical symptom. 11 patients developed fever. Other symptoms, including cough(in eleven of seventeen patients), rhinorrhea(in two), diarrhea(in two), vomiting(in two), were also observed. A small minority of patients had lymphocytopenia. Alanine transaminase or transaminase increased in three cases. According to chest CT scan, 11 patients showed unilateral pneumonia, 8 patients had no pulmonary infiltration. No serious complications such as acute respiratory syndrome and acute lung injury occurred in all patients. Conclusion: The clinical characteristics of 2019-nCoV infection in children were different from adult. The overall condition of children were mild and have a good prognosis.

positive: Characteristic of COVID-19 infection in pediatric patients: early findings from two Italian Pediatric Research Networks Detailed data on clinical presentations and outcomes of children with COVID-19 in Europe are still lacking. In this descriptive study, we report on 130 children with confirmed COVID-19 diagnosed by 28 centers (mostly hospitals), in 10 regions in Italy, during the first months of the pandemic. Among these, 67 (51.5%) had a relative with COVID-19 while 34 (26.2%) had comorbidities, with the most frequent being respiratory, cardiac, or neuromuscular chronic diseases. Overall, 98 (75.4%) had an asymptomatic or mild disease, 11 (8.5%) had moderate disease, 11 (8.5%) had a severe disease, and 9 (6.9%) had a critical presentation with infants below 6 months having significantly increased risk of critical disease severity (OR 5.6, 95% CI 1.3 to 29.1). Seventy-five (57.7%) children were hospitalized, 15 (11.5%) needed some respiratory support, and nine (6.9%) were treated in an intensive care unit. All recovered.Conclusion:This descriptive case series of children with COVID-19, mostly encompassing of cases enrolled at hospital level, suggest that COVID-19 may have a non-negligible rate of severe presentations in selected pediatric populations with a relatively high rates of comorbidities. More studies are needed to further understand the presentation and outcomes of children with COVID-19 in children with special needs. What is Known: â¢ There is limited evidence on the clinical presentation and outcomes of children with COVID-19 in Europe, and almost no evidence on characteristics and risk factors of severe cases. What is New: â¢ Among a case series of 130 children, mostly diagnosed at hospital level, and with a relatively high rate (26.2%) of comorbidities, about three-quarter had an asymptomatic or mild disease. â¢ However, 57.7% were hospitalized, 11.5% needed some respiratory support, and 6.9% were treated in an intensive care unit.

positive: The severity of COVID-19 in children on immunosuppressive medication

positive: Comparing dynamics and determinants of SARS-CoV-2 transmissions among health care workers of adult and pediatric settings in central Paris Background: From the start of the pandemic, health-care workers (HCW) have paid a heavy toll to the coronavirus disease-19 (COVID-19) outbreak. Objectives: To describe the dynamics and determinants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in HCW. Design: Prospective observational study conducted from February 24th until April 10th, 2020. Setting: Comparison of a 1,500-bed adult and a 600-bed pediatric setting of a tertiary-care university hospital located in central Paris. Participants: All symptomatic HCW screened for SARS-CoV-2 on a nasopharyngeal swab. Measurements: HCW screened positive were prospectively questioned on their profession, symptoms, occupational and non-occupational exposures to SARS-CoV-2. Results: Among 1344 symptomatic HCW tested, 373 were positive (28%) and 336 (90%) corresponding questionnaires were completed. Three hospitalizations and no death were reported. Most HCW (70%) had patient-facing occupational activities (22% in COVID-19 dedicated units). The total number of HCW cases peaked on March 23rd, then decreased slowly, concomitantly with a continuous increase of compliance to preventive measures (including universal medical masking and personal protective equipment (PPE) for direct care to COVID-19 patients). Attack rates were of 3.2% and 2.3% in the adult and pediatric setting, respectively (p=0.0022). In the adult setting, HCW more frequently reported exposure to COVID-19 patients without PPE (25% versus 15%, p=0.046). Report of contacts with children attending out-of-home care facilities dramatically decreased over the study period. Limitations: Lack of COVID-19 negative controls and recall bias. Conclusion: Universal masking, reinforcement of hand hygiene, and PPE with medical masks for patients' care allowed protection of HCW and containment of the outbreak. Residual transmissions were related to persistent exposures with undiagnosed patients or colleagues and not to contacts with children attending out-of-home care facilities.

positive: Vertical Transmission of Coronavirus Disease 19 (COVID-19) from Infected Pregnant Mothers to Neonates: A Review Background: Since early December 2019, the Coronavirus Disease 19 (COVID-19) infection has been prevalent in China and eventually spread to other countries. There are a few published cases of COVID-19 occurring during pregnancy and due the possibility of mother-fetal vertical transmission, there is a concern that the fetuses may be at risk of congenital COVID-19. Methods: We reviewed the risk of vertical transmission of COVID-19 to the fetus of infected mothers by using data of published articles or official websites up to March 4, 2020. Results: A total of 31 infected pregnant mothers with COVID-19 were reported. No COVID-19 infection was detected in their neonates or placentas. Two mothers died from COVID-19-related respiratory complications after delivery. Conclusions: Currently, based on limited data, there is no evidence for intrauterine transmission of COVID-19 from infected pregnant women to their fetuses. Mothers may be at increased risk for more severe respiratory complications.

positive: How is immunosuppressive status affecting children and adults in SARS-CoV-2 infection? A systematic review Abstract Objectives SARS-CoV-2 infection has now a global resonance. Data on how COVID-19 is affecting immunocompromised patients are however few. With our study we aimed to systematically review the current knowledge on SARS-CoV-2 cases in children and adults with immunosuppression, to evaluate outcomes in this special population. Methods A systematic review of literature was carried out to identify relevant articles, searching the EMBASE, Medline, and Google Scholar databases. Studies reporting data on pre-defined outcomes and related to immunosuppressed adults and children with SARS-CoV-2 were included. Results Sixteen relevant articles were identified with 110 immunosuppressed patients, mostly presenting cancer, along with transplantation and immunodeficiency. Cancer was more often associated with a more severe course, but not necessarily with a bad prognosis. Our data show that both children and adults with immunosuppression seem to have a favorable disease course, as compared to the general population. Conclusion Immunosuppressed patients with COVID-19 seem to be few in relation to the overall figures, and to present a favorable outcome as compared to other comorbidities. This might be explained by a hypothetical protective role of a weaker immune response, determining a milder disease presentation and thus underdiagnosis. Nevertheless, surveillance on this special population should be encouraged.

positive: ANOSMIA AND AGEUSIA: NOT AN UNCOMMON PRESENTATION OF COVID-19 INFECTION IN CHILDREN AND ADOLESCENTS. Since the emergence of a cluster of viral pneumonia cases in Wuhan, Hubei Province, People's Republic of China, at the end of December 2019, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), a novel coronavirus also known as "coronavirus disease 2019 (COVID-19)," as of 7 April 2020, more than 1,214,466 cases of COVID-19 have been reported in more than 200 countries and territories, resulting in more than 67,767 deaths. The disease was recognized by World Health Organization (WHO) as a pandemic on 11 March 2020. Published reports of adult patients with COVID-19 infection described symptoms including fever, cough, fatigue, sputum production, headache, dyspnoea and diarrhoea. Children usually showed milder respiratory symptoms or were asymptomatic, while loss of taste or sensation of smell were seldom reported. In this paper, we report three cases of pediatric patients with COVID-19 infection who presented with anosmia and/or ageusia.

positive: Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study OBJECTIVES: To describe the characteristics of children and adolescents affected by an outbreak of Kawasaki-like multisystem inflammatory syndrome and to evaluate a potential temporal association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN: Prospective observational study. SETTING: General paediatric department of a university hospital in Paris, France. PARTICIPANTS: 21 children and adolescents (aged ≤18 years) with features of Kawasaki disease who were admitted to hospital between 27 April and 11 May 2020 and followed up until discharge by 15 May 2020. MAIN OUTCOME MEASURES: The primary outcomes were clinical and biological data, imaging and echocardiographic findings, treatment, and outcomes. Nasopharyngeal swabs were prospectively tested for SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR) and blood samples were tested for IgG antibodies to the virus. RESULTS: 21 children and adolescents (median age 7.9 (range 3.7-16.6) years) were admitted with features of Kawasaki disease over a 15 day period, with 12 (57%) of African ancestry. 12 (57%) presented with Kawasaki disease shock syndrome and 16 (76%) with myocarditis. 17 (81%) required intensive care support. All 21 patients had noticeable gastrointestinal symptoms during the early stage of illness and high levels of inflammatory markers. 19 (90%) had evidence of recent SARS-CoV-2 infection (positive RT-PCR result in 8/21, positive IgG antibody detection in 19/21). All 21 patients received intravenous immunoglobulin and 10 (48%) also received corticosteroids. The clinical outcome was favourable in all patients. Moderate coronary artery dilations were detected in 5 (24%) of the patients during hospital stay. By 15 May 2020, after 8 (5-17) days of hospital stay, all patients were discharged home. CONCLUSIONS: The ongoing outbreak of Kawasaki-like multisystem inflammatory syndrome among children and adolescents in the Paris area might be related to SARS-CoV-2. In this study an unusually high proportion of the affected children and adolescents had gastrointestinal symptoms, Kawasaki disease shock syndrome, and were of African ancestry.

positive: A single-center, retrospective study of COVID-19 features in children: a descriptive investigation BACKGROUND: Compared to adults, there are relatively few studies on COVID-19 infection in children, and even less focusing on the unique features of COVID-19 in children in terms of laboratory findings, locations of computerized tomography (CT) lesions, and the role of CT in evaluating clinical recovery. The objective of this study is to report the results from patients at Wuhan Children’s Hospital, located within the initial center of the outbreak. METHODS: Clinical, imaging, and laboratory data of 76 children were collected retrospectively and analyzed with the Fisher exact test and Cox regression statistical methods. RESULTS: Among 50 children with a positive COVID-19 real-time reverse-transcriptase polymerase chain reaction (PCR), five had negative PCR results initially but showed positive results in subsequent tests. Eight (16%) patients had lymphopenia, seven (14%) with thrombocytopenia, four (8%) with lymphocytosis, two (4%) with thrombocytosis, ten (20%) with elevated C-reactive protein, four (8%) with hemoglobin above, and six (12%) with below standard reference values. Seven (14%) of the 50 had no radiologic evidence of disease on chest CT. For the 43 patients who had abnormal CT findings, in addition to previously reported patterns of ground-glass opacity (67%), local patchy shadowing (37%), local bilateral patchy shadowing (21%), and lesion location of lower lobes (65%), other CT features include that an overwhelming number of pediatric patients had lesions in the subpleural area (95%) and 22 of the 28 lower lobe lesions were in the posterior segment (78%). Lesions in most of the 15 patients (67%) who received chest CT at discharge were not completely absorbed, and 26% of these pediatric patients had CT lesions that were either unchanged or worse. CONCLUSIONS: There were a few differences between COVID-19 children and COVID-19 adults in terms of laboratory findings and CT characteristics. CT is a powerful tool to detect and characterize COVID-19 pneumonia but has little utility in evaluating clinical recovery for children. These results oppose current COVID-19 hospital discharge criteria in China, as one requirement is that pulmonary imaging must show significant lesion absorption prior to discharge. These differences between pediatric and adult cases of COVID-19 may necessitate pediatric-specific discharge criteria.

positive: Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults AIM: The coronavirus disease 2019 (COVID-19) pandemic has affected hundreds of thousands of people. Data on symptoms and prognosis in children are rare. METHODS: A systematic literature review was carried out to identify papers on COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), using the MEDLINE and Embase databases between January 1 and March 18, 2020. RESULTS: The search identified 45 relevant scientific papers and letters. The review showed that children have so far accounted for 1%-5% of diagnosed COVID-19 cases, they often have milder disease than adults and deaths have been extremely rare. Diagnostic findings have been similar to adults, with fever and respiratory symptoms being prevalent, but fewer children seem to have developed severe pneumonia. Elevated inflammatory markers were less common in children, and lymphocytopenia seemed rare. Newborn infants have developed symptomatic COVID-19, but evidence of vertical intrauterine transmission was scarce. Suggested treatment included providing oxygen, inhalations, nutritional support and maintaining fluids and electrolyte balances. CONCLUSIONS: The coronavirus disease 2019 has occurred in children, but they seemed to have a milder disease course and better prognosis than adults. Deaths were extremely rare.

positive: Neurologic and Radiographic Findings Associated With COVID-19 Infection in Children. Importance Neurological manifestations have been reported in adults with coronavirus disease 2019 (COVID-19), which is caused by the highly pathogenic virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objective To report the neurological manifestations of children with COVID-19. Design, Setting, and Participants In this case-series study, patients younger than 18 years who presented with SARS-CoV-2 infection and neurological symptoms to Great Ormond Street Hospital for Children (London, UK) between March 1, 2020, and May 8, 2020, were included after infection was confirmed by either a quantitative reverse transcription-polymerase chain reaction assay by nasopharyngeal swab or a positive test result for IgG antibodies against SARS-CoV-2 in serum. Main Outcomes and Measures Clinical and paraclinical features were retrieved from electronic patient records. Results Of the 27 children with COVID-19 pediatric multisystem inflammatory syndrome, 4 patients (14.8%) who were previously healthy had new-onset neurological symptoms. Symptoms included encephalopathy, headaches, brainstem and cerebellar signs, muscle weakness, and reduced reflexes. All 4 patients required intensive care unit admission for the treatment of COVID-19 pediatric multisystem inflammatory syndrome. Splenium signal changes were seen in all 4 patients on magnetic resonance imaging of the brain. In the 2 patients whose cerebrospinal fluid was tested, samples were acellular, with no evidence of infection on polymerase chain reaction or culture (including negative SARS-CoV-2 polymerase chain reaction results) and negative oligoclonal band test results. In all 3 patients who underwent electroencephalography, a mild excess of slow activity was found. Tests for N-methyl-d-aspartate receptor, myelin oligodendrocyte glycoprotein, and aquaporin-4 autoantibodies had negative results in all patients. In all 3 patients who underwent nerve conduction studies and electromyography, mild myopathic and neuropathic changes were seen. Neurological improvement was seen in all patients, with 2 making a complete recovery by the end of the study. Conclusions and Relevance In this case-series study, children with COVID-19 presented with new neurological symptoms involving both the central and peripheral nervous systems and splenial changes on imaging, in the absence of respiratory symptoms. Additional research is needed to assess the association of neurological symptoms with immune-mediated changes among children with COVID-19.

positive: å¿ç«¥2019å ç¶ç æ¯ç æ£è çè¸é¨CTè¡¨ç°åä¸´åºç¹å¾./ å¿ç«¥2019å ç¶ç æ¯ç æ£è çè¸é¨CTè¡¨ç°åä¸´åºç¹å¾./ Chest CT findings and clinical features of coronavirus disease 2019 in children OBJECTIVES: To describe the CT features and clinical characteristics of pediatric patients with coronavirus disease 2019 (COVID-19). METHODS: A total of 9 COVID-19 infected pediatric patients were included in this study. Clinical history, laboratory examination, and detailed CT imaging features were analyzed. All patients underwent the first CT scanning on the same day of being diagnosed by real-time reverse-transcription polymerase chain reaction (rRT-PCR). A low-dose CT scan was performed during follow-up. RESULTS: All the child patients had positive results. Four patients had cough and one patient had fever. One patient presented both cough and fever. Two children presented other symptoms like sore throat and stuffy nose. One child showed no clinical symptom. Five patients had positive initial CT findings with subtle lesions like ground-glass opacity (GGO) or spot-like mixed consolidation. Three patients were reported with negative results in the initial and follow-up CT examination. One patient was reported with initial negative CT findings but turning positive during the first follow-up. All patients had absorbed lesions on follow-up CT images after treatment. CONCLUSIONS: Pediatric COVID-19 patients have certain imaging and clinical features as well as disease prognosis. Children with COVID-19 tend to have normal or subtle CT findings and relatively better outcome.

positive: SARS-COV-2 infection in children and newborns: a systematic review A recent outbreak of a novel Coronavirus responsible for a Severe Acute Respiratory Syndrome (SARS-CoV-2) is spreading globally. The aim of this study was to systematically review main clinical characteristics and outcomes of SARS-CoV-2 infections in pediatric age. An electronic search was conducted in PubMed database. Papers published between 1 January and 1 May 2020 including children aged 0-18 years were selected. Sixty-two studies and three reviews were included, with a total sample size of 7480 children (2428/4660 males, 52.1%; weighted mean age 7.6 years). Patients showed mainly mild (608/1432, 42.5%) and moderate (567/1432, 39.6%) signs of the infection. About 2% of children were admitted to the pediatric intensive care unit. The most commonly described symptoms were fever (51.6%) and cough (47.3%). Laboratory findings were often unremarkable. Children underwent a chest CT scan in 73.9% of all cases, and 32.7% resulted normal. Overall, the estimated mortality was 0.08%. A higher proportion of newborns was severely ill (12%) and dyspnea was the most common reported sign (40%).Conclusion: SARS-CoV-2 affects children less severely than adults. Laboratory and radiology findings are mainly nonspecific. Larger epidemiological and clinical cohort studies are needed to better understand possible implications of COVID-19 infection in children.What is Known:â¢ A novel Coronavirus has been recently identified as responsible for a new Severe Acute Respiratory Syndrome (SARS-CoV-2) spreading globally.â¢ There is limited evidence on SARS-CoV2 infection in children.What is New:â¢ Systematically reviewed available evidence showed that children with SARS-CoV-2 infection may have a less severe pattern of disease in comparison to adults.â¢ Blood tests and radiology findings are mainly nonspecific in children but may help to identify those who are severely ill.

positive: Diagnosis of COVID-19 in children: the story evolves

positive: Rethinking COVID-19 in children: Lessons learned from pediatric viral and inflammatory cardiovascular diseases

positive: Severe acute respiratory syndrome (SARS) in neonates and children. Severe acute respiratory syndrome (SARS) runs a more benign course in children during the acute phase. Infants born to mothers with the disease did not acquire the infection through vertical transmission. The treatment strategy for children with SARS has not been standardised and is based on adult experience. Thus far, no deaths have been reported in the paediatric age group. Exercise impairment and residual radiological abnormalities were present six months after diagnosis. It is important to assess these patients on a regular basis to detect and provide appropriate management for any persistent or emerging long term sequelae in the physical, psychological, and social domains. This review describes the current understanding of SARS coronavirus infection in newborns and children.

positive: COVID‐19 is milder in children possibly due to cross immunity It has been unclear why the new severe acute respiratory syndrome coronavirus (sars‐CoV‐2) hits a small minority hard, while the vast majority of children appear to be protected and develop mild or no disease (1,2). The editorial by Brodin suggests some possible mechanisms why it is so (1). I would like to emphasize the significance of cross immunity due to previous exposure to seasonal coronavirus; it may be a plausible explanation for why children appear to be protected (2,3).

positive: COVID-19 in Children with Brain-Based Developmental Disabilities: A Rapid Review Background. The prevalence of symptomatic COVID-19 in children remains low to date. In just a few months, COVID-19 has affected millions of people worldwide, and as of the date of this publication, the pandemic continues. Based on the current available evidence, children do not appear to be at higher risk of contracting COVID-19 than adults. However, children with neurological and neuromuscular conditions are vulnerable to the respiratory complications of other viral infections. Objectives. To assess whether children with brain-based developmental disabilities were more likely to develop COVID-19 and have complications or poorer outcomes following infection. Methods. We conducted a two-week rapid review on studies with primary data regarding children aged between zero and 18 years old with brain-based developmental disabilities, or who were at risk of developing such disabilities, with confirmed or suspected COVID-19. We performed our literature searches on April 18, 2020. Results. Our search strategy identified 538 individual records, of which four were included in our review. Of the 50 COVID-19 pediatric patients reported in the included studies, a total of seven children were at risk of developing brain-based disabilities. Symptoms ranged in severity. However, generally, patients were discharged or saw improvements in their symptoms by the end of the study period. No deaths were reported. Discussion. Our study highlights a knowledge gap regarding the impact of COVID-19 in children with brain-based developmental disabilities.

positive: Serology confirms SARS-CoV-2 infection in PCR-negative children presenting with Paediatric Inflammatory Multi-System Syndrome BACKGROUND: During the COVID-19 outbreak, reports have surfaced of children who present with features of a multisystem inflammatory syndrome with overlapping features of Kawasaki disease and toxic shock syndrome - Paediatric Inflammatory Multisystem Syndrome- temporally associated with SARS-CoV-2 pandemic (PIMS-TS). Initial reports find that many of the children are PCR-negative for SARS-CoV-2, so it is difficult to confirm whether this syndrome is a late complication of viral infection in an age group largely spared the worst consequences of this infection, or if this syndrome reflects enhanced surveillance. METHODS: Children hospitalised for symptoms consistent with PIMS-TS between 28 April and 8 May 2020, and who were PCR-negative for SARS-CoV-2, were tested for antibodies to viral spike glycoprotein using an ELISA test. RESULTS: Eight patients (age range 7–14 years, 63% male) fulfilled case-definition for PIMS-TS during the study period. Six of the eight patients required admission to intensive care. All patients exhibited significant IgG and IgA responses to viral spike glycoprotein. Further assessment showed that the IgG isotypes detected in children with PIMS-TS were of the IgG1 and IgG3 subclasses, a distribution similar to that observed in samples from hospitalised adult COVID-19 patients. In contrast, IgG2 and IgG4 were not detected in children or adults. IgM was not detected in children, which contrasts with adult hospitalised adult COVID-19 patients of whom all had positive IgM responses. CONCLUSIONS: Strong IgG antibody responses can be detected in PCR-negative children with PIMS-TS. The low detection rate of IgM in these patients is consistent with infection having occurred weeks previously and that the syndrome onset occurs well after the control of SARS-CoV-2 viral load. This implies that the disease is largely immune-mediated. Lastly, this indicates that serology can be an appropriate diagnostic tool in select patient groups.

positive: No evidence of SARS-Cov-2 infection by PCR or serology in children with pseudochilblain Despite its aggressive clinical course, leading to 6.4% fatality rate as of May 25, 2020 (https://qap.ecdc.europa.eu/public/extensions/COVID-19/COVID-19.html), COVID-19 turned out to be only marginally aggressive in children. In a report from Lombardy, 18/88 COVID-19 hospitalized adults (20%) had developed cutaneous manifestations: erythematous rash, widespread urticarial, and chickenpox-like vesicles. Trunk was the main involved region. Itching was low or absent and usually lesions healed in few days. An unexpected outbreak of acute pseudochilblain skin lesions is being reported from different countries and related to COVID-19.

positive: COVID-19: lessons to date from China. The pandemic due to a novel coronavirus has been sweeping across different regions of the globe since January 2020. Early reports of this infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) consisted of mostly adult patients. As the outbreak spreads rapidly beyond the epicentre of Wuhan, it becomes clear that infants and children of all ages are susceptible to this infection. In China, there have been more than 1200 paediatric cases. Most paediatric patients acquire the infection through household contact with infected adults. The disease in children is usually self-limiting and most infected children will recover uneventfully within 7-10 days. Other than symptoms of the respiratory tract, many children may present with gastrointestinal symptoms. Older children are more likely to have asymptomatic infection. Although deaths related to SARS-CoV-2 are rarely reported in the paediatric age group, young children and those with underlying medical conditions are more likely to develop severe illness. Only a small fraction of neonates born to infected mother would acquire the virus by vertical transmission. Because a large proportion of children and adolescents may have asymptomatic or mildly symptomatic infection, children are likely to play an important role in community transmission of this infection. Screening of children who have a definitive contact history will facilitate early diagnosis and isolation of all infected children. This review summarises the lessons learned in China with regard to the current understanding of SARS-CoV-2 infection in the paediatric population.

positive: Severe COVID-19 during Pregnancy and Possible Vertical Transmission There are few cases of pregnant women with novel corona virus 2019 (COVID-19) in the literature, most of them with a mild illness course. There is limited evidence about in utero infection and early positive neonatal testing. A 41-year-old G3P2 with a history of previous cesarean deliveries and diabetes mellitus presented with a 4-day history of malaise, low-grade fever, and progressive shortness of breath. A nasopharyngeal swab was positive for COVID-19, COVID-19 serology was negative. The patient developed respiratory failure requiring mechanical ventilation on day 5 of disease onset. The patient underwent a cesarean delivery, and neonatal isolation was implemented immediately after birth, without delayed cord clamping or skin-to-skin contact. The neonatal nasopharyngeal swab, 16 hours after delivery, was positive for severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) real-time polymerase chain reaction (RT-PCR), and immunoglobulin (Ig)-M and IgG for SARS-CoV-2 were negative. Maternal IgM and IgG were positive on postpartum day 4 (day 9 after symptom onset). We report a severe presentation of COVID-19 during pregnancy. To our knowledge, this is the earliest reported positive PCR in the neonate, raising the concern for vertical transmission. We suggest pregnant women should be considered as a high-risk group and minimize exposures for these reasons. Key Points: We report a severe presentation of COVID-19 in pregnancy requiring invasive ventilatory support. This is a case of positive RT-PCR in first day of life, suggesting possible vertical transmission. There were no detectable maternal antibodies for COVID-19 until after delivery.

positive: We urgently need guidelines for managing COVID‐19 in children with comorbidities I read with great interest the systematic review by Ludvigsson on the coronavirus disease 2019 (COVID-19) (1). The author needs to be complimented for a well-timed, rigorous and rapid synthesis of the evidence from the rather scant data available on how the virus affects children. The review, which focused on all papers published up to 19 March, drew important conclusions that have significant practical implications for those involved in providing acute care for children suffering from this disease.

positive: Authors’ reply to correspondence in response to “Will children reveal their secret? The coronavirus dilemma” The role of ACE2 receptor in SARS-CoV-2 infection and in COVID-19 outcomes is still debated, especially in children.

positive: Why is COVID-19 so mild in children? There is an urgent need to understand why the course of the coronavirus that started in late 2019 (COVID-19) is affecting different groups of individuals with varying severity during the ongoing global pandemic. Greater knowledge of the disease, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), will help us to prioritise our limited health resources. Because the virus is new, and no vaccine is yet available, everyone is naïve and susceptible to being infected with SARS-CoV2. The virus will continue to spread until an effective vaccine exists or sufficient members of our global population have been infected to establish herd immunity. At the moment, the best way to minimize loss of life and severe cases requiring intensive care is to try and shelter vulnerable groups of individuals and slow down the spread of the virus.

positive: 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 1519 articles were identified by initial literature search, and finally six studies, 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. Keywords: COVID-19; children; intravenous immunoglobulin; rapid review.

positive: COVID‐19 multisystem inflammatory syndrome in three teenagers with confirmed SARS‐CoV‐2 infection Coronavirus disease 2019 (COVID‐19) is generally a relatively mild illness in children. An emerging disease entity coined as pediatric inflammatory multisystem syndrome temporally associated with SARS‐CoV‐2 (PIMS‐TS) has been reported recently, but is very rare and only affects a very small minority of children. Here we describe the clinical presentations and outcomes of three teenagers with serologically‐confirmed SARS‐CoV‐2 infection admitted to a pediatric intensive care unit for PIMS‐TS. Although their initial presentations were very similar, their COVID‐19‐related disease varied in severity.

positive: COVID-19 in Children, Pregnancy and Neonates: A Review of Epidemiologic and Clinical Features The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has spread rapidly across the globe. In contrast to initial reports, recent studies suggest that children are just as likely as adults to become infected with the virus but have fewer symptoms and less severe disease. In this review, we summarize the epidemiologic and clinical features of children infected with SARS-CoV-2 reported in pediatric case series to date. We also summarize the perinatal outcomes of neonates born to women infected with SARS-CoV-2 in pregnancy. We found 11 case series including a total of 333 infants and children. Overall, 83% of the children had a positive contact history, mostly with family members. The incubation period varied between 2 and 25 days with a mean of 7 days. The virus could be isolated from nasopharyngeal secretions for up to 22 days and from stool for more than 30 days. Co-infections were reported in up to 79% of children (mainly mycoplasma and influenza). Up to 35% of children were asymptomatic. The most common symptoms were cough (48%; range 19%-100%), fever (42%; 11%-100%) and pharyngitis (30%; 11%-100%). Further symptoms were nasal congestion, rhinorrhea, tachypnoea, wheezing, diarrhea, vomiting, headache and fatigue. Laboratory test parameters were only minimally altered. Radiologic findings were unspecific and included unilateral or bilateral infiltrates with, in some cases, ground-glass opacities or consolidation with a surrounding halo sign. Children rarely needed admission to intensive care units (3%), and to date, only a small number of deaths have been reported in children globally. Nine case series and 2 case reports described outcomes of maternal SARS-CoV-2 infection during pregnancy in 65 women and 67 neonates. Two mothers (3%) were admitted to intensive care unit. Fetal distress was reported in 30% of pregnancies. Thirty-seven percent of women delivered preterm. Neonatal complications included respiratory distress or pneumonia (18%), disseminated intravascular coagulation (3%), asphyxia (2%) and 2 perinatal deaths. Four neonates (3 with pneumonia) have been reported to be SARS-CoV-2 positive despite strict infection control and prevention procedures during delivery and separation of mother and neonates, meaning vertical transmission could not be excluded.

positive: The role of children in transmission of SARS-CoV-2: A rapid review BACKGROUND: Understanding the role of children in the transmission of SARS-CoV-2 is urgently required given its policy implications in relation to the reopening of schools and intergenerational contacts. METHODS: We conducted a rapid review of studies that investigated the role of children in the transmission of SARS-CoV-2. We synthesized evidence for four categories: 1) studies reporting documented cases of SARS-CoV-2 transmission by infected children; 2) studies presenting indirect evidence on the potential of SARS-CoV-2 transmission by (both symptomatic and asymptomatic) children; 3) studies reporting cluster outbreaks of COVID-19 in schools; 4) studies estimating the proportions of children infected by SARS-CoV-2, and reported results narratively. RESULTS: A total of 16 unique studies were included for narrative synthesis. There is limited evidence detailing transmission of SARS-CoV-2 from infected children. We found two studies that reported a 3-month-old whose parents developed symptomatic COVID-19 seven days after caring for the infant and two children who may have contracted COVID-19 from the initial cases at a school in New South Wales. In addition, we identified six studies presenting indirect evidence on the potential for SARS-CoV-2 transmission by children, three of which found prolonged virus shedding in stools. There is little data on the transmission of SARS-CoV-2 in schools. We identified only two studies reporting outbreaks of COVID-19 in school settings and one case report of a child attending classes but not infecting any other pupils or staff. Lastly, we identified six studies estimating the proportion of children infected; data from population-based studies in Iceland, Italy, South Korea, Netherlands, California and a hospital-based study in the UK suggest children may be less likely to be infected. CONCLUSIONS: Preliminary results from population-based and school-based studies suggest that children may be less frequently infected or infect others, however current evidence is limited. Prolonged faecal shedding observed in studies highlights the potentially increased risk of faeco-oral transmission in children. Further seroprevalence studies (powered adequately for the paediatric population) are urgently required to establish whether children are in fact less likely to be infected compared to adults. NOTE: We plan to update this rapid review as new data becomes available. These updates are available at https://www.ed.ac.uk/usher/uncover/completed-uncover-reviews.

positive: Chest computed tomography in children with COVID-19 respiratory infection BACKGROUND: Infection with COVID-19 is currently rare in children. OBJECTIVE: To describe chest CT findings in children with COVID-19. MATERIALS AND METHODS: We studied children at a large tertiary-care hospital in China, during the period from 28 January 2019 to 8 February 2020, who had positive reverse transcriptase polymerase chain reaction (RT-PCR) for COVID-19. We recorded findings at any chest CT performed in the included children, along with core clinical observations. RESULTS: We included five children from 10 months to 6 years of age (mean 3.4 years). All had had at least one CT scan after admission. Three of these five had CT abnormality on the first CT scan (at 2 days, 4 days and 9 days, respectively, after onset of symptoms) in the form of patchy ground-glass opacities; all normalised during treatment. CONCLUSION: Compared to reports in adults, we found similar but more modest lung abnormalities at CT in our small paediatric cohort.

positive: Epidemiological and Clinical Characteristics of Children with Coronavirus Disease 2019 Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly identified pathogen which mainly spreads by droplets. Most published studies focused on adult patients with coronavirus disease 2019 (COVID-19), but data concerning pediatric patients is limited. This study aimed to determine epidemiological characteristics and clinical features of pediatric patients with COVID-19. Methods: We reviewed and analyzed data on pediatric patients with laboratory-confirmed COVID-19, including basic information, epidemiological history, clinical manifestations, laboratory and radiologic findings, treatment, outcome and follow-up results. Results: From January 20th to February 27th of 2020, a total of 74 pediatric patients with COVID-19 were included in this study. Of the 68 cases whose epidemiological data were complete, 65 (65/68, 95.59%) cases were household contacts of adults whose symptoms developed earlier. Forty (59.46%) of the infected children were male, and the median age and body weight are 6 (0.10-15.08) years and 24 (4.20-87.00) kg, respectively. Except for one critically ill case, 20 (27.03%) patients did not show any symptoms of infection, 24 (32.43%) patients had acute upper respiratory tract infection and 29 (39.19%) patients were diagnosed with mild pneumonia. Cough (24/74, 32.43%) and fever (20, 27.03%) were the predominant symptoms of 44 (59.46%) symptomatic patients at onset of the illness. Abnormalities in leukocyte count were found in 23 (31.08%) children and 10 (13.51%) children presented with abnormal lymphocyte count. Of the 34 (45.95%) patients who had nucleic acid testing results for common respiratory pathogens, 19 (19 / 34, 51.35%) showed co-infection with other pathogens other than SARS-CoV-2.Ten (13.51%) children had RT-PCR analysis of SARS-CoV-2 for fecal specimens and 8 of them showed prolonged existence of SARS-CoV-2 RNA 11 (5-23) days after nasopharynx swabs turning negative. Abnormalities in chest imaging were observed in 37 (50.00%) patients and 28 (37.84%) of them only presented with nontypical changes.All children had good prognosis with a median hospitalization duration of 11 days and follow-up period of 16.5 days. During the follow-up period, all the patients remained in quarantine at designated site and home for two 14-day obervation periods and showed no clinical manifestation,but 3 of the 8 cases with prolonged fecal shedding of SARS-CoV-2 still showed positive result of feces test.

positive: COVID-19: Four Paediatric Cases in Malaysia Abstract Objective This is a brief report of 4 paediatric cases of COVID-19 infection in Malaysia Background COVID-19, a coronavirus, first detected in Wuhan, China has now spread rapidly to over 60 countries and territories around the world, infecting more than 85000 individuals. As the case count amongst children is low, there is need to report COVID-19 in children to better understand the virus and the disease. Cases In Malaysia, until end of February 2020, there were four COVID-19 paediatric cases with ages ranging from 20 months to 11 years. All four cases were likely to have contracted the virus in China. The children had no symptoms or mild flu-like illness. The cases were managed symptomatically. None required antiviral therapy. Discussion There were 2 major issues regarding the care of infected children. Firstly, the quarantine of an infected child with a parent who tested negative was an ethical dilemma. Secondly, oropharyngeal and nasal swabs in children were at risk of false negative results. These issues have implications for infection control. Consequently, there is a need for clearer guidelines for child quarantine and testing methods in the management of COVID-19 in children.

positive: 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 from their inception to March, 31 2020 were searched for randomized controlled trials, 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 of indirect evidence with 6008 patients were included. 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) and probability of negative PCR test (RR=0.98, 95 CI% 0.82 to 1.18). Arbidol had no benefit on probability of negative PCR test (RR=1.27, 95% CI 0.93 to 1.73). Hydroxychloroquine was not associated with increasing the probability of negative PCR result (RR=0.93, 95% CI 0.73 to 1.18). 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. Keywords: Antiviral agents; children; COVID-19; meta-analysis; rapid review.

positive: COVID-19 in 7780 pediatric patients: A systematic review BACKGROUND: Studies summarizing the clinical picture of COVID-19 in children are lacking. This review characterizes clinical symptoms, laboratory, and imaging findings, as well as therapies provided to confirmed pediatric cases of COVID-19. METHODS: Adhering to PRISMA guidelines, we searched four medical databases (PubMed, LitCovid, Scopus, WHO COVID-19 database) between December 1, 2019 to May 14, 2020 using the keywords “novel coronavirus”, “COVID-19” or “SARS-CoV-2”. We included published or in press peer-reviewed cross-sectional, case series, and case reports providing clinical signs, imaging findings, and/or laboratory results of pediatric patients who were positive for COVID-19. Risk of bias was appraised through the quality assessment tool published by the National Institutes of Health. PROSPERO registration # CRD42020182261. FINDINGS: We identified 131 studies across 26 countries comprising 7780 pediatric patients. Although fever (59·1%) and cough (55·9%) were the most frequent symptoms 19·3% of children were asymptomatic. Patchy lesions (21·0%) and ground-glass opacities (32·9%) depicted lung radiograph and computed tomography findings, respectively. Immunocompromised children or those with respiratory/cardiac disease comprised the largest subset of COVID-19 children with underlying medical conditions (152 of 233 individuals). Coinfections were observed in 5.6% of children and abnormal laboratory markers included serum D-dimer, procalcitonin, creatine kinase, and interleukin-6. Seven deaths were reported (0·09%) and 11 children (0·14%) met inclusion for multisystem inflammatory syndrome in children. INTERPRETATION: This review provides evidence that children diagnosed with COVID-19 have an overall excellent prognosis. Future longitudinal studies are needed to confirm our findings and better understand which patients are at increased risk for developing severe inflammation and multiorgan failure. FUNDING: Parker B. Francis and pilot grant from 2R25-HL126140. Funding agencies had no involvement in the study.

positive: Clinical characteristics and diagnostic challenges of pediatric COVID-19: A systematic review and meta-analysis Background/Purpose Current studies on pediatric coronavirus disease 2019 (COVID-19) are rare. The clinical characteristics and spectrum are still unknown. Facing this unknown and emerging pathogen, we aimed to collect current evidence about COVID-19 in children. Methods We performed a systematic review in PubMed and Embase to find relevant case series. Because some reports were published in Chinese journals, the journals and publications of the Chinese Medical Association related to COVID-19 were completely reviewed. A random effects model was used to pool clinical data in the meta-analysis. Results Nine case series were included. In the pooled data, most of patients (75%) had a household contact history. The disease severity was mainly mild to moderate (98%). Only 2 children (2%) received intensive care. Fever occurred in 59% of the patients, while cough in 46%. Gastrointestinal symptoms (12%) were uncommon. There are 26% children are asymptomatic. The most common radiographic finding was ground glass opacities (48%). Currently, there is no evidence of vertical transmission to neonates born to mothers with COVID-19. Compared with the most relevant virus, SARS-CoV, SARS-CoV-2 causes less severe disease. Conclusion COVID-19 has distinct features in children. The disease severity is mild. Current diagnosis is based mainly on typical ground glass opacities on chest CT, epidemiological suspicion and contact tracing.

positive: Additional hypotheses about why COVID-19 is milder in children than adults

positive: Severe acute respiratory syndrome among children. OBJECTIVE To study the epidemiologic, clinical, laboratory, and radiologic features, prognostic indicators, and short-term to medium-term outcomes for children with severe acute respiratory syndrome (SARS) and to validate the performance characteristics of a clinical case definition, calculated with respect to SARS-associated coronavirus (SARS-CoV) seroconversion. METHODS Children <18 years of age, from a single-site outbreak, who satisfied a clinical case definition for SARS, with subsequent serologic confirmation, were treated according to a standard protocol and prospectively monitored. RESULTS Forty-four children were included. The median age was 12 years. Forty-two children (95.5%) demonstrated an epidemiologic link. Fever, cough, malaise, coryza, sputum production, headache, myalgia, lymphopenia, and elevated lactate dehydrogenase levels were common presenting features. Radiographic findings were nonspecific, but high-resolution computed tomography of the thorax was an early diagnostic aid. A specific reverse transcription-polymerase chain reaction assay for SARS-CoV yielded positive results for <50% of children. Of 9 children who developed hypoxemia, 8 were treated with methylprednisolone. Of 5 children who received intensive care, 3 required assisted ventilation. All children recovered, and serious adverse events in response to treatment were not observed. The outcomes at 3 to 6 months after disease onset, including exercise tolerance, pulmonary functions, and psychologic status, were favorable. An age of >12 years was associated with methylprednisolone therapy for severe illness. After exclusion of the only infant, an age of >12 years was associated with oxygen requirements. Sore throat, high neutrophil count at presentation, and peak neutrophilia were independent factors predicting severe illness. The clinical case definition demonstrated good sensitivity, specificity, and positive and negative predictive values (97.8%, 92.7%, 88%, and 98.7%, respectively) for diagnostic accuracy. CONCLUSIONS Children are susceptible to SARS-CoV infection. Teenagers resemble adults with respect to disease progression and may develop severe illness. The short-term to medium-term outcomes are good. Sore throat and initial and peak neutrophilia seem to be predictors of severe illness. Our clinical case definition performed well in the epidemic.

positive: A Saudi G6PD Deficient Girl Died with Pediatric Multisystem Inflammatory Syndrome-COVID-19 Reports on pediatric multisystem inflammatory syndrome (PMIS) temporally related to coronavirus disease 2019 (COVID-19) are increasing. African and Afro-Caribbean children constituted about 47% of the cases in these reports. Despite the fact that glucose-6-phosphatase dehydrogenase (G6PD) deficiency is common among this population, the G6PD status of these cases has not been reported in these reports. We reported the first case of PMIS related to COVID-19 from Saudi Arabia. This case was a Saudi G6PD deficient girl who died with PMIS related to COVID-19. G6PD deficiency induces redox imbalance and exaggerates the inflammatory response; thus, it might contribute to the development or the grave outcome of our case. We urgently need to assess the association between G6PD deficiency and COVID-19 in a large study as the G6PD deficiency may be a useful predictor for the progression of the COVID-19.

positive: Re: SARS-CoV-2 testing and outcomes in the first 30 days after the first case of COVID-19 at an Australian children's hospital

positive: COVID-19 and pediatric inflammatory bowel disease: How to manage it? Pediatric gastroenterologists, family members, and caregivers of patients with inflammatory bowel disease (IBD) are on alert; they are all focused on implementing prophylactic measures to prevent infection by severe acute respiratory syndrome coronavirus 2, evaluating the risks in each patient, guiding them in their treatment, and keeping IBD in remission. To face the current issues of the coronavirus disease pandemic, we have developed a synthesis of the main recommendations of the literature directed at pediatric gastroenterologists in control of patients with pediatric IBD and adapted to the national reality.

positive: Reduced inflammatory responses to SARS-CoV-2 infection in children presenting to hospital with COVID19 in China Background Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children is associated with better outcomes than in adults. The inflammatory response to COVID-19 infection in children remains poorly characterised. Methods We retrospectively analysed the medical records of 127 laboratory-confirmed COVID-19 patients aged 1 month to 16 years from Wuhan and Jingzhou of Hubei Province. Patients presented between January 25th and March 24th 2020. Information on clinical features, laboratory results, plasma cytokines/chemokines and lymphocyte subsets were analysed. Findings Children admitted to hospital with COVID-19 were more likely to be male (67.7%) and the median age was 7.3 [IQR 4.9] years. All but one patient with severe disease was aged under 2 and the majority (5/7) had significant co-morbidities. Despite 53% having viral pneumonia on CT scanning only 2 patients had low lymphocyte counts and no differences were observed in the levels of plasma proinflammatory cytokines, including interleukin (IL)-2, IL-4, IL-6, tumour necrosis factor (TNF)-alpha; and interferon (IFN)-gamma; between patients with mild, moderate or severe disease. Interpretations We demonstrated that the immune responses of children to COVID-19 infection is significantly different from that seen in adults. Our evidence suggests that SARS-CoV-2 does not trigger a robust inflammatory response or "cytokine storm" in children with COVID-19, and this may underlie the generally better outcomes seen in children with this disease. These data also imply anti-cytokine therapies may not be effective in children with moderate COVID-19.

positive: Novel Coronavirus Infection (COVID‐19) in Children Younger Than One Year: A Systematic Review of Symptoms, Management and Outcomes AIM: This aim of this systematic review and meta‐analysis was to evaluate the clinical characteristics of COVID‐19 in neonates and children under one year of age. METHODS: A systematic literature review of the MEDLINE, PubMed, CINAHL, Embase and EBSCO databases was carried out for studies from 1 January to 7 April 2020. We included all papers that addressed clinical manifestations, laboratory results, imaging findings and outcomes in infants and neonates. RESULTS: Our search identified 77 peer‐reviewed papers and 18 papers covering 160 infants were reviewed. One paper was from Vietnam and the other 17 were from China: eight were cross‐sectional studies, eight were case reports, one was a case series and one was a prospective cohort study. The most common clinical symptoms were fever (54%) and cough (33%). Most infants were treated symptomatically, with frequent use of various empirical medications. Infants and neonates tended to have more severe COVID‐19 disease than older children: 11 (7%) were admitted to intensive care and one infant died. The mortality rate was 0.006%, with favourable outcomes in most cases. CONCLUSION: Infants and neonates were more vulnerable to more severe COVID‐19 disease than older children, but morbidity and mortality were low.

positive: "Women and children last"-effects of the covid-19 pandemic on reproductive, perinatal, and paediatric health.

positive: Coronavirus disease 2019 (COVID-19) in children: a systematic review of imaging findings BACKGROUND: COVID-19 is a novel coronavirus infection that can cause a severe respiratory illness and has been declared a pandemic by the World Health Organization (WHO). Because children appear to be less severely affected than adults, their imaging appearances have not been extensively reported. OBJECTIVE: To systematically review available literature regarding imaging findings in paediatric cases of COVID-19. MATERIALS AND METHODS: We searched four databases (Medline, Embase, Cochrane, Google Scholar) for articles describing imaging findings in children with COVID-19. We included all modalities, age <18 years, and foreign language articles, using descriptive statistics to identify patterns and locations of imaging findings, and their association with outcomes. RESULTS: Twenty-two articles were included, reporting chest imaging findings in 431 children, of whom 421 (97.7%) underwent CT. Criteria for imaging were lacking. At diagnosis, 143/421 (34.0%) had a normal CT. Abnormalities were more common in the lower lobes and were predominantly unilateral. The most common imaging pattern was ground-glass opacification (159/255, 62.4%). None of the studies described lymphadenopathy, while pleural effusions were rare (three cases). Improvement at follow-up CT imaging (3–15 days later) was seen in 29/100 (29%), remained normal in 25/100 (25%) and progressed in 9/100 (9%). CONCLUSION: CT chest findings in children with COVID-19 are frequently normal or mild. Lower lobes are predominantly affected by patchy ground-glass opacification. Appearances at follow-up remain normal or improve in the majority of children. Chest CT imaging adds little to the further management of the patient and should be reserved for severe cases or for identifying alternative diagnoses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00247-020-04726-w) contains supplementary material, which is available to authorized users.

positive: Viral Etiology and Outcome of Severe Lower Respiratory Tract Infections among Critically Ill Children Admitted to the Picu OBJECTIVE: To determine the viral etiology of severe lower respiratory tract infections (LRTIs), their clinical significance and prognosis among critically ill children. DESIGN: A prospective descriptive study was carried out. SETTING: Pediatric Intensive Care Unit (PICU) of Istanbul Medeniyet University, Goztepe Training and Research Hospital, Istanbul, Turkey. PATIENTS: A total of 115 patients hospitalized in the PICU were evaluated for inclusion in the study. Children with underlying comorbidities and those who did not require mechanical ventilation were excluded. MAIN VARIABLES OF INTEREST: Demographic, clinical, laboratory test and radiographic data were recorded. RESULTS: A total of 63 patients were eligible for the study. The most common diagnosis was bronchiolitis (57.1%). Respiratory syncytial virus (RSV) was the most frequent causal virus (36.5%). The most common complication was acute respiratory distress syndrome (ARDS) (28.6%). Multiple viral infection was identified in 20.6% of the patients, the most common in this subgroup being rhinovirus. Patients with bocavirus infection had a higher likelihood of needing invasive mechanical ventilation (IMV) at presentation. Children who died were likely to be < 12 months old, have ARDS, hepatitis, pneumomediastinum, multiple viral infection, and required IMV support with an increased duration of MV. Additionally, they were found to have a high Pediatric Risk of Mortality III score, Predicted Death Rate and increased need for inotropic support at admission. CONCLUSIONS: Our study showed critically ill children with LRTI without known risk factors to have high mortality when aged < 12 months, in the presence of multiple agents and when certain complications (ARDS, hepatitis) and X-ray findings were identified.

positive: Mild SARS-COV-2 infections in children might be based on evolutionary biology and linked with host reactive oxidative stress (ROS) and antioxidant capabilities Summary Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection leads to significant morbidity and mortality in elderly. Children typically have mild illness with rare mortalities. Age and comorbid medical conditions are the most important determinant of the infection outcome. Currently there is no clear explanation for difference in disease severity and outcome in different age groups. Based on evolutionary biology and translational research this review suggests that high antioxidant capacity of children leading to a balanced redox state is the key factor for mild SARS-COV-2 infections in this age group. On the other hand, elderly with low antioxidant capacity and ACE2 expression is prone to severe infections by redox sensitive immune modulation.

positive: Children with coronavirus disease 2019: A review of demographic, clinical, laboratory, and imaging features in pediatric patients There is a current outbreak of coronavirus disease 2019 (COVID‐19), with a global spread. With the rapid increase in the number of infections, an increase is observed in the number of children with COVID‐19. Most research findings are regarding adult cases, which are not always transferrable to children. Evidence‐based studies are still expected to formulate clinical decisions for pediatric patients. In this review, we included 2597 pediatric patients that reported recently and evaluated the demographic, clinical, laboratory, and imaging features of children with COVID‐19. We found that even lymphopenia was the most common lab finding in adults; it infrequently occurred in children (9.8%). Moreover, elevated creatine kinase MB isoenzyme was much more commonly observed in children (27.0%) than that in adults, suggesting that heart injury would be more likely to occur in pediatric patients. Our analysis may contribute to determine the spectrum of disease in children and to develop strategies to control the disease transmission.

positive: Responding to the accumulation of adverse childhood experiences in the wake of the COVID-19 pandemic: implications for practice In early 2020, the world as we knew it began to change dramatically and rapidly with the COVID-19 outbreak. Social distancing restrictions and lockdown measures have been the most effective course of action and an inarguably imperative approach at this time. However, in trying to keep the global population safe, social distancing measures unwittingly placed children already experiencing maltreatment and disadvantage in harm’s way. This paper will consider the evidence base which attests to the importance of considering the accumulation of adversity when seeking to understand risk and impact of child maltreatment and disadvantage. Given the unique and unprecedented circumstances which have accompanied the COVID-19 outbreak, and the dearth of research pertaining to the impact of pandemics on child welfare, the paper draws on an emerging body of literature about the effect of natural disasters, conflict and significant global events on child maltreatment. The paper synthesises the research to date in order to call attention to the cumulative impact of the COVID-19 pandemic on children already experiencing abuse and neglect. The paper concludes with an outline of the implications for practice in the helping professions.

positive: Managing COVID-19 Iinfection in pediatric patients. Children are less likely to be infected with SARS-CoV-2 than adults and often have a milder course of illness and a lower case fatality rate. Children account for an estimated 1% to 5% of those diagnosed with COVID-19.1 Even so, pre-school-aged children, infants, and children with underlying health conditions may still be at risk for severe disease and complications.2 Unique aspects of COVID-19 presentation and course in children and possible vertical transmission to newborns from COVID-19-positive mothers are discussed.

positive: Clinical Analysis of 25 Novel Coronavirus Infections in Children. BACKGROUND To describe the characteristics of clinical manifestations of children with 2019 novel coronavirus (2019-nCoV) infection in Chongqing. METHODS All 25 children with laboratory-confirmed 2019-nCoV infection by real-time reverse transcription-PCR (RNA-PCR) were admitted from the 4 designated treatment hospitals of 2019-nCoV in Chongqing from January 19 to March 12, 2020. Clinical data and epidemiological history of these patients were retrospectively collected and analyzed. RESULTS The diagnosis was confirmed through RNA-PCR testing. Among the 25 cases, 14 were males and 11 were females. The median age was 11.0 (6.3-14.5) years (range 0.6-17.0 years). All children were related to a family cluster outbreak, and 7 children (28%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 8 (32%) asymptomatic, 4 (16%) very mild cases and 13 (52%) common cases. No severe or critical cases were identified. The most common symptoms were cough (13 cases, 52%) and fever (6 cases, 24%). The duration time of clinical symptoms was 13.0 (8.0-25.0) days. In the 25 cases, on admission, 21 cases (84%) had normal white blood cell counts, while only 2 cases (8%) more than 10 × 10/L and 2 cases (8%) less than 4 × 10/L, respectively; 22 cases(88%) had normal CD4+ T lymphocyte counts, while in the remaining 3 cases(8%) this increased mildly; 23 cases had normal CD8+ T lymphocyte counts, while in the remaining 2 cases (8%) CD8+ T lymphocyte counts were mildly increased as well. All Lymphocyte counts were normal. There were no statistical differences of lab results between the groups of asymptomatic cases, mild cases and common cases. There were only 13 cases with abnormal CT imaging, most of which were located in the subpleural area of the bottom of the lung. All patients were treated with interferon, 6 cases combined with Ribavirin, and 12 cases combined with lopinavir or ritonavir. The days from onset to RNA turning negative was 15.20 ± 6.54 days. There was no significant difference of RNA turning negative between the groups of interferon, interferon plus ribavirin and interferon plus lopinavir or ritonavir treatment. All the cases recovered and were discharged from hospital. CONCLUSIONS The morbidity of 2019-nCoV infection in children is lower than in adults and the clinical manifestations and inflammatory biomarkers in children are nonspecific and milder than that in adults. RNA-PCR test is still the most reliable diagnostic method, especially for asymptomatic patients.

positive: Severe and fatal forms of COVID-19 in children ABSTRACT OBJECTIVES: The aim of this study was to describe severe forms of novel coronavirus disease 2019 in children, including patient characteristics, clinical, laboratory, and imaging findings, as well as the disease management and outcomes. METHODS: This was a retrospective, single-center, observational study conducted in a pediatric intensive and high-dependency care unit (PICU, HDU) in an urban hospital in Paris. All patients, aged from 1 month to 18 years, admitted for confirmed or highly suspected SARS-CoV-2 were included. RESULTS: We analyzed the data of 27 children. Comorbidities (n = 19, 70 %) were mainly neurological (n = 7), respiratory, (n = 4), or sickle cell disease (n = 4). SARS-CoV-2 PCR results were positive in 24 children (nasopharyngeal swabs). The three remaining children had a chest CT scan consistent with COVID-19. Respiratory involvement was observed in 24 patients (89%). Supportive treatments were invasive mechanical ventilation (n = 9), catecholamine (n = 4), erythropheresis (n = 4), renal replacement therapy (n = 1), and extracorporeal membrane oxygenation (n = 1). Five children died, of whom three were without past medical history. CONCLUSION: This study highlighted the large spectrum of clinical presentation and time course of disease progression as well as the non-negligible occurrence of pediatric life-threatening and fatal cases of COVID-19 mostly in patients with comorbidities. Additional laboratory investigations are needed to further analyze the mechanism underlying the variability of SARS-Cov-2 pathogenicity in children

positive: Severe and fatal forms of COVID-19 in children OBJECTIVES: The aim of this study was to describe severe forms of novel coronavirus disease 2019 in children, including patient characteristics, clinical, laboratory, and imaging findings, as well as the disease management and outcomes. METHODS: This was a retrospective, single-center, observational study conducted in a pediatric intensive and high-dependency care unit (PICU, HDU) in an urban hospital in Paris. All patients, aged from 1 month to 18 years, admitted for confirmed or highly suspected SARS-CoV-2 were included. RESULTS: We analyzed the data of 27 children. Comorbidities (n=19, 70%) were mainly neurological (n=7), respiratory, (n=4), or sickle cell disease (n=4). SARS-CoV-2 PCR results were positive in 24 children (nasopharyngeal swabs). The three remaining children had a chest CT scan consistent with COVID-19. Respiratory involvement was observed in 24 patients (89%). Supportive treatments were invasive mechanical ventilation (n=9), catecholamine (n=4), erythropheresis (n=4), renal replacement therapy (n=1), and extracorporeal membrane oxygenation (n=1). Five children died, of whom three were without past medical history. CONCLUSION: This study highlighted the large spectrum of clinical presentation and time course of disease progression as well as the non-negligible occurrence of pediatric life-threatening and fatal cases of COVID-19 mostly in patients with comorbidities. Additional laboratory investigations are needed to further analyze the mechanism underlying the variability of SARS-Cov-2 pathogenicity in children.

positive: Understanding the age divide in COVID-19: why are children overwhelmingly spared? The rapid emergence and subsequent global dissemination of SARS-CoV-2 disease (COVID-19) has resulted in over 4 million cases worldwide. The disease has a marked predilection for adults, and children are relatively spared. Understanding the age-based differences in pathophysiological pathways and processes relevant to the onset and progression of disease both in the clinical course and in experimental disease models may hold the key to the identification of therapeutic targets. The differences in the clinical course are highlighted by the lack of progression of the SARS-CoV-2 infection beyond mild symptoms in a majority of children, whereas in adults the disease progresses to acute lung injury and an acute respiratory distress syndrome (ARDS)-like phenotype with high mortality. The pathophysiological mechanisms leading to decreased lung injury in children may involve the decreased expression of the mediators necessary for viral entry into the respiratory epithelium and differences in the immune system responses in children. Specifically, decreased expression of proteins, including angiotensin-converting enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) in the airway epithelium in children may prevent viral entry. The immune system differences may include a relative preponderance of CD4(+) T cells, decreased neutrophil infiltration, decreased production of proinflammatory cytokines, and increased production of immunomodulatory cytokines in children compared with adults. Notably, the developing lung in children may have a greater capacity to recover and repair after viral infection. Understanding the relative contributions of the above processes to the protective phenotype in the developing lung can guide the trial of the appropriate therapies in adults.

positive: Epidemiological features and viral shedding in children with SARS‐CoV‐2 infection BACKGROUND: A pandemic of SARS‐CoV‐2 infection broke out all over the world, however, epidemiological data and viral shedding in pediatric patients are limited. METHODS: We conducted a retrospective, multi‐center study, and followed up with all children from the families with SARS‐CoV‐2 infected members in Zhejiang Province, China. All infections were confirmed by testing the SARS‐CoV‐2 RNA with RT‐PCR method, and epidemiological data between children and adults in the same families was compared. Effect of antiviral therapy was evaluated observationally and fecal viral excretion times among groups with different antiviral regiments were compared with Kaplan Meier plot. RESULTS: By February 29, 2020, 1298 cases from 883 families were confirmed with SARS‐CoV‐2 infection and 314 of which were families with children. Incidence of infection in child close contacts was significantly lower than that in adult contacts (13.2% vs 21.2%). The mean age of 43 pediatric cases was 8.2 years and mean incubation period was 9.1 days. Forty (93.0%) were family clustering. Thirty‐three children had COVID‐19 (20 pneumonia) with mild symptoms and 10 were asymptomatic. Fecal SARS‐CoV‐2 RNA detection was positive in 91.4% (32/35) cases and some children had viral excretion time over 70 days. Viral clearance time was not different among the groups treated with different antiviral regiments. No subsequent infection was observed in family contacts of fecal‐viral‐excreting children. CONCLUSION: Children have lower susceptibility of SARS‐CoV‐2 infection, longer incubation and fecal viral excretion time. Positive results of fecal SARS‐CoV‐2 RNA detection were not used as indication for hospitalization or quarantine. This article is protected by copyright. All rights reserved.

negative: The Father-Daughter Dinner Dance: A Waltz With Ethics and COVID-19 Commentary on "The Father-Daughter Dinner Dance: A Waltz With Ethics and COVID-19"

negative: COVID-19 pandemic and mental health consequences: systematic review of the current evidence BACKGROUND: During the COVID-19 pandemic general medical complications have received the most attention, whereas only few studies address the potential direct effect on mental health of SARS-CoV-2 and the neurotropic potential. Furthermore, the indirect effects of the pandemic on general mental health are of increasing concern, particularly since the SARS-CoV-1 epidemic (2002-2003) was associated with psychiatric complications. METHODS: We systematically searched the database Pubmed including studies measuring psychiatric symptoms or morbidities associated with COVID-19 among infected patients and among none infected groups the latter divided in psychiatric patients, health care workers and non-health care workers. RESULTS: A total of 43 studies were included. Out of these, only two studies evaluated patients with confirmed COVID-19 infection, whereas 41 evaluated the indirect effect of the pandemic (2 on patients with preexisting psychiatric disorders, 20 on medical health care workers, and 19 on the general public). 18 of the studies were case-control studies/compared to norm, while 25 of the studies had no control groups. The two studies investigating COVID-19 patients found a high level of post-traumatic stress symptoms (PTSS) (96.2%) and significantly higher level of depressive symptoms (p=0.016). Patients with preexisting psychiatric disorders reported worsening of psychiatric symptoms. Studies investigating health care workers found increased depression/depressive symptoms, anxiety, psychological distress and poor sleep quality. Studies of the general public revealed lower psychological well-being and higher scores of anxiety and depression compared to before COVID-19, while no difference when comparing these symptoms in the initial phase of the outbreak to four weeks later. A variety of factors were associated with higher risk of psychiatric symptoms and/or low psychological well-being including female gender, poor-self-related health and relatives with COVID-19. CONCLUSION: Research evaluating the direct neuropsychiatric consequences and the indirect effects on mental health is highly needed to improve treatment, mental health care planning and for preventive measures during potential subsequent pandemics.

negative: Age-adjusted associations between comorbidity and outcomes of COVID-19: a review of the evidence Background: Current evidence suggests that older people and people with underlying comorbidities are at increased risk of severe disease and death following hospitalisation with COVID-19. As comorbidity increases with age, it is necessary to understand the age-adjusted relationship between comorbidity and COVID-19 outcomes, in order to enhance planning capabilities and our understanding of COVID-19. Methods: We conducted a rapid, comprehensive review of the literature up to 10 April 2020, to assess the international empirical evidence on the association between comorbidities and severe or critical care outcomes of COVID-19, after accounting for age, among hospitalised patients with COVID-19. Results: After screening 579 studies, we identified seven studies eligible for inclusion and these were synthesised narratively. All were from China. The emerging evidence base mostly indicates that after adjustment for age (and in some cases other potential confounders), obesity, hypertension, diabetes mellitus, chronic obstructive airways disease (COPD), and cancer are all associated with worse outcomes. The largest study, using a large nationwide sample of COVID-19 patients in China, found that those with multiple comorbidities had more than twice the risk of a severe outcome or death compared with patients with no comorbidities, after adjusting for age and smoking (HR=2.59, 95% CI 1.61, 4.17). Conclusions: This review summarises for clinicians, policymakers, and academics the most robust evidence to date on this topic, to inform the management of patients and control measures for tackling the pandemic. Given the intersection of comorbidity with ethnicity and social disadvantage, these findings also have important implications for health inequalities. As the pandemic develops, further research should confirm these trends in other settings outside China and explore mechanisms by which various underlying health conditions increase risk of severe COVID-19.

negative: The relationship between a trusted adult and adolescent outcomes: a protocol of a scoping review. BACKGROUND Although documentation of harm towards children and young people has existed for centuries, it was not until the 1960s that it became a specific focus for health professionals. Since that time, the importance of protective social networks has become better understood. The concept of trusted adults has come into sharper focus, with children being encouraged to develop networks of dependable adults to turn to for support in times of need. While many child protection processes highlight risks to younger children, there has been less emphasis on older children. The role of trusted adults may be particularly important during adolescence, due to burgeoning independence, developing sexuality, relationship formation, and associated vulnerabilities. While important choices relating to health and education are made during this period, there is little formal evidence relating to the impact of trusted adults on such outcomes. This review therefore aims to focus on the role and influence of trusted adults for adolescents. METHODS This study is a scoping review. A broad range of databases will be searched, including MEDLINE, ERIC, Education Abstracts, Web of Science, ASSIA, Sociological Abstracts, and PsycINFO. Predefined inclusion/exclusion criteria will be used, with a focus on outcomes relating to health and education. Two reviewers will blind screen papers independently at all screening stages, with conflicts being resolved by a third reviewer. Quantitative and qualitative studies, as well as unpublished (grey) literature/reports, will be included. We will use the World Health Organization's 'second decade' definition of adolescence. We aim to collate and map evidence in a broad overview and produce meta-analyses of homogenous data. Where this is not possible, a narrative summary will be produced. DISCUSSION There appears to be sparse knowledge regarding the role of trusted adults for adolescents. Potential benefits to health and wellbeing may impact on educational attainment, and vice versa. These areas are of particular relevance during the second decade, when decisions that affect future direction, achievement, and wellbeing are being made. The increased understanding of the role of trusted adults provided by this review may help to inform practice and policy and lead to potential benefits for the health and education of adolescents. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD 42017076739.

negative: Neonatal Late Onset Infection with Severe Acute Respiratory Syndrome Coronavirus 2 Objective To date, no information on late-onset infection in newborns to mother with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contracted in pregnancy are available. This study aimed to evaluate postdischarge SARS-CoV-2 status of newborns to mothers with COVID-19 in pregnancy that, at birth, were negative to SARS-CoV-2. Study Design This is an observational study of neonates born to mothers with coronavirus disease 2019 (COVID-19). Results Seven pregnant women with documented SARS-CoV-2 infection have been evaluated in our institution. One woman had a spontaneous abortion at 8 weeks of gestational age, four women recovered and are still in follow-up, and two women delivered. Two newborns were enrolled in the study. At birth and 3 days of life, newborns were negative to SARS-CoV-2. At 2-week follow-up, one newborn tested positive although asymptomatic. Conclusion Our findings highlight the importance of follow-up of newborns to mothers with COVID-19 in pregnancy, since they remain at risk of contracting the infection in the early period of life and long-term consequences are still unknown. Key Points: Newborns to mothers with coronavirus disease 2019 (COVID-19) in pregnancy can acquire the infection later after birth. Newborns to mothers with COVID-19 in pregnancy need a long-term follow-up, even if they tested negative at birth. Specific guidelines for the long-term follow-up of newborns to mothers with COVID-19 in pregnancy are needed.

negative: Vaccinating children against influenza: overall cost-effective with potential for undesirable outcomes BACKGROUND: The present study aims to assess the cost-effectiveness of an influenza vaccination program for children in the Netherlands. This requires an evaluation of the long-term impact of such a program on the burden of influenza across all age groups, using a transmission model that accounts for the seasonal variability in vaccine effectiveness and the shorter duration of protection following vaccination as compared to natural infection. METHODS: We performed a cost-effectiveness analysis based on a stochastic dynamic transmission model that has been calibrated to reported GP visits with influenza-like illness in the Netherlands over 11 seasons (2003/2004 to 2014/2015). We analyzed the costs and effects of extending the current program with vaccination of children aged 2–16 years at 50% coverage over 20 consecutive seasons. We measured the effects in quality-adjusted life-years (QALYs) and we adopted a societal perspective. RESULTS: The childhood vaccination program is estimated to have an average incremental cost-effectiveness ratio (ICER) of €3944 per QALY gained and is cost-effective in the general population (across 1000 simulations; conventional Dutch threshold of €20,000 per QALY gained). The childhood vaccination program is not estimated to be cost-effective for the target-group itself with an average ICER of €57,054 per QALY gained. Uncertainty analyses reveal that these ICERs hide a wide range of outcomes. Even though introduction of a childhood vaccination program decreases the number of infections, it tends to lead to larger epidemics: in 23.3% of 1000 simulations, the childhood vaccination program results in an increase in seasons with a symptomatic attack rate larger than 5%, which is expected to cause serious strain on the health care system. In 6.4% of 1000 simulations, the childhood vaccination program leads to a net loss of QALYs. These findings are robust across different targeted age groups and vaccination coverages. CONCLUSIONS: Modeling indicates that childhood influenza vaccination is cost-effective in the Netherlands. However, childhood influenza vaccination is not cost-effective when only outcomes for the children themselves are considered. In approximately a quarter of the simulations, the introduction of a childhood vaccination program increases the frequency of seasons with a symptomatic attack rate larger than 5%. The possibility of an overall health loss cannot be excluded.

negative: Aetiology of childhood pneumonia in a well vaccinated South African birth cohort: a nested case-control study of the Drakenstein Child Health Study Summary Background Pneumonia is a leading cause of mortality and morbidity in children globally. The cause of pneumonia after introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) has not been well studied in low-income and middle-income countries, and most data are from cross-sectional studies of children admitted to hospital. We aimed to longitudinally investigate the incidence and causes of childhood pneumonia in a South African birth cohort. Methods We did a nested case-control study of children in the Drakenstein Child Health Study who developed pneumonia from May 29, 2012, to Dec 1, 2014. Children received immunisations including acellular pertussis vaccine and PCV13. A nested subgroup had nasopharyngeal swabs collected every 2 weeks throughout infancy. We identified pneumonia episodes and collected blood, nasopharyngeal swabs, and induced sputum specimens. We used multiplex real-time PCR to detect pathogens in nasopharyngeal swabs and induced sputum of pneumonia cases and in nasopharyngeal swabs of age-matched and site-matched controls. To show associations between organisms and pneumonia we used conditional logistic regression; results are presented as odds ratios (ORs) with 95% CIs. Findings 314 pneumonia cases occurred (incidence of 0·27 episodes per child-year, 95% CI 0·24–0·31; median age 5 months [IQR 3–9]) in 967 children during 1145 child-years of follow-up. 60 (21%) cases of pneumonia were severe (incidence 0·05 episodes per child-year [95% CI 0·04–0·07]) with a case fatality ratio of 1% (three deaths). A median of five organisms (IQR 4–6) were detected in cases and controls with nasopharyngeal swabs, and a median of six organisms (4–7) recorded in induced sputum (p=0·48 compared with nasopharyngeal swabs). Bordetella pertussis (OR 11·08, 95% CI 1·33–92·54), respiratory syncytial virus (8·05, 4·21–15·38), or influenza virus (4·13, 2·06–8·26) were most strongly associated with pneumonia; bocavirus, adenovirus, parainfluenza virus, Haemophilus influenzae, and cytomegalovirus were also associated with pneumonia. In cases, testing of induced sputum in addition to nasopharyngeal swabs provided incremental yield for detection of B pertussis and several viruses. Interpretation Pneumonia remains common in this highly vaccinated population. Respiratory syncytial virus was the most frequently detected pathogen associated with pneumonia; influenza virus and B pertussis were also strongly associated with pneumonia. Testing of induced sputum increases the yield for detection of several organisms. New vaccines and strategies are needed to address the burden of childhood pneumonia. Funding Bill & Melinda Gates Foundation, Medical Research Council South Africa, National Research Foundation South Africa, National Institute of Health, and H3Africa.

negative: COVID-19 and the US response: accelerating health inequities Health inequities have long defined health and the healthcare system in the USA. The clinical and research capacity across the USA is unparalleled, yet compared to other high and even some middle-income countries, the average health indicators of the population remain suboptimal in 2020, a finding at least in part explained by inequity in healthcare access. In this context, COVID-19 has rapidly emerged as a major threat to the public’s health. While it was initially thought that severe acute respiratory syndrome coronavirus 2 would be the great equaliser as it would not discriminate, it is clear that COVID-19 incidence and mortality have rapidly reinforced health disparities drawn by historical and contemporary inequities. Here, we synthesise the data highlighting specific risks among particular marginalised and under-resourced communities including those in jails, prisons and detention centers, immigrants and the undocumented, people with disabilities and people experiencing homelessness across the USA. The drivers of these disparities are pervasive structural risks including limited access to preventive services, inability to comply with physical distancing recommendations, underlying health disparities and intersecting stigmas particularly affecting racial and ethnic minorities across the country, including African Americans, Latinx Americans and Native Americans. Advancing the COVID-19 response, saving lives and restarting the economy necessitate rapidly addressing these inequities rather than ignoring and even reinforcing them.

negative: Are They Just Two Children COVID-19 Cases Confused With Flu? COVID-19, an emerging infectious disease, has quickly spread all over the world. All human populations are susceptible to this disease. Here we present two pediatric COVID-19 cases, both of whom exhibited negative SARS-CoV-2 nucleic acid tests upon nasopharyngeal swab and were initially diagnosed with influenza A infection. COVID-19 was later confirmed in both patients by serum antibodies of SARS-CoV-2 and nucleic acid test on stool samples. Because children are susceptible to many respiratory pathogens, especially influenza, we concluded that children can be coinfected with multiple pathogens, and more attention should be paid to the exploration of SARS-CoV-2 during the pandemic of COVID-19. This report shows the possibility of misdiagnosis or missed diagnosis of children with COVID-19. We suggest that highly suspected pediatric COVID-19 cases with negative nucleic acid tests on nasopharyngeal swabs should be further checked by performing a nucleic acid test on stool samples and testing serum for antibodies against SARS-CoV-2.

negative: The impact of the Covid-19 pandemic in the precipitation of intimate partner violence Intimate Partner Violence (IPV) is a global pandemic and many have been victims of it long before Covid-19. International organizations have documented an increase in IPV reports during the current pandemic, raising awareness of the potential causes for such an increase. Reflecting on risk factors associated with IPV, and the underlying need of the perpetrators to exert control over the victims, it becomes increasingly important to understand how the current policies of social distancing, self-isolation, and lockdown can precipitate episodes of IPV. Furthermore, access to specialized services and health care can be compromised, and health care professionals face new challenges and demands imposed by the pandemic while managing IPV cases. This article begins by examining the main risk factors more commonly associated with IPV in the literature. It proceeds by reflecting on how these risk factors may be exacerbated during the Covid-19 pandemic, which can explain the increased number of reports. Finally, it emphasizes the new challenges faced by health care professionals, while assisting IPV victims during the pandemic and provides possible recommendations on actions to implement during and beyond the Covid-19 pandemic to prevent such cases.

negative: Psychological Effects of COVID-19 on Children of Health Care Workers

negative: Systematic evidence-based review: outcomes from exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability PURPOSE: Exome and genome sequencing (ES/GS) are performed frequently in patients with congenital anomalies, developmental delay, or intellectual disability (CA/DD/ID), but the impact of results from ES/GS on clinical management and patient outcomes is not well characterized. A systematic evidence review (SER) can support future evidence-based guideline development for use of ES/GS in this patient population. METHODS: We undertook an SER to identify primary literature from January 2007 to March 2019 describing health, clinical, reproductive, and psychosocial outcomes resulting from ES/GS in patients with CA/DD/ID. A narrative synthesis of results was performed. RESULTS: We retrieved 2654 publications for full-text review from 7178 articles. Only 167 articles met our inclusion criteria, and these were primarily case reports or small case series of fewer than 20 patients. The most frequently reported outcomes from ES/GS were changes to clinical management or reproductive decision-making. Two studies reported on the reduction of mortality or morbidity or impact on quality of life following ES/GS. CONCLUSION: There is evidence that ES/GS for patients with CA/DD/ID informs clinical and reproductive decision-making, which could lead to improved outcomes for patients and their family members. Further research is needed to generate evidence regarding health outcomes to inform robust guidelines regarding ES/GS in the care of patients with CA/DD/ID.

negative: Histopathology and genetic susceptibility in COVID-19 pneumonia BACKGROUND: The clinical features of COVID-19 pneumonia range from a mild illness to patients with a very severe illness with acute hypoxemic respiratory failure requiring ventilation and Intensive Care Unit admission. AIMS: To provide a brief overview of the existing evidence for such differences in host response and outcome, and generate hypotheses for divergent patterns and avenues for future research, by highlighting similarities and differences in histopathological appearance between COVID-19 and influenza as well as previous coronavirus outbreaks, and by discussing predisposition through genetics and underlying disease. MATERIALS AND METHOD: We assessed the available early literature for histopathological patterns of COVID-19 pneumonia and underlying risk factors. RESULT: The histopathological spectrum of COVID-19 pneumonia includes variable patterns of epithelial damage, vascular complications, fibrosis and inflammation. Risk factors for a fatal disease include older age, respiratory disease, diabetes mellitus, obesity and hypertension. DISCUSSION: While some risk factors and their potential role in COVID-19 pneumonia are increasingly recognized, little is known about the mechanisms behind episodes of sudden deterioration or the infrequent idiosyncratic clinical demise in otherwise healthy and young subjects. CONCLUSION: The answer to many of the remaining questions regarding COVID-19 pneumonia pathogenesis may in time be provided by genotyping as well careful clinical, serological, radiological and histopathological phenotyping.

negative: Effects of armed conflict on child health and development: A systematic review. BACKGROUND Armed conflicts affect more than one in 10 children globally. While there is a large literature on mental health, the effects of armed conflict on children's physical health and development are not well understood. This systematic review summarizes the current and past knowledge on the effects of armed conflict on child health and development. METHODS A systematic review was performed with searches in major and regional databases for papers published 1 January 1945 to 25 April 2017. Included studies provided data on physical and/or developmental outcomes associated with armed conflict in children under 18 years. Data were extracted on health outcomes, displacement, social isolation, experience of violence, orphan status, and access to basic needs. The review is registered with PROSPERO: CRD42017036425. FINDINGS Among 17,679 publications screened, 155 were eligible for inclusion. Nearly half of the 131 quantitative studies were case reports, chart or registry reviews, and one-third were cross-sectional studies. Additionally, 18 qualitative and 6 mixed-methods studies were included. The papers describe mortality, injuries, illnesses, environmental exposures, limitations in access to health care and education, and the experience of violence, including torture and sexual violence. Studies also described conflict-related social changes affecting child health. The geographical coverage of the literature is limited. Data on the effects of conflict on child development are scarce. INTERPRETATION The available data document the pervasive effect of conflict as a form of violence against children and a negative social determinant of child health. There is an urgent need for research on the mechanisms by which conflict affects child health and development and the relationship between physical health, mental health, and social conditions. Particular priority should be given to studies on child development, the long term effects of exposure to conflict, and protective and mitigating factors against the harmful effects of armed conflict on children.

negative: Bronchiectasis exacerbation study on azithromycin and amoxycillin-clavulanate for respiratory exacerbations in children (BEST-2): study protocol for a randomized controlled trial BACKGROUND: Bronchiectasis unrelated to cystic fibrosis (CF) is being increasingly recognized in children and adults globally, both in resource-poor and in affluent countries. However, high-quality evidence to inform management is scarce. Oral amoxycillin-clavulanate is often the first antibiotic chosen for non-severe respiratory exacerbations, because of the antibiotic-susceptibility patterns detected in the respiratory pathogens commonly associated with bronchiectasis. Azithromycin has a prolonged half-life, and with its unique anti-bacterial, immunomodulatory, and anti-inflammatory properties, presents an attractive alternative. Our proposed study will test the hypothesis that oral azithromycin is non-inferior (within a 20% margin) to amoxycillin-clavulanate at achieving resolution of non-severe respiratory exacerbations by day 21 of treatment in children with non-CF bronchiectasis. METHODS: This will be a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group trial involving six Australian and New Zealand centers. In total, 170 eligible children will be stratified by site and bronchiectasis etiology, and randomized (allocation concealed) to receive: 1) azithromycin (5 mg/kg daily) with placebo amoxycillin-clavulanate or 2) amoxycillin-clavulanate (22.5 mg/kg twice daily) with placebo azithromycin for 21 days as treatment for non-severe respiratory exacerbations. Clinical data and a parent-proxy cough-specific quality of life (PC-QOL) score will be obtained at baseline, at the start and resolution of exacerbations, and on day 21. In most children, blood and deep-nasal swabs will also be collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 21. The main secondary outcome is the PC-QOL score. Other outcomes are: time to next exacerbation; requirement for hospitalization; duration of exacerbation, and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood inflammatory markers will be reported where available. DISCUSSION: Currently, there are no published randomized controlled trials (RCT) to underpin effective, evidence-based management of acute respiratory exacerbations in children with non-CF bronchiectasis. To help address this information gap, we are conducting two RCTs. The first (bronchiectasis exacerbation study; BEST-1) evaluates the efficacy of azithromycin and amoxycillin-clavulanate compared with placebo, and the second RCT (BEST-2), described here, is designed to determine if azithromycin is non-inferior to amoxycillin-clavulanate in achieving symptom resolution by day 21 of treatment in children with acute respiratory exacerbations. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR) number http://ACTRN12612000010897. http://www.anzctr.org.au/trial_view.aspx?id=347879

negative: Rapid review protocol: zinc for the prevention or treatment of COVID-19 and other coronavirus-related respiratory tract infections Abstract Background . The global COVID-19 pandemic has prompted an urgent search for effective interventions. SARS-CoV-2 mortality/morbidity risk increases with age and for those chronic disease co-morbidities, both of which are associated with lower zinc status, as is the risk of infection. Methods Rapid review methods will be applied to a systematic review of zinc for the prevention or treatment of SARS-CoV-2 and viral respiratory tract infections in humans. Included are published studies reporting randomised and quasi-randomised controlled trials that compare zinc intervention to placebo and/or other comparator interventions. English and Chinese language databases will be searched for primary studies of viral respiratory tract infections and clinical trial registries for SARS-CoV-2 infections. Due to concerns about indirectness, studies evaluating non-SARS-CoV-2 coronavirus infections will be rated down by one level, and non-specific or confirmed non-coronavirus viral infections will be rated down by two levels. Review constraints include 1) using Google translate when screening articles published in languages other than English or Chinese and limited translation 2) following calibration, only one reviewer will screen articles, extract data, appraise quality and conduct the analysis, 3) prioritising data extraction and meta-analyses of SARS-CoV-2 studies and critical outcomes of other viral infections, followed by high risk groups and 4) reporting important preliminary findings prior to peer review if necessary. Discussion . The application of these rapid review methods and broadening the inclusion criteria to include other coronavirus-related viral respiratory tract infections aims to enable a timely evidence appraisal of priority research questions and dissemination of results.

negative: Covid-19 and children with cancer: are they at increased risk of infection?

negative: Common phobias among Egyptian primary schoolchildren: an emergency trigger for panic disorder due to corona pandemic. (Special Issue: Coronavirus disease (COVID-19).) BACKGROUND: In the wake of the adverse situation we are currently facing globally due to the coronavirus pandemic outbreak, it is normal to feel stressed, confused, and scared but what is abnormal is to turn this to panic Phobias are more pronounced than fears They develop when a person has an exaggerated or unrealistic sense of danger that may be evolved to experience panic attacks AIM: Our objective was to identify the prevalence of most common phobias as well as panic disorder (PD) due to the coronavirus pandemic among Egyptian primary schoolchildren and their determinants METHODS: A cross-sectional study was conducted among 2015 schoolchildren from 3 to 6 grades in three governorates of Egypt Seven types of phobias were investigated: Agoraphobia, phobias from darkness, animal, untreatable illness (mainly coronavirus), insects, height, and social phobia The child's self-reported PD symptoms were assessed using DSM-IV with psychiatric diagnoses RESULTS: Almost two-thirds of the surveyed primary schoolchildren have phobias of the low score (9) versus one-third who had high phobias score (61 % vs 35%, respectively) with highly significant difference (p 0 001) The most prevalent phobias were from heights (66 5%) followed by darkness (60 0%) The important predictors of phobias were: Being a male child, living in an urban area, and studying at governmental school at fifth or sixth-grade residence The prevalence of PD due to the corona epidemic is very high, it is reported by almost half of the surveyed primary schoolchildren Fear of losing any of their family members, especially grandparents, was reported to be the highest PD symptom (97%) CONCLUSION AND RECOMMENDATION: Phobia from heights and darkness was the most common The prevalence of PD due to the coronavirus epidemic is reported to be very high Calming down children who might be experienced with a phobia that is triggering their PD is recommended

negative: Predicting COVID-19 Incidence Using Anosmia and Other COVID-19 Symptomatology: Preliminary Analysis Using Google and Twitter OBJECTIVE: To determine the relative correlations of Twitter and Google Search user trends concerning smell loss with daily coronavirus disease 2019 (COVID-19) incidence in the United States, compared to other severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) symptoms. To describe the effect of mass media communications on Twitter and Google Search user trends. STUDY DESIGN: Retrospective observational study. SETTING: United States. SUBJECTS AND METHODS: Google Search and “tweet” frequency concerning COVID-19, smell, and nonsmell symptoms of COVID-19 generated between January 1 and April 8, 2020, were collected using Google Trends and Crimson Hexagon, respectively. Spearman coefficients linking each of these user trends to COVID-19 incidence were compared. Correlations obtained after excluding a short timeframe (March 22 to March 24) corresponding to the publication of a widely read lay media publication reporting anosmia as a symptom of infection was performed for comparative analysis. RESULTS: Google searches and tweets concerning all nonsmell symptoms (0.744 and 0.761, respectively) and COVID-19 (0.899 and 0.848) are more strongly correlated with disease incidence than smell loss (0.564 and 0.539). Twitter users tweeting about smell loss during the study period were more likely to be female (52%) than users tweeting about COVID-19 more generally (47%). Tweet and Google Search frequency pertaining to smell loss increased significantly (>2.5 standard deviations) following a widely read media publication linking smell loss and SARS-CoV-2 infection. CONCLUSIONS: Google Search and tweet frequency regarding fever and shortness of breath are more robust indicators of COVID-19 incidence than anosmia. Mass media communications represent important confounders that should be considered in future analyses.

negative: A framework for identifying and mitigating the equity harms of COVID-19 policy interventions Abstract: Introduction Coronavirus disease 2019 (COVID-19) is a global pandemic. Governments have implemented combinations of ‘lockdown’ measures of various stringencies, including school and workplace closures, cancellations of public events, and restrictions on internal and external movements. These policy interventions are an attempt to shield high risk individuals and to prevent overwhelming countries’ healthcare systems, or, colloquially, ‘flatten the curve’. However, these policy interventions may come with physical and psychological health harms, group and social harms, and opportunity costs. These policies may particularly affect vulnerable populations and not only exacerbate pre-existing inequities, but also generate new ones. Methods We developed a conceptual framework to identify and categorise adverse effects of COVID-19 lockdown measures. We based our framework on Lorenc and Oliver’s framework for the adverse effects of public health interventions and the PROGRESS-Plus equity framework. To test its application we purposively sampled COVID-19 policy examples from around the world and evaluated them for the potential physical, psychological, and social harms, as well as opportunity costs, in each of the PROGRESS-Plus equity domains: Place of residence, Race/ethnicity, Occupation, Gender/sex, Religion, Education, Socioeconomic status, Social capital, Plus (age, and disability). Results We found examples of inequitably distributed adverse effects for each COVID-19 lockdown policy example, stratified by LMIC and HIC, in every PROGRESS-Plus equity domain. We identified known policy interventions intended to mitigate some of these adverse effects. The same harms (anxiety; depression; food insecurity; loneliness; stigma; violence) appear to be repeated across many groups, and are exacerbated by several COVID-19 policy interventions. Conclusion Our conceptual framework highlights the fact that COVID-19 policy interventions can generate or exacerbate interactive and multiplicative equity harms. Applying this framework can help in three ways: (1) identifying areas where a policy intervention may generate inequitable adverse effects; (2) mitigating policy and practice interventions by facilitating the systematic examination of relevant evidence; and (3) planning for lifting COVID-19 lockdowns and policy interventions around the world.

negative: Demographic profile and outcome analysis of a tertiary level pediatric intensive care unit Objective : To study the profile and outcome of children admitted to a tertiary level pediatric intensive care unit (PICU) in India.Methods : Prospective study of patient demographics, PRISM III scores, diagnoses, treatment, morbidity and mortality of all PICU admissions.Results : 948 children were admitted to the PICU. Mean age was 41.48 months. Male to female ratio was 2.95:1. Mean PRISM III score on admission was 18.50. Diagnoses included respiratory (19.7%), cardiac (9.7%), neurological (17.9%), infectious (12.5%), trauma (11.7%), other surgical (8.8%).196 children (20.68%) required mechanical ventilation. Average duration of ventilation was 6.39 days. 27 children (30.7 children /1000 admissions) had acute respiratory distress syndrome. Gross mortality was 6.7% (59 patients). PRISMIII adjusted mortality was directly proportional to PRISMIII scores. 49.5% of nonsurvivors had multiorgan failure. Average length of PICU stay was 4.52 +/−2.6 days. Complications commonly encountered Were atelectasis (6.37%), accidental extubation (2%), and pneumothorax (0.9%). Incidence of nosocomial infections was 16.86%.Conclusion : Our data appears to be similar with regards to PRISMIII scores and adjusted mortality, length of the PICU stay, and duration of ventilation, to previously published western data. Multiorgan failure remains a major cause of death. As expected, Dengue and malaria were common. Incidence of nosocomial infections was somewhat high. Interestingly, more boys got admitted to the PICU as compared to girls. Clearly more studies are required to assess the overall outcomes of critically ill children in India

negative: Management of newborns exposed to mothers with confirmed or suspected COVID-19 There is limited information about newborns with confirmed or suspected COVID-19. Particularly in the hospital after delivery, clinicians have refined practices in order to prevent secondary infection. While guidance from international associations is continuously being updated, all facets of care of neonates born to women with confirmed or suspected COVID-19 are center-specific, given local customs, building infrastructure constraints, and availability of protective equipment. Based on anecdotal reports from institutions in the epicenter of the COVID-19 pandemic close to our hospital, together with our limited experience, in anticipation of increasing numbers of exposed newborns, we have developed a triage algorithm at the Penn State Hospital at Milton S. Hershey Medical Center that may be useful for other centers anticipating a similar surge. We discuss several care practices that have changed in the COVID-19 era including the use of antenatal steroids, delayed cord clamping (DCC), mother–newborn separation, and breastfeeding. Moreover, this paper provides comprehensive guidance on the most suitable respiratory support for newborns during the COVID-19 pandemic. We also present detailed recommendations about the discharge process and beyond, including providing scales and home phototherapy to families, parental teaching via telehealth and in-person education at the doors of the hospital, and telehealth newborn follow-up.

negative: ASSESSING THE ROLE OF ZINC IN COVID-19 INFECTIONS AND MORTALITY: IS ZINC DEFICIENCY A RISK FACTOR FOR COVID-19? Variables responsible for the differential COVID-19 pandemic severity among countries remain undefined. Zinc, a micronutrient required for immunocompetence, is found deficient in populations. We hypothesized the differential COVID-19 severity observed among European countries could be associated with the Zn-deficiency prevalence. The COVID-19 data from different stages of pandemic i.e., 8 April, 12 and 26 May 2020, were analyzed for covariation with the estimated Zn-deficiency. A significant, relatively stable, but negative correlation of Zn-deficiency with cases per million for the time period (r(20): -0.4930 to -0.5335, p-value: 0.02720 to 0.0154) and a steady improvement of covariation with deaths per million (r(20): -0.4056; p-value: 0.0760 on 26 May 2020) was observed. Considering, Zinc 's key immunomodulatory role, widespread deficiency along with the self- and prescribed intervention in different target groups, e.g. children, women, elderly, carefully planned dedicated exploratory studies to understand the basis of the observed association are advisable.

negative: Comment les enfants et adolescents avec le trouble déficit d'attention/hyperactivité (TDAH) vivent-ils le confinement durant la pandémie COVID-19 ?/ [How do children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD) experience lockdown during the COVID-19 outbreak?] OBJECTIVES: During the COVID-19 pandemic, the French government has decided a general lockdown. This unprecedented situation has raised concerns about children's and adolescent's mental health. Children and adolescents diagnosed with attention deficit hyperactivity disorder (ADHD) may find this context of restrained activity particularly tricky. The objectives of our study are to gather information about the well-being and global life conditions of children and adolescents with ADHD during the COVID-19 outbreak in France. METHODS: We designed a survey including both open-ended questions and questionnaire items for parents of children and adolescents with ADHD. Parents responded to the following open-ended questions: 1) "How is your child doing since the lockdown?" 2) "How is life at home since the lockdown?" 3) "If you had a remote service provision with a mental health professional (e.g. by telephone or video technology), please share your thoughts and any suggestions with us" 4) "Please share any other items that you think are important about ADHD symptoms of your child and the lockdown situation". This survey was posted on social media on the 6th of April and disseminated by French ADHD-parent and patient organizations. The present article reports the descriptive, qualitative and textometrical analyses of the survey. RESULTS: Between day 20 and 30 of lockdown, 538 parents responded to the survey, and we included 533 responses in the final analysis. The vast majority of responders were women 95 % (95 % CI 93,50; 97,18) with children whose mean age was 10,5 (95 % CI 7.58; 13.44). Since the lockdown, 34.71 % (95 % CI 30.70; 38.94) of children experienced a worsening in well-being, 34.33 % (95 % CI 30.34; 38.56) showed no significant changes and 30.96 % (95 % CI 27.09; 35.10) were doing better according to their parents. The thematic analysis showed that an improvement of their children's anxiety was one of the main topics addressed by parents. This improvement related to less school-related strain and flexible schedules that respected their children's rhythm. Improved self-esteem was another topic that parents linked with a lesser exposure of their children to negative feed-back. Parents repeatedly reported both inattention and hyperactivity/impulsivity. However, optimal lockdown life conditions seemed to compensate for the impact of ADHD symptoms (e.g. sufficient space at home, presence of a garden). Some parents reported worsening of general well-being in their children, and this manifested as oppositional/defiant attitudes and emotional outbursts. Parents also cited sleep problems and anxiety in this context. As regards everyday life during lock-down, at-home schooling was another major topic-parents described that their children struggled to complete school-related tasks and that teachers seemed to have forgotten about academic accommodations. The lockdown situation seems to have raised parents' awareness of the role of inattention and ADHD symptoms in their children's learning difficulties. Due to potential selection biases, the results of our survey may not be generalizable to all children and adolescents with ADHD. The main strengths of this rapid survey-based study lies in the reactivity of the participants and the quality and diversity of their responses to the open-ended questions. CONCLUSIONS: According to their parents, most children and adolescents with ADHD experience stability or improvement of their well-being. An improvement in school-related anxiety and the flexible adjustment to the children's' rhythms as well as parents' increased awareness of the difficulties their children experience are among the key topics in parents' descriptions.

negative: Health Equity, Social Policy, and Promoting Recovery from COVID-19. The COVID-19 pandemic has revealed starkly and publicly the close interconnections between social and economic inequality, health equity, and population health. To better understand what social policies would best promote population health, economic recovery, and preparedness for future pandemics, we must look both upstream and abroad for inspiration. In this essay, I argue for a suite of near-term and longer-term interventions, including universal health insurance and paid sick leave, upgraded wage insurance policies, tax reform, investments in parental leave, child care, and education, and upgraded government record systems. Policies that equalize the distribution of the social determinants of health and promote social solidarity will also improve population health and economic performance and allow us to confront future pandemics more successfully.

negative: The clinical spectrum of encephalitis in COVID-19 disease: the ENCOVID multicentre study Background: Several preclinical and clinical investigations have argued for nervous system involvement in SARS-CoV-2 infection. Some sparse case reports have described various forms of encephalitis in COVID-19 disease, but very few data have focused on clinical presentations, clinical course, response to treatment and outcomes yet. Objective: to describe the clinical phenotype, laboratory and neuroimaging findings of encephalitis associated with SARS-CoV-2 infection, their relationship with respiratory function and inflammatory parameters and their clinical course and response to treatment. Design: The ENCOVID multicentre study was carried out in 13 centres in northern Italy between February 20th and May 31st, 2020. Only patients with altered mental status and at least two supportive criteria for encephalitis with full infectious screening, CSF, EEG, MRI data and a confirmed diagnosis of SARS-CoV-2 infection were included. Clinical presentation and laboratory markers, severity of COVID-19 disease, response to treatment and outcomes were recorded. Results: Out of 45 cases screened, twenty-five cases of encephalitis positive for SARS-CoV-2 infection with full available data were included. The most common symptoms at onset were delirium (68%), aphasia/dysarthria (24%) and seizures (24%). CSF showed hyperproteinorrachia and/or pleocytosis in 68% of cases whereas SARS-CoV-2 RNA by RT-PCR resulted negative. Based on MRI, cases were classified as ADEM (n=3), limbic encephalitis (LE, n=2), encephalitis with normal imaging (n=13) and encephalitis with MRI alterations (n=7). ADEM and LE cases showed a delayed onset compared to the other encephalitis (p=0.001) and were associated with previous more severe COVID-19 respiratory involvement. Patients with MRI alterations exhibited worse response to treatment and final outcomes compared to other encephalitis. Conclusions and relevance: We found a wide clinical spectrum of encephalitis associated with COVID19 infection, underlying different pathophysiological mechanisms. Response to treatment and final outcome strongly depended on specific CNS-manifestations.

negative: Are Clinicians Contributing to Excess African American COVID-19 Deaths? Unbeknownst to Them, They May Be African Americans are overrepresented among reported coronavirus disease 2019 (COVID-19) cases and deaths. There are a multitude of factors that may explain the African American disparity in COVID-19 outcomes, including higher rates of comorbidities. While individual-level factors predictably contribute to disparate COVID-19 outcomes, systematic and structural factors have not yet been reported. It stands to reason that implicit biases may fuel the racial disparity in COVID-19 outcomes. To address this racial disparity, we must apply a health equity lens and disaggregate data explicitly for African Americans, as well as other populations at risk for biased treatment in the health-care system.

negative: Access to primary healthcare during lockdown measures for COVID-19 in rural South Africa: a longitudinal cohort study OBJECTIVES: Public health interventions designed to interrupt COVID-19 transmission could have deleterious impacts on primary healthcare access. We sought to identify whether implementation of the nationwide lockdown (shelter-in-place) order in South Africa affected ambulatory clinic visitation in rural Kwa-Zulu Natal (KZN). DESIGN: Prospective, longitudinal cohort study SETTING: Data were analyzed from the Africa Health Research Institute Health and Demographic Surveillance System, which includes prospective data capture of clinic visits at eleven primary healthcare clinics in northern KwaZulu-Natal PARTICIPANTS: A total of 36,291 individuals made 55,545 clinic visits during the observation period. EXPOSURE OF INTEREST: We conducted an interrupted time series analysis with regression discontinuity methods to estimate changes in outpatient clinic visitation from 60 days before through 35 days after the lockdown period. OUTCOME MEASURES: Daily clinic visitation at ambulatory clinics. In stratified analyses we assessed visitation for the following sub-categories: child health, perinatal care and family planning, HIV services, non-communicable diseases, and by age and sex strata. RESULTS: We found no change in total clinic visits/clinic/day from prior to and during the lockdown (−6.9 visits/clinic/day, 95%CI −17.4, 3.7) or trends in clinic visitation over time during the lockdown period (−0.2, 95%CI −3.4, 3.1). We did detect a reduction in child healthcare visits at the lockdown (−7.2 visits/clinic/day, 95%CI −9.2, −5.3), which was seen in both children <1 and children 1–5. In contrast, we found a significant increase in HIV visits immediately after the lockdown (8.4 visits/clinic/day, 95%CI 2.4, 14.4). No other differences in clinic visitation were found for perinatal care and family planning, non-communicable diseases, or among adult men and women. CONCLUSIONS: In rural KZN, the ambulatory healthcare system was largely resilient during the national-wide lockdown order. A major exception was child healthcare visitation, which declined immediately after the lockdown but began to normalize in the weeks thereafter. Future work should explore efforts to decentralize chronic care for high-risk populations and whether catch-up vaccination programs might be required in the wake of these findings.

negative: Anticipating the impact of the COVID-19 pandemic on TB patients and TB control programmes The COVID-19 pandemic has currently overtaken every other health issue throughout the world. There are numerous ways in which this will impact existing public health issues. Here we reflect on the interactions between COVID-19 and tuberculosis (TB), which still ranks as the leading cause of death from a single infectious disease globally. There may be grave consequences for existing and undiagnosed TB patients globally, particularly in low and middle income countries (LMICs) where TB is endemic and health services poorly equipped. TB control programmes will be strained due to diversion of resources, and an inevitable loss of health system focus, such that some activities cannot or will not be prioritised. This is likely to lead to a reduction in quality of TB care and worse outcomes. Further, TB patients often have underlying co-morbidities and lung damage that may make them prone to more severe COVID-19. The symptoms of TB and COVID-19 can be similar, with for example cough and fever. Not only can this create diagnostic confusion, but it could worsen the stigmatization of TB patients especially in LMICs, given the fear of COVID-19. Children with TB are a vulnerable group especially likely to suffer as part of the “collateral damage”. There will be a confounding of symptoms and epidemiological data through co-infection, as happens already with TB–HIV, and this will require unpicking. Lessons for COVID-19 could be learned from the vast experience of running global TB control programmes, while the astonishingly rapid and relatively well co-ordinated response to COVID-19 demonstrates how existing programmes could be significantly improved.

negative: Provision of Pediatric Immunization Services During the COVID-19 Pandemic: an Assessment of Capacity Among Pediatric Immunization Providers Participating in the Vaccines for Children Program - United States, May 2020. Recent reports suggest that routine childhood immunization coverage might have decreased during the coronavirus disease 2019 (COVID-19) pandemic (1,2). To assess the capacity of pediatric health care practices to provide immunization services to children during the pandemic, a survey of practices participating in the Vaccines for Children (VFC) program was conducted during May 12-20, 2020. Data were weighted to account for the sampling design; thus, all percentages reported are weighted. Among 1,933 responding practices, 1,727 (89.8%) were currently open; 1,397 (81.1%) of these reported offering immunization services to all of their patients. When asked whether the practice would likely be able to accommodate new patients to assist with provision of immunization services through August, 1,135 (59.1%) respondents answered affirmatively. These results suggest that health care providers appear to have the capacity to deliver routinely recommended childhood vaccines, allowing children to catch up on vaccines that might have been delayed as a result of COVID-19-related effects on the provision of or demand for routine well child care. Health care providers and immunization programs should educate parents on the need to return for well-child and immunization visits or refer patients to other practices, if they are unable to provide services (3).

negative: Assessing the Real-Time Mental Health Challenges of COVID-19 in Individuals With Serious Mental Illnesses: Protocol for a Quantitative Study BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has caused significant stress and mental health problems among the general public. However, persons at greatest risk for poor mental health outcomes, such as people with serious mental illness, have been largely overlooked. OBJECTIVE: This paper presents the protocol for a study that aims to examine the mental health impact of COVID-19 and social distancing behaviors in people with serious mental illness and the behaviors undertaken to prevent COVID-19 infection in this group. METHODS: Participants will include individuals with serious mental illness (eg, schizophrenia, bipolar disorder) and nonpsychiatric control participants who are currently participating in or have previously participated in several ongoing parent observational studies. Data will be collected from April 2020 through August 2020. Participants will complete phone interviews at 2 time points to assess their current emotional functioning and discuss the measures they have taken to prevent COVID-19 infection. Baseline (pre-COVID-19) mental health, sampled by ecological momentary assessment over an extended period, will be compared with current mental health, also sampled by ecological momentary assessment over an extended period. Demographic, cognitive, and psychosocial factors at baseline will be used to examine risk and resilience to current mental health and coping. RESULTS: The inclusion of participants for the first round of telephone assessments started on April 3, 2020 and will be completed by May 31, 2020. As of April 30, 2020, 101 individuals had completed these first-round assessments. The second round of telephone assessments will likely occur between June 1, 2020, and August 31, 2020. Study results will be published in peer-reviewed scientific journals. CONCLUSIONS: Our findings will have broad implications for understanding the psychological consequences of COVID-19 among vulnerable persons with serious mental illness and will provide the opportunity to identify targets to reduce negative outcomes in the future. We also hope our efforts will provide a roadmap and resources for other researchers who would like to implement a similar approach. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/19203.

negative: Congenital cardiac interventions during the peak phase of COVID-19 pandemics in the country in a pandemics hospital in Istanbul INTRODUCTION: In this report, we aim to present our algorithm and results of patients with congenital cardiac disorders who underwent surgical or interventional procedures during the peak phase of the pandemics in our country. PATIENTS AND METHODS: The first COVID-19 case was diagnosed in Turkey on 11 March, 2020, and the peak phase seemed to end by the end of April. All the patients whom were referred, treated, or previously operated but still at the hospital during the peak phase of COVID-19 pandemics in the country were included into this retrospective study. Patient’s diagnosis, interventions, adverse events, and early post-procedural courses were studied. RESULTS: Thirty-one patients with various diagnoses of congenital cardiovascular disorders were retrospectively reviewed. Ages of the patients ranged between 2 days and 16 years. Seventeen cases were males and 14 cases were females. Elective cases were postponed. Priority was given to interventional procedures, and five cases were treated percutaneously. Palliative procedures were preferred in patients whom presumably would require long hospital stay. Corrective procedures were not hesitated in prioritised stable patients. Mortality occurred in one patient. Eight patients out of 151 ICU admissions were diagnosed with COVID-19, and they were transferred to COVID-19 ICU immediately. Three nurses whom also took care of the paediatric cases became infected with SARS-CoV-2; however, the children did not catch the disease. CONCLUSION: Mandatory and emergent congenital cardiac percutaneous and surgical procedures may be performed with similar postoperative risks as there are no pandemics with meticulous care and preventive measures.

negative: The mental health impact of the covid-19 pandemic onhealthcare workers, and interventions to help them: a rapid systematic review Background: The covid-19 pandemic has heavily burdened, and in some cases overwhelmed, healthcare systems throughout the world. Healthcare workers are not only at heightened risk of infection, but also of adverse mental health outcomes. Identification of organizational, collegial and individual risk and resilience factors impacting the mental health of healthcare workers are needed to inform preparedness planning and sustainable response. Methods: We performed a rapid systematic review to identify, assess and summarize available research on the mental health impact of the covid-19 pandemic on healthcare workers. On 11 May 2020, we utilized the Norwegian Institute of Public Health's Live map of covid-19 evidence, the visualization of a database of 20,738 screened studies, to identify studies for inclusion. We included studies reporting on any type of mental health outcome in any type of healthcare workers during the pandemic. We described interventions reported by the studies, and narratively summarized mental health-related outcomes, as study heterogeneity precluded meta-analysis. We assessed study quality using design-specific instruments. Results: We included 59 studies, reporting on a total of 54,707 healthcare workers. The prevalence of general psychological distress across the studies ranged from 7-97% (median 37%), anxiety 9-90% (median 24%), depression 5-51% (median 21%), and sleeping problems 34-65% (median 37%). Seven studies reported on implementing mental health interventions, and most focused on individual symptom reduction, but none reported on effects of the interventions. In most studies, healthcare workers reported low interest in and use of professional help, and greater reliance on social support and contact with family and friends. Exposure to covid-19 was the most commonly reported correlate of mental health problems, followed by female gender, and worry about infection or about infecting others. Social support correlated with less mental health problems. Discussion: Healthcare workers in a variety of fields, positions, and exposure risks are reporting anxiety, depression, sleep problems, and distress during the covid-19 pandemic, but most studies do not report comparative data on mental health symptoms. before the pandemic. There seems to be a mismatch between risk factors for adverse mental health outcomes among healthcare workers in the current pandemic and their needs and preferences, and the individual psychopathology focus of current interventions. Efforts to help healthcare workers sustain healthy relationships to colleagues, family and friends over time may be paramount to safeguard what is already an important source of support during the prolonged crisis. Expanding interventions' focus to incorporate organizational, collegial and family factors to support healthcare workers responding to the pandemic could improve acceptability and efficacy of interventions. Other: The protocol for this review is available online. No funding was received.

negative: Three further ways that the COVID-19 pandemic will affect health outcomes

negative: Combinations of physical activity, sedentary time, and sleep duration and their associations with depressive symptoms and other mental health problems in children and adolescents: a systematic review. BACKGROUND For optimal health benefits, the Canadian 24-Hour Movement Guidelines for Children and Youth (aged 5-17 years) recommend an achievement of high levels of physical activity (≥60 min of moderate-to-vigorous physical activity), low levels of sedentary behaviour (≤2 h of recreational screen time), and sufficient sleep (9-11 h for children or 8-10 h for adolescents) each day. The objective of this systematic review was to examine how combinations of physical activity, sedentary time, and sleep duration relate to depressive symptoms and other mental health indicators among children and adolescents. METHODS Literature was obtained through searching Medline, EMBASE, PsycINFO, and SportDiscus up to September 30, 2019. Peer-reviewed studies published in English or French were included if they met the following criteria: population (apparently healthy children and adolescents with a mean age of 5-17 years), intervention/exposure (combinations of physical activity, sedentary time, and sleep duration), and outcomes (depressive symptoms and other mental health indicators). A risk of bias assessment was completed for all included studies using the methods described in the Cochrane Handbook. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to assess the quality of evidence for each health indicator. Narrative syntheses were employed to describe the results due to high levels of heterogeneity across studies. RESULTS A total of 13 cross-sectional studies comprised in 10 papers met inclusion criteria. Data across studies involved 115,540 children and adolescents from 12 countries. Overall, the findings indicated favourable associations between meeting all 3 recommendations and better mental health indicators among children and adolescents when compared with meeting none of the recommendations. There was evidence of a dose-response gradient between an increasing number of recommendations met and better mental health indicators. Meeting the screen time and sleep duration recommendations appeared to be associated with more mental health benefits than meeting the physical activity recommendation. The quality of evidence reviewed was "very low" according to GRADE. CONCLUSIONS The findings indicate favourable associations between meeting all 3 movement behaviour recommendations in the 24-h guidelines and better mental health indicators among children and adolescents. There is a clear need for high-quality studies that use robust measures of all movement behaviours and validated measures of mental health to increase our understanding in this topic area.

negative: Operation of ultrasonography services in a dedicated paediatric hospital and a university hospital in Greece under the COVID-19 pandemic Ultrasonography (US) is one of the most common diagnostic imaging tests in children. During the coronavirus disease 2019 (COVID-19) pandemic, it is important to operate with a plan designed to protect health care workers, to prevent transmission of infection from child and parents to another child or an accompanying person in the US suite, and to save valuable protective material and resources. Measures during routine US in children can be challenging both in general hospitals with paediatric units and in dedicated paediatric hospitals. Special considerations include: a) cancellation or rescheduling of unnecessary imaging tests, b) a relevant questionnaire on the request form informing about patient and accompanying person’s symptoms and likely exposure in addition to general triage, c) appropriate patient and parent protective measures, d) recruitment and selection of US machines in different protected areas depending on the possibility or certainty for the infection, e) regular personnel protective measures and personal hand hygiene, f) routine disinfection of probes and adjacent surfaces and g) machine/room deep disinfection, if required. Our purpose is to present the modified US services in children during the COVID-19 pandemic in two hospitals based on the instructions of the national organization of public health in Greece and what is known about the mode of transmission of the virus.

negative: COVID-19 pandemic and mitigation strategies: implications for maternal and child health and nutrition Coronavirus disease 2019 (COVID-19) continues to ravage health and economic metrics globally, including progress in maternal and child nutrition. Although there has been focus on rising rates of childhood wasting in the short term, maternal and child undernutrition rates are also likely to increase as a consequence of COVID-19 and its impacts on poverty, coverage of essential interventions, and access to appropriate nutritious foods. Key sectors at particular risk of collapse or reduced efficiency in the wake of COVID-19 include food systems, incomes, and social protection, health care services for women and children, and services and access to clean water and sanitation. This review highlights key areas of concern for maternal and child nutrition during and in the aftermath of COVID-19 while providing strategic guidance for countries in their efforts to reduce maternal and child undernutrition. Rooted in learnings from the exemplars in Global Health's Stunting Reduction Exemplars project, we provide a set of recommendations that span investments in sectors that have sustained direct and indirect impact on nutrition. These include interventions to strengthen the food-supply chain and reducing food insecurity to assist those at immediate risk of food shortages. Other strategies could include targeted social safety net programs, payment deferrals, or tax breaks as well as suitable cash-support programs for the most vulnerable. Targeting the most marginalized households in rural populations and urban slums could be achieved through deploying community health workers and supporting women and community members. Community-led sanitation programs could be key to ensuring healthy household environments and reducing undernutrition. Additionally, several COVID-19 response measures such as contact tracing and self-isolation could also be exploited for nutrition protection. Global health and improvements in undernutrition will require governments, donors, and development partners to restrategize and reprioritize investments for the COVID-19 era, and will necessitate data-driven decision making, political will and commitment, and international unity.

negative: [Investigation on demands for antenatal care services among 2 002 pregnant women during the epidemic of COVID-19 in Shanghai] Objective: To identify problems and demands for antenatal care (ANC) among pregnant women in different trimesters of pregnancy in Shanghai for optimizing ANC service during the epidemic of COVID-19. Method: s Organized by maternal and child health care institute in the 16 districts of Shanghai, a cross sectional study was conducted among pregnant women who came to pregnancy registration in the community health centers or attended ANC in midwifery hospitals from February 7 to February 12, 2020. Consented participating women completed a semi-structured online questionnaire voluntarily. Data was analyzed using frequency,chi-square test and scoring. Result: s A total of 2 002 valid questionnaires were collected from 183 community health centers and 67 midwifery hospitals. About 94.6%(1 894/2 002) of the pregnant women worried about being infected during the COVID-19 epidemic, and 14.7% (294/2 002) demanded for psychological consultation. Time-lapse appointments for ANC were requested by 87.7% (1 756/2 002) of the participants for avoiding presenting themselves in people-density places. Compared with other pregnancy trimesters, pregnant women in the second trimester were more willing to reduce the frequency of ANC (35.2% versus 39.5% versus 48.1%, P<0.01). Compared with multiparas, primiparas were more willing to have online consultation and guidance (49.2% versus 63.8%, P<0.01). Regarding the needs for health knowledge on COVID-19, personal protection against 2019 novel coronavirus (2019-nCoV) was the most concerned for pregnant women, and 71.0% (1 421/2 002) of them preferred to obtain knowledge through health applications, official Weibo and WeChat. Conclusions: Pregnant women in Shanghai critically concern about the risk of 2019-nCoV infections, and highly demand knowledge and measures on prevention and protection from COVID-19. They ask for having time-lapse appointments for ANC and online access to health information and services. Maternal and child care institutes should understand the demands of pregnant women, optimize the means of ANC service, and provide tailored and accessible health education and service for the safety of mother and child.

negative: Impacts of COVID-19 on vulnerable children in temporary accommodation in the UK

negative: Comparison of Hospitalized Patients With ARDS Caused by COVID-19 and H1N1 Background Since the outbreak of coronavirus disease 2019 (COVID-19) in China in December 2019, considerable attention has been focused on its elucidation. However, it is also important for clinicians and epidemiologists to differentiate COVID-19 from other respiratory infectious diseases such as influenza viruses. Research question The aim of this study was to explore the different clinical presentations between COVID-19 and influenza A (H1N1) pneumonia in patients with ARDS. Study Design and Methods This analysis was a retrospective case-control study. Two independent cohorts of patients with ARDS infected with either COVID-19 (n = 73) or H1N1 (n = 75) were compared. Their clinical manifestations, imaging characteristics, treatments, and prognosis were analyzed and compared. Results The median age of patients with COVID-19 was higher than that of patients with H1N1, and there was a higher proportion of male subjects among the COVID-19 cohort (P < .05). Patients with COVID-19 exhibited higher proportions of nonproductive coughs, fatigue, and GI symptoms than those of patients with H1N1 (P < .05). Patients with H1N1 had higher Sequential Organ Failure Assessment (SOFA) scores than patients with COVID-19 (P < .05). The Pao 2/Fio 2 of 198.2 mm Hg in the COVID-19 cohort was significantly higher than the Pao 2/Fio 2 of 107.0 mm Hg in the H1N1 cohort (P < .001). Ground-glass opacities was more common in patients with COVID-19 than in patients with H1N1 (P < .001). There was a greater variety of antiviral therapies administered to COVID-19 patients than to H1N1 patients. The in-hospital mortality of patients with COVID-19 was 28.8%, whereas that of patients with H1N1 was 34.7% (P = .483). SOFA score-adjusted mortality of H1N1 patients was significantly higher than that of COVID-19 patients, with a rate ratio of 2.009 (95% CI, 1.563-2.583; P < .001). Interpretation There were many differences in clinical presentations between patients with ARDS infected with either COVID-19 or H1N1. Compared with H1N1 patients, patients with COVID-19-induced ARDS had lower severity of illness scores at presentation and lower SOFA score-adjusted mortality.

negative: Multicenter initial guidance on use of antivirals for children with COVID-19/SARS-CoV-2 BACKGROUND: Although Coronavirus Disease 2019 (COVID-19) is mild in nearly all children, a small proportion of pediatric patients develops severe or critical illness. Guidance is therefore needed regarding use of agents with potential activity against severe acute respiratory syndrome coronavirus 2 in pediatrics. METHODS: A panel of pediatric infectious diseases physicians and pharmacists from 18 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of best available evidence and expert opinion. RESULTS: Given the typically mild course of pediatric COVID-19, supportive care alone is suggested for the overwhelming majority of cases. The panel suggests a decision-making framework for antiviral therapy that weighs risks and benefits based on disease severity as indicated by respiratory support needs, with consideration on a case-by-case basis of potential pediatric risk factors for disease progression. If an antiviral is used, the panel suggests remdesivir as the preferred agent. Hydroxychloroquine could be considered for patients who are not candidates for remdesivir or when remdesivir is not available. Antivirals should preferably be used as part of a clinical trial if available. CONCLUSIONS: Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For those rare children who develop severe or critical disease, this guidance offer an approach for decision-making regarding antivirals, informed by available data. As evidence continues to evolve rapidly, the need for updates to the guidance is anticipated.

negative: Beyond predicting the number of infections: predicting who is likely to be COVID negative or positive This study provides the first attempt to identify people at greater risk of COVID-19 infection, enabling more targeted infectious disease prevention and control, which are especially important in the ongoing shortage of COVID-19 testing. We conducted a primary survey of 521 adults on April 1-10, 2020 in Iran, where the official infection rate was 0.08%. In our sample, 3% reported being COVID-19 positive and 15% were unsure of their status. This relatively high positive rate enabled us to conduct the analysis at the 5% significance level. At the time of the survey, 44% of the adults worked from home; 26% still went to work in their workplaces; 27% had stopped working due to the COVID-19 pandemic; and 3% were unemployed. Adults who exercised more were more likely to be COVID-19 negative. Each additional hour of exercise per day predicted a 78% increase in the likelihood of being COVID-19 negative. Adults with chronic medical illnesses were 48% more likely to be COVID-19 negative. In terms of work situation, those who worked from home were the most likely to be COVID-19 negative, and those who had stopped working were the most likely to be COVID-19 positive. Individuals in larger organizations were less likely to be COVID-19 positive. Given the testing shortage in many countries, we identify a novel approach to predict the likelihood of COVID-19 infection by a set of personal and work situation characteristics, in order to help to identify individuals with more or less risk of contracting the virus. We hope this research opens a new research avenue to identify the individual risk factors of COVID-19 infection to enable more targeted infectious disease prevention, communication, testing, and control to complement the effort to expand testing capacity.

negative: Covid-19: schools set to close across UK except for children of health and social care workers.

negative: Negative attitude of highly educated parents and health care workers towards future vaccinations in the Dutch childhood vaccination program. BACKGROUND It is unknown whether further expansion of the Dutch childhood vaccination program with other vaccines will be accepted and whom should be targeted in educational strategies. AIM To determine attitudes of parents towards possible future vaccinations for their children and the behavioural determinants associated with a negative attitude. DESIGN Questionnaire study. METHODS Parents of children aged between 3 months and 5 years of day-care centres were asked to fill out a questionnaire. Determinants of a negative attitude to comply with possible future vaccinations against example diseases such as pneumonia or influenza, hepatitis B, TBC, smallpox and SARS were assessed using polytomous logistic regression analysis. RESULTS Of the 283 respondents, 123 (43%) reported a positive attitude towards all vaccinations, 129 (46%) reported to have a positive attitude to have their child vaccinated against some diseases and 31 (11%) had no intention to comply with any new vaccination. Determinants of a fully negative attitude were a high education of the parent (odds ratio [OR] 3.3, 95% confidence interval [95% CI]: 1.3-8.6), being a health care worker (OR 4.2, 95% CI: 1.4-12.6), absence of religion (OR 2.6, 95% CI: 1.0-6.7), perception of vaccine ineffectiveness (OR 6.9, 95% CI: 2.5-18.9) and the perception that vaccinations cause asthma or allergies (OR 82.4, 95% CI: 8.9-766.8). CONCLUSION Modifiable determinants for a negative attitude to comply with new vaccinations are mainly based on lack of specific knowledge. These barriers to vaccinations might be overcome by improving health education in the vaccination program, especially when targeted at educated parents and health care workers.

negative: Opioid Use Disorder and COVID-19: Biological Plausibility for Worsened Outcomes. BACKGROUND Alarms have been raised that COVID-19 may disproportionately affect certain populations with substance use disorders, particularly Opioid Use Disorder (OUD), however warnings have largely focused on social risks such as reduced availability of services. Objectives: This commentary highlights three plausible biological mechanisms for potentially worsened outcomes in patients with OUD who contract COVID-19. Results: Opioid-related respiratory depression may amplify risks of hypoxemia from COVID-19 viral pneumonia. Complex opioid immune modulation may impact host response to COVID-19, though the effect direction and clinical significance are unclear. Drug-drug interactions may affect individuals with OUD who are co-administered medications for OUD and medications for COVID-19, particularly due to cardiac adverse effects. Conclusions/Importance: There are plausible biological mechanisms for potentially worsened outcomes in patients with OUD who contract COVID-19; these mechanisms require further study, and should be considered in individuals with OUD.

negative: Effect of advanced nursing care on psychological disorder in patients with COVID-19: A protocol of systematic review BACKGROUND: This study will explore the effect of advanced nursing care (ANC) on psychological disorder (PD) in patients with Coronavirus Disease 2019 (COVID-19). METHODS: This study will search the following electronic databases up to June 30, 2020: Cochrane Library, PUBMED, EMBASE, PsycINFO, Web of Science, OpenGrey, Cumulative Index to Nursing and Allied Health Literature, CNKI, and WANGFANG. We will not impose any language limitations. Two authors will independently identify titles/abstracts and full-text of all potential studies, and will collect data from eligible studies. Additionally, study quality will be assessed by Cochrane risk of bias. If necessary, we will conduct meta-analysis if sufficient trials are included. RESULTS: This study will explore the effect of ANC on PD in patients with COVID-19 through outcome indicators. CONCLUSION: The findings of this study may supply summarized evidence of ANC for the management of PD in COVID-19. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020187610.

negative: Where have all the children gone? - Pediatric perspectives on COVID-19 in NYC

negative: Role of children in the transmission of the COVID-19 pandemic: a rapid scoping review BACKGROUND: As a response to the COVID-19 pandemic, most countries have adopted measures of social distance, with the childhood population being one of the main focus of attention in these measures. METHODS: A rapid scoping review was carried out by searching PubMed to know if children are more contagious than adults, and the proportion of asymptomatic cases in children. Google Scholar and MedRxiv/bioRxiv were also searched. The time period was restricted from 1 December 2019 until 28 May 2020. Only studies published in English, Italian, French or Spanish were included. RESULTS: Fourteen out of 1099 identified articles were finally included. Studies included cases from China (n=9 to 2143), China and Taiwan (n=536), Korea (n=1), Vietnam (n=1), Australia (n=9), Geneva (n=40), the Netherlands (n=116), Ireland (n=3) and Spain (population-based study of IgG, n=8243). Although no complete data were available, between 15% and 55%–60% were asymptomatic, and 75%–100% of cases were from family transmission. Studies analysing school transmission showed children as not a driver of transmission. Prevalence of COVID-19 IgG antibody in children <15 years was lower than the general population in the Spanish study. CONCLUSIONS: Children are not transmitters to a greater extent than adults. There is a need to improve the validity of epidemiological surveillance to solve current uncertainties, and to take into account social determinants and child health inequalities during and after the current pandemic.

negative: Comorbidities, clinical signs and symptoms, laboratory findings, imaging features, treatment strategies, and outcomes in adult and pediatric patients with COVID-19: A systematic review and meta-analysis Introduction Since December 2019, a novel coronavirus (SARS-CoV-2) has triggered a world-wide pandemic with an enormous medical, societal, and economic toll. Thus, our aim was to gather all available information regarding comorbidities, clinical signs and symptoms, outcomes, laboratory findings, imaging features, and treatments in patients with coronavirus disease 2019 (COVID-19). Methods EMBASE, PubMed/ Medline, Scopus, and Web of Science were searched for studies published in any language between December 1st, 2019 and March 28th. Original studies were included if the exposure of interest was an infection with SARS-CoV-2 or confirmed COVID-19. The primary outcome was the risk ratio of comorbidities, clinical signs and symptoms, imaging features, treatments, outcomes, and complications associated with COVID-19 morbidity and mortality. We performed random-effects pairwise meta-analyses for proportions and relative risks, I2, Tau2, and Cochrane Q, sensitivity analyses, and assessed publication bias. Results: 148 met the inclusion criteria for the systematic review and meta-analysis with 12149 patients (5739 female) and a median age was 47.0 [35.0-64.6]. 617 patients died from COVID-19 and its complication, while 297 patients were reported as asymptomatic. Older age (SMD: 1.25 [0.78- 1.72]; p < 0.001), being male (RR = 1.32 [1.13-1.54], p = 0.005) and pre-existing comorbidity (RR = 1.69 [1.48-1.94]; p < 0.001) were identified as risk factors of in-hospital mortality. The heterogeneity between studies varied substantially (I2; range: 1.5-98.2%). Publication bias was only found in eight studies (Eggers test: p < 0.05). Conclusions: Our meta-analyses revealed important risk factors that are associated with severity and mortality of COVID-19.

negative: COVID-19 in patients with rheumatic disease in Hubei province, China: a multicentre retrospective observational study BACKGROUND: In the ongoing COVID-19 pandemic, the susceptibility of patients with rheumatic diseases to COVID-19 remains unclear. We aimed to investigate susceptibility to COVID-19 in patients with autoimmune rheumatic diseases during the ongoing COVID-19 pandemic. METHODS: We did a multicentre retrospective study of patients with autoimmune rheumatic diseases in Hubei province, the epicentre of the COVID-19 outbreak in China. Patients with rheumatic diseases were contacted through an automated telephone-based survey to investigate their susceptibility to COVID-19. Data about COVID-19 exposure or diagnosis were collected. Families with a documented history of COVID-19 exposure, as defined by having at least one family member diagnosed with COVID-19, were followed up by medical professionals to obtain detailed information, including sex, age, smoking history, past medical history, use of medications, and information related to COVID-19. FINDINGS: Between March 20 and March 30, 2020, 6228 patients with autoimmune rheumatic diseases were included in the study. The overall rate of COVID-19 in patients with an autoimmune rheumatic disease in our study population was 0·43% (27 of 6228 patients). We identified 42 families in which COVID-19 was diagnosed between Dec 20, 2019, and March 20, 2020, in either patients with a rheumatic disease or in a family member residing at the same physical address during the outbreak. Within these 42 families, COVID-19 was diagnosed in 27 (63%) of 43 patients with a rheumatic disease and in 28 (34%) of 83 of their family members with no rheumatic disease (adjusted odds ratio [OR] 2·68 [95% CI 1·14–6·27]; p=0·023). Patients with rheumatic disease who were taking hydroxychloroquine had a lower risk of COVID-19 infection than patients taking other disease-modifying anti-rheumatic drugs (OR 0·09 [95% CI 0·01–0·94]; p=0·044). Additionally, the risk of COVID-19 was increased with age (adjusted OR 1·04 [95%CI 1·01–1·06]; p=0·0081). INTERPRETATION: Patients with autoimmune rheumatic disease might be more susceptible to COVID-19 infection than the general population. FUNDING: National Natural Science Foundation of China and the Tongji Hospital Clinical Research Flagship Program.

negative: An urgent call to address the nutritional status of women and children in Nepal during COVID-19 crises Due to the ongoing nationwide lockdown in Nepal, women and children face a greater risk of malnutrition and eventually leading to mortality and morbidity. To harness the progress made so far in improving the nutritional status of women and children, a focus on nutrition should be a part of the COVID-19 response plan.

negative: Susceptibility to and transmission of COVID-19 amongst children and adolescents compared with adults: a systematic review and meta-analysis Background The degree to which children and young people are infected by and transmit the SARS-CoV-2 virus is unclear. Clinical series and testing cohorts based upon screening of symptomatic cases provide biased estimates of susceptibility in children. The role of children and young people in transmission of SARS-CoV-2 is dependent on susceptibility, symptoms, viral load, social contact patterns and behaviour. Methods We undertook a rapid systematic review of contact-tracing studies and population-screening studies to address the question What is the susceptibility to and transmission of SARS-CoV-2 by children and adolescents compared with adults? We searched PubMed and medRxiv on 16 May 2020 and identified 6327 studies, with additional studies identified through handsearching of cited references (2) and professional contacts (4). We assessed quality, summarized findings and undertook a random effects meta-analysis of contact-tracing studies. Results 18 studies met inclusion criteria; 9 contact-tracing, 8 population-screening and 1 systematic-review. Meta-analysis of contact tracing studies showed that the pooled odds ratio of being an infected contact in children compared with adults for all contact tracing studies was 0.44 (0.29, 0.69) with substantial heterogeneity (63%). Findings from a systematic review of household clusters of COVID-19 found 3/31 (10%) were due to a child index case and a population-based school contact tracing study found minimal transmission by child or teacher index cases. Findings from population-screening studies were heterogenous and not suitable for meta-analysis. Large studies from Iceland, the Netherlands and Spain and an Italian municipal study showed markedly lower SARS-CoV-2 prevalence amongst children and young people, however studies from Stockholm, England and municipalities in Switzerland and Germany showed showed no difference in infection prevalence between adults and children. Conclusions There is preliminary evidence that children and young people have lower susceptibility to SARS-CoV-2, with a 56% lower odds of being an infected contact. There is weak evidence that children and young people play a lesser role in transmission of SARS-CoV-2 at a population level. Our study provides no information on the infectivity of children.

negative: Coinfection and Other Clinical Characteristics of COVID-19 in Children BACKGROUND AND OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly identified pathogen that mainly spreads by droplets. Most published studies have been focused on adult patients with coronavirus disease 2019 (COVID-19), but data concerning pediatric patients are limited. In this study, we aimed to determine epidemiological characteristics and clinical features of pediatric patients with COVID-19. METHODS: We reviewed and analyzed data on pediatric patients with laboratory-confirmed COVID-19, including basic information, epidemiological history, clinical manifestations, laboratory and radiologic findings, treatment, outcome, and follow-up results. RESULTS: A total of 74 pediatric patients with COVID-19 were included in this study. Of the 68 case patients whose epidemiological data were complete, 65 (65 of 68; 95.59%) were household contacts of adults. Cough (32.43%) and fever (27.03%) were the predominant symptoms of 44 (59.46%) symptomatic patients at onset of the illness. Abnormalities in leukocyte count were found in 23 (31.08%) children, and 10 (13.51%) children presented with abnormal lymphocyte count. Of the 34 (45.95%) patients who had nucleic acid testing results for common respiratory pathogens, 19 (51.35%) showed coinfection with other pathogens other than SARS-CoV-2. Ten (13.51%) children had real-time reverse transcription polymerase chain reaction analysis for fecal specimens, and 8 of them showed prolonged existence of SARS-CoV-2 RNA. CONCLUSIONS: Pediatric patients with COVID-19 presented with distinct epidemiological, clinical, and radiologic characteristics from adult patients. Nearly one-half of the infected children had coinfection with other common respiratory pathogens. It is not uncommon for pediatric patients to have prolonged fecal shedding of SARS-CoV-2 RNA during the convalescent phase.

negative: Gender equity and public health outcomes: The COVID-19 experience This paper extends the growing research on the impact of gender equity on public health outcomes using the ongoing Covid-19 pandemic as its research setting. Specifically, it introduces a conceptual model incorporating the impact of gender equity and human development on women’s representation in legislature and public health expenditure, and their combined impact with human environment (population density, aging population and urban population) on important public health outcomes in the Covid-19 context, including the total number of tests, diagnosed, active and critical cases, and deaths. Data from 210 countries shows support for many of the hypothesized relationships in the conceptual model. The results provide useful insights about the factors that influence the representation of women in political systems around the world and its impact on public health outcomes. The authors also discuss implications for public health policy-makers to ensure efficient and effective delivery of public health services in future.

negative: Children may be less affected than adults by novel coronavirus (COVID-19)

negative: ‘What is Inconvenient for You is Life-saving for Me’: How Health Inequities are playing out during the COVID-19 Pandemic The COVID-19 pandemic has had a significant impact globally. Most affected, however, are those individuals and groups routinely disadvantaged by the social injustice created by the misdistribution of power, money, and resources. Simple measures that prevent the spread of COVID-19, such as frequent hand washing and social distancing, are unavailable to millions of people in the wealthiest of nations and in the poorest of nations. Disadvantaged groups are impacted more directly and in disproportionately higher numbers due to existing poor health, and the disruption of services central to securing an income and an education will have lasting consequences for their futures. The unintended effect of exclusionary government policies is that privileged citizens and healthcare systems are also at greater risk. This paper seeks to highlight the impact of COVID-19 on those already suffering health inequities through consideration of some of the social determinants of health on groups in affluent and poorer nations. It also highlights some of the factors that may assist in tackling health inequities as we emerge from this pandemic.

negative: If not now, then when? The importance of intervening early to provide family-based environments for all children

negative: [Clinical features of asymptomatic or subclinical COVID-19 in children]. OBJECTIVE To study the clinical features of asymptomatic or subclinical coronavirus disease 2019 (COVID-19) in children. METHODS A retrospective analysis was performed for the clinical data of 53 children who were confirmed with asymptomatic or subclinical COVID-19, including epidemiological history, clinical typing, co-infection, time to clearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid in nasopharyngeal swabs, laboratory examination results, length of hospital stay, and treatment outcome. RESULTS The children with asymptomatic or subclinical COVID-19 accounted for 30.5% (53/174) in children with COVID-19 hospitalized in the COVID-19 ward of Wuhan Children's Hospital. All cases occurred with familial aggregation. Among the 53 children, 35 (66%) had asymptomatic infection and 18 (34%) had subclinical infection. Mycoplasma infection was found in 17 children (32%). For the 53 children, the mean time to clearance of SARS-CoV-2 nucleic acid in nasopharyngeal swabs was 9±4 days. Most laboratory markers were maintained within the normal range. The mean hospital stay was 11±4 days. Lung CT of 18 children with subclinical COVID-19 showed ground-glass opacities, linear opacities, and patchy opacities, with relatively limited lesions. CONCLUSIONS There is a high proportion of children with asymptomatic or subclinical COVID-19 among the children with COVID-19 hospitalized in the COVID-19 ward. The transmission risk of asymptomatic or subclinical COVID-19 should be taken seriously.

negative: Characteristics and outcomes of oral antibiotic treated pulmonary exacerbations in children with cystic fibrosis Abstract Background Pulmonary exacerbations (PEx) in children with cystic fibrosis (CF) are frequently treated in the outpatient setting with oral antibiotics. However, little is known about the characteristics of PEx managed on an outpatient basis and the effectiveness of oral antibiotic therapy. We sought to prospectively evaluate clinical and laboratory changes associated with oral antibiotic treatment for PEx. Methods Children with CF between 8 and 18 years of age prescribed two weeks of oral antibiotics for a PEx were eligible to enroll. The study consisted of a visit within 48 h of starting antibiotics and a second visit within one week of antibiotic completion. Twenty-eight participants were evaluated by exacerbation score, quality of life measurements, lung function, sputum microbiology and inflammation. Results Oral antibiotic treatment was associated with a significant improvement in exacerbation score and quality of life measured by the CF Questionnaire-Revised (CFQ-R) respiratory domain. Following treatment, forced expiratory volume in 1 s (FEV1) % predicted increased [median (range)] 9% (−8%, 31%), and 22 (81%) subjects returned to 90% or higher of baseline FEV1. Bacterial density of the primary organism identified on sputum culture decreased significantly with a median (range) decrease of 0.8 log10 cfu/mL (−8 log10, 2 log10, p = 0.03). Sputum neutrophil elastase [−37 μg/mL (−464, 272), p = 0.02] and IL-1β [−2.8 × 103μg/mL (−6.9 × 104, 3.3 × 104), p = 0.03] decreased significantly following treatment in this cohort. Conclusions Treatment of PEx with oral antibiotics was associated with measurable improvements in patient reported outcomes, lung function, bacterial density and sputum inflammatory markers.

negative: Adjustment and coronavirus: How to prepare for COVID-19 pandemic-related adjustment disorder worldwide? As the 2019 novel coronavirus (COVID-19) is spreading worldwide in 2020, there is a growing concern about the impact of the pandemic on mental health. Multiple stressors associated with the pandemic, such as health-related stressors, job loss, and work-related stressors, could increase the prevalence of adjustment disorders worldwide. The present article acknowledges adjustment disorder as a highly relevant mental health outcome of the pandemic that should be addressed by mental health professionals. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

negative: COVID-19 and SCA: an old friend comes to the rescue In this issue of Blood, DeBaun(1) proposes a forward-thinking evidence-based strategy to limit the impact of the SARS-CoV-2 coronavirus disease (COVID-19) pandemic on children with sickle cell anemia (SCA) at high risk for stroke. DeBaun argues that rapid initiation of low- and fixed-dose (10 mg/kg per day) hydroxyurea treatment while the children are receiving prophylactic chronic transfusions, and before blood supply is disrupted, ensures that when blood shortages do occur, the clinical benefit of hydroxyurea will be more quickly established, and the children will be better protected.

negative: Appréhender le COVID-19 au fil de l'eau en tant que psychiatre d'enfant et d'adolescent./ [Appreciating COVID-19 as a child and adolescent psychiatrist on the move] COVID-19 is a multi-organ disease due to an infection with the SARS-CoV2 virus. It has become a pandemic in early 2020. The disease appears less devastating in children and adolescents. However, stress, quarantine and eventually mourning have major impacts on development. It is difficult to describe what this pandemic implies for a child psychiatrist, other than by giving a first-hand account. I propose to go through the main ethical questions that have arisen; to describe how my hospital team has reorganized itself to meet the new demands and questions, in particular by opening a unit dedicated to people with autism and challenging behaviors affected by COVID-19; and to address, in a context of national discussion, how the discipline has sought to understand the conditions of a certain well-being during quarantine. Finally, I will try to conclude with more speculative reflections on re-opening.

negative: The burden, admission, and outcome of COVID-19 in Africa: protocol for a systematic review and meta-analysis. Background: According to the World Health Organization (WHO), the outbreak of coronavirus disease in 2019 (COVID-19) has been declared as pandemic and public health emergency that infected more than 5 million people worldwide at the time of writing this protocol. Strong evidence for the burden, admission, and outcome of COVID-19 has not been published in Africa. Therefore, this protocol will be served as a guideline to conduct a systematic review and meta-analysis of the burden, admission, and outcome of COVID-19 in Africa. Methods: Published and unpublished studies on the burden, admission, and outcome of COVID-19 in Africa and written in any language will be included. Databases (PubMed / MEDLINE, Google Scholar, Google, EMBASE, Web of Science, Microsoft Academic, WHO COVID-19 database, Cochran Library, Africa Wide Knowledge, and Africa Index Medicus) from December 2019 to May 2020 will be searched. Two independent reviewers will select, screen, extract data, and assess the risk of bias. The proportion will be measured using a random-effects model. Subgroup analysis will be conducted to manage hetrogeinity. The presence of publication bias will be assessed using Egger's test and visual inspection of the funnel plots. This systematic and meta-analysis review protocol will be reported per the PRISMA-P guidelines. Conclusion: This systematic review and meta-analysis protocol will be expected to quantify the burden, admission, and outcome of COVID-19 in Africa. Systematic review registration: This protocol was submitted for registration with the International Prospective Register of Systematic Reviews (PROSPERO) in March 2020 and accepted with the registration number: CRD42020179321(https://www.crd.york.ac.uk/PROSPERO).

negative: The Impact of COVID-19 on HIV Treatment and Research: A Call to Action The impact of the COVID-19 pandemic is far reaching, with devastating effects on individuals, communities, and societies across the world. People with chronic health conditions may be at greater risk of contracting or experiencing complications from COVID-19. In addition to illness or death for those who contract the virus, the physical distancing required to flatten the curve of new cases is having a negative impact on the economy, the effects of which intersect with mental health and other existing health concerns, thus affecting marginalized communities. Given that HIV also has a disproportionate impact on marginalized communities, COVID-19 is affecting people with HIV (PWH) in unique ways and will continue to have an impact on HIV research and treatment after the COVID-19 crisis passes. Using the biopsychosocial framework to contextualize the impact of COVID-19 on PWH, the purpose of this review article is to: (1) outline the similarities and differences between the COVID-19 and HIV pandemics; (2) describe the current and future impact of COVID-19 on PWH; and (3) outline a call to action for scientists and practitioners to respond to the impact of COVID-19 on HIV prevention and treatment.

negative: Elucidation of the antiviral mechanism of cystine and theanine through transcriptome analysis of mice and comparison with COVID-19 gene set data We previously showed that oral administration of cystine and theanine (CT) to mice confers resistance to influenza virus infection. In human studies, CT prevented colds in healthy subjects and enhanced antibody production after influenza vaccination in elderly individuals with a poor nutritional status. The mechanism of action of CT is thought to be glutathione (GSH)-mediated regulation of intracellular redox, which might affect innate immune systems such as macrophages to exert physiological effects. The effect of CT on influenza is independent of viral type, and this treatment has a broad range of antiviral activities. To explore the mechanisms of CT in viral infection, we performed transcriptome profiling of spleen tissues isolated from influenza A virus (IAV)-infected mice. We identified unique gene signatures in response to CT in the IAV-infected mice. Genes upregulated by CT included redox-regulated genes such as GCLC/GCLM (subunits of glutamate cysteine ligase, a rate-limiting enzyme of GSH biosynthesis), TXN1, TXN2, TXNRD2, and SOD1, suggesting that the intracellular redox environment is substantially altered by CT. However, genes downregulated in response to CT included chemokine/chemokine receptor genes (CCL5, CCL19, CXCL9, CXCL12, CXCR3, CXCR4, and ACKR3), some of which are related to cytokine storm. A comparison with public COVID-19-related gene set data showed that the upregulated gene signature was highly similar to the downregulated gene sets of SARS-CoV/SARS-CoV-2-infected cells and the upregulated gene set of attenuated SARS-CoV-infected cells. In conclusion, the unique gene signatures observed in response to orally administered CT in IAV-infected mouse spleen tissues suggested that CT may attenuate viral infection, replication and associated symptoms such as cytokine storm.

negative: Returning Chinese school-aged children and adolescents to physical activity in the wake of COVID-19: Actions and precautions

negative: Renal outcomes of neonates with early presentation of posterior urethral valves: a 10-year single center experience OBJECTIVE: Evaluate renal outcomes and early predictive factors in infants with congenital posterior urethral valves who required catheter or surgical urinary tract decompression within the first 7 days of life. STUDY DESIGN: A 10-year retrospective study at a single hospital. Primary outcomes were estimated glomerular filtration rate (eGFR) and development of end stage renal disease (ESRD). RESULTS: Of 35 infants, 50% developed eGFR <90 mL/min/1.73 m(2) and 15% progressed to ESRD. Nadir creatinine, need for invasive ventilation in the newborn period, and need for surgical diversion after catheter diversion were associated with worse outcomes. 50% of infants requiring invasive ventilation as neonates developed eGFR <60 mL/min/1.73 m(2) in childhood. CONCLUSIONS: Half of infants with early presentation and intervention developed significant renal insufficiency in childhood, similar to children with later presentation or who had fetal intervention. Invasive ventilation in the newborn period and need for surgical urinary diversion are associated with worse outcomes.

negative: Adverse childhood experiences reported by adults --- five states, 2009. Adverse childhood experiences (ACEs) include verbal, physical, or sexual abuse, as well as family dysfunction (e.g., an incarcerated, mentally ill, or substance-abusing family member; domestic violence; or absence of a parent because of divorce or separation). ACEs have been linked to a range of adverse health outcomes in adulthood, including substance abuse, depression, cardiovascular disease, diabetes, cancer, and premature mortality. Furthermore, data collected from a large sample of health maintenance organization members indicated that a history of ACEs is common among adults and ACEs are themselves interrelated. To examine whether a history of ACEs was common in a randomly selected population, CDC analyzed information from 26,229 adults in five states using the 2009 ACE module of the Behavioral Risk Factor Surveillance System (BRFSS). This report describes the results of that analysis, which indicated that, overall, 59.4% of respondents reported having at least one ACE, and 8.7% reported five or more ACEs. The high prevalence of ACEs underscores the need for 1) additional efforts at the state and local level to reduce and prevent child maltreatment and associated family dysfunction and 2) further development and dissemination of trauma-focused services to treat stress-related health outcomes associated with ACEs.

negative: Psychiatric Training During a Global Pandemic: How COVID-19 Has Affected Clinical Care, Teaching, and Trainee Well-Being. The COVID-19 pandemic has altered many aspects of personal and professional life, including how psychiatry is practiced and how trainees are taught. This Open Forum outlines the challenges faced by psychiatric training directors in adult as well as child and adolescent psychiatry in meeting the educational needs of trainees amid this international crisis. Prioritizing trainee protection and education as well as high-quality treatment for patients, the authors discuss effective communication strategies, rapid telepsychiatry expansion into clinical practice, curricular adjustments, and the importance of well-being. This Open Forum concludes with reflections and considerations for training directors as they prepare for subsequent stages of the COVID-19 pandemic.

negative: Treatment, outcomes and costs of asthma exacerbations in Chilean children: a prospective multicenter observational study Abstract Objective To describe potential regional variations in therapies for severe asthma exacerbations in Chilean children and estimate the associated health expenditures. Methods Observational prospective cohort study in 14 hospitals over a one-year period. Children five years of age or older were eligible for inclusion. Days with oxygen supply and pharmacological treatments received were recorded from the clinical chart. A basic asthma hospitalization basket was defined in order to estimate the average hospitalization cost for a single patient. Six months after discharge, new visits to the Emergency Room (ER), use of systemic corticosteroids and adherence to the controller treatment were evaluated. Results 396 patients were enrolled. Patients from the public health system and from the north zone received significantly more days of oxygen, systemic corticosteroids and antibiotics. Great heterogeneity in antibiotic use among the participating hospitals was found, from 0 to 92.3% (ICC 0.34, 95% CI 0.16–0.52). The use of aminophylline, magnesium sulfate and ketamine varied from 0 to 36.4% between the different Pediatric Intensive Care Units (ICC 0.353, 95% CI 0.010–0.608). The average cost per inpatient was of $1910 USD. 290 patients (73.2%) completed the follow-up six months after discharge. 76 patients (26.2%) were not receiving any controller treatment and nearly a fourth had new ER visits and use of systemic corticosteroids due to new asthma exacerbations. Conclusions Considerable practice variation in asthma exacerbations treatment was found among the participating hospitals, highlighting the poor outcome of many patients after hospital discharge, with an important health cost.

negative: Unintended Consequence: Influenza plunges with public health response to COVID-19 in Singapore

negative: Prior diagnoses and medications as risk factors for COVID-19 in a Los Angeles Health System With the continuing coronavirus disease 2019 (COVID-19) pandemic coupled with phased reopening, it is critical to identify risk factors associated with susceptibility and severity of disease in a diverse population to help shape government policies, guide clinical decision making, and prioritize future COVID-19 research. In this retrospective case-control study, we used de-identified electronic health records (EHR) from the University of California Los Angeles (UCLA) Health System between March 9(th), 2020 and June 14(th), 2020 to identify risk factors for COVID-19 susceptibility (severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) PCR test positive), inpatient admission, and severe outcomes (treatment in an intensive care unit or intubation). Of the 26,602 individuals tested by PCR for SARS-CoV-2, 992 were COVID-19 positive (3.7% of Tested), 220 were admitted in the hospital (22% of COVID-19 positive), and 77 had a severe outcome (35% of Inpatient). Consistent with previous studies, males and individuals older than 65 years old had increased risk of inpatient admission. Notably, individuals self-identifying as Hispanic or Latino constituted an increasing percentage of COVID-19 patients as disease severity escalated, comprising 24% of those testing positive, but 40% of those with a severe outcome, a disparity that remained after correcting for medical comorbidities. Cardiovascular disease, hypertension, and renal disease were premorbid risk factors present before SARS-CoV-2 PCR testing associated with COVID-19 susceptibility. Less well-established risk factors for COVID-19 susceptibility included pre-existing dementia (odds ratio (OR) 5.2 [3.2–8.3], p=2.6 × 10(−10)), mental health conditions (depression OR 2.1 [1.6–2.8], p=1.1 × 10(−6)) and vitamin D deficiency (OR 1.8 [1.4–2.2], p=5.7 × 10(−6)). Renal diseases including end-stage renal disease and anemia due to chronic renal disease were the predominant premorbid risk factors for COVID-19 inpatient admission. Other less established risk factors for COVID-19 inpatient admission included previous renal transplant (OR 9.7 [2.8–39], p=3.2×10(−4)) and disorders of the immune system (OR 6.0 [2.3, 16], p=2.7×10(−4)). Prior use of oral steroid medications was associated with decreased COVID-19 positive testing risk (OR 0.61 [0.45, 0.81], p=4.3×10(−4)), but increased inpatient admission risk (OR 4.5 [2.3, 8.9], p=1.8×10(−5)). We did not observe that prior use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers increased the risk of testing positive for SARS-CoV-2, being admitted to the hospital, or having a severe outcome. This study involving direct EHR extraction identified known and less well-established demographics, and prior diagnoses and medications as risk factors for COVID-19 susceptibility and inpatient admission. Knowledge of these risk factors including marked ethnic disparities observed in disease severity should guide government policies, identify at-risk populations, inform clinical decision making, and prioritize future COVID-19 research.

negative: BigO: A public health decision support system for measuring obesogenic behaviors of children in relation to their local environment Obesity is a complex disease and its prevalence depends on multiple factors related to the local socioeconomic, cultural and urban context of individuals. Many obesity prevention strategies and policies, however, are horizontal measures that do not depend on context-specific evidence. In this paper we present an overview of BigO (http://bigoprogram.eu), a system designed to collect objective behavioral data from children and adolescent populations as well as their environment in order to support public health authorities in formulating effective, context-specific policies and interventions addressing childhood obesity. We present an overview of the data acquisition, indicator extraction, data exploration and analysis components of the BigO system, as well as an account of its preliminary pilot application in 33 schools and 2 clinics in four European countries, involving over 4,200 participants.

negative: Assessing the Real-Time Mental Health Challenges of COVID-19 in Individuals With Serious Mental Illnesses: Protocol for a Quantitative Study BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has caused significant stress and mental health problems among the general public. However, persons at greatest risk for poor mental health outcomes, such as people with serious mental illness, have been largely overlooked. OBJECTIVE: This paper presents the protocol for a study that aims to examine the mental health impact of COVID-19 and social distancing behaviors in people with serious mental illness and the behaviors undertaken to prevent COVID-19 infection in this group. METHODS: Participants will include individuals with serious mental illness (eg, schizophrenia, bipolar disorder) and nonpsychiatric control participants who are currently participating in or have previously participated in several ongoing parent observational studies. Data will be collected from April 2020 through August 2020. Participants will complete phone interviews at 2 time points to assess their current emotional functioning and discuss the measures they have taken to prevent COVID-19 infection. Baseline (pre-COVID-19) mental health, sampled by ecological momentary assessment over an extended period, will be compared with current mental health, also sampled by ecological momentary assessment over an extended period. Demographic, cognitive, and psychosocial factors at baseline will be used to examine risk and resilience to current mental health and coping. RESULTS: The inclusion of participants for the first round of telephone assessments started on April 3, 2020 and will be completed by May 31, 2020. As of April 30, 2020, 101 individuals had completed these first-round assessments. The second round of telephone assessments will likely occur between June 1, 2020, and August 31, 2020. Study results will be published in peer-reviewed scientific journals. CONCLUSIONS: Our findings will have broad implications for understanding the psychological consequences of COVID-19 among vulnerable persons with serious mental illness and will provide the opportunity to identify targets to reduce negative outcomes in the future. We also hope our efforts will provide a roadmap and resources for other researchers who would like to implement a similar approach. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/19203

negative: COVID-19 and children with cancer: Parents' experiences, anxieties, and support needs Background Children with cancer were considered to be extremely clinically vulnerable to severe COVID-19 disease if they were to contract SARS-CoV-2 due to immune suppression as a result of anti-cancer treatment. The aim was to explore experiences, information and support needs, and decision-making of parents with a child with cancer in response to the early phase of the COVID-19 pandemic in the UK. Methods Parents of a child with cancer completed a survey in April 2020, as the UK moved into a period of "lockdown", with restrictions of movement outside of the home. An online survey was developed to capture parents' experiences, information and support needs, and decision-making, using closed statements and open text boxes. Descriptive quantitative analyses and qualitative thematic content analysis were undertaken. Findings 171 parents/caregivers completed the survey. 85% of parents worried about the virus and the majority of parents were vigilant about virus (92%) or cancer symptoms (93.4%). For two-thirds (69.6%) hospital was no longer considered a safe place. Parents worried about their own health (81.1%) and about the child getting the virus from them (89.1%). Eight overarching themes, related to the virus: 1) risk of infection, 2) information, guidance and advice, 3) health care provision, 4) fears and anxieties; or related to lockdown/isolation: 5) psychological and social impact, 6) keeping safe under lockdown, 7) provisions and dependence, and 8) employment and income. Interpretation This is the first study to report experiences of parents of a child with cancer during the SARS-CoV-2/COVID-19 pandemic. The study demonstrated that the majority of parents are worried about SARS-CoV-2, and worried about transmitting the virus to their child. Hospital was no longer a safe place, and parents were worried about suboptimal cancer care. Parents describe fear and anxiety and the psychological, social and economic impact of isolation as a family.

negative: Executive function training in very preterm children: a randomized controlled trial Objective of the current study was to assess whether game-formatted executive function (EF) training, is effective in improving attention, EF and academic performance in very preterm and/or extremely low birthweight children aged 8–12 years. A multi-center, double-blind, placebo- and waitlist controlled randomized trial (NTR5365) in two academic hospitals in The Netherlands was performed. Eighty-five very preterm children with parent-rated attention problems on the Child Behavior Checklist were randomized to one of three treatment conditions: EF training, placebo training or waitlist condition. EF or placebo training was completed at home (6 weeks, 25 sessions of 30–45 min each). At baseline, 2 weeks after training or being on the waitlist, and five months after first follow-up visit, children underwent assessments of primary outcomes (parent and teacher ratings of attention) and secondary outcomes (parent and teacher ratings of daily-life EF, computerized EF tasks and academic performance). Linear mixed model analyses were performed for all outcome measures. There were no significant differences in improvement over time on parent- and teacher ratings of attention, parent- and teacher ratings of daily-life EF, computerized EF tasks, and academic performance (arithmetic and reading) between the EF training, placebo training and waitlist condition. In conclusion, game-formatted EF training does not improve attention, EF or academic performance in very preterm children with parent-rated attention problems. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00787-020-01561-0) contains supplementary material, which is available to authorized users.

negative: Rhinovirus infections in infancy and early childhood. Rhinovirus (RV) infections occur early and recurrently in life, imposing a significant burden of disease on infants and young children. They are the most frequent causative agents of both upper and lower respiratory tract infections in this age group and are associated with a broad variety of clinical outcomes, ranging from asymptomatic infections to severe respiratory disease requiring hospitalisation. In addition to their impact on short-term morbidity, RVs are also debated as important pathogens in the development of recurrent wheeze and/or asthma. Several studies in infants at high-risk for atopy and asthma and in hospitalised children have demonstrated that recurrent wheezing illnesses induced by RVs early in life are a risk factor for the development of asthma later in childhood. However, underlying mechanisms are poorly understood. The question whether RVs are directly involved in the development of childhood wheeze and asthma, or whether symptomatic RV infections only represent a proxy for infants prone to develop obstructive lung diseases, is still open. In this review we provide an overview on the role of RVs as important disease-causing agents from infancy to early childhood and discuss their contribution to the subsequent development of childhood wheeze and/or asthma.

negative: Pyeloplasty in children: perioperative results and long-term outcomes of robotic-assisted laparoscopic surgery compared to open surgery. BACKGROUND A few studies have compared robotic-assisted laparoscopic pyeloplasty (RALP) with open pyeloplasty (OP) in children, but no previous study includes a long-term follow-up of renal function and hydronephrosis in combination with a thorough prospective follow-up of the RALP patients of at least 2 years. OBJECTIVE To analyze perioperative results and long-term outcome of children with obstruction of the ureteropelvic junction, operated on with RALP compared to OP. PATIENTS AND METHODS Children ≤15 years operated on with RALP or OP from 2000 through 2013 were reviewed. Patient demographics, perioperative data, postoperative complications, and long-term outcome were evaluated. The outcome was based on pre- and postoperative examination of renal function, hydronephrosis and flank pain. RESULTS 129 pyeloplasties (84 OP, 39 RALP, 6 reoperations) on 123 patients were included. RALP had significantly longer operative time and shorter postoperative hospital stay, compared to OP. No difference was found in postoperative need of morphine or complication rates. Mean follow-up for RALP with ultrasound was 29 and 25 months with renal scan, compared to 34 and 28 months, respectively, for OP. The success rate for flank pain was 96 and 94 %, for hydronephrosis 93 and 95 %, and renal function 94 and 92 %, for RALP and OP, respectively. CONCLUSIONS RALP is a safe method, with advantages compared to OP, and with the same success rate. This study supports the use of RALP in children.

negative: Should we wait or not? The preferable option for patients with stage IV oral cancer in COVID-19 pandemic BACKGROUND: The coronavirus infection is rapidly spreading, putting a strain on health care services across the globe. Patients with oral cancer are susceptible often immunosuppressed due to the disease and/or the treatment received. METHODS: We performed a simulation of the currently available data using a multistate and hazards model to provide an objective model for counseling and decision making for health care workers. RESULTS: Stage IV patients with oral cancer who did not receive treatment had progression of disease and an increased mortality rate compared to patients who receive treatment but did not contract COVID-19. The patients who received treatment and got affected with COVID-19 had a far worse impact and higher mortality rate than all other groups. CONCLUSION: Isolation and deferring treatment for stage IV patients with oral cancer, so as to avoid hospital visits and contraction of COVID-19, is an advisable strategy based on this model.

negative: Demystifying the myths about COVID-19 infection and its societal importance

negative: Validation of the Arabic Version of the Early Childhood Oral Health Impact Scale (ECOHIS) BACKGROUND: Assessment of the adverse effects of oral health problems on oral health-related quality of life (OHRQoL) is essential to ensure the well-being of children. The Early Childhood Oral Health Impact Scale (ECOHIS) is an instrument that was designed to assess caregivers’ perceptions of OHRQoL in preschool children. Although it has been translated into many languages, it has yet to be validated in Arabic. Therefore, this study aimed to translate this questionnaire to Arabic (A-ECOHIS) and test its psychometric properties. METHODS: Questionnaire responses from three samples of caregivers of preschool children ≤ 6 years of age were collected: (i) community-based (n = 422), from preschools selected as a stratified random sample; (ii) clinic-based, from those seeking pediatric dental care at a university clinic (n = 246); and (iii) a test-retest sample (n = 68), a clinic-based group of caregivers who completed questionnaires twice about siblings who were not receiving dental care. Children received a dental examination to assess their decayed, missed, filled teeth (dmft) scores. Convergent validity was evaluated by assessing the A-ECOHIS scores in relation to the response to a global question. Discriminant validity was evaluated by comparing the scores of children with varying levels of oral disease. Internal consistency was assessed by calculating Cronbach’s alpha, and the test-retest reliability was assessed using intra-class correlation coefficients (ICCs). RESULTS: The A-ECOHIS scores of the questionnaire sections and the global oral health rating were significantly correlated; Spearman correlation coefficients were, r = 0.55, P ≤ 0.01 (overall score), r = 0.54, P ≤ 0.01 (child section), and r = 0.51, P ≤ 0.01 (family section). The mean A-ECOHIS scores were also statistically significantly higher in children with higher dmft scores compared with lower dmft, and in the clinic-based sample compared with the community sample. The Cronbach’s alpha value of the the child, family sections and overall questionnaire were, 0.80, 0.78, and 0.85, respectively. The intra-class correlation coefficient (ICC) of A-ECOHIS was 0.86. CONCLUSION: The A-ECOHIS performed well on all psychometric tests to which it was applied. Thus, it is a valid and reliable instrument that can be used in Arabic-speaking caregivers of preschoolers aged 2 to 6 years.

negative: Outcome of a public consultation on the Draft Opinion of the EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA) on a guidance on the scientific requirements for health claims related to gut and immune function

negative: Nasopharyngeal microbiota composition of children is related to the frequency of upper respiratory infection and acute sinusitis BACKGROUND: Upper respiratory infections (URI) and their complications are a major healthcare burden for pediatric populations. Although the microbiology of the nasopharynx is an important determinant of the complications of URI, little is known of the nasopharyngeal (NP) microbiota of children, the factors that affect its composition, and its precise relationship with URI. RESULTS: Healthy children (n = 47) aged 49–84 months from a prospective cohort study based in Wisconsin, USA, were examined. Demographic and clinical data and NP swab samples were obtained from participants upon entry to the study. All NP samples were profiled for bacterial microbiota using a phylogenetic microarray, and these data were related to demographic characteristics and upper respiratory health outcomes. The composition of the NP bacterial community of children was significantly related prior to the history of acute sinusitis (R(2) = 0.070, P < 0.009). History of acute sinusitis was associated with significant depletion in relative abundance of taxa including Faecalibacterium prausnitzii and Akkermansia spp. and enrichment of Moraxella nonliquefaciens. Enrichment of M. nonliquefaciens was also a characteristic of baseline NP samples of children who subsequently developed acute sinusitis over the 1-year study period. Time to develop URI was significantly positively correlated with NP diversity, and children who experienced more frequent URIs exhibited significantly diminished NP microbiota diversity (P ≤ 0.05). CONCLUSIONS: These preliminary data suggest that previous history of acute sinusitis influences the composition of the NP microbiota, characterized by a depletion in relative abundance of specific taxa. Diminished diversity was associated with more frequent URIs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40168-016-0179-9) contains supplementary material, which is available to authorized users.

negative: Infections and asthma. Infections have a variety of influences in the asthmatic patient. Respiratory syncytial virus (RSV) is the most common cause of wheezing illnesses in children under the age of 2 years and may be a risk factor for the inception of asthma in the first decade of life. Once asthma has become recognized clinically, rhinovirus is the leading cause of acute asthma exacerbations in adults and older children. Certain respiratory infections may induce chronic lower airway inflammation that may contribute to disease progression or severity in asthma. Paradoxically, some infections may even protect against the development of asthma. This article reviews the evidence for these associations and the mechanisms proposed to explain these various outcomes.

negative: The COVID-19 pandemic: Technology use to support the wellbeing of children

negative: Chloroquine Dosing Recommendations for Pediatric COVID‐19 Supported by Modeling and Simulation As chloroquine (CHQ) is part of the Dutch Centre for Infectious Disease Control coronavirus disease 2019 (COVID‐19) experimental treatment guideline, pediatric dosing guidelines are needed. Recent pediatric data suggest that existing World Health Organization (WHO) dosing guidelines for children with malaria are suboptimal. The aim of our study was to establish best‐evidence to inform pediatric CHQ doses for children infected with COVID‐19. A previously developed physiologically‐based pharmacokinetic (PBPK) model for CHQ was used to simulate exposure in adults and children and verified against published pharmacokinetic data. The COVID‐19 recommended adult dosage regimen of 44 mg/kg total was tested in adults and children to evaluate the extent of variation in exposure. Based on differences in area under the concentration‐time curve from zero to 70 hours (AUC(0–70h)) the optimal CHQ dose was determined in children of different ages compared with adults. Revised doses were re‐introduced into the model to verify that overall CHQ exposure in each age band was within 5% of the predicted adult value. Simulations showed differences in drug exposure in children of different ages and adults when the same body‐weight based dose is given. As such, we propose the following total cumulative doses: 35 mg/kg (CHQ base) for children 0–1 month, 47 mg/kg for 1–6 months, 55 mg/kg for 6 months–12 years, and 44 mg/kg for adolescents and adults, not to exceed 3,300 mg in any patient. Our study supports age‐adjusted CHQ dosing in children with COVID‐19 in order to avoid suboptimal or toxic doses. The knowledge‐driven, model‐informed dose selection paradigm can serve as a science‐based alternative to recommend pediatric dosing when pediatric clinical trial data is absent.

negative: Making sense of perceptions of risk of diseases and vaccinations: a qualitative study combining models of health beliefs, decision-making and risk perception BACKGROUND: Maintaining high levels of childhood vaccinations is important for public health. Success requires better understanding of parents' perceptions of diseases and consequent decisions about vaccinations, however few studies have considered this from the theoretical perspectives of risk perception and decision-making under uncertainty. The aim of this study was to examine the utility of subjective risk perception and decision-making theories to provide a better understanding of the differences between immunisers' and non-immunisers' health beliefs and behaviours. METHODS: In a qualitative study we conducted semi-structured in-depth interviews with 45 Australian parents exploring their experiences and perceptions of disease severity and susceptibility. Using scenarios about 'a new strain of flu' we explored how risk information was interpreted. RESULTS: We found that concepts of dread, unfamiliarity, and uncontrollability from the subjective perception of risk and ambiguity, optimistic control and omission bias from explanatory theories of decision-making under uncertainty were useful in understanding why immunisers, incomplete immunisers and non-immunisers interpreted severity and susceptibility to diseases and vaccine risk differently. Immunisers dreaded unfamiliar diseases whilst non-immunisers dreaded unknown, long term side effects of vaccines. Participants believed that the risks of diseases and complications from diseases are not equally spread throughout the community, therefore, when listening to reports of epidemics, it is not the number of people who are affected but the familiarity or unfamiliarity of the disease and the characteristics of those who have had the disease that prompts them to take preventive action. Almost all believed they themselves would not be at serious risk of the 'new strain of flu' but were less willing to take risks with their children's health. CONCLUSION: This study has found that health messages about the risks of disease which are communicated as though there is equality of risk in the population may be unproductive as these messages are perceived as unbelievable or irrelevant. The findings from this study have implications beyond the issue of childhood vaccinations as we grapple with communicating risks of new epidemics, and indeed may usefully contribute to the current debate especially in the UK of how these theories of risk and decision-making can be used to 'nudge' other health behaviours.

negative: Protecting children from iatrogenic harm during COVID19 pandemic Critical care management of patients with COVID-19 has been influenced by a mixture of public, media and societal pressure, as well as clinical and anecdotal observations from many prominent researchers and key opinion leaders. These factors may have affected the principles of evidence-based medicine and encouraged the widespread use of non-tested pharmacological and aggressive respiratory support therapies, even in intensive care units (ICUs). The COVID-19 pandemic has predominantly affected adult populations, while children appear to be relatively spared of severe disease. Notwithstanding, paediatric intensive care (PICU) clinicians may already have been influenced by changes in practices of adult ICUs, and these changes may pose unintended consequences to the vulnerable population in the PICU. In this article, we analyse several potential iatrogenic causes of the detrimental effects of the current pandemic to children and highlight the risks underlying a sudden change of clinical practice.

negative: Comorbidity and Sociodemographic determinants in COVID-19 Mortality in an US Urban Healthcare System Background: New York City is the US epicenter of the coronavirus disease 2019 (COVID-19) pandemic. Early international data indicated that comorbidity contributes significantly to poor prognosis and fatality in patients infected with SARS-CoV-2. It is not known to what degree medical comorbidity and sociodemographic determinants impact COVID-19 mortality in the US. Methods: Evaluation of de-identified electronic health records of 7,592 COVID-19 patients confirmed by SARS-CoV-2 lab tests in New York City. Medical comorbidites and outcome of mortality, and other covariates, including clinical, sociodemographic, and medication measures were assessed by bivariate and multivariate logistic regression models. Results: Of common comorbid conditions (hypertension, chronic kidney disease, chronic obstructive pulmonary disease, asthma, obesity, diabetes, HIV, cancer), when adjusted for covariates, chronic kidney disease remained significantly associated with increased odds of mortality. Patients who had more than one comorbidities, former smokers, treated with Azithromycin without Hydroxychloroquine, reside within the boroughs of Brooklyn and Queens Higher had higher odds of death. Conclusions: Increasing numbers of comorbid factors increase COVID-19 mortality, but several clinical and sociodemographic factors can mitigate risk. Continued evaluation of COVID-19 in large diverse populations is important to characterize individuals at risk and improve clinical outcomes.

negative: [The impact of Covid-19 pandemic on breastfeeding and birth care. The importance of recovering good practices.] The SARS-CoV-2 pandemic has had a major impact on birth care and lactation. The lack of knowledge regarding the transmission mechanisms and the potential risks for the mother and the newborn, even when the vertical transmission of the virus has not been demonstrated, has led to the abandonment of practices such as skin-to-skin and the early initiation of breastfeeding (BF), which offer great benefits for maternal and child health. Taking into account the available scientific evidence and the protective effect of BF, the World Health Organization (WHO), and other organisms recommend, in cases of suspected or confirmed SARS-CoV-2 infection of the mother, maintaining mother-child contact and BF, adopting preventive measure procedures to minimize the risk of contagion. These measures include hand hygiene, before and after contact with the newborn and the use of a mask. If a temporary separation of mother and child is required, it is recommended to feed the newborn with expressed breast milk. The presence of IgA antibodies against SARS-CoV-2 has been confirmed in the milk of infected women, so BF could reduce the clinical impact of the disease in the infant, if it becomes infected.

negative: The Public Health Response to the COVID-19 Pandemic for People with Disabilities() With the rapidly changing landscape of the Covid-19 outbreak, how to best address the needs and continue to protect the health and well-being of people with disabilities (PwDs) is a global public health priority. In this commentary we identify three public health areas of ongoing need and offer possible strategies to address each. These areas include: the types of data that would help clarify risks for PwDs and help assure their safety long term; the prevention, treatment and mitigation measures for PwDs that are needed through the duration of the outbreak; and the issues of equity in access to and quality of medical care for PwDs. Because of the rapid nature of the public health response, it is critical to reassess and readjust our approach to best address the needs of PwDs in the months and years to come and to incorporate these new practices into future emergency preparedness responses.

negative: Use and validity of child neurodevelopment outcome measures in studies on prenatal exposure to psychotropic and analgesic medications - A systematic review. In recent years there has been increased attention to child neurodevelopment in studies on medication safety in pregnancy. Neurodevelopment is a multifactorial outcome that can be assessed by various assessors, using different measures. This has given rise to a debate on the validity of various measures of neurodevelopment. The aim of this review was twofold. Firstly we aimed to give an overview of studies on child neurodevelopment after prenatal exposure to central nervous system acting medications using psychotropics and analgesics as examples, giving special focus on the use and validity of outcome measures. Secondly, we aimed to give guidance on how to conduct and interpret medication safety studies with neurodevelopment outcomes. We conducted a systematic review in the MEDLINE, Embase, PsycINFO, Web of Science, Scopus, and Cochrane databases from inception to April 2019, including controlled studies on prenatal exposure to psychotropics or analgesics and child neurodevelopment, measured with standardised psychometric instruments or by diagnosis of neurodevelopmental disorder. The review management tool Covidence was used for data-extraction. Outcomes were grouped as motor skills, cognition, behaviour, emotionality, or "other". We identified 110 eligible papers (psychotropics, 82 papers, analgesics, 29 papers). A variety of neurodevelopmental outcome measures were used, including 27 different psychometric instruments administered by health care professionals, 15 different instruments completed by parents, and 13 different diagnostic categories. In 23 papers, no comments were made on the validity of the outcome measure. In conclusion, establishing neurodevelopmental safety includes assessing a wide variety of outcomes important for the child's daily functioning including motor skills, cognition, behaviour, and emotionality, with valid and reliable measures from infancy through to adolescence. Consensus is needed in the scientific community on how neurodevelopment should be assessed in medication safety in pregnancy studies. Review registration number: CRD42018086101 in the PROSPERO database.

negative: Shifting from survival to supporting resilience in children and families in the COVID-19 pandemic: Lessons for informing U.S. mental health priorities This commentary contextualizes potential mental health outcomes for children during and after the COVID-19 pandemic within the risk and resilience literature. Individual, familial, and community-level factors that may increase risk for mental health challenges for children as well as factors associated with positive adaptation in the face of adversity are considered. We highlight the value of considering children's resilience within a systemic perspective by considering family-centered approaches including both short-term and long-term evidence-informed mental health practices. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

negative: Leveraging parent-child interaction therapy and telehealth capacities to address the unique needs of young children during the COVID-19 public health crisis. COVID-19 and related efforts to mitigate its spread have dramatically transformed the structure and predictability of modern childhood, resulting in growing concerns children may be particularly vulnerable to serious mental health consequences. Worldwide stay-at-home directives and emergency changes in healthcare policy and reimbursement have smoothed the trail for broad implementation of technology-based remote mental health services for children. Parent-Child Interaction Therapy (PCIT) is particularly well-positioned to address some of the most pressing child and parental needs that arise during stressful times, and telehealth formats of PCIT, such as Internet-delivered PCIT (iPCIT), have already been supported in controlled trials. This commentary explores PCIT implementation during the COVID-19 public health crisis and the challenges encountered in the move toward Internet-delivered services. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

negative: Psychosocial impact of COVID-19 BACKGROUND: Along with its high infectivity and fatality rates, the 2019 Corona Virus Disease (COVID-19) has caused universal psychosocial impact by causing mass hysteria, economic burden and financial losses. Mass fear of COVID-19, termed as "coronaphobia", has generated a plethora of psychiatric manifestations across the different strata of the society. So, this review has been undertaken to define psychosocial impact of COVID-19. METHODS: Pubmed and GoogleScholar are searched with the following key terms- "COVID-19", "SARS-CoV2", "Pandemic", "Psychology", "Psychosocial", "Psychitry", "marginalized", "telemedicine", "mental health", "quarantine", "infodemic", "social media" and" "internet". Few news paper reports related to COVID-19 and psychosocial impacts have also been added as per context. RESULTS: Disease itself multiplied by forced quarantine to combat COVID-19 applied by nationwide lockdowns can produce acute panic, anxiety, obsessive behaviors, hoarding, paranoia, and depression, and post-traumatic stress disorder (PTSD) in the long run. These have been fueled by an "infodemic" spread via different platforms of social media. Outbursts of racism, stigmatization, and xenophobia against particular communities are also being widely reported. Nevertheless, frontline healthcare workers are at higher-risk of contracting the disease as well as experiencing adverse psychological outcomes in form of burnout, anxiety, fear of transmitting infection, feeling of incompatibility, depression, increased substance-dependence, and PTSD. Community-based mitigation programs to combat COVID-19 will disrupt children's usual lifestyle and may cause florid mental distress. The psychosocial aspects of older people, their caregivers, psychiatric patients and marginalized communities are affected by this pandemic in different ways and need special attention. CONCLUSION: For better dealing with these psychosocial issues of different strata of the society, psychosocial crisis prevention and intervention models should be urgently developed by the government, health care personnel and other stakeholders. Apt application of internet services, technology and social media to curb both pandemic and infodemic needs to be instigated. Psychosocial preparedness by setting up mental organizations specific for future pandemics is certainly necessary.

negative: Household Transmission of SARS-CoV-2 from Adults to Children

negative: Hematopoietic cellular aging is not accelerated during the first 2 years of life in children born preterm BACKGROUND: Prematurity in itself and exposure to neonatal intensive care triggers inflammatory processes and oxidative stress, leading to risk for disease later in life. The effects on cellular aging processes are incompletely understood. METHODS: Relative telomere length (RTL) was measured by qPCR in this longitudinal cohort study with blood samples taken at birth and at 2 years of age from 60 children (16 preterm and 44 term). Viral respiratory infections the first year were evaluated. Epigenetic biological DNA methylation (DNAm) age was predicted based on methylation array data in 23 children (11 preterm and 12 term). RTL change/year and DNAm age change/year was compared in preterm and term during the 2 first years of life. RESULTS: Preterm infants had longer telomeres than term born at birth and at 2 years of age, but no difference in telomere attrition rate could be detected. Predicted epigenetic DNAm age was younger in preterm infants, but rate of DNAm aging was similar in both groups. CONCLUSIONS: Despite early exposure to risk factors for accelerated cellular aging, children born preterm exhibited preserved telomeres. Stress during the neonatal intensive care period did not reflect accelerated epigenetic DNAm aging. Early-life aging was not explained by preterm birth. IMPACT: Preterm birth is associated with elevated disease risk later in life. Preterm children often suffer from inflammation early in life. Stress-related telomere erosion during neonatal intensive care has been proposed. Inflammation-accelerated biological aging in preterm is unknown. We find no accelerated aging due to prematurity or infections during the first 2 years of life.

negative: Recent Trends and Future Directions in Research Regarding Parents with Intellectual and Developmental Disabilities PURPOSE OF REVIEW: This report updates research on parents with IDD and their children published since 2014. RECENT FINDINGS: Since 2014, a plethora of studies using large administrative databases in different countries support a contextual approach to understand why parents with IDD and their children may have worse outcomes than other families. In most studies, increased risk of ill health in women with IDD and health and developmental problems in their children were fully or partially accounted for by socioeconomic and psychosocial hardships. New research has found that pregnant women with IDD tend to have risk factors for pregnancy, birth, and postpartum complications that may contribute to adverse child outcomes. Intervention research is gradually becoming more contextualized. SUMMARY: More studies are needed on multicultural aspects of parenting, programs that could help parents with IDD overcome social and health disadvantages, comprehensive and coordinated service models that start during pregnancy, innovative parent support arrangements, parenting education for teens and young adults with IDD, use of technology, and dissemination and implementation of evidence-based programs.

negative: Using altmetrics for detecting impactful research in quasi-zero-day time-windows: the case of COVID-19 On December 31st 2019, the World Health Organization (WHO) China Country Office was informed of cases of pneumonia of unknown etiology detected in Wuhan City. The cause of the syndrome was a new type of coronavirus isolated on January 7th 2020 and named Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2). SARS-CoV-2 is the cause of the coronavirus disease 2019 (COVID-19). Since January 2020 an ever increasing number of scientific works have appeared in literature. Identifying relevant research outcomes at very early stages is challenging.In this work we use COVID-19 as a use-case for investigating: (i) which toos and frameworkds are mostly used for early scholarly communication; (ii) to what extent altmetrics can be used to identify potential impactful research in tight (i.e. {\em quasi-zero-day}) time-windows. A literature review with rigorous eligibility criteria is performed for gathering a sample composed of scientific papers about SARS-CoV-2/COVID-19 appeared in literature in the tight time-window ranging from January 15th 2020 to February 24th 2020. This sample is used for building a knowledge graph that represents the knowledge about papers and indicators formally. This knowledge graph feeds a data analysis process which is applied for experimenting with altmetrics as impact indicators. We find moderate correlation among traditional citation count, citations on social media, and mentions on news and blogs. This suggests there is a common intended meaning of the citational acts associated with aforementioned indicators. Additionally, we define a method that harmonises different indicators for providing a multi-dimensional impact indicator.

negative: Sleep disturbances among medical workers during the outbreak of COVID-2019 BACKGROUND: The outbreak of Corona Virus Disease-2019 (COVID-19) has posed unprecedented pressure and threats to healthcare workers in Wuhan and the entire country. AIMS: To assess the effect of the COVID-19 outbreak on the sleep quality of healthcare workers in a children’s healthcare centre in Wuhan. METHODS: A cross-sectional, anonymized, self-reported questionnaire survey was conducted at the Children’s Healthcare Centre of Renmin Hospital, Wuhan University, Wuhan, China. The questionnaire consisted of three parts, including socio-demographic characteristics and COVID-19 epidemic-related factors, the Pittsburgh sleep quality index (PSQI), and Zung’s self-rating anxiety scale (SAS) and self-rating depression scale (SDS). RESULTS: In total, 47 out of 123 (38%) participants with PSQI scores > 7 were identified as having sleep disturbance. A logistic regression analysis showed that sleep disturbance was independently associated with being an only child (adjusted odds ratio (OR) and 95% confidence interval (CI) 3.40 (1.21–9.57), P < 0.05), exposure to COVID-19 patients (adjusted OR and 95% CI 2.97 (1.08–8.18), P < 0.05) and depression (adjusted OR and 95% CI 2.83 (1.10–7.27), P < 0.05). CONCLUSIONS: We observed that, during the outbreak of COVID-19, sleep disturbance was highly prevalent among paediatric healthcare workers, and sleep disturbance was independently associated with being an only child, exposure to COVID-19 patients and depression. Therefore, more mental health services are required for front-line paediatric healthcare workers in Wuhan.

negative: Child protection in the time of COVID‐19 As the number of cases of coronavirus disease 2019 (COVID‐19) caused by the virus SARS‐CoV‐2 rises exponentially in Australia with consequences for the health system and society at large, we need to remember that during this pandemic that necessary social distancing measures, effective school closures and rising unemployment levels may lead to an increased risk for child abuse and neglect.

negative: Translating COVID-19 Evidence to Maximize Physical Therapists’ Impact and Public Health Response Coronavirus disease 2019 (COVID-19) has sounded alarm bells throughout global health systems. Late May, 2020, over 100,000 COVID-19 related deaths were reported in the United State, the highest number of any country. This article describes COVID-19 as the next historical turning point in the physical therapy profession’s growth and development. The profession has had over a 100-year tradition of responding to epidemics including poliomyelitis; two world wars and geographical regions experiencing conflicts and natural disasters; and the epidemic of noncommunicable diseases (NCDs). The evidence-based role of non-invasive interventions (non-pharmacologic/non-surgical) that hallmark physical therapist practice has emerged as being highly relevant today in addressing COVID-19 in two primary ways. First, despite some unique features, COVID-19 presents as acute respiratory distress syndrome (ARDS) in its severe acute stage. ARDS is well familiar to physical therapists in intensive care units. Body positioning and mobilization, prescribed based on comprehensive assessments/examinations, counter the negative sequelae of recumbency and bedrest; augment gas exchange and reduce airway closure, deconditioning and critical illness complications; and maximize long-term functional outcomes. Physical therapists have an indisputable role across the COVID-19 care continuum. Second, over 90% of individuals who contract and die from COVID-19 have co-morbidities, most notably cardiovascular disease, hypertension, chronic lung disease, type 2 diabetes mellitus, and obesity. Physical therapists need to redouble their efforts to address NCDs by assessing patients for risk factors and manifestations and institute evidence-based health education (smoking cessation, whole-food plant-based nutrition, weight control, physical activity/exercise), and/or support patients’ efforts when these are managed by other professionals. Effective health education is a core competency for addressing risk of COVID-19 as well as NCDs. COVID-19 is a wake-up call to the profession, an opportunity to assert its role throughout the COVID-19 care continuum and augment public health initiatives by reducing the impact of the current pandemic.

negative: The outbreak of coronavirus disease in China: Risk perceptions, knowledge, and information sources among prenatal and postnatal women BACKGROUND: The COVID-19 pandemic has created anxiety among members of the public, including all women over the childbirth continuum, who are considered to be at a greater risk of contracting most infectious diseases. Understanding the perspectives of health care consumers on COVID-19 will play a crucial role in the development of effective risk communication strategies. This study aimed to examine COVID-19-related risk perceptions, knowledge, and information sources among prenatal and postnatal Chinese women during the initial phase of the COVID-19 pandemic. METHODS: A cross-sectional survey design was adopted, and a four-section online questionnaire was used to collect data. Using a social media platform, the online survey was administered to 161 participants during the outbreak of COVID-19 in Nanjing, China, in February 2020. RESULTS: The participants perceived their risk of contracting and dying from COVID-19 to be lower than their risk of contracting influenza, however many of them were worried that they might contract COVID-19. The participants demonstrated adequate knowledge about COVID-19. The three major sources from which they obtained information about COVID-19 were doctors, nurses/midwives, and the television, and they placed a high level of confidence in these sources. There was no significant relationship between the perceived risk of contracting COVID-19 and knowledge about this disease. CONCLUSION: The present findings offer valuable insights to healthcare professionals, including midwives, who serve on the frontline and provide care to pregnant women. Although the participants were adequately knowledgeable about COVID-19, they had misunderstood some of the recommendations of the World Health Organization.

negative: Mental health considerations for children & adolescents in COVID-19 Pandemic Children are not indifferent to the significant psychological impact of the COVID-19 Pandemic. They experience fears, uncertainties, substantial changes to their routines, physical and social isolation alongside high level of parental stress. Understanding their emotions and responses is essential to properly address their needs during this pandemic. In this article, we highlight children’s vulnerability, provide an overview of common symptoms of distress in different age groups, and summarize the interventions and resources available to promote child mental health and wellbeing during these challenging times. We advocate that prioritizing mental health including child & adolescent mental health is an essential component of any universal, community led response to COVID-19 Pandemic.

negative: Upper respiratory infection during pregnancy and neurodevelopmental outcomes among offspring Abstract Objective Maternal infection during pregnancy is associated with psychiatric disorders among offspring. The aim of this study was to investigate associations between upper respiratory infection (URI) in pregnancy and measures of cognitive and behavioral outcomes in child offspring. Materials and methods A longitudinal study of 534 mother-child pairs with information regarding prenatal exposures collected through an interview conducted on average one year after delivery and subsequent participation in a childhood cognitive and psychosocial assessment between the ages 5–12years. Childhood cognition was measured using the Peabody Picture Vocabulary Test (PPVT-III) and the Beery-Buktenica Test of Visual Motor Integration-Fifth Edition (VMI-5) and behavioral function measured using the Child Behavior Checklist (CBCL) and teacher-report using the Teacher Report Form (TRF). Adjusted mean differences (adjMD) in outcome measures were calculated between mothers reporting the presence or absence of a URI during pregnancy. Results URI during pregnancy was not associated with the two measures of cognition given to offspring, but was associated with modest increases in total behavioral problems reported by mothers (adjMD: 3.72; CI: 1.91–5.54) and teachers (adjMD: 2.74; CI: 0.97–4.50). We observed differences in CBCL and TRF scores based on timing of URI: infections in mid-pregnancy (lunar months 4–5) were associated with poorer scores than were infections in early pregnancy (lunar months 2–3). Conclusions In general, URI in pregnancy was not associated with decrements in childhood cognition, but may be associated with behavior problems.

negative: Learning in times of lockdown: how Covid-19 is affecting education and food security in India A vast majority of the relief and rehabilitation packages announced in the months following the nationwide lockdown in India have focused on economic rehabilitation. However, the education sector has remained absent from this effort, including in India’s central government’s 250 billion dollar stimulus package. In this paper, we discuss the implications of lockdown-induced school and rural child-care center closures on education and health outcomes for the urban and rural poor. We especially focus on food and nutritional security of children who depend on school feeding and supplementary nutrition programs. We argue that the impacts are likely to be much more severe for girls as well as for children from already disadvantaged ethnic and caste groups. We also discuss ways in which existing social security programs can be leveraged and strengthened to ameliorate these impacts.

negative: Multisystem Resilience for Children and Youth in Disaster: Reflections in the Context of COVID-19 In the context of rising disasters worldwide and the challenges of the COVID-19 pandemic, this commentary considers the implications of findings in resilience science on children and youth for disaster preparation and response. The multisystem challenges posed by disasters are illustrated by the COVID-19 pandemic. We discuss the significance of disasters in the history of resilience science and the emergence of a unifying systems definition of resilience. Principles of a multisystem perspective on resilience and major findings on what matters for young people in disasters are delineated with reference to the pandemic. Striking parallels are noted in the psychosocial resilience factors identified at the level of individual children, families, schools, and communities. These parallels suggest that adaptive capacities associated with resilience in these interacting systems reflect interconnected networks and processes that co-evolved and may operate in concert. As resilience science moves toward integrated theory, knowledge, and applications in practice, particularly in disaster risk reduction and resilience promotion, more focus will be needed on multisystem and multidisciplinary research, communication, training, and planning.

negative: Long-term outcome of surgical excision for treatment of cervicofacial granulomatous lymphadenitis in children PURPOSE: Granulomatous inflammation is a common cause of subacute cervicofacial lymphadenitis in children. Nontuberculous mycobacterial (NTM) infections and cat-scratch disease (CSD) are the most frequent causes. Optimal treatment, which may include surgery, antibiotic treatment or wait-and-see approach, is debatable. The goal of this study was to compare the short- and long-term outcome of various surgical procedures. METHODS: Case series with a chart review of all children treated by surgical excision of granulomatous lymph nodes in the cervicofacial area from 2000 to 2016 at two tertiary care centers. RESULTS: Forty patients were included in this study. The median age at first symptoms was 3.7 years (13 months–14 years). Mean follow-up was 5.8 years (6 months–15.3 years). 25 patients fit with diagnosis of NTM infection, 6 with CSD while diagnosis remained uncertain in 9 patients. The primary surgical procedure consisted of total excision (n = 27), incision/drainage (n = 9) or incomplete excision (n = 4). None of the patients treated by primary complete excision needed further intervention contrary to the group of patients with incomplete surgical procedures where additional surgical management was required in 54%. At follow-up, all patients were healthy without evidence of recurrence. CONCLUSION: We advocate early surgical intervention with complete excision to reach quick resolution and reduce the need for additional surgery. The long-term outcome was favorable.

negative: Does the protein corona take over the selectivity of molecularly imprinted nanoparticles? The biological challenges to recognition. "Plastic antibodies" are nano-sized biomimetics prepared by the molecular imprinting technology, which have the robustness of polymers, but specificity and selectivity alike natural receptors making them ideal for analytical uses. The current challenge is to translate plastic antibodies to in vivo applications for diagnosis, drug delivery, theranostic, therefore it is crucial to evaluate the effect of the biological sample complexity on the selectivity and the formation of protein corona (PCs), which ultimately dictate the fate of circulating nanoparticles. A set (n = 4) of plastic antibodies (nanoMIPs) against different proteins was prepared. Quantitative (iBAC) shotgun proteomics permitted to define the PC composition of nanoMIPs in human plasma, the relative protein abundances, the correlation between PC and the plasma dilution. NanoMIPs showed >200 proteins PC, while ~150 proteins were found on controls, suggesting the imprinting process influences the nanoparticle's structure hence the protein uptake. NanoMIPs and controls shared the 44% of the PC, but PC iBAQ values on nanoMIPs were 10-100 times higher than controls, suggesting PC/nanoMIPs interactions were far stronger than PC/non imprinted particles. PCs were richer in small proteins and in immunoglobulins, indicating a defensive response, while the selectivity was negatively challenged in the crowded plasma sample. SIGNIFICANCE: The formation and the composition of the protein corona (PC) is key to decide the fate of nanoparticles when in vivo, therefore there is the strong need to study the composition of the PC. To enable and to support the translation of the use of plastic antibodies (nanoMIPs), prepared by means of the molecular imprinting technique, to the clinical practice and to in vivo uses, the present work evaluates the effects of the complexity of the biological sample (plasma) on nanoMIPs composed of highly crosslinked polyacrylamide and acrylamide derivatives. Proteomic study offers an in depth insight of the protein corona formed in plasma on nanoMIPs. A set of nanoMIPs synthesized and raised to recognize either small or large proteins was tested. The selection abilities of the nanoMIPs when placed in plasma at different dilutions was studied. Quantitative shotgun proteomics allowed to define the composition of the formed protein corona (PC) enabling to detail the protein compositions, the relative abundances, its correlation to the biological sample composition and the correlation between PC and nanoMIP's imprinted template. In plasma, all the nanoMIPs gained a PC composed of more than 200 proteins. Type of protein recruited for the corona, molecular weight and abundance in the PC were studied. The PC on the nanoMIPs appeared to be driven by the protein composition of the plasma, while the template protein, towards which a nanoMIP was imprinted and that was proven to have high affinity for, did not influence the PC.

negative: A concept analysis of children with complex health conditions: implications for research and practice BACKGROUND: This concept analysis aimed to clarify the meaning of “children with complex health conditions” and endorse a definition to inform future research, policy, and practice. METHODS: Using Walker and Avant’s (2011)‘s approach, we refined the search strategy with input from our team, including family representatives. We reviewed the published and grey literature. We also interviewed 84 health, social, and educational stakeholders involved in the care of children with complex health conditions about their use/understanding of the concept. RESULTS: We provided model, borderline, related, and contrary cases for clarification purposes. We identified defining attributes that nuance the concept: (1) conditions and needs’ breadth; (2) uniqueness of each child/condition; (3) varying extent of severity over time; 4) developmental age; and (5) uniqueness of each family/context. Antecedents were chronic physical, mental, developmental, and/or behavioural condition(s). There were individual, family, and system consequences, including fragmented services. CONCLUSIONS: Building on previous definitions, we proposed an iteration that acknowledges the conditions’ changing trajectories as involving one or more chronic condition(s), regardless of type(s), whose trajectories can change over time, requiring services across sectors/settings, oftentimes resulting in a lower quality of life. A strength of this paper is the integration of the stakeholders’/family’s voices into the development of the definition.

negative: Breastfeeding of Infants Born to Mothers with COVID-19: A Rapid Review Abstract 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 4481 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. Keywords: Breastfeeding; COVID-19; infant; mother-to-child transmission; rapid Review.

negative: 32 Special Considerations for Infants and Young Children • The care of infants and small children with suspected asthma deserves special consideration because of the potential to modulate the disease process early on and alleviate the increased morbidity associated with uncontrolled asthma in this age group. • After confounders and masqueraders of asthma have been excluded in the evaluation of children with suspected asthma, recurrent wheezing in infants and young children still comprises a heterogeneous group of conditions with different risk factors and prognoses. • The diagnosis of asthma in infants and small children is often based on clinical grounds and complicated by the lack of clinically available tools that meet the criteria for the definition of asthma used in older children and adults such as airway inflammation, bronchial hyperresponsiveness and airflow limitation. • Difficulties in the management of asthma include limited effective and convenient delivery devices, complete dependence on the caregivers to carry out the treatment regimen, and an inadequate selection of medications completely devoid of adverse effects. • A partnership approach with emphasis on education, monitoring and training is key in the effective management of chronic cough or recurrent wheezing illnesses in very young children. • Clinical trials using as needed treatment interventions have shown favorable efficacy outcomes, aimed at preventing severe exacerbations in young children with recurrent wheezing; however, trials aimed at primary prevention are still lacking.

negative: Prenatal exposure to acid-suppressant medications and the risk of recurrent wheeze at 3 years of age in children with a history of severe bronchiolitis

negative: Shifting from survival to supporting resilience in children and families in the COVID-19 pandemic: Lessons for informing U.S. mental health priorities. This commentary contextualizes potential mental health outcomes for children during and after the COVID-19 pandemic within the risk and resilience literature. Individual, familial, and community-level factors that may increase risk for mental health challenges for children as well as factors associated with positive adaptation in the face of adversity are considered. We highlight the value of considering children's resilience within a systemic perspective by considering family-centered approaches including both short-term and long-term evidence-informed mental health practices. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

negative: 'Drawing on Wisdom to Cope with Adversity:' A Systematic Review Protocol of Older Adults' Mental and Psychosocial Health During Acute Respiratory Disease Propagated-Type Epidemics and Pandemics (COVID-19, SARS-CoV, MERS, and Influenza). Background: Mental health has become one of the fundamental priorities during the COVID-19 pandemic. Situations like physical distancing as well as being constantly tagged as the most vulnerable group could expose older adults to mental and psychosocial burdens. Nonetheless, there is little clarity about the impact of the COVID-19 pandemic or similar pandemics in the past on the mental illness, wellbeing, and psychosocial health of the older population compared to other age groups. Objectives: To describe the patterns of older adults' mental and psychosocial health related to acute respiratory disease propagated-type epidemics and pandemics and to evaluate the differences with how other age groups respond. Eligibility criteria: quantitative and qualitative studies evaluating mental illness, wellbeing, or psychosocial health outcomes associated with respiratory propagated epidemics and pandemics exposure or periods (COVID-19, SARS-CoV, MERS, and Influenza) in people 65 years or older. Data source: Original articles published until June 1st, 2020, in any language searched in the electronic healthcare and social sciences database: MEDLINE, Embase, CINAHL, PsycINFO, Scopus, WHO Global literature on coronavirus disease database, China National Knowledge Infrastructure ( - CNKI). Furthermore, EPPI Centre's COVID-19 living systematic map and the publicly available publication list of the COVID-19 living systematic review will be incorporated for preprints and recent COVID-19 publications. Data extraction: Two independent reviewers will extract predefined parameters. The risk of bias will be assessed. Data synthesis: Data synthesis will be performed according to study type and design, type of epidemic and pandemic, types of outcomes (mental health and psychosocial outcomes), and participant characteristics (e.g., sex, race, age, socioeconomic status, food security, presence of dependency in daily life activities independent/dependent older adults). Comparison between sex, race, and other age groups will be performed qualitatively, and quantitatively if enough data is available. The risk of bias and study heterogeneity will be reported for quantitative studies. Conclusion: This study will provide information to take actions to address potential mental health difficulties during the COVID-19 pandemic in older adults and to understand responses on this age group. Furthermore, it will be useful to identify potential groups that are more vulnerable or resilient to the mental-health challenges of the current worldwide pandemic.

negative: International Expert Consensus Statement on Chest Imaging in Pediatric COVID-19 Patient Management: Imaging Findings, Imaging Study Reporting and Imaging Study Recommendations The coronavirus disease 2019 (COVID-19) has quickly spread since it was first detected in December of 2019 to a global pandemic with over 1.7 million confirmed cases in over 200 countries around the world at the time this document is being prepared. Due to the novel nature of the virus and the rapidly evolving understanding of the disease, there is a great deal of uncertainty surrounding the diagnosis and management of COVID-19 pneumonia in pediatric patients. Chest imaging plays an important role in evaluation of pediatric patients with COVID-19, however there is currently little information available describing imaging manifestations of pediatric COVID-19 and even less discussing utilization of imaging studies in pediatric patients. To specifically address these concerns, a group of international experts in pediatric thoracic imaging from 5 continents convened to create a consensus statement describing the imaging manifestations of COVID-19 in the pediatric population, discussing the potential utility of structured reporting during the coronavirus 2019 pandemic, and generating consensus recommendations for utilization of chest radiographs (CXR) and computed tomography (CT) in the evaluation of pediatric patients with COVID-19. The results were compiled into 2 structured reporting algorithms (one for CXR and one for chest CT) and 8 consensus recommendations for utilization of chest imaging in pediatric COVID-19 infection.

negative: Respiratory Virus Co-infection in Acute Respiratory Infections in Children PURPOSE OF REVIEW: This investigation aims to understand the role and burden of viral co-infections for acute respiratory illnesses in children. Co-infection can be either viral-viral or viral-bacterial and with new technology there is more information on the role they play on the health of children. RECENT FINDINGS: With the proliferation of multiplex PCR for rapid diagnosis of multiple viruses as well as innovations on identification of bacterial infections, research has been attempting to discover how these co-infections affect each other and the host. Studies are aiming to discern if the epidemiology of viruses seen at a population level is related to the interaction between different viruses on a host level. Studies are also attempting to discover the burden of morbidity and mortality of these viral-viral co-infections on the pediatric population. It is also becoming important to understand the interplay of certain viruses with specific bacteria and understanding the impact of viral-bacterial co-infections. SUMMARY: RSV continues to contribute to a large burden of disease for pediatric patients with acute respiratory illnesses. However, recent literature suggests that viral-viral co-infections do not add to this burden and might, in some cases, be protective of severe disease. Viral-bacterial co-infections, on the other hand, are most likely adding to the burden of morbidity in pediatric patients because of the synergistic way they can infect the nasopharyngeal space. Future research needs to focus on confirming these conclusions as it could affect hospital cohorting, role of molecular testing, and therapeutic interventions.

negative: Epidemiology of viral respiratory infections in children undergoing heart surgery Abstract Background Acute viral respiratory infections (VRI) are the most common diseases in humans and are associated with high morbidity and mortality in infants and the elderly. Children with congenital heart disease (CHD) are more susceptible to get severe forms of VRI due to their altered lung mechanics, leading to several complications, such as increased hospital stay, longer mechanical ventilation, and higher mortality. This study aimed to identify the frequency of VRI in children with CHD undergoing cardiac surgery, and to compare the major outcomes according to the presence or absence of a VRI. Methods This was a longitudinal, observational cohort study. Nasopharyngeal secretion samples were collected pre- and postoperatively for patients undergoing cardiac surgery, from May 2013 to May 2014. Respiratory viruses were detected using CLART Pneumovir®. Results Forty-eight patients were enrolled. We found a VRI preoperatively in 16 children with CHD before surgery (33.3%), and the frequency of new infections was 8.3% (4 patients). However, in this study, in univariate analyses, the two groups did not differ in any of the studied outcomes. In the multivariate regression models, adjusting for age and STAT category, the presence of a VRI did not show a significant effect on the major outcomes. Conclusions In conclusion, VRI was frequent in children undergoing open-heart surgery, but the presence of a VRI did not impact on major outcomes in this cohort.

negative: Congenital diaphragmatic hernia presenting with symptoms within the first day of life; outcomes from a non-ECMO centre in Denmark BACKGROUND: Between 1998 and 2015, we report on the survival of congenital diaphragmatic hernia (CDH)-infants presenting with symptoms within the first 24 h of life, treated at Odense University Hospital (OUH), a tertiary referral non-extracorporeal membrane oxygenation (ECMO) hospital for paediatric surgery. METHODS: We performed a retrospective cohort study of prospectively identified CDH-infants at our centre. Data from medical records and critical information systems were obtained. Baseline data included mode of delivery and infant condition. Outcome data included 24-h, 28-day, and 1 year mortality rates and management data included intensive care treatment, length of stay in the intensive care unit, time of discharge from hospital, and surgical intervention. Descriptive analyses were performed for all variables. Survivors and non-survivors were compared for baseline and treatment data. RESULTS: Ninety-five infants were identified (44% female). Of these, 77% were left-sided hernias, 52% were diagnosed prenatally, and 6.4% had concurrent malformations. The 28-day mortality rate was 21.1%, and the 1 year mortality rate was 22.1%. Of the 21 non-survivors, nine died within the first 24 h, and 10 were sufficiently stabilised to undergo surgery. A statistically significant difference was observed between survivors and non-survivors regarding APGAR score at 1 and 5 min., prenatal diagnosis, body length at birth, and delivery at OUH. CONCLUSIONS: Our outcome results were comparable to published data from other centres, including centres using ECMO.

negative: Telehealth for Family Guidance: Acceptance and Commitment Therapy, Parent-Focused Preference Assessment, and Activity-Based Instruction for the Support of Children with Autism Spectrum Disorder and Their Families A 5-stage protocol was used to support Board Certified Behavior Analysts providing telehealth support for children with autism spectrum disorder and their families. Stage 1 of the protocol involves 2 acceptance and commitment therapy exercises. Specifically, the Valued Living Questionnaire is used to identify a family member’s values, and the Bull’s-Eye Values Survey is employed to determine the extent to which a family member is living in accordance with stated values. Stage 2 of the protocol involves administering an adult version of the Meaningful Activity Participation Assessment to identify preferred activities of parents of a child with autism spectrum disorder. During Stage 3 of the protocol, the goals and objectives of a child with autism spectrum disorder are yoked to the preferred activities of a family member in order to promote child–parent engagement. Stage 4 of the protocol is focused on parent-implemented interventions, and Stage 5 of the protocol is designed as a primer for comprehensive support within an acceptance and commitment therapy model. The 5-stage protocol provides guidelines for Board Certified Behavior Analysts interested in structuring telehealth sessions and optimizing engagement between a family member and a child with autism spectrum disorder.

negative: SARS-CoV-2 Seroprevalence Rates of Children in Louisiana During the State Stay at Home Order. Children (less than 19 years) account for 20% of the US population but currently represent less than 2% of coronavirus disease 2019 (COVID-19) cases. Because infected children often have few or no symptoms and may not be tested, the extent of infection in children is poorly understood. METHODS During the March 18th-May 15th 2020 Louisiana Stay At Home Order, 1690 blood samples from 812 individuals from a Childrens Hospital were tested for antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Demographics, COVID-19 testing, and clinical presentation abstracted from medical records were compared with local COVID-19 cases. RESULTS In total, 62 subjects (7.6%) were found to be seropositive. The median age was 11 years with 50.4% female. The presenting complaint of seropositive patients was chronic illness (43.5%). Only 18.2% had a previous positive COVID-19 PCR or antibody test. Seropositivity was significantly associated with parish (counties), race, and residence in a low-income area. Importantly, seropositivity was linearly correlated with cumulative COVID-19 case number for all ages by parish. CONCLUSION In a large retrospective study, the seropositivity prevalence for SARS-CoV-2 in children in Louisiana during the mandated Stay At Home Order was 7.6%. Residence location, race, and lower socioeconomic factors were linked to more frequent seropositivity in children and correlated to regional COVID-19 case rates. Thus, a significant number of children in Louisiana had SARS-CoV-2 infections that went undetected and unreported and may have contributed to virus transmission.

negative: COVID-19 and homelessness in England: a modelling study of theCOVID-19 pandemic among people experiencing homelessness, and theimpact of a residential intervention to isolate vulnerable people andcare for people with symptoms Background: There is an ongoing pandemic of the viral respiratory disease COVID-19. People experiencing homelessness are vulnerable to infection and severe disease. Health and housing authorities in England have developed a residential intervention that aims to isolate those vulnerable to severe disease (COVID-PROTECT) and care for people with symptoms (COVID CARE). Methods: We used a discrete-time Markov chain model to forecast COVID-19 infections among people experiencing homelessness, given strong containment measures in the general population and some transmission among 35,817 people living in 1,065 hostels, and 11,748 people sleeping rough (the 'do nothing' scenario). We then estimated demand for beds if those eligible are offered COVID-PROTECT and COVID-CARE. We estimated the reduction in the number of COVID-19 cases, deaths, and hospital admissions that could be achieved by these interventions. We also conducted sensitivity and scenario analyses to identify programme success factors. Results: In a 'do nothing' scenario, we estimate that 34% of the homeless population could get COVID-19 between March and August 2020, with 364 deaths, 4,074 hospital admissions and 572 critical care admissions. In our 'base intervention' scenario, demand for COVID-PROTECT peaks at 9,934 beds, and demand for COVID-CARE peaks at 1,366 beds. The intervention could reduce transmission by removing symptomatic individuals from the community, and preventing vulnerable individuals from being infected. This could lead to a reduction of 164 deaths, 2,624 hospital admissions, and 248 critical care admissions over this period. Sensitivity analyses showed that the number of deaths is sensitive to transmission of COVID-19 in COVID-PROTECT. If COVID-PROTECT capacity is limited, scenario analyses show the benefit of prioritising people who are vulnerable to severe disease. Conclusion: Supportive accommodation can mitigate the impact of the COVID-19 pandemic on the homeless population of England, and reduce the burden on acute hospitals.

negative: Is nasopharyngeal swab comparable with nasopharyngeal aspirate to detect SARS-CoV-2 in children? The tests currently used for the direct identification of SARS-CoV-2 include specimens taken from the upper and the lower respiratory tract. In our paediatric department all children undergo both nasopharyngeal swab and nasopharyngeal aspirate, performed from both nostrils, on admission and after 24 hours. We decided to compare these two methods of detection of SARS-CoV-2. Considering nasopharyngeal aspirate as the gold standard, we calculated sensitivities and specificities of nasopharyngeal swab. Based on our results, we suggest to prefer the collection of aspirates whenever possible.

negative: The experience of women infected by the COVID-19 during pregnancy in Brazil: a qualitative study protocol BACKGROUND: The Coronavirus disease (COVID-19) is highly infectious, with the recent World Health Organization decree confirming a global public health emergency. The outcomes related to maternal and fetal health among pregnant women infected with the virus are still poorly understood. The world population has been waiting for answers and remains constantly alert about the pandemic’s progress. It is not yet known what impact this pandemic experience will have on the population’s mental health, especially pregnant women. METHOD: We aim to understand and discuss the experiences of women who were infected by COVID-19 during pregnancy, in relation to the illness process, community relations, and social media influences. This is a qualitative study in which we will interview women who were infected by COVID-19 during pregnancy and received medical care from a tertiary university hospital specializing in women’s health in Brazil. We will use the techniques of Semi-Directed Interviews of Open and In-depth Questions, socio-demographic and health data sheets, and Field Diaries. We will use purposive sampling and the criterion of theoretical saturation for its construction. The interviews will be conducted by phone or video call, with audio recorded for later transcription. The treatment of the data will be completed through Thematic Analysis and discussed in light of the Health Psychology framework, with the production of categories that answer the proposed research questions. DISCUSSION: It is expected that the results contribute to the understanding about the demands that come to the health professional of women infected by COVID-19 during pregnancy in a pandemic situation. RESUMO EM PORTUGUÊS (PORTUGUESE ABSTRACT): INTRODUÇÃO: A doença causada pelo coronavírus (COVID-19) é altamente infecciosa, com a recente declaração da Organização Mundial de Saúde confirmando emergência global de saúde pública. Os desfechos relacionados a saúde materno-fetal entre gestantes infectadas pelo vírus ainda são pouco conhecidos. A população mundial tem aguardado respostas e se mantém constantemente em alerta sobre o progresso da pandemia. Ainda não se sabe qual será o impacto da experiência da pandemia sobre a saúde mental da população, especialmente entre mulheres grávidas. MÉTODO: O objetivo deste estudo é compreender e discutir as experiências de mulheres infectadas pelo COVID-19 durante a gravidez, em relação ao processo de adoecimento, às relações comunitárias e a influência de mídias sociais. Este é um estudo qualitativo em que serão entrevistadas mulheres infectadas pelo COVID-19 durante a gestação, atendidas em um hospital universitário terciário especializado em saúde da mulher no Brasil. Serão usadas as técnicas de Entrevistas Semi-Dirigidas de Perguntas Abertas em Profundidade, ficha de dados sociodemográficos e de saúde e diários de campo. A amostra será selecionada intencionalmente, usando o critério de saturação teórica para a sua construção. As entrevistas serão conduzidas por telefone ou videoconferência, com áudio gravado para posterior transcrição. O tratamento dos dados seguirá a Análise Temática e os resultados serão discutidos sob conceitos de Psicologia da Saúde, com a produção de categorias que respondam as questões de pesquisa propostas. DISCUSSÃO: Espera-se que os resultados contribuam para a compreensão de demandas emergentes entre profissionais de saúde para mulheres infectadas pelo COVID-19 durante a gestação em situação de pandemia.

negative: Psychological Impact and Associated Factors During the Initial Stage of the Coronavirus (COVID-19) Pandemic Among the General Population in Spain The outbreak of COVID-19 in Spain started at the end of February. By 9th April 2020 Spain was the second country in confirmed cases and in deaths. On March 14, 2020, the Spanish Government declared the state of alarm to limit viral transmission. During such state, citizens must stay confined at home with few justified exceptions. This whole situation drastically changed the life of the population, which can cause a wide range of psychosocial impacts. This study explored the psychological impact of the COVID-19 pandemic in the general adult population (N = 3055) during the first stages of the outbreak in Spain, as well as their anxiety, stress and depression levels. We also examined the extent to which the following variables were associated to participants’ mental health: (1) demographics; (2) degree of concern about the pandemic; (3) environmental conditions during the home confinement, (4) changes in daily life as a consequence of the pandemic; (5) contact with the COVID-19 disease; (6) actual and perceived severity of the crisis; (7) information about the COVID-19, (8) perceived health status and (9) leisure activities conducted within the last 24 h. Our results show that Spanish consider the current COVID-19 health crisis as fairly severe, and the majority felt that the COVID-19 crisis had greatly impacted on their daily life, including changes in their daily routines and cancelation of important activities. About 36% of the participants reported moderate to severe psychological impact, 25% showed mild to severe levels of anxiety, 41% reported depressive symptoms, and 41% felt stressed. Women, young, and those who that lost their job during the health crisis showed the strongest negative psychological symptoms. What worried Spaniards the most was the likelihood of suffering an economic crisis derived from the pandemic. We found factors associated with better mental health, such as being satisfied with the information received about the health crisis, conducting leisure activities, and the perception of being in good health. These findings can be used to design psychological interventions to help coping with COVID-19 pandemic, both in Spain and other countries.

negative: Health Equity, Social Policy, and Promoting Recovery from COVID-19 The COVID-19 pandemic has revealed starkly and publicly the close interconnections between social and economic inequality, health equity, and population health. To better understand what social policies would best promote population health, economic recovery, and preparedness for future pandemics, we must look both upstream and abroad for inspiration. In this essay, I argue for a suite of near-term and longer-term interventions, including universal health insurance and paid sick leave, upgraded wage insurance policies, tax reform, investments in parental leave, child care, and education, and upgraded government record systems. Policies that equalize the distribution of the social determinants of health and promote social solidarity will also improve population health and economic performance and allow us to confront future pandemics more successfully.

negative: Staying Home, Staying Safe? A Short-Term Analysis of COVID-19 on Dallas Domestic Violence Abstract COVID-19 has wreaked havoc on the lives of persons around the world and social scientists are just beginning to understand its consequences on human behavior. One policy that public health officials put in place to help stop the spread of the virus were stay-at-home/shelter-in-place lockdown-style orders. While designed to protect people from the coronavirus, one potential and unintended consequence of such orders could be an increase in domestic violence – including abuse of partners, elders or children. Stay-at-home orders result in perpetrators and victims being confined in close quarters for long periods of time. In this study, we use data from Dallas, Texas to examine the extent to which a local order was associated with an increase in domestic violence. Our results provide some evidence for a short-term spike in the 2 weeks after the lockdown was instituted but a decrease thereafter. We note that it is difficult to determine just how much the lockdown was the cause of this increase as the domestic violence trend was increasing prior to the order.

negative: Promoting healthy movement behaviours among children during the COVID-19 pandemic

negative: Child poverty, food insecurity, and respiratory health during the COVID-19 pandemic

negative: COVID-19 - Enacting a ‘new normal’ for people who use drugs The COVID-19 crisis has magnified existing social, economic and political inequities. People who use drugs are particularly vulnerable due to criminalisation and stigma and often experience underlying health conditions, higher rates of poverty, unemployment and homelessness, as well as a lack of access to vital resources – putting them at greater risk of infection. On the other hand, COVID-19 presents an opportunity to confront the mistakes of the past and re-negotiate a new social contract. The International Network of People who use Drugs (INPUD) believe that this crisis must be an occasion to rethink the function of punishment, to reform the system and to work towards ending the war on drugs. This commentary presents a set of recommendations to UN agencies, governments, donor agencies, academics and researchers and civil society, challenging these actors to work alongside people who use drugs to enact a new reality based on solidarity and cooperation, protection of health and restoration of rights and dignity and most importantly to mobilise to win the peace.

negative: Ethical decision-making for children with neuromuscular disorders in the COVID-19 crisis The sudden appearance and proliferation of COVID-19 has forced societies and governmental authorities across the world to confront the possibility of resource constraints when critical care facilities are overwhelmed by the sheer numbers of grievously ill patients. As governments and health care systems develop and update policies and guidelines regarding the allocation of resources, patients and families affected by chronic disabilities, including many neuromuscular disorders that affect children and young adults, have become alarmed at the possibility that they may be determined to have less favorable prognoses due to their underlying diagnoses and thus be assigned to lower priority groups. It is important for health care workers, policymakers, and government officials to be aware that the long term prognoses for children and young adults with neuromuscular disorders are often more promising than previously believed, due to a better understanding of the natural history of these diseases, benefits of multidisciplinary supportive care, and novel molecular therapies that can dramatically improve the disease course. Although the realities of a global pandemic have the potential to require a shift from our usual, highly individualistic standards of care to crisis standards of care, shifting priorities should nonetheless be informed by good facts. Resource allocation guidelines with the potential to affect children and young adults with neuromuscular disorders should take into account the known trajectory of acute respiratory illness in this population, and rely primarily on contemporary long-term outcome data.

negative: Comparison of Mycoplasma pneumoniae Infections in asthmatic children versus asthmatic adults. BACKGROUND Mycoplasma pneumoniae has been implicated in asthma exacerbations and chronic asthma. A 2-year longitudinal study has been conducted to investigate the role of M. pneumoniae infections in 168 and 20 hospitalized children and adults, respectively, with asthma exacerbation compared with outpatients (88 children and 48 adults) with chronic asthma (without an exacerbation). The prevalence of Chlamydia pneumoniae and respiratory viruses was also assessed in these 2 populations. METHODS Lung function testing, blood sampling and microbiological testing (polymerase chain reaction, culture and serology) were performed for 256 children and 68 adults followed by a 7-week, follow-up visit with repeated blood sampling for serological testing and phone interviews at 6 and 12 months later. RESULTS M. pneumoniae infection was more prevalent in children with chronic asthma (13.6%) compared with children with exacerbation (7.1%), while the reverse was true in adults (6.3 vs. 10.0%, respectively). However, these differences were not statistically significant. Acute C. pneumoniae infection was identified in 3.9% of children and 7.4% adults. Children seen for chronic asthma were significantly more likely to be infected with C. pneumoniae than children hospitalized for an asthma exacerbation. Viruses were the most prevalent microorganisms detected in children with an asthma exacerbation. No differences in the outcome parameters were identified between M. pneumoniae-infected and noninfected patients. CONCLUSIONS The present study suggests that M. pneumoniae does not play a direct role in the pathogenicity of acute or chronic asthma in most children.

negative: AI4COVID-19: AI enabled preliminary diagnosis for COVID-19 from cough samples via an app BACKGROUND: The inability to test at scale has become humanity's Achille's heel in the ongoing war against the COVID-19 pandemic. A scalable screening tool would be a game changer. Building on the prior work on cough-based diagnosis of respiratory diseases, we propose, develop and test an Artificial Intelligence (AI)-powered screening solution for COVID-19 infection that is deployable via a smartphone app. The app, named AI4COVID-19 records and sends three 3-s cough sounds to an AI engine running in the cloud, and returns a result within 2 min. METHODS: Cough is a symptom of over thirty non-COVID-19 related medical conditions. This makes the diagnosis of a COVID-19 infection by cough alone an extremely challenging multidisciplinary problem. We address this problem by investigating the distinctness of pathomorphological alterations in the respiratory system induced by COVID-19 infection when compared to other respiratory infections. To overcome the COVID-19 cough training data shortage we exploit transfer learning. To reduce the misdiagnosis risk stemming from the complex dimensionality of the problem, we leverage a multi-pronged mediator centered risk-averse AI architecture. RESULTS: Results show AI4COVID-19 can distinguish among COVID-19 coughs and several types of non-COVID-19 coughs. The accuracy is promising enough to encourage a large-scale collection of labeled cough data to gauge the generalization capability of AI4COVID-19. AI4COVID-19 is not a clinical grade testing tool. Instead, it offers a screening tool deployable anytime, anywhere, by anyone. It can also be a clinical decision assistance tool used to channel clinical-testing and treatment to those who need it the most, thereby saving more lives.

negative: School closure, COVID-19 and lunch programme: Unprecedented undernutrition crisis in low-middle income countries The coronavirus disease 2019 pandemic has affected nearly 70% of children and teenagers around the world due to school closure policies. School closure is implemented widely in order to prevent viral transmission and its impact on the broader community, based on preliminary recommendations and evidence from influenza. However, there is debate with regard to the effectiveness of school closures. Growing evidence suggests that a child's SARS-CoV-2 infection is often mild or asymptomatic and that children may not be major SARS-CoV-2 transmitters; thus, it is questionable if school closures prevent transmission significantly. This question is important as a majority of children in low- and middle-income countries depend on free school meals; unexpected long-term school closure may adversely impact nutrition and educational outcomes. Food insecurity is expected to be higher during the pandemic. In this viewpoint, we argue for a more thorough exploration of potential adverse impacts of school closures in low- and middle-income countries and recommend actions to ensure that the health and learning needs of vulnerable populations are met in this time of crisis.

negative: Autologous hematopoietic stem cell transplantation for high-risk brain tumors in children Autologous hematopoietic stem cell transplant (AHSCT) has been advocated as a form of salvage therapy for children with high-risk or relapsed brain tumors but only limited data are available currently. We report the outcomes of pediatric brain tumors treated with AHSCT in a quaternary referral center in Hong Kong over 10 years (June 1996–May 2006). Thirteen patients with medulloblastoma (n = 9), cerebral primitive neuroectodermal tumor (n = 1), ependymoma (n = 1), germ cell tumor (n = 1) and cerebellar rhabdoid (n = 1) were transplanted because of tumor residual (n = 1) or recurrence (n = 12). Uniform upfront treatment protocols were adopted according to specific tumor types. Prior to AHSCT, 8 patients (61.5%) achieved complete remission and 5 (38.5%) were in partial remission. Conditioning employed thiotepa 300 mg/m(2), etoposide 250 mg/m(2 )and carboplatin 500 mg/m(2) daily for 3 days. Toxicity included mucositis and neutropenic fever in all patients, grade 4 hepatic toxicity in 4 patients (including hepatic veno-occlusive disease in 2 patients) and grade 4 renal toxicity in 1 patient. The 5-year event-free survival was 53.9%. Five patients died of disease recurrence or progression 8–21 months after transplant with a median disease-free period of 8 months post-transplant. One died of transplant-related complications in the early post-transplant period. Seven survived for a median of 5.4 years (maximum follow-up of 9.8 years), with six having Lansky-Karnofsky performance score above 80. All survivors had complete remission before transplant though 2 had leptomeningeal spread. We conclude that AHSCT can achieve long-term survival in children with recurrent brain tumor. However, those with macroscopic residual tumor before transplant cannot be salvaged.

negative: Smoking prevalence and COVID-19 in Europe INTRODUCTION: This ecological study investigates the association between smoking prevalence and COVID-19 occurrence and mortality in 38 European nations as of 30(th) May 2020. METHODS: Data were collected from Our World in Data. Regression analysis was conducted to adjust for potential confounding factors such as economic activity (GDP), the rate of COVID-19 testing, and the stringency of COVID-19 control policies. RESULTS: There was a statistically significant negative association between smoking prevalence and the prevalence of COVID-19 across the 38 European nations after controlling for confounding factors (p = 0.001). A strong association was found between the prevalence of COVID-19 per million people and economic activity (p = 0.002) and the rate of COVID-19 testing (p = 0.0006). Nations with stricter policy enactment showed fewer COVID-19 cases per million people, but the association was not significant (p = 0.122). Delaying policy enactment was associated with a greater prevalence of COVID-19 (p = 0.0535). Evidence of a direct association between smoking prevalence and COVID-19 mortality was not found (p = 0.626). There was a strong positive association between COVID-19 mortality rate and the prevalence of COVID-19 cases (p < 0.0001) as well as the proportion of the population over 65 years of age (p = 0.0034) and a negative association with the rate of COVID-19 testing (p = 0.0023). CONCLUSIONS: We found a negative association between smoking prevalence and COVID-19 occurrence at the population level in 38 European countries. This association may not imply a true or causal relationship, and smoking is not advocated as a prevention or treatment of COVID-19.

negative: Effects of Micronutrients or Conditional Amino Acids on COVID-19 Related Outcomes: An Evidence Analysis Center Scoping Review Abstract Recent narrative reviews have described the potential efficacy of providing individuals infected with COVID-19 with additional micronutrients to reduce disease severity. While there are compelling reasons why providing additional micronutrients or conditional amino acids may affect COVID-19-related outcomes, evidence is lacking. The objective of this scoping review is to explore and describe the literature examining the effect of providing additional micronutrients or conditional amino acids (glutamine, arginine) in adults with conditions or infections similar to COVID-19 infection on COVID-19 related health outcomes. A literature search of the MEDLINE database and hand-search of Cochrane Database of systematic reviews retrieved 1,423 unique studies, and eight studies were included in this scoping review. Four studies examined a target population with ventilator-related pneumonia and acute respiratory distress syndrome, while the other four studies included patients who were at risk for ventilator-associated pneumonia. Interventions included intravenous vitamin C, intramuscular vitamin D, enteral and intramuscular vitamin E, enteral zinc sulfate, and oral and parenteral glutamine. In six of the eight included studies, baseline status of the nutrient of interest was not reported and, thus, it is uncertain how outcomes may vary in the context of nutrient deficiency or insufficiency compared to sufficiency. In the absence of direct evidence examining efficacy of providing additional micronutrients or conditional amino acids to standard care, registered dietitian nutritionists (RDNs) must rely on clinical expertise, and indirect evidence to guide medical nutrition therapy (MNT) for patients infected with COVID-19.

negative: An HIV testing conundrum: balancing the health and privacy considerations of multiple stakeholders. Legal standards for HIV testing are evolving in an attempt to achieve an ethical equilibrium between the privacy rights of infected or potentially infected individuals and public health considerations that seek to limit the spread and severity of the disease through early recognition and treatment. Although guided by US Centers for Disease Control and Prevention recommendations, these standards are determined by state law. In this case, an ethical dilemma is presented and discussed in which the privacy interests of an HIV-infected individual come into conflict with the health considerations of an inadvertently exposed neurology resident and her unborn child, a conundrum amplified by the restricted HIV testing laws of the state in which the incident took place.

negative: Clinical outcomes of SARS-CoV-2 pandemic in long-term care facilities for people with epilepsy: observational study Objectives: COVID-19 is spreading in long-term care facilities with devastating outcomes worldwide, especially for people with chronic health conditions. There is a pressing need to adopt effective measures prevention and containment of in such settings. Design: Retrospective cohort study assessing the effect of enhanced surveillance and early preventative strategies and comparing outcomes for people with severe epilepsy and other comorbidities Setting: Three long-term care facilities: Chalfont Centre for Epilepsy (CCE), St. Elisabeth (STE), and The Meath (TM) with different models of primary and specialist care involvement, in the United Kingdom Participants: 286 long-term residents (age range 19-91 years), 740 carers who had been in contact with the residents during the observation period between 16 March and 05 June 2020. Interventions: Early preventative and infection control measures with identification and isolation of symptomatic cases, with additional enhanced surveillance and isolation of asymptomatic residents and carers at one site (CCE) Main outcome measures: Infection rate for SARS-CoV-2 among residents and carers, asymptomatic rate and case fatality rate, if available. Results: During a 12-week observation period, we identified 29 people (13 residents) who were SARS-CoV-2 positive with confirmed outbreaks amongst residents in two long-term care facilities (CCE, STE). At CCE, two out of 98 residents were symptomatic and tested positive, one of whom died. A further seven individuals testing positive on weekly enhanced surveillance had a completely asymptomatic course. One asymptomatic carer tested positive after contact with confirmed COVID-19 patients in another institution. Since 30 April 2020, during on-site weekly enhanced surveillance all 275 caregivers tested repeatedly negative. At STE, three out of 146 residents were symptomatic and tested positive, a fourth tested positive during hospital admission for symptoms not related to COVID-19. Since April 6, 2020, 105/215 carers presenting with typical symptoms for COVID-19 were tested, of whom 15 tested positive. At TM, testing of symptomatic carers only started from early/mid-April, whilst on-site testing, even of symptomatic residents, was not available until recently. During the observation period, eight of 80 residents were symptomatic but none was tested. Twenty-six of 250 carers were symptomatic and were tested, of whom two tested positive. Conclusions: Infection outbreaks in long-term care facilities for vulnerable people with epilepsy can be quickly contained, but only if asymptomatic cases are identified through enhanced surveillance at individual and care staff level. We observed a low rate of morbidity and mortality which confirmed that preventative measures with isolation of suspected and confirmed cases of COVID-19 can reduce resident-to-resident and reverse resident-to-carer transmission.

negative: Adults with congenital heart disease during the coronavirus disease 2019 (COVID-19) pandemic: are they at risk?

negative: Debate: COVID‐19 and children in India The COVID‐19 pandemic impact on children is a growing concern. The United Nations and its agencies (the World Health Organization and UNICEF), Indian Association For Child and Adolescent Mental Health and National Institute of Mental Health and Neuroscience in India warn about the broader impacts on children and call for urgent action to support the world’s children amidst the pandemic which may have lasting consequences. The COVID‐19 pandemic and unprecedented control measures to prevent its spread have disrupted nearly every aspect of children’s lives – their health, development, learning, behaviour and their families’ economic security, including protection from violence and abuse. Given this background, there is an urgent need for action through screening to minimize the mental health issues of children in India who constitute a substantial proportion of the population.

negative: Exploring the Experiences of Child Welfare-Focused Therapeutic Service Providers The importance of mental and behavioral health for child welfare clients is well-documented; yet, little is known about the challenges therapeutic service providers (TSPs) experience working in child welfare practice. To explore this topic, five focus groups were conducted with 40 TSPs in a contracted mental and behavioral health agency and data were analyzed following an inductive thematic process. Eleven primary challenges were identified, including the difficulty of navigating numerous involved parties, an overwhelmed work environment, legal intersections common to child welfare cases, unrealistic agency expectations, and heighten case complexity when working with child welfare populations. Findings are organized across system, agency, and client levels and add to the understanding of TSP perspectives working with child welfare. Targeted interventions are discussed, such as efforts to promote realistic expectations and training strategies, as well as directions for future research to improve the intersection between child welfare and mental and behavioral health.

negative: Malnutrition Care during the COVID-19 Pandemic: Considerations for Registered Dietitian Nutritionists Evidence Analysis Center Recent evidence examining adults infected with COVID-19 has indicated a significant impact of malnutrition on health outcomes. Individuals who have multiple comorbidities, are older adults, or who are malnourished are at increased risk of being admitted to the intensive care unit and of mortality from COVID-19 infections. Hence, nutrition care to identify and address malnutrition is critical in treating and preventing further adverse health outcomes from COVID-19 infection. This document provides guidance and practice considerations for Registered Dietitian Nutritionists (RDNs) providing nutrition care for adults with suspected or confirmed COVID-19 infection in the hospital, outpatient, or homecare settings. In addition, this document discusses and provides considerations for RDNs working with individuals at risk of malnutrition secondary to food insecurity during the COVID-19 pandemic.

negative: COVID-19 and smoking: A systematic review of the evidence COVID-19 is a coronavirus outbreak that initially appeared in Wuhan, Hubei Province, China, in December 2019, but it has already evolved into a pandemic spreading rapidly worldwide(1,2). As of 18 March 2020, a total number of 194909 cases of COVID-19 have been reported, including 7876 deaths, the majority of which have been reported in China (3242) and Italy (2505)(3). However, as the pandemic is still unfortunately under progression, there are limited data with regard to the clinical characteristics of the patients as well as to their prognostic factors(4). Smoking, to date, has been assumed to be possibly associated with adverse disease prognosis, as extensive evidence has highlighted the negative impact of tobacco use on lung health and its causal association with a plethora of respiratory diseases(5). Smoking is also detrimental to the immune system and its responsiveness to infections, making smokers more vulnerable to infectious diseases(6). Previous studies have shown that smokers are twice more likely than non-smokers to contract influenza and have more severe symptoms, while smokers were also noted to have higher mortality in the previous MERS-CoV outbreak(7,8). Given the gap in the evidence, we conducted a systematic review of studies on COVID-19 that included information on patients’ smoking status to evaluate the association between smoking and COVID-19 outcomes including the severity of the disease, the need for mechanical ventilation, the need for intensive care unit (ICU) hospitalization and death. The literature search was conducted on 17 March 2020, using two databases (PubMed, ScienceDirect), with the search terms: [‘smoking’ OR ‘tobacco’ OR ‘risk factors’ OR ‘smoker*’] AND [‘COVID-19’ OR ‘COVID 19’ OR ‘novel coronavirus’ OR ‘sars cov-2’ OR ‘sars cov 2’] and included studies published in 2019 and 2020. Further inclusion criteria were that the studies were in English and referred to humans. We also searched the reference lists of the studies included. A total of 71 studies were retrieved through the search, of which 66 were excluded after full-text screening, leaving five studies that were included. All of the studies were conducted in China, four in Wuhan and one across provinces in mainland China. The populations in all studies were patients with COVID-19, and the sample size ranged from 41 to 1099 patients. With regard to the study design, retrospective and prospective methods were used, and the timeframe of all five studies covered the first two months of the COVID-19 pandemic (December 2019, January 2020). Specifically, Zhou et al.(9) studied the epidemiological characteristics of 191 individuals infected with COVID-19, without, however, reporting in more detail the mortality risk factors and the clinical outcomes of the disease. Among the 191 patients, there were 54 deaths, while 137 survived. Among those that died, 9% were current smokers compared to 4% among those that survived, with no statistically significant difference between the smoking rates of survivors and non-survivors (p=0.21) with regard to mortality from COVID-19. Similarly, Zhang et al.(10) presented clinical characteristics of 140 patients with COVID-19. The results showed that among severe patients (n=58), 3.4% were current smokers and 6.9% were former smokers, in contrast to non-severe patients (n=82) among which 0% were current smokers and 3.7% were former smokers , leading to an OR of 2.23; (95% CI: 0.65–7.63; p=0.2). Huang et al.(11) studied the epidemiological characteristics of COVID-19 among 41 patients. In this study, none of those who needed to be admitted to an ICU (n=13) was a current smoker. In contrast, three patients from the non-ICU group were current smokers, with no statistically significant difference between the two groups of patients (p=0.31), albeit the small sample size of the study. The largest study population of 1099 patients with COVID-19 was provided by Guan et al.(12) from multiple regions of mainland China. Descriptive results on the smoking status of patients were provided for the 1099 patients, of which 173 had severe symptoms, and 926 had non-severe symptoms. Among the patients with severe symptoms, 16.9% were current smokers and 5.2% were former smokers, in contrast to patients with non-severe symptoms where 11.8% were current smokers and 1.3% were former smokers. Additionally, in the group of patients that either needed mechanical ventilation, admission to an ICU or died, 25.5% were current smokers and 7.6% were former smokers. In contrast, in the group of patients that did not have these adverse outcomes, only 11.8% were current smokers and 1.6% were former smokers. No statistical analysis for evaluating the association between the severity of the disease outcome and smoking status was conducted in that study. Finally, Liu et al.(13) found among their population of 78 patients with COVID-19 that the adverse outcome group had a significantly higher proportion of patients with a history of smoking (27.3%) than the group that showed improvement or stabilization (3.0%), with this difference statistically significant at the p=0.018 level. In their multivariate logistic regression analysis, the history of smoking was a risk factor of disease progression (OR=14.28; 95% CI: 1.58–25.00; p= 0.018). We identified five studies that reported data on the smoking status of patients infected with COVID-19. Notably, in the largest study that assessed severity, there were higher percentages of current and former smokers among patients that needed ICU support, mechanical ventilation or who had died, and a higher percentage of smokers among the severe cases(12). However, from their published data we can calculate that the smokers were 1.4 times more likely (RR=1.4, 95% CI: 0.98–2.00) to have severe symptoms of COVID-19 and approximately 2.4 times more likely to be admitted to an ICU, need mechanical ventilation or die compared to non-smokers (RR=2.4, 95% CI: 1.43–4.04). In conclusion, although further research is warranted as the weight of the evidence increases, with the limited available data, and although the above results are unadjusted for other factors that may impact disease progression, smoking is most likely associated with the negative progression and adverse outcomes of COVID-19.

negative: Children with coronavirus disease 2019: A review of demographic, clinical, laboratory, and imaging features in pediatric patients There is a current outbreak of coronavirus disease 2019 (COVID-19), with a global spread. With the rapid increase in the number of infections, an increase is observed in the number of children with COVID-19. Most research findings are regarding adult cases, which are not always transferrable to children. Evidence-based studies are still expected to formulate clinical decisions for pediatric patients. In this review, we included 2597 pediatric patients that reported recently and evaluated the demographic, clinical, laboratory, and imaging features of children with COVID-19. We found that even lymphopenia was the most common lab finding in adults; it infrequently occurred in children (9.8%). Moreover, elevated creatine kinase MB isoenzyme was much more commonly observed in children (27.0%) than that in adults, suggesting that heart injury would be more likely to occur in pediatric patients. Our analysis may contribute to determine the spectrum of disease in children and to develop strategies to control the disease transmission.

negative: The silent deaths of the elderly in long-term care facilities during the Covid-19 pandemic: The role of forensic pathology. The Covid-19 pandemic is currently a major global public health problem. We know that the elderly and people with chronic diseases contract the infection more easily and they develop clinically more serious and often lethal forms. To date, the reasons for this have been generically attributed to old age and underlying diseases. Most Covid-19 deaths occurred in long-term care facilities because the residents are elderly people with chronic illness living in close contact. Therefore, facilities have become epidemic outbreaks. Forensic knowledge is very limited because an autopsy is rarely performed. Post-mortem investigations can help increase knowledge about Covid-19 and identify any undiagnosed pathologies in life. Therefore, forensic investigations play a role in protecting a frail population. Autopsies should be encouraged on elderly people who died of Covid-19.

negative: The mental health impact of providing spine care during COVID-19

negative: Clinical recommendations on lung cancer management during the COVID-19 pandemic Coronavirus disease 2019 (COVID-19) is spreading worldwide, and has been declared as an international public health concern. Patients with lung cancer are highly susceptible to infection compared to healthy individuals because of systemic immunosuppression induced by malignancy and anticancer therapy. Furthermore, patients with cancer demonstrate poorer outcomes following infection. Hence, patients with lung cancer should be considered a priority group for COVID-19 prevention. Furthermore, the routine treatment of patients with cancer has been affected during the COVID-19 pandemic, and patients may not have been able to undergo timely and effective antitumor treatment, thereby indicating a poor prognosis. Here, we provide some suggestions for early identification of COVID-19 and differential diagnosis in patients with lung cancer who have fever and respiratory symptoms. Our medical team also provide clinical recommendations on lung cancer management during the COVID-19 pandemic, for carrying out meticulous and individualized clinical management of lung cancer patients and maximum protection to effectively prevent COVID-19. KEY POINTS: Significant findings of the study This article provides suggestions for early identification of COVID-19 and differential diagnosis in patients with lung cancer with fever and respiratory symptoms. What this study adds This article makes clinical recommendations on lung cancer management during the COVID-19 pandemic.

negative: COVID-19 and Individual Genetic Susceptibility/Receptivity: Role of ACE1/ACE2 Genes, Immunity, Inflammation and Coagulation. Might the Double X-Chromosome in Females Be Protective against SARS-CoV-2 Compared to the Single X-Chromosome in Males? In December 2019, a novel severe acute respiratory syndrome (SARS) from a new coronavirus (SARS-CoV-2) was recognized in the city of Wuhan, China. Rapidly, it became an epidemic in China and has now spread throughout the world reaching pandemic proportions. High mortality rates characterize SARS-CoV-2 disease (COVID-19), which mainly affects the elderly, causing unrestrained cytokines-storm and subsequent pulmonary shutdown, also suspected micro thromboembolism events. At the present time, no specific and dedicated treatments, nor approved vaccines, are available, though very promising data come from the use of anti-inflammatory, anti-malaria, and anti-coagulant drugs. In addition, it seems that males are more susceptible to SARS-CoV-2 than females, with males 65% more likely to die from the infection than females. Data from the World Health Organization (WHO) and Chinese scientists show that of all cases about 1.7% of women who contract the virus will die compared with 2.8% of men, and data from Hong Kong hospitals state that 32% of male and 15% of female COVID-19 patients required intensive care or died. On the other hand, the long-term fallout of coronavirus may be worse for women than for men due to social and psychosocial reasons. Regardless of sex- or gender-biased data obtained from WHO and those gathered from sometimes controversial scientific journals, some central points should be considered. Firstly, SARS-CoV-2 has a strong interaction with the human ACE2 receptor, which plays an essential role in cell entry together with transmembrane serine protease 2 (TMPRSS2); it is interesting to note that the ACE2 gene lays on the X-chromosome, thus allowing females to be potentially heterozygous and differently assorted compared to men who are definitely hemizygous. Secondly, the higher ACE2 expression rate in females, though controversial, might ascribe them the worst prognosis, in contrast with worldwide epidemiological data. Finally, several genes involved in inflammation are located on the X-chromosome, which also contains high number of immune-related genes responsible for innate and adaptive immune responses to infection. Other genes, out from the RAS-pathway, might directly or indirectly impact on the ACE1/ACE2 balance by influencing its main actors (e.g., ABO locus, SRY, SOX3, ADAM17). Unexpectedly, the higher levels of ACE2 or ACE1/ACE2 rebalancing might improve the outcome of COVID-19 in both sexes by reducing inflammation, thrombosis, and death. Moreover, X-heterozygous females might also activate a mosaic advantage and show more pronounced sex-related differences resulting in a sex dimorphism, further favoring them in counteracting the progression of the SARS-CoV-2 infection.

negative: Outcome after introduction of laparoscopic appendectomy in children: A cohort study. INTRODUCTION Acute appendicitis in children is common and the optimal treatment modality is still debated, even if recent data suggest that laparoscopic surgery may result in shorter postoperative length of stay without an increased number of complications. The aim of the study was to compare the outcome of open and laparoscopic appendectomies during a transition period. MATERIALS AND METHODS This was a retrospective cohort study with prospectively collected data. All patients who underwent an operation for suspected appendicitis at the Astrid Lindgren Children's Hospital in Stockholm between 2006 and 2010 were included in the study. RESULTS 1745 children were included in this study, of whom 1010 had a laparoscopic intervention. There were no significant differences in the rate of postoperative abscesses, wound infections, readmissions or reoperations between the two groups. The median operating time was longer for laparoscopic appendectomy than for open appendectomy, 51 vs. 37minutes (p<0.05). The postoperative length of stay was similar in the two groups. A simple comparison between the groups suggested that laparoscopic appendectomy had a shorter median postoperative length of stay, 43 vs. 57hours (p<0.05). However, there was a trend in time for a shorter postoperative length of stay, and a trend for more of the procedures to be performed laparoscopically over time so on regression analysis, the apparent decrease in length of stay with laparoscopy could be ascribed to the general trend toward decreased length of stay over time, with no specific additional effect of laparoscopy. CONCLUSIONS Our data show no difference in outcome between open and laparoscopic surgery for acute appendicitis in children in regard of complications. The initial assumption that the patients treated with laparoscopic surgery had a shorter postoperative stay was not confirmed with linear regression, which showed that the assumed difference was due only to a trend toward shorter postoperative length of stay over time, regardless of the surgical intervention.

negative: Improving transitions in care for children with complex and medically fragile needs: a mixed methods study BACKGROUND: Children with medical complexity are a small yet resource intensive population in the Canadian health care system. The process for discharging these children from hospital to home is not yet optimal. The overall goal of this project was to develop recommendations to be included in a provincial strategy to support transitions in care for children with complex and medically fragile needs. METHODS: A wide assortment of stakeholders participated in this mixed method, multiphase project. During Phase 1, data was gathered from a range of sources to document families’ experiences transitioning from an inpatient hospital stay back to their home communities. In Phase 2, pediatricians, nurses, and health administrators participated in key stakeholder interviews to identify barriers and facilitators to a successful transition in care for children and families with complex care needs. A multi-sector consensus meeting was held during Phase 3 to discuss study findings and refine key recommendations for inclusion in a provincial strategy. RESULTS: Six case studies were developed involving children and families discharged home with a variety of complex care needs. Children ranged in age from 15 days to 9 years old. Nine telephone interviews were conducted in Phase 2 with pediatricians, nurses, and administrators from across the province. A variety of inter-institutional communication challenges were described as a major barrier to the transition process. A consistent message across all interviews was the need for improved coordination to facilitate transitions in care. The consensus meeting to review study findings included physicians, nurses, paramedics, senior administrators, and policy analysts from different health and government sectors and resulted in six recommendations for inclusion in a provincial strategy. CONCLUSIONS: This project identified policy and practice gaps that currently exist related to transitions in care for children with complex and medically fragile needs and their families. Our collaborative patient-centred approach to understanding how children and families currently navigate transitions in care provided a foundation for developing recommendations for a provincial wide strategy.

negative: The role of pulmonary CT scans for children during the COVID-19 pandemic

negative: COVID-19 and routine childhood immunization in Africa: leveraging systems thinking and implementation science to improve immunization system performance Abstract One of the routine health services that is being disrupted by coronavirus disease 2019 (COVID-19) in Africa is childhood immunization. This is because the immunization system relies on functioning health facilities and stable communities to be effective. Its disruption increases the risk of epidemics of vaccine-preventable diseases which can increase child mortality. Therefore, policymakers must quickly identify robust and context-specific strategies to rapidly scale-up routine immunization in order to mitigate the impact of COVID-19 on their national immunization performance. To achieve this, we propose a paradigm shift towards systems thinking and use of implementation science in immunization decision making. Systems thinking can inform a more nuanced and holistic understanding of the interrelationship that between COVID-19, its control strategies and childhood immunization. Tools like causal loop diagrams can be used to explicitly illustrate the systems structure by identifying the feedback loops. Once mapped and leverage points for interventions have been identified, implementation science can be used to guide the rapid uptake and utilization of multifaceted evidence-based innovations in complex practice settings. As Africa re-strategize for the post-2020 era, these emerging fields can contribute significantly in accelerating progress towards universal access to vaccines for all children on the continent despite COVID-19.

negative: Any unique image biomarkers associated with COVID-19? OBJECTIVE: To define the uniqueness of chest CT infiltrative features associated with COVID-19 image characteristics as potential diagnostic biomarkers. METHODS: We retrospectively collected chest CT exams including n = 498 on 151 unique patients RT-PCR positive for COVID-19 and n = 497 unique patients with community-acquired pneumonia (CAP). Both COVID-19 and CAP image sets were partitioned into three groups for training, validation, and testing respectively. In an attempt to discriminate COVID-19 from CAP, we developed several classifiers based on three-dimensional (3D) convolutional neural networks (CNNs). We also asked two experienced radiologists to visually interpret the testing set and discriminate COVID-19 from CAP. The classification performance of the computer algorithms and the radiologists was assessed using the receiver operating characteristic (ROC) analysis, and the nonparametric approaches with multiplicity adjustments when necessary. RESULTS: One of the considered models showed non-trivial, but moderate diagnostic ability overall (AUC of 0.70 with 99% CI 0.56–0.85). This model allowed for the identification of 8–50% of CAP patients with only 2% of COVID-19 patients. CONCLUSIONS: Professional or automated interpretation of CT exams has a moderately low ability to distinguish between COVID-19 and CAP cases. However, the automated image analysis is promising for targeted decision-making due to being able to accurately identify a sizable subsect of non-COVID-19 cases. KEY POINTS: • Both human experts and artificial intelligent models were used to classify the CT scans. • ROC analysis and the nonparametric approaches were used to analyze the performance of the radiologists and computer algorithms. • Unique image features or patterns may not exist for reliably distinguishing all COVID-19 from CAP; however, there may be imaging markers that can identify a sizable subset of non-COVID-19 cases.

negative: Blood transfusion utilization in hospitalized COVID‐19 patients BACKGROUND: The acute respiratory illness designated coronavirus disease 2019 (COVID‐19) was first reported in Wuhan, China, in December 2019 and caused a worldwide pandemic. Concerns arose about the impact of the COVID‐19 pandemic on blood donations and potential significant blood transfusion needs in severely ill COVID‐19 patients. Data on blood usage in hospitalized COVID‐19 patients are scarce. STUDY DESIGN AND METHODS: We performed a retrospective observational study of blood component transfusions in the first 4 weeks of COVID‐19 ward admissions. The study period began 14 days before the first COVID‐19 cohort wards opened in our hospital in March 2020 and ended 28 days afterward. The number of patients and blood components transfused in the COVID‐19 wards was tabulated. Transfusion rates of each blood component were compared in COVID‐19 wards versus all other inpatient wards. RESULTS: COVID‐19 wards opened with seven suspected patients and after 4 weeks had 305 cumulative COVID‐19 admissions. Forty‐one of 305 hospitalized COVID‐19 patients (13.4%) received transfusions with 11.1% receiving red blood cells (RBCs), 1.6% platelets (PLTs), 1.0% plasma, and 1.0% cryoprecipitate (cryo). COVID‐19 wards had significantly lower transfusion rates compared to non‐COVID wards for RBCs (0.03 vs 0.08 units/patient‐day), PLTs (0.003 vs 0.033), and plasma (0.002 vs 0.018; all p < 0.0001). Cryo rates were similar (0.008 vs 0.009, p = 0.6). CONCLUSIONS: Hospitalized COVID‐19 patients required many fewer blood transfusions than other hospitalized patients. COVID‐19 transfusion data will inform planning and preparation of blood resource utilization during the pandemic.

negative: High altitude reduces infection rate of COVID-19 but not case-fatality rate Coronavirus disease 19 (COVID-19) is a pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). It is suggested that life at high altitude may reduce COVID infections and case-fatality rates (cases/deaths). We study data from Peru COVID-19 pandemics, which first case was recorded on March 6th, 2020. By June 13, 2020 there were 6498 deaths, and 224,132 SARS-CoV-2 positives. Using data from 185 capitals of provinces with altitudes ranging from 3 to 4342 m, we confirm previous reports that infection with COVID-19 at high altitude is reduced. However, case-fatality rate is not dependent of altitude. We have also presented first evidence that female protection towards death by COVID-19 is reduced as altitude of residence increases.

negative: The paediatric global musculoskeletal task force - ‘towards better MSK health for all’ There is increasing concern about the emerging global non-communicable diseases (NCDs) burden. The focus has mainly been on NCDs in adults but it is important that MSK morbidity in both children and adults is included in strategic planning. There have been considerable advances in the understanding and treatment options for children and young people (CYP) and clinical outcomes are improving for those who can access such high quality care. However vast inequity exists and there are many CYP who live in areas of the world with high burden of health care challenges, compounded by paucity of specialist care and limited access to treatments. The Paediatric Global Musculoskeletal Task Force aims to raise awareness about unmet needs for CYP with MSK conditions, promotion of MSK health through lifestyle and the avoidance of injury. We aim to leverage change through ‘working together better’.

negative: Awareness, Attitudes, and Actions Related to COVID-19 Among Adults With Chronic Conditions at the Onset of the U.S. Outbreak: A Cross-sectional Survey BACKGROUND: The evolving outbreak of coronavirus disease 2019 (COVID-19) is requiring social distancing and other measures to protect public health. However, messaging has been inconsistent and unclear. OBJECTIVE: To determine COVID-19 awareness, knowledge, attitudes, and related behaviors among U.S. adults who are more vulnerable to complications of infection because of age and comorbid conditions. DESIGN: Cross-sectional survey linked to 3 active clinical trials and 1 cohort study. SETTING: 5 academic internal medicine practices and 2 federally qualified health centers. PATIENTS: 630 adults aged 23 to 88 years living with 1 or more chronic conditions. MEASUREMENTS: Self-reported knowledge, attitudes, and behaviors related to COVID-19. RESULTS: A fourth (24.6%) of participants were “very worried” about getting the coronavirus. Nearly a third could not correctly identify symptoms (28.3%) or ways to prevent infection (30.2%). One in 4 adults (24.6%) believed that they were “not at all likely” to get the virus, and 21.9% reported that COVID-19 had little or no effect on their daily routine. One in 10 respondents was very confident that the federal government could prevent a nationwide outbreak. In multivariable analyses, participants who were black, were living below the poverty level, and had low health literacy were more likely to be less worried about COVID-19, to not believe that they would become infected, and to feel less prepared for an outbreak. Those with low health literacy had greater confidence in the federal government response. LIMITATION: Cross-sectional study of adults with underlying health conditions in 1 city during the initial week of the COVID-19 U.S. outbreak. CONCLUSION: Many adults with comorbid conditions lacked critical knowledge about COVID-19 and, despite concern, were not changing routines or plans. Noted disparities suggest that greater public health efforts may be needed to mobilize the most vulnerable communities. PRIMARY FUNDING SOURCE: National Institutes of Health.

negative: Pneumonia in children admitted to the national referral hospital in Bhutan: A prospective cohort study Abstract Objectives The study aim was to describe the etiological profile and clinical characteristics of pneumonia among children hospitalized in Thimphu, Bhutan. Methods This prospective study enrolled children aged 2–59 months admitted to the Jigme Dorji Wangchuck National Referral Hospital with World Health Organization (WHO)-defined clinical pneumonia. Demographic and clinico-radiological data were collected through questionnaires, physical examination, and chest radiography. Blood samples and nasopharyngeal washing were collected for microbiological analysis including culture and molecular methods. Results From July 2017 to June 2018, 189 children were enrolled, of which 53.4% were infants. Pneumonia-related admissions were less frequent over the winter. Chest radiographies were obtained in 149 children; endpoints included pneumonia in 39 cases (26.2%), other infiltrates in 31 (20.8%), and were normal in 79 children (53.0%). Non-contaminated bacterial growth was detected in 8/152 (5.3%) blood cultures, with only two cases of Streptococcus pneumoniae. Viral detection in upper respiratory secretions was common, with at least one virus detected in 103/115 (89.6%). The three most-commonly isolated viruses were respiratory syncytial virus (52/115; 45.2%), rhinovirus (42/115; 36.5%), and human parainfluenza virus (19/115; 16.5%). A third of patients with viral infections showed mixed infections. Case fatality rate was 3.2% (6/189). Conclusion Respiratory viral infections predominated among this cohort of WHO-defined clinical pneumonia cases, whereas bacterial aetiologies were uncommon, highlighting the epidemiologic transition that Bhutan seems to have reached.

negative: The role of children in the spread of COVID-19: Using household data from Bnei Brak, Israel, to estimate the relative susceptibility and infectivity of children One of the significant unanswered questions about COVID-19 epidemiology relates to the role of children in transmission. In this study we estimate susceptibility and infectivity of children compared to those of adults. Understanding the age-structured transmission dynamics of the outbreak provides precious and timely information to guide epidemic modelling and public health policy. Data were collected from households in the city of Bnei Brak, Israel, in which all household members were tested for COVID-19 using PCR. To estimate relative transmission parameters in the absence of data on who infected whom, we developed an estimation method based on a discrete stochastic dynamic model of the spread of the epidemic within a household. The model describes the propagation of the disease between household members allowing for susceptibility and infectivity parameters to vary among two age groups. The parameter estimates are obtained by a maximum likelihood method, where the likelihood function is computed based on the stochastic model via simulations. Inspection of the data reveals that children are less likely to become infected compared to adults (25% of children infected over all households, 44% of adults infected over all households, excluding index cases), and the chances of becoming infected increases with age. An interesting exception is that infants up to age one year are more likely to be infected than children between one and four. Using our modelling approach, we estimate that the susceptibility of children (under 20 years old) is 45% [40%, 55%] of the susceptibility of adults. The infectivity of children was estimated to be 85% [65%,110%] relative to that of adults. It is widely observed that the percentage of children within confirmed cases is low. A common explanation is that children who are infected are less likely to develop symptoms than adults, and thus are less likely to be tested. We estimate that children are less susceptible to infection, which is an additional factor explaining their relatively low rate of occurrence within confirmed cases. Moreover, our results indicate that children, when infected, are somewhat less prone to infect others compared to adults; however, this result is not statistically significant. The resulting estimates of susceptibility and infectivity of children compared to adults are crucial for deciding on appropriate interventions, and for controlling the epidemic outbreak and its progress. These estimates can guide age-dependent public health policy such as school closure and opening. However, while our estimates of children's susceptibility and infectivity are lower than those of adults within a household, it is important to bear in mind that their role in the spread of COVID-19 outside the household, is also affected by different contact patterns and hygiene habits.

negative: The Australasian COVID-19 Trial (ASCOT) to assess clinical outcomes in hospitalised patients with SARS-CoV-2 infection (COVID-19) treated with lopinavir/ritonavir and/or hydroxychloroquine compared to standard of care: A structured summary of a study protocol for a randomised controlled trial OBJECTIVES: To determine if lopinavir/ritonavir +/- hydroxychloroquine will reduce the proportion of participants who survive without requiring ventilatory support, 15 days after enrolment, in adult participants with non-critically ill SARS-CoV-2 infection. TRIAL DESIGN: ASCOT is an investigator-initiated, multi-centre, open-label, randomised controlled trial. Participants will have been hospitalised with confirmed COVID-19, and will be randomised 1:1:1:1 to receive lopinavir /ritonavir, hydroxychloroquine, both or neither drug in addition to standard of care management. PARTICIPANTS: Participants will be recruited from >80 hospitals across Australia and New Zealand, representing metropolitan and regional centres in both public and private sectors. Admitted patients will be eligible if aged ≥ 18 years, have confirmed SARS-CoV-2 by nucleic acid testing in the past 12 days and are expected to remain an inpatient for at least 48 hours from the time of randomisation. Potentially eligible participants will be excluded if admitted to intensive care or requiring high level respiratory support, are currently receiving study drugs or their use is contraindicated due to allergy, drug interaction or comorbidities (including baseline QTc prolongation of 470ms for women or 480ms for men), or death is anticipated imminently. INTERVENTION AND COMPARATOR: Participants will be randomised 1:1:1:1 to: Group 1: standard of care; Group 2: lopinavir (400mg) / ritonavir (100mg) twice daily for 10 days in tablet form; Group 3: hydroxychloroquine (800mg) 4x200mg administered 12 hours apart on Day 1, followed by 400mg twice a day for 6 days; Group 4: lopinavir /ritonavir plus hydroxychloroquine. MAIN OUTCOMES: Proportion of participants alive and not having required intensive respiratory support (invasive or non-invasive ventilation) at 15 days after enrolment. A range of clinical and virological secondary outcomes will also be evaluated. RANDOMISATION: The randomisation schedule will be generated by an independent statistician. Randomisation will be stratified by site and will be in permuted blocks of variable block size. The randomised sequence allocation will only be accessible to the data management group, and site investigators will have individual participant allocation provided through a web-based trial enrolment platform. BLINDING (MASKING): This is an open-label study, with researchers assessing the laboratory outcomes blinded to treatment allocation. No unblinding procedures relating to potential adverse effects are therefore required. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): We assumed that 5% of participants receiving standard of care would meet the primary outcome, aimed to evaluate whether interventions could lead to a relative risk of 0.5, assuming no interaction between intervention arms. This corresponds to a required sample size of 610 per arm, with a 5% two-sided significance level (alpha) and 80% power. The total sample size therefore is planned to be 2440. TRIAL STATUS: ASCOT protocol version 3, May 5, 2020. Recruitment opened April 4, 2020 and is ongoing, with planned completion of enrolment July 31, 2021. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12620000445976). Prospectively registered April 6, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

negative: Asthma and COVID-19 in children - a systematic review and call for data RATIONALE: Whether asthma constitutes a risk factor for COVID-19 is unclear. METHODS: We performed a systematic literature search in three stages: First, we reviewed PubMed, EMBASE and CINAHL for systematic reviews of SARS-CoC-2 and COVID-19 in pediatric populations, and reviewed their primary articles; next, we searched PubMed for studies on COVID-19 or SARS-CoV-2 and asthma/wheeze, and evaluated whether the resulting studies included pediatric populations; lastly, we repeated the second search in BioRxiv.org and MedRxiv.org to find pre-prints that may have information on pediatric asthma. RESULTS: In the first search, eight systematic reviews were found, of which five were done in pediatric population; after reviewing 67 primary studies we found no data on pediatric asthma as a comorbidity for COVID-19. In the second search, we found 25 results in PubMed, of which five reported asthma in adults, but none included data on children. In the third search, 14 pre-prints in MedRxiv were identified with data on asthma, but again none with pediatric data. We found only one report by the U.S. CDC stating that 40/345 (~11.5%) children with data on chronic conditions had “chronic lung diseases including asthma”. CONCLUSION: There is scarcely any data on whether childhood asthma (or other pediatric respiratory diseases) constitute risk factors for SARS-CoV-2 infection or COVID-19 severity. Studies are needed that go beyond counting the number of cases in the pediatric age range.

negative: A mild type of childhood Covid-19 - A case report Abstract This case is about a 9-year-old child diagnosed with COVID-19, with a history of epidemiology; SARS-CoV-2 nucleic acids testing was positive, while chest CT examination was negative. The clinical classification was light. Nonetheless, isolation measures should still be taken to avoid infecting others.

negative: Proactive case detection of common childhood illnesses by community health workers: a systematic review. Introduction Identifying design features and implementation strategies to optimise community health worker (CHW) programmes is important in the context of mixed results at scale. We systematically reviewed evidence of the effects of proactive case detection by CHWs in low-income and middle-income countries (LMICs) on mortality, morbidity and access to care for common childhood illnesses. Methods Published studies were identified via electronic databases from 1978 to 2017. We included randomised and non-randomised controlled trials, controlled before-after studies and interrupted time series studies, and assessed their quality for risk of bias. We reported measures of effect as study investigators reported them, and synthesised by outcomes of mortality, disease prevalence, hospitalisation and access to treatment. We calculated risk ratios (RRs) as a principal summary measure, with CIs adjusted for cluster design effect. Results We identified 14 studies of 11 interventions from nine LMICs that met inclusion criteria. They showed considerable diversity in intervention design and implementation, comparison, outcomes and study quality, which precluded meta-analysis. Proactive case detection may reduce infant mortality (RR: 0.52-0.94) and increase access to effective treatment (RR: 1.59-4.64) compared with conventional community-based healthcare delivery (low certainty evidence). It is uncertain whether proactive case detection reduces mortality among children under 5 years (RR: 0.04-0.80), prevalence of infectious diseases (RR: 0.06-1.02), hospitalisation (RR: 0.38-1.26) or increases access to prompt treatment (RR: 1.00-2.39) because the certainty of this evidence is very low. Conclusion Proactive case detection may provide promising benefits for child health, but evidence is insufficient to draw conclusions. More research is needed on proactive case detection with rigorous study designs that use standardised outcomes and measurement methods, and report more detail on complex intervention design and implementation. PROSPERO registration number CRD42017074621.

negative: Septic shock, necrotizing pneumonitis, and meningoencephalitis caused by Mycoplasma pneumoniae in a child: a case report. Mycoplasma pneumoniae is an important causative agent of respiratory infection in childhood. Although the infection caused by M. pneumoniae is classically described as benign, severe and life-threatening pulmonary and extrapulmonary complications can occur. This study describes the first case of septic shock related to M. pneumoniae in a child with necrotizing pneumonitis, severe encephalitis, and multiple organs involvement, with a favorable outcome after lobectomy and systemic corticosteroids.

negative: Protecting children in low-income and middle-income countries from COVID-19

negative: EAACI position statement on asthma exacerbations and severe asthma Asthma exacerbations and severe asthma are linked with high morbidity, significant mortality and high treatment costs. Recurrent asthma exacerbations cause a decline in lung function and, in childhood, are linked to development of persistent asthma. This position paper, from the European Academy of Allergy and Clinical Immunology, highlights the shortcomings of current treatment guidelines for patients suffering from frequent asthma exacerbations and those with difficult‐to‐treat asthma and severe treatment‐resistant asthma. It reviews current evidence that supports a call for increased awareness of (i) the seriousness of asthma exacerbations and (ii) the need for novel treatment strategies in specific forms of severe treatment‐resistant asthma. There is strong evidence linking asthma exacerbations with viral airway infection and underlying deficiencies in innate immunity and evidence of a synergism between viral infection and allergic mechanisms in increasing risk of exacerbations. Nonadherence to prescribed medication has been identified as a common clinical problem amongst adults and children with difficult‐to‐control asthma. Appropriate diagnosis, assessment of adherence and other potentially modifiable factors (such as passive or active smoking, ongoing allergen exposure, psychosocial factors) have to be a priority in clinical assessment of all patients with difficult‐to‐control asthma. Further studies with improved designs and new diagnostic tools are needed to properly characterize (i) the pathophysiology and risk of asthma exacerbations, and (ii) the clinical and pathophysiological heterogeneity of severe asthma.

negative: The role of children in transmission of SARS-CoV-2: A rapid review Background: Understanding the role of children in the transmission of SARS-CoV-2 is urgently required given its policy implications in relation to the reopening of schools and intergenerational contacts. Methods: We conducted a rapid review of studies that investigated the role of children in the transmission of SARS-CoV-2. We synthesized evidence for four categories: 1) studies reporting documented cases of SARS-CoV-2 transmission by infected children; 2) studies presenting indirect evidence on the potential of SARS-CoV-2 transmission by (both symptomatic and asymptomatic) children; 3) studies reporting cluster outbreaks of COVID-19 in schools; 4) studies estimating the proportions of children infected by SARS-CoV-2, and reported results narratively. Results: A total of 16 unique studies were included for narrative synthesis. There is limited evidence detailing transmission of SARS-CoV-2 from infected children. We found two studies that reported a 3-month-old whose parents developed symptomatic COVID-19 seven days after caring for the infant and two children who may have contracted COVID-19 from the initial cases at a school in New South Wales. In addition, we identified six studies presenting indirect evidence on the potential for SARS-CoV-2 transmission by children, three of which found prolonged virus shedding in stools. There is little data on the transmission of SARS-CoV-2 in schools. We identified only two studies reporting outbreaks of COVID-19 in school settings and one case report of a child attending classes but not infecting any other pupils or staff. Lastly, we identified six studies estimating the proportion of children infected; data from population-based studies in Iceland, Italy, South Korea, Netherlands, California and a hospital-based study in the UK suggest children may be less likely to be infected. Conclusions: Preliminary results from population-based and school-based studies suggest that children may be less frequently infected or infect others, however current evidence is limited. Prolonged faecal shedding observed in studies highlights the potentially increased risk of faeco-oral transmission in children. Further seroprevalence studies (powered adequately for the paediatric population) are urgently required to establish whether children are in fact less likely to be infected compared to adults. Note: We plan to update this rapid review as new data becomes available. These updates are available at https://www.ed.ac.uk/usher/uncover/completed-uncover-reviews.

negative: Mental health during the COVID-19 pandemic in two longitudinal UK population cohorts Background: The impact of COVID-19 on mental health is unclear. Evidence from longitudinal studies with pre pandemic data are needed to address (1) how mental health has changed from pre-pandemic levels to during the COVID-19 pandemic and (2), whether there are groups at greater risk of poorer mental health during the pandemic? Methods: We used data from COVID-19 surveys (completed through April/May 2020), nested within two large longitudinal population cohorts with harmonised measures of mental health: two generations of the Avon Longitudinal Study of Parents and Children (ALPSAC): the index generation ALSPAC-G1 (n= 2850, mean age 28) and the parents generation ALSPAC-G0 (n= 3720, mean age = 59) and Generation Scotland: Scottish Family Health Study (GS, (n= 4233, mean age = 59), both with validated pre-pandemic measures of mental health and baseline factors. To answer question 1, we used ALSPAC-G1, which has identical mental health measures before and during the pandemic. Question 2 was addressed using both studies, using pre-pandemic and COVID-19 specific factors to explore associations with depression and anxiety in COVID-19. Findings: In ALSPAC-G1 there was evidence that anxiety and lower wellbeing, but not depression, had increased in COVID-19 from pre-pandemic assessments. The percentage of individuals with probable anxiety disorder was almost double during COVID-19: 24% (95% CI 23%, 26%) compared to pre-pandemic levels (13%, 95% CI 12%, 14%), with clinically relevant effect sizes. In both ALSPAC and GS, depression and anxiety were greater in younger populations, women, those with pre-existing mental and physical health conditions, those living alone and in socio-economic adversity. We did not detect evidence for elevated risk in key workers or health care workers. Interpretation: These results suggest increases in anxiety and lower wellbeing that may be related to the COVID-19 pandemic and/or its management, particularly in young people. This research highlights that specific groups may be disproportionally at risk of elevated levels of depression and anxiety during COVID-19 and supports recent calls for increasing funds for mental health services. Funding: The UK Medical Research Council (MRC), the Wellcome Trust and University of Bristol.

negative: Psychiatric Training During a Global Pandemic: How COVID-19 Has Affected Clinical Care, Teaching, and Trainee Well-Being The COVID-19 pandemic has altered many aspects of personal and professional life, including how psychiatry is practiced and how trainees are taught. This Open Forum outlines the challenges faced by psychiatric training directors in adult as well as child and adolescent psychiatry in meeting the educational needs of trainees amid this international crisis. Prioritizing trainee protection and education as well as high-quality treatment for patients, the authors discuss effective communication strategies, rapid telepsychiatry expansion into clinical practice, curricular adjustments, and the importance of well-being. This Open Forum concludes with reflections and considerations for training directors as they prepare for subsequent stages of the COVID-19 pandemic.

negative: Preliminary Estimates of the Prevalence of Selected Underlying Health Conditions Among Patients with Coronavirus Disease 2019 - United States, February 12-March 28, 2020 On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic (1). As of March 28, 2020, a total of 571,678 confirmed COVID-19 cases and 26,494 deaths have been reported worldwide (2). Reports from China and Italy suggest that risk factors for severe disease include older age and the presence of at least one of several underlying health conditions (3,4). U.S. older adults, including those aged ≥65 years and particularly those aged ≥85 years, also appear to be at higher risk for severe COVID-19-associated outcomes; however, data describing underlying health conditions among U.S. COVID-19 patients have not yet been reported (5). As of March 28, 2020, U.S. states and territories have reported 122,653 U.S. COVID-19 cases to CDC, including 7,162 (5.8%) for whom data on underlying health conditions and other known risk factors for severe outcomes from respiratory infections were reported. Among these 7,162 cases, 2,692 (37.6%) patients had one or more underlying health condition or risk factor, and 4,470 (62.4%) had none of these conditions reported. The percentage of COVID-19 patients with at least one underlying health condition or risk factor was higher among those requiring intensive care unit (ICU) admission (358 of 457, 78%) and those requiring hospitalization without ICU admission (732 of 1,037, 71%) than that among those who were not hospitalized (1,388 of 5,143, 27%). The most commonly reported conditions were diabetes mellitus, chronic lung disease, and cardiovascular disease. These preliminary findings suggest that in the United States, persons with underlying health conditions or other recognized risk factors for severe outcomes from respiratory infections appear to be at a higher risk for severe disease from COVID-19 than are persons without these conditions.

negative: Projected geographic disparities in healthcare worker absenteeism from COVID-19 school closures and the economic feasibility of child care subsidies: a simulation study BACKGROUND: School closures have been enacted as a measure of mitigation during the ongoing COVID-19 pandemic. It has been shown that school closures could cause absenteeism amongst healthcare workers with dependent children, but there remains a need for spatially granular analyses of the relationship between school closures and healthcare worker absenteeism to inform local community preparedness. METHODS: We provide national- and county-level simulations of school closures and unmet child care needs across the United States. We develop individual simulations using county-level demographic and occupational data, and model school closure effectiveness with age-structured compartmental models. We perform multivariate quasi-Poisson ecological regressions to find associations between unmet child care needs and COVID-19 vulnerability factors. RESULTS: At the national level, we estimate the projected rate of unmet child care needs for healthcare worker households to range from 7.5% to 8.6%, and the effectiveness of school closures to range from 3.2% (R(0) = 4) to 7.2% (R(0) = 2) reduction in fewer ICU beds at peak demand. At the county-level, we find substantial variations of projected unmet child care needs and school closure effects, ranging from 1.9% to 18.3% of healthcare worker households and 5.7% to 8.8% reduction in fewer ICU beds at peak demand (R(0) = 2). We find significant positive associations between estimated levels of unmet child care needs and diabetes prevalence, county rurality, and race (p < 0.05). We estimate costs of absenteeism and child care and observe from our models that an estimated 71.1% to 98.8% of counties would find it less expensive to provide child care to all healthcare workers with children than to bear the costs of healthcare worker absenteeism during school closures. CONCLUSIONS: School closures are projected to reduce peak ICU bed demand, but could disrupt healthcare systems through absenteeism, especially in counties that are already particularly vulnerable to COVID-19. Child care subsidies could help circumvent the ostensible tradeoff between school closures and healthcare worker absenteeism.

negative: Supporting children and families through the pandemic, and after: The case for a US child allowance Abstract The COVID-19 pandemic has precipitated a contraction in economic activity that is unprecedented in both its nature and speed. In doing so, it has exposed who is protected and supported by modern welfare states, and who is not. While the US has a relatively robust set of social insurance and assistance programs for older Americans and working-age Americans who become unemployed or disabled, it lacks – in contrast to many other wealthy nations – a comparably strong universal or wide-reaching mechanism to support families with children. The US emergency relief packages enacted to date will undoubtedly mitigate the economic effects of the current crisis for many families, but because this legislation relies on the existing social policy infrastructure, its intended cash relief reinforces current inequalities and underserves families with children, with a particular impact on immigrant families and families of color. To protect all families with children through the immediate crisis and beyond, existing gaps and inequities in the US social safety net must be addressed. The creation of a national US child allowance offers a concrete and evidence-based way in which to do so. This analysis outlines key shortcomings in the existing system of US public support for families with children, the ways in which these shortcomings have been exacerbated in the COVID-19 economic response package to date, and how a national child allowance can provide the immediate relief families need during the pandemic and the unfolding economic downturn, as well as lay the foundation for positive health and development for all children in the years to follow.

negative: COVID-19 in Wuhan: Sociodemographic characteristics and hospital support measures associated with the immediate psychological impact on healthcare workers BACKGROUND: The outbreak of COVID-19 has laid unprecedented threats and challenges to health workers (HWs) in Wuhan, China. We aimed to assess the sociodemographic characteristics and hospital support measures associated with the immediate psychological impact on HWs at Tongji Hospital in Wuhan during COVID-19 outbreak. METHODS: We conducted a single-center, cross-sectional survey of HWs via online questionnaires between February 8th and 10th, 2020. We evaluated stress, depression and anxiety by IES-R, PHQ-9, and GAD-7, respectively. We also designed a questionnaire to assess the perceptions of threat of COVID-19, and the satisfactions of the hospital's support measures. Multivariate logistic regressions were used to identify associated variables of acute stress, depression, and anxiety. FINDINGS: We received 5062 completed questionnaires (response rate, 77.1%). 29.8%, 13.5% and 24.1% HWs reported stress, depression and anxiety symptoms. Women (odds ratio [OR], 1.31; 95% CI, 0.47–0.97; p = 0.032), years of working >10 years (OR, 2.02; 95% CI, 1.47–2.79; p<0.001), concomitant chronic diseases (OR, 1.51; 95% CI, 1.27–1.80; p<0.001), history of mental disorders (OR, 3.27; 95% CI, 1.77–6.05; p<0.001), family members or relatives confirmed or suspected (OR, 1.23; 95% CI, 1.02–1.48; p = 0.03), hospital-based and department-based care (OR, 0.76; 95% CI, 0.60–0.97; p = 0.024) and full coverage of all departments for avoiding nosocomial infection (OR, 0.69; 95% CI, 0.53–0.89; p = 0.004) were associated with stress. INTERPRETATION: Women and those who have more than 10 years of working, concomitant chronic diseases, history of mental disorders, and family members or relatives confirmed or suspected are susceptible to stress, depression and anxiety among HWs during the pandemic. In addition, since HWs often have a greater stigma against mental problems than the general public, it is worthwhile to address the needs of the HWs during this pandemic and to provide appropriate psychological supports for those people at high risk of mental problems.

negative: Covid-19 and breastfeeding: what’s the risk?

negative: The respiratory health of urban indigenous children aged less than 5 years: study protocol for a prospective cohort study BACKGROUND: Despite the burden of acute respiratory illnesses (ARI) among Aboriginal and Torres Strait Islander children being a substantial cause of childhood morbidity and associated costs to families, communities and the health system, data on disease burden in urban children are lacking. Consequently evidence-based decision-making, data management guidelines, health resourcing for primary health care services and prevention strategies are lacking. This study aims to comprehensively describe the epidemiology, impact and outcomes of ARI in urban Aboriginal and Torres Strait Islander children (hereafter referred to as Indigenous) in the greater Brisbane area. METHODS/DESIGN: An ongoing prospective cohort study of Indigenous children aged less than five years registered with a primary health care service in Northern Brisbane, Queensland, Australia. Children are recruited at time of presentation to the service for any reason. Demographic, epidemiological, risk factor, microbiological, economic and clinical data are collected at enrolment. Enrolled children are followed for 12 months during which time ARI events, changes in child characteristics over time and monthly nasal swabs are collected. Children who develop an ARI with cough as a symptom during the study period are more intensely followed-up for 28 (±3) days including weekly nasal swabs and parent completed cough diary cards. Children with persistent cough at day 28 post-ARI are reviewed by a paediatrician. DISCUSSION: Our study will be one of the first to comprehensively evaluate the natural history, epidemiology, aetiology, economic impact and outcomes of ARIs in this population. The results will inform studies for the development of evidence-based guidelines to improve the early detection, prevention and management of chronic cough and setting of priorities in children during and after ARI. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry Registration Number: 12614001214628. Registered 18 November 2014

negative: Immediate impact of COVID-19 on transplant activity in the Netherlands Abstract The rapid emergence of the COVID-19 pandemic is unprecedented and poses an unparalleled obstacle in the sixty-five year history of organ transplantation. Worldwide, the delivery of transplant care is severely challenged by matters concerning - but not limited to - organ procurement, risk of SARS-CoV-2 transmission, screening strategies of donors and recipients, decisions to postpone or proceed with transplantation, the attributable risk of immunosuppression for COVID-19 and entrenched health care resources and capacity. The transplant community is faced with choosing a lesser of two evils: initiating immunosuppression and potentially accepting detrimental outcome when transplant recipients develop COVID-19 versus postponing transplantation and accepting associated waitlist mortality. Notably, prioritization of health care services for COVID-19 care raises concerns about allocation of resources to deliver care for transplant patients who might otherwise have excellent 1-year and 10-year survival rates. Children and young adults with end-stage organ disease in particular seem more disadvantaged by withholding transplantation because of capacity issues than from medical consequences of SARS-CoV-2. This report details the nationwide response of the Dutch transplant community to these issues and the immediate consequences for transplant activity. Worrisome, there was a significant decrease in organ donation numbers affecting all organ transplant services. In addition, there was a detrimental effect on transplantation numbers in children with end-organ failure. Ongoing efforts focus on mitigation of not only primary but also secondary harm of the pandemic and to find right definitions and momentum to restore the transplant programs.

negative: Saving the lives of mothers and children.

negative: Incidence of COVID-19 in a cohort of adult and paediatric patients with rheumatic diseases treated with targeted biologic and synthetic disease-modifying anti-rheumatic drugs OBJECTIVES: To investigate the incidence of COVID-19 in a cohort of adult and paediatric patients with rheumatic diseases receiving targeted biologic and synthetic disease modifying anti-rheumatic drugs (tDMARDs) and to explore the possible effect of these treatments in the clinical expression of COVID-19. METHODS: A cross-sectional study comprising of a telephone survey and electronic health records review was performed including all adult and paediatric patients with rheumatic diseases treated with tDMARDs in a large rheumatology tertiary centre in Barcelona, Spain. Demographics, disease activity, COVID-19 related symptoms and contact history data were obtained from the start of the 2020 pandemic. Cumulative incidence of confirmed cases (SARS-CoV-2 positive PCR test) was compared to the population estimates for the same city districts from a governmental COVID-19 health database. Suspected cases were defined following WHO criteria and compared to those without compatible symptoms. RESULTS: 959 patients with rheumatic diseases treated with tDMARDs were included. We identified 11 confirmed SARS-CoV-2 positive cases in the adult cohort and no confirmed positive cases in the paediatric cohort. COVID-19 incidence rates of the rheumatic patient cohort were very similar to that of the general population [(0.48% (95% CI 0.09 to 8.65%)] and [0.58% (95% CI 5.62 to 5.99%)], respectively. We found significant differences in tDMARDs proportions between the suspected and non-suspected cases (p=0.002). CONCLUSION: Adult and paediatric patients with rheumatic diseases on tDMARDs do not seem to present a higher risk of COVID-19 or a more severe disease outcome when compared to general population.

negative: Hazardous Postoperative Outcomes of Unexpected COVID-19 Infected Patients: A Call for Global Consideration of Sampling all Asymptomatic Patients Before Surgical Treatment BACKGROUND: In December 2019, a novel coronavirus was identified as the cause of many pneumonia cases in China and eventually declared as a pandemic as the virus spread globally. Few reports were published on the outcome of surgical procedures in diagnosed COVID-19 patients and even fewer on the surgical outcomes of asymptomatic undiagnosed COVID-19 surgical patients. We aimed to review all published data regarding surgical outcomes of preoperatively asymptomatic untested coronavirus disease 2019 (COVID-19) patients. METHODS: This report is a review on the perioperative period in COVID-19 patients who were preoperatively asymptomatic and not tested for COVID-19. Searches were conducted in PubMed April 4th, 2020. All publications, of any design, were considered for inclusion. RESULTS: Four reports were identified through our literature search, comprising 64 COVID-19 carriers, of them 51 were diagnosed only in the postoperative period. Synthesis of these reports, concerning the postoperative outcomes of patients diagnosed with COVID-19 during the perioperative period, suggested a 14/51 (27.5%) postoperative mortality rate and severe mostly pulmonic complications, as well as medical staff exposure and transmission. CONCLUSIONS: COVID-19 may have potential hazardous implications on the perioperative course. Our review presents results of unacceptable mortality rate and a high rate of severe complications. These observations warrant further well-designed studies, yet we believe it is time for a global consideration of sampling all asymptomatic patients before surgical treatment.

negative: COVID-19 pandemic in the African continent: forecasts of cumulative cases, new infections, and mortality Background: Africa is the last major region to capitulate to the SARS-CoV-2 (COVID-19) pandemic. The first confirmed COVID-19 case in the region was reported on February 14, but what lies ahead in terms of the course and magnitude of infection remains speculative. To the best of our knowledge, no study, using a robust methodology, provides the immediate and long-term trajectory of COVID-19 for the entire region or accounts for its local context. This paper is the first systematic attempt to provide estimates on how many people would contract the virus and how many would die in the coming few months across Africa. Methods: The forecasts on caseloads and incidences are from a co-variate-based instrumental variable regression model. Fatality rates from Italy and China were further applied to generate mortality estimates after adjustments were made for differences in age-structure, health service quality, and living standards between each of the African countries and those of the reference population. We cover all countries that reported a confirmed case as of March 31, 2020. Results: By the end of June, 16,283,085 people will contract COVID-19 (95% CI 718,403 to 98, 358, 799). With a cumulative caseload of 5,413,4517 (95% CI 1,332,953 to 8,489,940) and 906,625 (95% CI 173, 821 to 4,742,917) Northern and Eastern Africa will respectively be the most and least affected sub-regions in the continent. Cumulative COVID-19 cases on June 30, 2020 are expected to reach 2,912, 864 (95% CI 465,028 to 18,286,358) in Southern Africa, 2,787, 913 (95% CI 517, 489 to 15,056,314) in Western Africa, and 1,185,742 (95% CI 229, 111 to 6,138,692) in Central Africa. New infections (incidence) for the month of April are expected to be the highest in Djibouti, 32.8 per 1000 (95% CI 6.25 to 171.77), while Morocco 1045 (95% CI 167 to 6,547) will register the highest number of deaths. Conclusion: Our study shows that countries that are least urbanized and have a low level of socio-economic development, hence least connected to the outside world, are likely to register lower and slower transmissions, at least at the early stage of the epidemic. However, the same set of enabling factors that worked for their benefit are likely to go against them in implementing interventions that have lessened the impact of the disease elsewhere.

negative: Distribution of Patients at Risk for Complications Related to COVID-19 in the United States: Model Development Study BACKGROUND: Coronavirus disease (COVID-19) has spread exponentially across the United States. Older adults with underlying health conditions are at an especially high risk of developing life-threatening complications if infected. Most intensive care unit (ICU) admissions and non-ICU hospitalizations have been among patients with at least one underlying health condition. OBJECTIVE: The aim of this study was to develop a model to estimate the risk status of the patients of a nationwide pharmacy chain in the United States, and to identify the geographic distribution of patients who have the highest risk of severe COVID-19 complications. METHODS: A risk model was developed using a training test split approach to identify patients who are at high risk of developing serious complications from COVID-19. Adult patients (aged ≥18 years) were identified from the Walgreens pharmacy electronic data warehouse. Patients were considered eligible to contribute data to the model if they had at least one prescription filled at a Walgreens location between October 27, 2019, and March 25, 2020. Risk parameters included age, whether the patient is being treated for a serious or chronic condition, and urban density classification. Parameters were differentially weighted based on their association with severe complications, as reported in earlier cases. An at-risk rate per 1000 people was calculated at the county level, and ArcMap was used to depict the rate of patients at high risk for severe complications from COVID-19. Real-time COVID-19 cases captured by the Johns Hopkins University Center for Systems Science and Engineering (CSSE) were layered in the risk map to show where cases exist relative to the high-risk populations. RESULTS: Of the 30,100,826 adults included in this study, the average age is 50 years, 15% have at least one specialty medication, and the average patient has 2 to 3 comorbidities. Nearly 28% of patients have the greatest risk score, and an additional 34.64% of patients are considered high-risk, with scores ranging from 8 to 10. Age accounts for 53% of a patient’s total risk, followed by the number of comorbidities (29%); inferred chronic obstructive pulmonary disease, hypertension, or diabetes (15%); and urban density classification (5%). CONCLUSIONS: This risk model utilizes data from approximately 10% of the US population. Currently, this is the most comprehensive US model to estimate and depict the county-level prognosis of COVID-19 infection. This study shows that there are counties across the United States whose residents are at high risk of developing severe complications from COVID-19. Our county-level risk estimates may be used alongside other data sets to improve the accuracy of anticipated health care resource needs. The interactive map can also aid in proactive planning and preparations among employers that are deemed critical, such as pharmacies and grocery stores, to prevent the spread of COVID-19 within their facilities.

negative: Age-dependent effects in the transmission and control of COVID-19 epidemics The COVID-19 pandemic has shown a markedly low proportion of cases among children1-4. Age disparities in observed cases could be explained by children having lower susceptibility to infection, lower propensity to show clinical symptoms or both. We evaluate these possibilities by fitting an age-structured mathematical model to epidemic data from China, Italy, Japan, Singapore, Canada and South Korea. We estimate that susceptibility to infection in individuals under 20 years of age is approximately half that of adults aged over 20 years, and that clinical symptoms manifest in 21% (95% credible interval: 12-31%) of infections in 10- to 19-year-olds, rising to 69% (57-82%) of infections in people aged over 70 years. Accordingly, we find that interventions aimed at children might have a relatively small impact on reducing SARS-CoV-2 transmission, particularly if the transmissibility of subclinical infections is low. Our age-specific clinical fraction and susceptibility estimates have implications for the expected global burden of COVID-19, as a result of demographic differences across settings. In countries with younger population structures-such as many low-income countries-the expected per capita incidence of clinical cases would be lower than in countries with older population structures, although it is likely that comorbidities in low-income countries will also influence disease severity. Without effective control measures, regions with relatively older populations could see disproportionally more cases of COVID-19, particularly in the later stages of an unmitigated epidemic.

negative: Partially latent class models for case–control studies of childhood pneumonia aetiology In population studies on the aetiology of disease, one goal is the estimation of the fraction of cases that are attributable to each of several causes. For example, pneumonia is a clinical diagnosis of lung infection that may be caused by viral, bacterial, fungal or other pathogens. The study of pneumonia aetiology is challenging because directly sampling from the lung to identify the aetiologic pathogen is not standard clinical practice in most settings. Instead, measurements from multiple peripheral specimens are made. The paper introduces the statistical methodology designed for estimating the population aetiology distribution and the individual aetiology probabilities in the Pneumonia Etiology Research for Child Health study of 9500 children for seven sites around the world. We formulate the scientific problem in statistical terms as estimating the mixing weights and latent class indicators under a partially latent class model (PLCM) that combines heterogeneous measurements with different error rates obtained from a case–control study. We introduce the PLCM as an extension of the latent class model. We also introduce graphical displays of the population data and inferred latent class frequencies. The methods are tested with simulated data, and then applied to Pneumonia Etiology Research for Child Health data. The paper closes with a brief description of extensions of the PLCM to the regression setting and to the case where conditional independence between the measures is relaxed.

negative: Asthma exacerbations: Origin, effect, and prevention Asthma is the most common chronic respiratory disease, affecting up to 10% of adults and 30% of children in the Western world. Despite advances in asthma management, acute exacerbations continue to occur and impose considerable morbidity on patients and constitute a major burden on health care resources. Respiratory tract viruses have emerged as the most frequent triggers for exacerbations in both children and adults; however, the mechanisms underlying these remain poorly understood. More recently, it has become increasingly clear that interactions might exist between viruses and other triggers, increasing the likelihood of an exacerbation. In this article we begin with an overview of the health, economic, and social burden that exacerbations of asthma carry with them. This is followed by a review of the pathogenesis of asthma exacerbations, highlighting the various triggers responsible and multiple interactions that exist between them. The final section first addresses what preventative measures are currently available for asthma exacerbations and subsequently examines which of the new treatments in development might lessen the burden of exacerbations in the future.

negative: COVID-19 and Neonatal Respiratory Care: Current Evidence and Practical Approach The novel coronavirus disease 2019 (COVID-19) pandemic has urged the development and implementation of guidelines and protocols on diagnosis, management, infection control strategies, and discharge planning. However, very little is currently known about neonatal COVID-19 and severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infections. Thus, many questions arise with regard to respiratory care after birth, necessary protection to health care workers (HCW) in the delivery room and neonatal intensive care unit (NICU), and safety of bag and mask ventilation, noninvasive respiratory support, deep suctioning, endotracheal intubation, and mechanical ventilation. Indeed, these questions have created tremendous confusion amongst neonatal HCW. In this manuscript, we comprehensively reviewed the current evidence regarding COVID-19 perinatal transmission, respiratory outcomes of neonates born to mothers with COVID-19 and infants with documented SARS-CoV-2 infection, and the evidence for using different respiratory support modalities and aerosol-generating procedures in this specific population. The results demonstrated that to date, neonatal COVID-19 infection is uncommon, generally acquired postnatally, and associated with favorable respiratory outcomes. The reason why infants display a milder spectrum of disease remains unclear. Nonetheless, the risk of severe or critical illness in young patients exists. Currently, the recommended respiratory approach for infants with suspected or confirmed infection is not evidence based but should include all routinely used types of support, with the addition of viral filters, proper personal protective equipment, and placement of infants in isolation rooms, ideally with negative pressure. As information is changing rapidly, clinicians should frequently watch out for updates on the subject. KEY POINTS: · Novel coronavirus disease 2019 (COVID-19) pandemic urged development of guidelines.. · Neonatal COVID-19 disease is uncommon.. · Respiratory outcomes in neonates seems favorable.. · Current neonatal respiratory care should continue.. · Clinicians should watch frequently for updates..

negative: Review article: COVID‐19 and liver disease—what we know on 1st May 2020 BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the causative pathogen of coronavirus disease 2019 (COVID‐19), became a global threat to human health. Liver impairment has been frequently reported as a common manifestation, although its clinical significance is still unclear, particularly in patients with underlying chronic liver disease (CLD). AIMS: To summarise the changes in liver function tests during SARS‐CoV‐2 infection and the impact of COVID‐19 in patients with underlying CLD. METHODS: A literature review using online database PubMed was done using the search terms “SARS‐CoV‐2”, “COVID‐19”, “liver”, “cirrhosis” and “liver transplantation”. RESULTS: COVID‐19 is frequently associated with different degrees of abnormal liver function tests, most notably transaminases, which are usually transitory and of mild degree. Available evidence suggests that liver injury may result from direct pathogenic effect by the virus, systemic inflammation or toxicity from commonly used drugs in this subset of patients. SARS‐CoV‐2 infection in children is associated with minimal or no increase in liver enzymes, thus the presence of abnormal liver function tests should trigger evaluation for underlying liver diseases. Although it seems that patients with CLD are not at greater risk for acquiring the infection, those with cirrhosis, hepatocellular carcinoma, non‐alcoholic fatty liver disease, autoimmune liver diseases or liver transplant may have a greater risk for severe COVID‐19. CONCLUSIONS: Abnormal liver function tests during the course of COVID‐19 are common, though clinically significant liver injury is rare. Further research is needed focusing on the effect of existing liver‐related comorbidities on treatment and outcome of COVID‐19.

negative: Human rhinoviruses, allergy, and asthma: a clinical approach. The prevalence of allergic diseases is increasing in Lithuania as in the world. The prevalence of allergic sensitization is often higher than 50% of the population. The "hygiene hypothesis" proposed that reduced immune-stimulation by infections may have resulted in the more widespread clinical expression of atopic disease. However, it alone does not provide an adequate explanation for the observed increase of allergic diseases. Human rhinovirus infections are the major infections with a worldwide distribution. Viral infections of the respiratory tract are the most common triggers of acute asthma exacerbations. These exacerbations are poorly responsive to current asthma therapies and new approaches to therapy are needed. The aim of this review is to present the current knowledge and clinical implications of human rhinovirus infection in allergy and asthma development and needs for further research. Recent evidence has shown that the immune responses to human rhinoviruses differ between asthmatic and nonasthmatic subjects. Novel insights into the mechanisms of virus-induced asthma exacerbations support the possibility that viral infections may be involved in the epithelial cells damage, inflammation, and airway hyperresponsiveness as well as in profibrotic response and induction of airway remodeling. The data of original investigations support the concept that the immune stimulation by rhinovirus infections contributes to the development of asthma, when an atopic host is infected with human rhinoviruses. Early rhinoviral wheezing is the predictor of subsequent asthma development in high-risk children. Synergistic effect of allergic sensitization, allergen exposure, and viral infection was suggested in the increased risk of hospitalization for asthma in both children and adults. Timing of allergen exposure may be important in a synergistic outcome. The increased susceptibility to rhinovirus infections was identified in atopic asthma. This review also presents the current options on the treatment and prevention of virus-induced asthma. Further studies are needed in order to differentiate between the response to viruses of healthy and atopic or nonatopic asthmatic children and adults. New research data may lead to novel strategies in treatment and prevention of asthma exacerbations as well as prevention of asthma induction.

negative: Covid-19: accelerating recovery Covid-19 infections and related illness and death are rightly at the forefront of our minds. It is critical that we consider how to reduce infections, treat those who are ill and protect health systems. We must, however, also consider how the pandemic is affecting the families of those infected, and how interventions to prevent the spread of the virus come with large negative economic and social consequences. We must begin to identify the ways in which we can soften these blows and recover from the negative consequences over the medium and long-term. We highlight here the importance of moving away the tendency to search for interventions to improve one outcome at a time. It will be essential, particularly in highly resource constrained settings, to look for accelerators, interventions which improve multiple outcomes simultaneously. We discuss how this will be especially important for groups who are at particular risk at this time, including of long-term negative outcomes. These include very young children, adolescents and those who have limited capacity to benefit from narrow interventions given critical needs in multiple domains. Searching for accelerators requires that we take a step back and look to identify common causes of negative outcomes and consider how we might address them. For many countries, recovery from this epidemic will be highly constrained by the limited availability of financial resources. Wise investments will be especially important at this time.

negative: Asthma and the Coronavirus Disease 2019 Pandemic: A Literature Review Even though respiratory viruses are one of the most common triggers for asthma exacerbations, not all of these viruses affect patients equally. There is no strong evidence supporting that patients with asthma have a higher risk of becoming seriously ill from coronavirus disease 2019 (COVID-19), although recent reports from the USA and the UK suggest that asthma is much more common in children and adults with mild to severe COVID-19 than has previously been reported in Asia and in Europe. As in previous severe acute respiratory syndrome (SARS) outbreaks, patients with asthma, especially children, appear to be less susceptible to the coronavirus with a low rate of asthma exacerbations. A different expression of viral receptors and T2 inflammation can be responsible for different outcomes. Future studies focused on asthma and on other allergic disorders are needed to provide a greater understanding of the impact of underlying asthma and allergic inflammation on COVID-19 susceptibility and disease severity. However, for the moment, it is crucial that asthmatic patients maintain their controller medication, from inhaled corticosteroids to biologics, without making any dose adjustments on their own or stopping the medication. New data are emerging daily, rapidly updating our understanding of this novel coronavirus.

negative: Association between intake of non-sugar sweeteners and health outcomes: systematic review and meta-analyses of randomised and non-randomised controlled trials and observational studies. OBJECTIVE To assess the association between intake of non-sugar sweeteners (NSS) and important health outcomes in generally healthy or overweight/obese adults and children. DESIGN Systematic review following standard Cochrane review methodology. DATA SOURCES Medline (Ovid), Embase, Cochrane CENTRAL, WHO International Clinical Trials Registry Platform, Clinicaltrials.gov, and reference lists of relevant publications. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Studies including generally healthy adults or children with or without overweight or obesity were eligible. Included study designs allowed for a direct comparison of no intake or lower intake of NSS with higher NSS intake. NSSs had to be clearly named, the dose had to be within the acceptable daily intake, and the intervention duration had to be at least seven days. MAIN OUTCOME MEASURES Body weight or body mass index, glycaemic control, oral health, eating behaviour, preference for sweet taste, cancer, cardiovascular disease, kidney disease, mood, behaviour, neurocognition, and adverse effects. RESULTS The search resulted in 13 941 unique records. Of 56 individual studies that provided data for this review, 35 were observational studies. In adults, evidence of very low and low certainty from a limited number of small studies indicated a small beneficial effect of NSSs on body mass index (mean difference -0.6, 95% confidence interval -1.19 to -0.01; two studies, n=174) and fasting blood glucose (-0.16 mmol/L, -0.26 to -0.06; two, n=52). Lower doses of NSSs were associated with lower weight gain (-0.09 kg, -0.13 to -0.05; one, n=17 934) compared with higher doses of NSSs (very low certainty of evidence). For all other outcomes, no differences were detected between the use and non-use of NSSs, or between different doses of NSSs. No evidence of any effect of NSSs was seen on overweight or obese adults or children actively trying to lose weight (very low to moderate certainty). In children, a smaller increase in body mass index z score was observed with NSS intake compared with sugar intake (-0.15, -0.17 to -0.12; two, n=528, moderate certainty of evidence), but no significant differences were observed in body weight (-0.60 kg, -1.33 to 0.14; two, n=467, low certainty of evidence), or between different doses of NSSs (very low to moderate certainty). CONCLUSIONS Most health outcomes did not seem to have differences between the NSS exposed and unexposed groups. Of the few studies identified for each outcome, most had few participants, were of short duration, and their methodological and reporting quality was limited; therefore, confidence in the reported results is limited. Future studies should assess the effects of NSSs with an appropriate intervention duration. Detailed descriptions of interventions, comparators, and outcomes should be included in all reports. SYSTEMATIC REVIEW REGISTRATION Prospero CRD42017047668.

negative: Breastfeeding during the COVID-19 pandemic: Suggestions on behalf of woman study group of AMD SARS-Cov2 infection has recently spread to Italy with important consequences on pregnancy management, mother and child health and mother-child contact. Breastfeeding improves the health of mother and child and reduces risk of neonatal infection with other pathogens that are likely to cause serious illness. To date no evidence confirmed COVID-19 vertical transmission from infected pregnant mother to their fetus. However it is well known that an infected mother can transmit the COVID-19 virus through respiratory droplets during breastfeeding or intimate contact. Thus, the mothers with known or suspected COVID-19 should adhere to standard and contact precautions during breastfeeding. Woman Study Group of AMD, after reviewing current knowledge about COVID-19 vertical transmission and the compatibility of breastfeeding in COVID-19 mother, the available recommendations from Health Care Organizations and main experts opinions, issued the following suggestions on breastfeeding during the COVID-19 pandemic, addressed both to mothers with and without diabetes. It should be considered that following suggestions may change in the future when more evidence is acquired regarding SARS-Cov2 infection.

negative: 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.

negative: Neonatal Resuscitation Where the Mother Has a Suspected or Confirmed Novel Coronavirus (SARS-CoV-2) Infection: Suggestion for a Pragmatic Action Plan Coronavirus disease 2019 (COVID-19), caused by the novel SARS-CoV-2 virus, is rapidly spreading across the world. As the number of infections increases, those of infected pregnant women and children will rise as well. Controversy exists whether COVID-19 can be transmitted in utero and lead to disease in the newborn. As this chance cannot be ruled out, strict instructions for the management of mothers and newborn infants are mandatory. This perspective aims to be a practical support tool for the planning of delivery and neonatal resuscitation of infants born by mothers with suspected or confirmed COVID-19 infection.

negative: Where do we go from here? A child rights-based response to COVID-19

negative: Metrics of early childhood growth in recent epidemiological research: A scoping review. Metrics to quantify child growth vary across studies of the developmental origins of health and disease. We conducted a scoping review of child growth studies in which length/height, weight or body mass index (BMI) was measured at ≥ 2 time points. From a 10% random sample of eligible studies published between Jan 2010-Jun 2016, and all eligible studies from Oct 2015-June 2016, we classified growth metrics based on author-assigned labels (e.g., 'weight gain') and a 'content signature', a numeric code that summarized the metric's conceptual and statistical properties. Heterogeneity was assessed by the number of unique content signatures, and label-to-content concordance. In 122 studies, we found 40 unique metrics of childhood growth. The most common approach to quantifying growth in length, weight or BMI was the calculation of each child's change in z-score. Label-to-content discordance was common due to distinct content signatures carrying the same label, and because of instances in which the same content signature was assigned multiple different labels. In conclusion, the numerous distinct growth metrics and the lack of specificity in the application of metric labels challenge the integration of data and inferences from studies investigating the determinants or consequences of variations in childhood growth.

negative: SARS-CoV-2: The Path of Prevention and Control. The 2019 coronavirus pandemic (COVID-19) continues to expand worldwide. Although the number of cases and the death rate among children and adolescents are reported to be low compared to adults, limited data have been reported. We urgently need to find treatment and vaccine to stop the epidemic. Vaccine development is in progress, but any approved and effective vaccine for COVID-19 is at least 12 to 18 months. The World Health Organization (WHO), the Center for Disease Control and Prevention (CDC), and the Food and Agriculture Organization (FAO) have issued instructions and strategies for containing COVID-19 outbreak to the general public, physicians, travelers and injured patients to follow so that the transmission to a healthy population can be prevented. In this review, we summarize demographic data, clinical characteristics, complications and outcomes and finally prevention and control of this serious pandemic.

negative: The implications of COVID-19 for the children of Africa

negative: European and United Kingdom COVID-19 Pandemic Experience: The same but different The global healthcare landscape has changed dramatically and rapidly in 2020. This has had an impact upon paediatricians and in particular respiratory paediatricians. The effects in Europe, with its mature healthcare system, have been far faster and greater than most authorities anticipated. Within six weeks of COVID-19 being declared a public health emergency by the World Health Organisation [WHO] in China, Europe had become the new epicentre of disease. A pandemic was finally declared by the WHO on March 11th 2020. Continued international travel combined with the slow response of some political leaders and a variable focus on economic rather than health consequences resulted in varying containment strategies in response to the threat of the initial wave of the pandemic. It is likely that this variation has contributed to widely differing outcomes across Europe. Common to all countries was the stark lack of preparations and initially poor co-ordination of responses between levels of government to this unforeseen but not unheralded global health crisis. In this article we highlight the impact of the first wave of the COVID-19 pandemic in Italy, Austria, Germany, and the United Kingdom.

negative: Psychometric Testing of Three COVID-19-Related Scales Among People with Mental Illness Fear of novel coronavirus 2019 (COVID-19) may result in psychological health problems among different populations. Moreover, believing COVID-19 information and preventive COVID-19 infection behaviors are relevant constructs associated with fear of COVID-19. Therefore, the present study validated three instruments assessing fear, beliefs, and preventive behaviors related to COVID-19 among individuals with mental illness. Moreover, relationships between the three constructs were examined. Individuals with mental illness (N = 400; 178 females; mean age = 46.91 years) completed the Fear of COVID-19 Scale (FCV-19S), Believing COVID-19 Information Scale (BCIS), Preventive COVID-19 Infection Behaviors Scale (PCIBS), and Depression Anxiety Stress Scale-21 (DASS-21). The FCV-19S, BCIS, and PCIBS demonstrated a single-factor structure with satisfactory fit indices. Moreover, believing COVID-19 information positively and significantly associated with fear of COVID-19, and fear of COVID-19 negatively and significantly associated with preventive behaviors and positively and significantly associated with psychological distress. The FCV-19S, BCIS, and PCIBS may assist healthcare providers in assessing COVID-19-related information among individuals with mental illness. Consequently, relevant programs may be designed to help individuals with mental illness going through the period of crisis.

negative: A score-based risk model for predicting severe COVID-19 infection as a key component of lockdown exit strategy Background: As many countries consider and employ various lockdown exit strategies, health authorities seek tools to provide differential targeted advice for social distancing based on personal risk for severe COVID-19. However, striking a balance between a scientifically precise multivariable risk prediction model, and a model which can easily be used by the general public, remains a challenge. A list of risk criteria, as defined by the CDC for example, provides a simple solution, but may be too inclusive by classifying a substantial portion of the population at high risk. Score-based risk classification tools may provide a good compromise between accuracy and simplicity. Objective: To create a score-based risk classification tool for severe COVID-19. Methods: The outcome was defined as a composite of being labeled severe during hospitalization or dying due to COVID-19. The risk classification tool was developed using retrospective data from all COVID-19 patients that were diagnosed until April 1st, 2020 in a large healthcare organization ("training set"). The developed tool combines 10 risk factors using simple summation, and defines three risk levels according to the patient's age and number of accumulated risk points - basic risk, high risk and very-high risk (the last two levels are also considered together as the elevated risk group). The tool's performance in accurately identifying individuals at risk was evaluated using a "temporal test set" of COVID-19 patients diagnosed between April 2nd and April 22nd, 2020, later than those used for model development. The tool's performance was also compared to that of the CDC's criteria. The healthcare organization's general population was used to evaluate the proportion of patients that would be classified to each of the model's risk levels and as elevated risk by the CDC criteria. Results: A total of 2,421, 2,624 and 4,631,168 individuals were included in the training, test, and general population cohorts, respectively. The outcome rate in the training and test sets was 5%. Overall, 18% of the general population would be classified at elevated risk by the model, with a resulting sensitivity of 92%, compared to 35% that would be defined as elevated risk by the CDC criteria, with a resulting sensitivity of 96%. Within the model's elevated risk groups, the high and very-high risk groups comprised 15% and 3% of the general population, with an incidence rate (PPV) of 15% and 33%, respectively. Discussion: A simple to communicate score-based risk classification tool classifies at elevated risk about half of the population that is considered to have an elevated risk by the CDC risk criteria, with only a 4% reduction in sensitivity. The model's ability to further divide the elevated risk population into two markedly different subgroups allows providing more refined recommendations to the general public and limiting the restrictions of social distancing to a smaller and more manageable subset of the population. This model was adopted by the Israeli ministry of health as its risk classification tool for COVID-19 lab tests prioritization and for targeting its instructions on risk management during the lockdown exit strategy.

negative: The COVID‐19 pandemic: A rapid global response for children with cancer from SIOP, COG, SIOP‐E, SIOP‐PODC, IPSO, PROS, CCI, and St Jude Global The COVID‐19 pandemic is one of the most serious global challenges to delivering affordable and equitable treatment to children with cancer we have witnessed in the last few decades. This Special Report aims to summarize general principles for continuing multidisciplinary care during the SARS‐CoV‐2 (COVID‐19) pandemic. With contributions from the leadership of the International Society for Pediatric Oncology (SIOP), Children's Oncology Group (COG), St Jude Global program, and Childhood Cancer International, we have sought to provide a framework for healthcare teams caring for children with cancer during the pandemic. We anticipate the burden will fall particularly heavily on children, their families, and cancer services in low‐ and middle‐income countries. Therefore, we have brought together the relevant clinical leads from SIOP Europe, COG, and SIOP‐PODC (Pediatric Oncology in Developing Countries) to focus on the six most curable cancers that are part of the WHO Global Initiative in Childhood Cancer. We provide some practical advice for adapting diagnostic and treatment protocols for children with cancer during the pandemic, the measures taken to contain it (e.g., extreme social distancing), and how to prepare for the anticipated recovery period.

negative: The Association Between Adverse Child Health, Psychological, Educational and Social Outcomes, and Nondependent Parental Substance: A Rapid Evidence Assessment BACKGROUND: Between 5% and 30% of children in high-income countries live with a substance misusing parent, the majority of which is below dependent levels. However, little is understood about the impact of nondependent parental substance misuse upon children. METHODS: We searched the international literature using rigorous systematic methods to identify studies examining parental substance misuse and adverse outcomes in children. The inclusion criteria were cross-sectional, longitudinal, case-control, and cohort studies; of children aged 0–18 years whose parents are high-risk substance misusers; reporting on their health, psychological, substance use, educational, and social outcomes. RESULTS: We identified 36 papers (from 33 unique studies), most of which were assessed as being of medium to high methodological quality (N= 28). Parental nondependent substance misuse was found to be associated with adversity in children, with strong evidence of an association with externalizing difficulties (N = 7 papers, all finding an association) and substance use (N = 23 papers, all finding an association) in adolescents and some evidence of adverse health outcomes in early childhood (N = 6/8 papers finding an association). There is less evidence of an association between parental substance misuse and adverse educational and social outcomes. The body of evidence was largest for parental alcohol misuse, with research examining the impact of parental illicit drug use being limited. CONCLUSION: Methodological limitations restrict our ability to make causal inference. Nonetheless, the prevalence of adverse outcomes in children whose parents are nondependent substance misusers highlights the need for practitioners to intervene with this population before a parent has developed substance dependency.

negative: Childhood severe acute respiratory syndrome, coronavirus infections and asthma Severe acute respiratory syndrome (SARS) is a new infectious disease caused by a novel coronavirus. Children appear to be less susceptible to the SARS coronavirus, although the other non‐SARS coronaviruses can cause respiratory infections in adults and in children of all ages. The exact reasons as to why SARS preferentially affects adults, and not children, are still unknown. Many hypotheses exist and need to be explored. During the outbreak of SARS, there did not appear to be an increase in asthma exacerbations in children.

negative: Sex differences in immune responses to SARS-CoV-2 that underlie disease outcomes A growing body of evidence indicates sex differences in the clinical outcomes of coronavirus disease 2019 (COVID-19)(1–4). However, whether immune responses against SARS-CoV-2 differ between sexes, and whether such differences explain male susceptibility to COVID-19, is currently unknown. In this study, we examined sex differences in viral loads, SARS-CoV-2-specific antibody titers, plasma cytokines, as well as blood cell phenotyping in COVID-19 patients. By focusing our analysis on patients with mild to moderate disease who had not received immunomodulatory medications, our results revealed that male patients had higher plasma levels of innate immune cytokines and chemokines including IL-8, IL-18, and CCL5, along with more robust induction of non-classical monocytes. In contrast, female patients mounted significantly more robust T cell activation than male patients during SARS-CoV-2 infection, which was sustained in old age. Importantly, we found that a poor T cell response negatively correlated with patients’ age and was predictive of worse disease outcome in male patients, but not in female patients. Conversely, higher innate immune cytokines in female patients associated with worse disease progression, but not in male patients. These findings reveal a possible explanation underlying observed sex biases in COVID-19, and provide important basis for the development of sex-based approach to the treatment and care of men and women with COVID-19.

negative: Coronavirus et COVID-19 : le point sur une pandémie galopante./ [Coronavirus and COVID-19 : focus on a galopping pandemic] The international community is currently facing a pandemic of acute respiratory syndrome caused by a new coronavirus, SARS-CoV-2. This syndrome has been named COVID-19 for CoronaVIrus Disease 2019 by the World Health Organization. The starting point of the epidemic is the city of Wuhan (China), where the virus is said to have been transmitted from animals to humans before inter-human transmission. This is the third epidemic caused by a coronavirus after those of severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) started in 2012. COVID-19 has rapidly spread to China and is currently spreading all over the world. The infection mainly affects patients over 40 years of age and mortality is increased in the presence of comorbidities. Children are pauci- or asymptomatic. The diagnosis is most often based on the detection of the viral genome in the nasopharynx by molecular biology methods. In the absence of specific anti-viral molecules, treatment is currently mainly symptomatic. It is clear that the COVID-19 pandemic is more difficult to control than what the first data suggested. The key strategy to SARS-CoV-2 is to limit its transmission. Preventive measures are mainly based on the application of adequate hand hygiene measures and disinfection of the environment, as well as measures of social distance aimed at limiting contacts in the population and protecting populations at risk.

negative: Psychological Outcomes Associated with Stay-at-Home Orders and the Perceived Impact of COVID-19 on Daily Life The COVID-19 pandemic has resulted in the widespread implementation of extraordinary physical distancing interventions (e.g., stay-at-home orders) to slow the spread of the virus. Although vital, these interventions may be socially and economically disruptive, contributing to adverse psychological outcomes. This study examined relations of both stay-at-home orders and the perceived impact of COVID-19 on daily life to psychological outcomes (depression, health anxiety, financial worry, social support, and loneliness) in a nationwide U.S. community adult sample (N = 500; 47% women, mean age = 40). Participants completed questionnaires assessing psychological outcomes, stay-at-home order status, and COVID-19’s impact on their daily life. Being under a stay-at-home order was associated with greater health anxiety, financial worry, and loneliness. Moreover, the perceived impact of COVID-19 on daily life was positively associated with health anxiety, financial worry, and social support, but negatively associated with loneliness. Findings highlight the importance of social connection to mitigate negative psychological consequences of the COVID-19 pandemic.

negative: Perinatal aspects on the covid-19 pandemic: a practical resource for perinatal–neonatal specialists BACKGROUND: Little is known about the perinatal aspects of COVID-19. OBJECTIVE: To summarize available evidence and provide perinatologists/neonatologists with tools for managing their patients. METHODS: Analysis of available literature on COVID-19 using Medline and Google scholar. RESULTS: From scant data: vertical transmission from maternal infection during the third trimester probably does not occur or likely it occurs very rarely. Consequences of COVID-19 infection among women during early pregnancy remain unknown. We cannot conclude if pregnancy is a risk factor for more severe disease in women with COVID-19. Little is known about disease severity in neonates, and from very few samples, the presence of SARS-CoV-2 has not been documented in human milk. Links to websites of organizations with updated COVID-19 information are provided. Infographics summarize an approach to the pregnant woman or neonate with suspected or confirmed COVID-19. CONCLUSIONS: As the pandemic continues, more data will be available that could lead to changes in current knowledge and recommendations.

negative: Malnutrition Care during the COVID-19 Pandemic: Considerations for Registered Dietitian Nutritionists Evidence Analysis Center Abstract Recent evidence examining adults infected with COVID-19 has indicated a significant impact of malnutrition on health outcomes. Individuals who have multiple comorbidities, are older adults, or who are malnourished are at increased risk of being admitted to the intensive care unit and of mortality from COVID-19 infections. Hence, nutrition care to identify and address malnutrition is critical in treating and preventing further adverse health outcomes from COVID-19 infection. This document provides guidance and practice considerations for Registered Dietitian Nutritionists (RDNs) providing nutrition care for adults with suspected or confirmed COVID-19 infection in the hospital, outpatient, or homecare settings. In addition, this document discusses and provides considerations for RDNs working with individuals at risk of malnutrition secondary to food insecurity during the COVID-19 pandemic.

negative: A systematic review of pharmacological therapies and their effectiveness on health-related quality of life outcomes in patients with juvenile-onset systemic lupus erythematosus. Juvenile-onset systemic lupus erythematosus (JSLE) presents with an aggressive course and high morbidity associated with disease and treatment. JSLE patients have a poorer health-related quality of life (HRQoL) when compared with age-matched patients with other rheumatologic disorders. We aim to summarize the impact of current pharmacological therapies on the HRQoL of JSLE patients. Search strategies were developed across seven databases. Randomized clinical trials (RCTs) and cohort studies comparing interventions to standard therapy, placebo or pre-post cohort comparisons for more than 4 weeks were included. The outcome included self-reported scales compared at baseline and a therapeutic time point. Risk of bias was evaluated by using the Cochrane risk of bias tool and the Newcastle-Ottawa quality assessment scale. A total of 2812 articles were narrowed down to 309 for full-text screening. Four RCTs and one prospective cohort study, with a total of 634 JSLE patients, met the inclusion criteria. Four of the studies had a controlled intervention plus standard therapy compared with standard therapy alone or placebo. Multiple indices were used to evaluate HRQoL. These included the Pediatric Quality of Life Inventory, Childhood Health Assessment Questionnaire, Simple Measure of Impact of Lupus Erythematosus in Youngsters tool, Kids Fatigue Severity Scale and Child Depression Inventory. A single study reported a significant improvement while remaining studies reported no difference or failed to report the statistical analysis. Although HRQoL is significantly impaired in JSLE, evidence regarding its improvement is limited due to the small number of eligible studies, heterogeneity in scales, and HRQoL domains. A universal HRQoL questionnaire for JSLE needs to be established and used in both the research and clinical setting. All studies should adhere to reporting guidelines.

negative: Inequality in acute respiratory infection outcomes in the United States: A review of the literature and its implications for public health policy and practice. Seasonal and pandemic respiratory viruses such as influenza and the novel coronavirus (SARS-COV-2) currently sweeping the globe have often been described as 'equal opportunity infectors', implying little socioeconomic disparity in susceptibility. However, early data from the COVID-19 pandemic has underscored that the burden of respiratory viruses actually reflect and magnify existing socioeconomic inequalities. We review the literature on socioeconomic and racial disparities in acute respiratory infection (ARI), as well as ARI-associated hospitalization and mortality. Our goal is to identify key principles of the relationship between socioeconomic inequality and ARI outcomes, as well as highlighting poorly understood areas that need to be addressed by research and policy in the wake of the COVID-19 pandemic. We find that there has been descriptive work in this area, but that there is a distinct lack of cohesive methodology in the literature exploring social determinants and ARI. We propose the fundamental cause theory is a useful framework for guiding future research of disparities in ARI and for the design of interventions to alleviate these disparities.

negative: Severe influenza among children and young adults with neurologic and neurodevelopmental conditions - Ohio, 2011. Children with neurologic and neurodevelopmental conditions are at increased risk for severe outcomes from influenza, including death. In April 2011, the Ohio Department of Health and CDC investigated an influenza outbreak that began in February 2011 in a residential facility for 130 children and young adults with neurologic and neurodevelopmental conditions. This report summarizes the characteristics and clinical courses of 13 severely ill residents with suspected or confirmed influenza; 10 were hospitalized, and seven died. Diagnosis is challenging in this population, and clinicians should consider influenza in patients with neurologic and neurodevelopmental conditions who have respiratory illness or a decline in baseline medical status when influenza is circulating in the community. Prompt testing, early and aggressive antiviral treatment, and antiviral chemoprophylaxis are important for these patients. When influenza is suspected, antiviral treatment should be given as soon as possible after symptom onset, ideally within 48 hours. Treatment should not wait for laboratory confirmation of influenza. During outbreaks, antiviral chemoprophylaxis should be provided to all residents of institutional facilities (e.g., nursing homes and long-term- care facilities), regardless of vaccination status. Residential facilities for patients with neurologic and neurodevelopmental conditions are encouraged to vaccinate all eligible residents and staff members against influenza.

negative: Safeguarding children with long-term conditions from COVID-19 Professor Alan Glasper, from the University of Southampton, discusses strategies to protect children with long-term health conditions from acquiring the disease caused by the SARS-CoV-2 virus.

negative: Effect of COVID-19 Pandemic and Lockdown on Children With Gastrointestinal Disorders

negative: Breastfeeding and coronavirus disease-2019: Ad interim indications of the Italian Society of Neonatology endorsed by the Union of European Neonatal & Perinatal Societies The recent COVID-19 pandemic has spread to Italy with heavy consequences on public health and economics. Besides the possible consequences of COVID-19 infection on a pregnant woman and the fetus, a major concern is related to the potential effect on neonatal outcome, the appropriate management of the mother-newborn dyad, and finally the compatibility of maternal COVID-19 infection with breastfeeding. The Italian Society on Neonatology (SIN) after reviewing the limited scientific knowledge on the compatibility of breastfeeding in the COVID-19 mother and the available statements from Health Care Organizations has issued the following indications that have been endorsed by the Union of European Neonatal & Perinatal Societies (UENPS). If a mother previously identified as COVID-19 positive or under investigation for COVID-19 is asymptomatic or paucisymptomatic at delivery, rooming-in is feasible, and direct breastfeeding is advisable, under strict measures of infection control. On the contrary, when a mother with COVID-19 is too sick to care for the newborn, the neonate will be managed separately and fed fresh expressed breast milk, with no need to pasteurize it, as human milk is not believed to be a vehicle of COVID-19. We recognize that this guidance might be subject to change in the future when further knowledge will be acquired about the COVID-19 pandemic, the perinatal transmission of SARS-CoV-2, and clinical characteristics of cases of neonatal COVID-19.

negative: [Attach importance to COVID-19 infection on maternal and infant outcomes]. 新型冠状病毒肺炎（COVID-19）是我国今冬突发的公共卫生事件，具有高度传染性的疾病。孕产妇作为一类特殊的人群，更成为感染防控的重点人群。基于现有的临床数据及研究资料，妊娠中晚期合并COVID-19感染孕妇的临床特征与非妊娠期成人患者相似，暂无证据表明COVID-19孕妇容易发展为重症肺炎或死亡。且尚未发现妊娠晚期新型冠状病毒感染可导致宫内垂直传播和乳汁传播的证据。后续的临床及科研工作中，应继续对妊娠合并COVID-19感染的临床病例进行收集、归纳和总结，并加强对COVID-19感染产妇及其新生儿的随访。.

negative: Comparing Chinese children and adults with RT-PCR positive COVID-19: A systematic review BACKGROUND: The various clinical manifestations of COVID-19 with RT-PCR positive patients have been reported. However, the differences in the clinical presentation between children and adults were unclear. Thus, we aimed to investigate the differences in the clinical manifestations and imaging characteristics between Chinese children and adults with COVID-19 by systematically analyzing the data derived from some latest literatures. METHODS: An extensive search of COVID-19 papers was conducted in PubMed and Chinese medical journal network, and relevant articles were selected based on some standard requirements. The included papers were analyzed for differences in clinical manifestation between children and adults with COVID-19 after the quality evaluation with the QUADAS-2 tool. The differences in the clinical features and CT findings were analyzed using a Pearson χ(2) test or Fisher's exact test. Patients who underwent CT examination were divided into the initial examination (0-4days) and follow-up examination groups (5-14 days). RESULTS: A total of 345patients (70 children and 275 adults) with RT- PCR (+) were included in our study (5 papers for children and 5 papers for adult groups). Significant differences between children and adults were found in exposure history ( p < 0.001, χ(2) = 166.890), fever ( p=,0.016, χ(2) = 5.757), white cell count ( p < 0.001, χ(2) = 14.043), and CT features in the initial ( p < 0.001, χ(2) = 60.653) and follow-up stages ( p < 0.001, χ(2) = 52.924); and the involved lung in the follow-up stage ( p＜0.001, χ(2) = 16.776). CONCLUSIONS: Some differences have been presented between children and adults with RT-PCR positive COVID-19, which are helpful in the management and protection of children with COVID-19.

negative: Projected geographic disparities in healthcare worker absenteeism from COVID-19 school closures and the economic feasibility of child care subsidies: a simulation study BACKGROUND: School closures have been enacted as a measure of mitigation during the ongoing coronavirus disease 2019 (COVID-19) pandemic. It has been shown that school closures could cause absenteeism among healthcare workers with dependent children, but there remains a need for spatially granular analyses of the relationship between school closures and healthcare worker absenteeism to inform local community preparedness. METHODS: We provide national- and county-level simulations of school closures and unmet child care needs across the USA. We develop individual simulations using county-level demographic and occupational data, and model school closure effectiveness with age-structured compartmental models. We perform multivariate quasi-Poisson ecological regressions to find associations between unmet child care needs and COVID-19 vulnerability factors. RESULTS: At the national level, we estimate the projected rate of unmet child care needs for healthcare worker households to range from 7.4 to 8.7%, and the effectiveness of school closures as a 7.6% and 8.4% reduction in fewer hospital and intensive care unit (ICU) beds, respectively, at peak demand when varying across initial reproduction number estimates by state. At the county level, we find substantial variations of projected unmet child care needs and school closure effects, 9.5% (interquartile range (IQR) 8.2–10.9%) of healthcare worker households and 5.2% (IQR 4.1–6.5%) and 6.8% (IQR 4.8–8.8%) reduction in fewer hospital and ICU beds, respectively, at peak demand. We find significant positive associations between estimated levels of unmet child care needs and diabetes prevalence, county rurality, and race (p<0.05). We estimate costs of absenteeism and child care and observe from our models that an estimated 76.3 to 96.8% of counties would find it less expensive to provide child care to all healthcare workers with children than to bear the costs of healthcare worker absenteeism during school closures. CONCLUSIONS: School closures are projected to reduce peak ICU and hospital demand, but could disrupt healthcare systems through absenteeism, especially in counties that are already particularly vulnerable to COVID-19. Child care subsidies could help circumvent the ostensible trade-off between school closures and healthcare worker absenteeism.

negative: Change in practice in gynecologic oncology during the COVID-19 pandemic: a social media survey OBJECTIVE: COVID-19 has affected gynecologic cancer management. The goal of this survey was to evaluate changes that occurred in gynecologic oncology practice during the COVID-19 pandemic. METHODS: A anonymous survey consisting of 33 questions (https://sites.google.com/view/gyncacovidfmartinelli) regarding interaction between gynecologic cancers and COVID-19 was distributed online via social media from April 9 to April 30, 2020. Basic descriptive statistics were applied. Analytics of survey-diffusion and generated-interest (visualizations, engagement rates, response rate) were analyzed. RESULTS: The survey received 20 836 visualizations, generating an average engagement rates by reach of 4.7%. The response rate was 30%. A total of 86% of respondents completed the survey, for a total of 187 physicians surveyed across 49 countries. The majority (143/187; 76%) were gynecologic oncologists, and most were ≤50 years old (146/187; 78%). A total of 49.7% (93/187) were facing the early phase of the COVID-19 pandemic, while 26.7% (50/187) and 23.5% (44/187) were in the peak and plateau phases, respectively. For 97.3% (182/187) of respondents COVID-19 affected or changed their respective clinical practice. Between 16% (27/165) (before surgery) and 25% (26/102) (before medical treatment) did not perform any tests to rule out COVID-19 infection among patients. The majority of respondents did not alter indications of treatment if patients were COVID-19-negative, while treatments were generally postponed in COVID-19-positive patients. Treatments were considered priority for: early stage high-risk uterine cancers (85/187; 45%), newly diagnosed epithelial ovarian cancer (76/187; 41%), and locally advanced cervical cancer (76/187; 41%). Treatment of early stage low-grade endometrioid endometrial cancer was deferred according to 49% (91/187) of respondents, with hormonal treatment as the option of therapy (31%; 56/178). A total of 77% (136/177) of respondents reported no changes in (surgical) treatment for early stage cervical cancer in COVID-19-negative patients, while treatment was postponed by 54% (96/177) of respondent, if the patient tested COVID-19-positive. Neoadjuvant chemotherapy for advanced ovarian cancers was considered by over one-third of respondents as well as hypofractionation of radiation treatment for locally advanced cervical cancers. CONCLUSION: COVID-19 affected the treatment of gynecologic cancers patients, both in terms of prioritization and identification of strategies to reduce hospital access and length of stay. Social media is a reliable tool to perform fast-tracking, worldwide surveys.

negative: Impact of the COVID-19 virus outbreak on movement and play behaviours of Canadian children and youth: a national survey BACKGROUND: Healthy childhood development is fostered through sufficient physical activity (PA; including time outdoors), limiting sedentary behaviours (SB), and adequate sleep; collectively known as movement behaviours. Though the COVID-19 virus outbreak has changed the daily lives of children and youth, it is unknown to what extent related restrictions may compromise the ability to play and meet movement behaviour recommendations. This secondary data analysis examined the immediate impacts of COVID-19 restrictions on movement and play behaviours in children and youth. METHODS: A national sample of Canadian parents (n = 1472) of children (5–11 years) or youth (12–17 years) (54% girls) completed an online survey that assessed immediate changes in child movement and play behaviours during the COVID-19 outbreak. Behaviours included PA and play, SB, and sleep. Family demographics and parental factors that may influence movement behaviours were assessed. Correlations between behaviours and demographic and parental factors were determined. For open-ended questions, word frequency distributions were reported. RESULTS: Only 4.8% (2.8% girls, 6.5% boys) of children and 0.6% (0.8% girls, 0.5% boys) of youth were meeting combined movement behaviour guidelines during COVID-19 restrictions. Children and youth had lower PA levels, less outside time, higher SB (including leisure screen time), and more sleep during the outbreak. Parental encouragement and support, parental engagement in PA, and family dog ownership were positively associated with healthy movement behaviours. Although families spent less time in PA and more time in SB, several parents reported adopting new hobbies or accessing new resources. CONCLUSIONS: This study provides evidence of immediate collateral consequences of the COVID-19 outbreak, demonstrating an adverse impact on the movement and play behaviours of Canadian children and youth. These findings can guide efforts to preserve and promote child health during the COVID-19 outbreak and crisis recovery period, and to inform strategies to mitigate potential harm during future pandemics.

negative: Deep-COVID: Predicting COVID-19 From Chest X-Ray Images Using Deep Transfer Learning The COVID-19 pandemic is causing a major outbreak in more than 150 countries around the world, having a severe impact on the health and life of many people globally. One of the crucial step in fighting COVID-19 is the ability to detect the infected patients early enough, and put them under special care. Detecting this disease from radiography and radiology images is perhaps one of the fastest way to diagnose the patients. Some of the early studies showed specific abnormalities in the chest radiograms of patients infected with COVID-19. Inspired by earlier works, we study the application of deep learning models to detect COVID-19 patients from their chest radiography images. We first prepare a dataset of 5,000 Chest X-rays from the publicly available datasets. Images exhibiting COVID-19 disease presence were identified by board-certified radiologist. Transfer learning on a subset of 2,000 radiograms was used to train four popular convolutional neural networks, including ResNet18, ResNet50, SqueezeNet, and DenseNet-121, to identify COVID-19 disease in the analyzed chest X-ray images. We evaluated these models on the remaining 3,000 images, and most of these networks achieved a sensitivity rate of 97\%($\pm$ 5\%), while having a specificity rate of around 90\%. While the achieved performance is very encouraging, further analysis is required on a larger set of COVID-19 images, to have a more reliable estimation of accuracy rates. Besides sensitivity and specificity rates, we also present the receiver operating characteristic (ROC), area under the curve (AUC), and confusion matrix of each model. The dataset, model implementations (in PyTorch), and evaluations, are all made publicly available for research community, here: https://github.com/shervinmin/DeepCovid.git

negative: An investigation of mental health status of children and adolescents in China during the outbreak of COVID-19 OBJECTIVE: : The sudden outbreak of Coronavirus Disease 2019 (COVID-19) has had a dramatic effect on the mental health of the public. In the present study, we demonstrated the psychological effects on children and adolescents associated with the epidemic . METHODS: : By using convenience sampling method, questionnaires, such as Spence Child Anxiety Scale, Child Depression Inventory and Coping style Scale, were distributed to participating 359 children and 3254 adolescents online. RESULTS: : The anxiety levels of children and adolescents were (23.87±15.79) and (29.27±19.79), respectively. 22.28% respondents were suffering from depressive symptoms. Seven significant factors associated with increased levels of anxiety, including female, resident in urban regions, emotion-focused coping style. Nine factors associated with increased levels of depression, such as smartphone addiction (OR 1.411, 95% CI 1.099–1.180), Internet addiction (OR 1.844, 95% CI 1.209–2.811), and resident in Hubei province (OR 3.107, 95% CI 1.252–7.708). Two additional factors associated with decreased levels of depressive symptoms: hours spend on Internet per day before the epidemic (OR 0.652, 95% CI 0.609–0.697) and tendency to apply problem-focused coping style (OR 0.937, 95% CI 0.923–0.951). CONCLUSION: : Our findings indicate that the COVID-19 outbreak has had a significant psychosocial impact on children and adolescents. Findings of current levels of anxiety and depression not only highlight the need to address emotional distress for children and adolescents during the epidemic but also provide researchers with scientific fundamentals to formulate targeted interventions based on the significant influencing factors.

negative: Pandemic related Health literacy - A Systematic Review of literature in COVID-19, SARS and MERS pandemics Background: Health literacy plays an essential role in ones ability to acquire and understand critical medical information in the COVID-19 infodemic and other pandemics. Purpose: To summarize the assessment, levels and determinants of pandemic related health literacy and its associated clinical outcomes. Data sources: Medline, Embase, PsychINFO, CINAHL, arXiv, bioRxiv, medRxiv, and Social Science Research Network. The start date was unrestricted and current as of 22 April 2020. Study selection Studies which evaluated health literacy related to novel coronavirus disease 2019 (COVID-19), Severe Acute Respiratory Syndrome (SARS) or Middle East Respiratory Syndrome (MERS) Data extraction Data on the characteristics of study designs, instruments, participants and level of health literacy were collected. Items used in instruments were grouped under the themes of knowledge, attitudes and practices. Determinants of health literacy were grouped into five domains (socio-demographic, medical, psychological/psychiatric, health systems related and others). Data synthesis: Of 2,065 articles screened, 70 articles were included. 21, 17 and 32 studies evaluated health literacy related to COVID-19, SARS and MERS, respectively. The rates of low pandemic health literacy ranged from 4.3 to 57.9% among medical-related populations and 4.0% to 82.5% among non-medical populations. Knowledge about symptoms and transmission of infection; worry about infection and, practices related to mask usage and hand hygiene was most frequently evaluated. Socio-demographic determinants of health literacy were most studied, where higher education level, older age and female gender were associated with better health literacy. No studies evaluated outcomes associated with health literacy. Limitations Non-English articles were excluded. Conclusion: The level of pandemic related health literacy is sub-optimal. Healthcare administrators need to be aware of health literacy determinants when formulating policies in pandemics.

negative: [Investigation on demands for antenatal care services among 2 002 pregnant women during the epidemic of COVID-19 in Shanghai]. Objective: To identify problems and demands for antenatal care (ANC) among pregnant women in different trimesters of pregnancy in Shanghai for optimizing ANC service during the epidemic of COVID-19. Method: s Organized by maternal and child health care institute in the 16 districts of Shanghai, a cross sectional study was conducted among pregnant women who came to pregnancy registration in the community health centers or attended ANC in midwifery hospitals from February 7 to February 12, 2020. Consented participating women completed a semi-structured online questionnaire voluntarily. Data was analyzed using frequency,chi-square test and scoring. Result: s A total of 2 002 valid questionnaires were collected from 183 community health centers and 67 midwifery hospitals. About 94.6%(1 894/2 002) of the pregnant women worried about being infected during the COVID-19 epidemic, and 14.7% (294/2 002) demanded for psychological consultation. Time-lapse appointments for ANC were requested by 87.7% (1 756/2 002) of the participants for avoiding presenting themselves in people-density places. Compared with other pregnancy trimesters, pregnant women in the second trimester were more willing to reduce the frequency of ANC (35.2% versus 39.5% versus 48.1%, P<0.01). Compared with multiparas, primiparas were more willing to have online consultation and guidance (49.2% versus 63.8%, P<0.01). Regarding the needs for health knowledge on COVID-19, personal protection against 2019 novel coronavirus (2019-nCoV) was the most concerned for pregnant women, and 71.0% (1 421/2 002) of them preferred to obtain knowledge through health applications, official Weibo and WeChat. Conclusions: Pregnant women in Shanghai critically concern about the risk of 2019-nCoV infections, and highly demand knowledge and measures on prevention and protection from COVID-19. They ask for having time-lapse appointments for ANC and online access to health information and services. Maternal and child care institutes should understand the demands of pregnant women, optimize the means of ANC service, and provide tailored and accessible health education and service for the safety of mother and child.

negative: Etiology and Impact of Coinfections in Children Hospitalized With Community-Acquired Pneumonia BACKGROUND: Recognition that coinfections are common in children with community-acquired pneumonia (CAP) is increasing, but gaps remain in our understanding of their frequency and importance. METHODS: We analyzed data from 2219 children hospitalized with CAP and compared demographic and clinical characteristics and outcomes between groups with viruses alone, bacteria alone, or coinfections. We also assessed the frequency of selected pairings of codetected pathogens and their clinical characteristics. RESULTS: A total of 576 children (26%) had a coinfection. Children with only virus detected were younger, more likely to be black, and more likely to have comorbidities such as asthma, compared with children infected with typical bacteria alone. Children with virus-bacterium coinfections had a higher frequency of leukocytosis, consolidation on chest radiography, parapneumonic effusions, intensive care unit admission, and need for mechanical ventilation and an increased length of stay, compared with children infected with viruses alone. Virus-virus coinfections were generally comparable to single-virus infections, with the exception of the need for oxygen supplementation, which was higher during the first 24 hours of hospitalization in some virus-virus pairings. CONCLUSIONS: Coinfections occurred in 26% of children hospitalized for CAP. Children with typical bacterial infections, alone or complicated by a viral infection, have worse outcomes than children infected with a virus alone.

negative: After COVID-19, a future for the world's children?

negative: Management strategies for children with COVID-19: ESPR practical recommendations During the outbreak of the COVID-19 pandemic, guidelines have been issued by international, national and local authorities to address management and the need for preparedness. Children with COVID-19 differ from adults in that they are less often and less severely affected. Additional precautions required in the management of children address their increased radiosensitivity, need for accompanying carers, and methods for dealing with children in a mixed adult-paediatric institution. In this guidance document, our aim is to define a pragmatic strategy for imaging children with an emphasis on proven or suspected COVID-19 cases. Children suspected of COVID-19 should not be imaged routinely. Imaging should be performed only when expected to alter patient management, depending on symptoms, preexisting conditions and clinical evolution. In order to prevent disease transmission, it is important to manage the inpatient caseload effectively by triaging children and carers outside the hospital, re-scheduling nonurgent elective procedures and managing symptomatic children and carers as COVID-19 positive until proven otherwise. Within the imaging department one should consider conducting portable examinations with COVID-19 machines or arranging dedicated COVID-19 paediatric imaging sessions and performing routine nasopharyngeal swab testing before imaging under general anaesthesia. Finally, regular personal hygiene, appropriate usage of personal protective equipment, awareness of which procedures are considered aerosol generating and information on how to best disinfect imaging machinery after examinations should be highlighted to all staff members. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00247-020-04749-3) contains supplementary material, which is available to authorized users.

negative: Personalized Risk-Benefit Ratio Adaptation of Breast Cancer Care at the Epicenter of COVID-19 Outbreak Northern Italy has been one of the European regions reporting the highest number of COVID-19 cases and deaths. The pandemic spread has challenged the National Health System, requiring reallocation of most of the available health care resources to treat COVID-19-positive patients, generating a competition with other health care needs, including cancer. Patients with cancer are at higher risk of developing critical illness after COVID-19 infection. Thus, mitigation strategies should be adopted to reduce the likelihood of infection in all patients with cancer. At the same time, suboptimal care and treatments may result in worse cancer-related outcome. In this article, we attempt to estimate the individual risk-benefit balance to define personalized strategies for optimal breast cancer management, avoiding as much as possible a general untailored approach. We discuss and report the strategies our Breast Unit adopted from the beginning of the COVID-19 outbreak to ensure the continuum of the best possible cancer care for our patients while mitigating the risk of infection, despite limited health care resources. IMPLICATIONS FOR PRACTICE: Managing patients with breast cancer during the COVID-19 outbreak is challenging. The present work highlights the need to estimate the individual patient risk of infection, which depends on both epidemiological considerations and individual clinical characteristics. The management of patients with breast cancer should be adapted and personalized according to the balance between COVID-19-related risk and the expected benefit of treatments. This work also provides useful suggestions on the modality of patient triage, the conduct of clinical trials, the management of an oncologic team, and the approach to patients' and health workers' psychological distress.

negative: Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 Infection: A Multi-institutional Study from New York City OBJECTIVE: To assess clinical characteristics and outcomes of SARS-CoV-2 associated multisystem inflammatory syndrome in children (MIS-C). STUDY DESIGN: Children with MIS-C admitted to pediatric intensive care units (PICU) in New York City between April 23 and May 23, 2020 were included. Demographic and clinical data were collected. RESULTS: Of 33 children with MIS-C, the median age was 10 years; 61% were male; 45% were Hispanic/Latino; 39% were black. Comorbidities were present in 45%. Fever (93%) and vomiting (69%) were the most common presenting symptoms. Depressed left ventricular ejection fraction (LVEF) was found in 63% of patients with median EF of 46.6% (IQR 39.5, 52.8). C-reactive protein, procalcitonin, D-dimer, and pro-B-type natriuretic peptide levels were elevated in all patients. For treatment, intravenous immunoglobulin was used in 18 (54%), corticosteroids in 17 (51%), tocilizumab in 12 (36%), remdesivir in 7 (21%), vasopressors in 17 (51%), mechanical ventilation in 5 (15%), extracorporeal membrane oxygenation (ECMO) in 1 (3%), and intra-aortic balloon pump in 1 (3%). The LVEF normalized in 95% of those with depressed EF. All patients were discharged home with median duration of PICU stay of 4.7 (4, 8) days and hospital stay of 7.8 (6, 10.1) days. One (3%) patient died after withdrawal of care secondary to stroke while on ECMO. CONCLUSIONS: Critically ill children with COVID-19 associated MIS-C have a spectrum of severity broader than described previously but still require careful supportive intensive care. Rapid, complete clinical and myocardial recovery was almost universal.

negative: The challenging battle of mankind against COVID-19 outbreak: Is this global international biological catastrophe the beginning of a new era?

negative: Global Community Child Health This special issue of IJERPH has published a range of studies in this developing field of Global Community Child Health research. A number of manuscripts submitted in response to our invitation describing ‘community-based interventions which impact on child health and wellbeing around the globe. In addition to rural community-based initiatives given that most children now live in cities we are also interested to hear about urban initiatives….’ We hope this issue will of great interest to the researchers and practitioners as well as academia from the fields of Global Health as well as Global Child Health because it comprised of 14 articles representing all five continents. Physical activity appears a key component of the scientific community’s current conception of child well-being judging from the four papers published addressing this area. This issue also has papers on childhood obesity to rubella vaccination. Despite of the journal’s strive for reaching out to a wider global child health community, this issue missed contributions relating to child safeguarding and social determinants of urban health.

negative: CUPID COVID-19: emergency department attendance by paediatric patients during COVID-19 - project protocol Background: Measures introduced to delay the spread of COVID-19 may result in avoidance of emergency departments (EDs) for non-COVID related illness. Clinicians and medical representative bodies such as the Irish Association for Emergency Medicine (IAEM) have expressed concern that some patients may not seek timely urgent medical intervention. Evidence from previous epidemics found that hospital avoidance during outbreaks of MERS and SARS was common. While ED attendance returned to normal following SARS and MERS, both outbreaks lasted 2-3 months. As the COVID-19 pandemic is forecast to extend into 2021, little is known about the impact COVID-19 will have on paediatric attendance at EDs as the pandemic evolves. Aims: This project aims to assess the impact of COVID-19 on paediatric emergency healthcare utilisation, to understand how the health seeking behaviour of parents may have altered due to the pandemic, and to identify how any barriers to accessing care can be removed. Methods: Administrative data records from five EDs across Ireland and one Urgent Care Centre will be analysed to identify changes in attendances at emergency healthcare. Qualitative inquiry will be utilised to capture the experience of staff providing emergency healthcare to paediatric patients during COVID-19, and their feedback on identified trends will inform the interpretation of findings. A cross-sectional survey of parents will capture experiences, concerns and decision-making on accessing healthcare for their children during the pandemic. Results and Conclusion: This information will help decision makers respond rapidly to meet the clinical needs of paediatric patients as the circumstances of the pandemic unfold and reduce the disruption to normal paediatric ED services during the onset of COVID-19. As the health of a child can deteriorate more rapidly than that of an adult, any delay in seeking care for an acutely ill child may have serious consequences.

negative: Child protection in the time of COVID-19 As the number of cases of coronavirus disease 2019 (COVID-19) caused by the virus SARS-CoV-2 rises exponentially in Australia with consequences for the health system and society at large, we need to remember that during this pandemic that necessary social distancing measures, effective school closures and rising unemployment levels may lead to an increased risk for child abuse and neglect.

negative: Recomendaciones para cirugía en pacientes con patologías oncológicas durante la pandemia COVID-19

negative: Fatal human bocavirus infection in an 18-month-old child with chronic lung disease of prematurity. A fatal case of human bocavirus 1 pulmonary infection in an 18-month-old prematurely born child is described. Despite conventional and oscillatory ventilatory support, intractable hyperinflation developed with bilateral pneumothorax and acute cardiac failure 3 days after the onset of respiratory symptoms.

negative: Hospitalization and Mortality among Black Patients and White Patients with Covid-19 BACKGROUND: Many reports on coronavirus disease 2019 (Covid-19) have highlighted age- and sex-related differences in health outcomes. More information is needed about racial and ethnic differences in outcomes from Covid-19. METHODS: In this retrospective cohort study, we analyzed data from patients seen within an integrated-delivery health system (Ochsner Health) in Louisiana between March 1 and April 11, 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes Covid-19) on qualitative polymerase-chain-reaction assay. The Ochsner Health population is 31% black non-Hispanic and 65% white non-Hispanic. The primary outcomes were hospitalization and in-hospital death. RESULTS: A total of 3626 patients tested positive, of whom 145 were excluded (84 had missing data on race or ethnic group, 9 were Hispanic, and 52 were Asian or of another race or ethnic group). Of the 3481 Covid-19-positive patients included in our analyses, 60.0% were female, 70.4% were black non-Hispanic, and 29.6% were white non-Hispanic. Black patients had higher prevalences of obesity, diabetes, hypertension, and chronic kidney disease than white patients. A total of 39.7% of Covid-19-positive patients (1382 patients) were hospitalized, 76.9% of whom were black. In multivariable analyses, black race, increasing age, a higher score on the Charlson Comorbidity Index (indicating a greater burden of illness), public insurance (Medicare or Medicaid), residence in a low-income area, and obesity were associated with increased odds of hospital admission. Among the 326 patients who died from Covid-19, 70.6% were black. In adjusted time-to-event analyses, variables that were associated with higher in-hospital mortality were increasing age and presentation with an elevated respiratory rate; elevated levels of venous lactate, creatinine, or procalcitonin; or low platelet or lymphocyte counts. However, black race was not independently associated with higher mortality (hazard ratio for death vs. white race, 0.89; 95% confidence interval, 0.68 to 1.17). CONCLUSIONS: In a large cohort in Louisiana, 76.9% of the patients who were hospitalized with Covid-19 and 70.6% of those who died were black, whereas blacks comprise only 31% of the Ochsner Health population. Black race was not associated with higher in-hospital mortality than white race, after adjustment for differences in sociodemographic and clinical characteristics on admission.

negative: G6PD Deficiency Overrepresented Among Pediatric COVID-19 Cases in One Saudi Children Hospital Fluorescent spot test for glucose-6-phosphate dehydrogenase (G6PD) deficiency was performed in 5 boys and 14 girls who had confirmed COVID-19. Out of those, 4 (80%) boys and 5 (36%) girls were found to be G6PD deficient.

negative: Asthma in children during the COVID-19 pandemic: lessons from lockdown and future directions for management

negative: Appropriate care for neonates born to mothers with COVID‐19 disease The global COVID‐19 pandemic has been associated with high rates of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) transmission, morbidity and mortality in the general population. Evidence‐based guidance on caring for babies born to mothers with COVID‐19 is needed. There is currently insufficient evidence to suggest vertical transmission between mothers and their newborn infants. However, transmission can happen after birth from mothers or other carers. Based on the currently available data, prolonged skin‐to‐skin contact and early and exclusive breastfeeding remain the best strategies to reduce the risks of morbidity and mortality for both the mother with COVID‐19 and her baby.

negative: Finding ordinary magic in extraordinary times: child and adolescent resilience during the COVID-19 pandemic

negative: Clinical characteristics and antimicrobial susceptibilities of viridans streptococcal bacteremia during febrile neutropenia in patients with hematologic malignancies: a comparison between adults and children BACKGROUND: This study was performed to compare the clinical characteristics and antibiotic susceptibilities of viridans streptococcal bacteremia (VSB) between febrile neutropenic adults and children with hematologic malignancies. METHODS: The consecutive medical records of neutropenic patients with hematologic malignancies who were admitted to the Catholic Blood and Marrow Transplantation Center between April 2009 and July 2012, and who were subsequently diagnosed with VSB were reviewed retrospectively. A comparison was made between the clinical and laboratory characteristics of adults and pediatric patients and also between patients with cefepime susceptible or not susceptible VSB. RESULTS: A total of 202 episodes (141 in adults, 61 in children) of VSB were identified. Among them, 26 (12.9%) cases had severe complications including four (2.0%) cases of death attributable to VSB. For antibacterial prophylaxis, most adults received ciprofloxacin (97.1%), but children more frequently received trimethoprim/sulfamethoxazole (86.9%). Oral mucositis (p = 0.005) and abdominal pain (p = 0.001) were found more frequently in adults, and cough was found more frequently in children (p = 0.004). The occurrence rates of severe complications and death attributable to VSB were not significantly different between adults and children. Susceptibility rate to cefepime was significantly higher in adults than children (85.7% vs. 66.1%, p = 0.002). However, in multivariate analysis, cefepime susceptibility had no impact on clinical outcome. CONCLUSIONS: There was no significant difference in clinical outcome between adults and children with VSB despite a difference in cefepime susceptibility. Hence, different antibiotic treatment strategies may not be necessary.

negative: Perceptions of the adult US population regarding the novel coronavirus outbreak The Coronavirus Disease 2019 (COVID-19) outbreak is spreading globally. Although COVID-19 has now been declared a pandemic and risk for infection in the United States (US) is currently high, at the time of survey administration the risk of infection in the US was low. It is important to understand the public perception of risk and trust in sources of information to better inform public health messaging. In this study, we surveyed the adult US population to understand their risk perceptions about the COVID-19 outbreak. We used an online platform to survey 718 adults in the US in early February 2020 using a questionnaire that we developed. Our sample was fairly similar to the general adult US population in terms of age, gender, race, ethnicity and education. We found that 69% of the respondents wanted the scientific/public health leadership (either the CDC Director or NIH Director) to lead the US response to COVID-19 outbreak as compared to 14% who wanted the political leadership (either the president or Congress) to lead the response. Risk perception was low (median score of 5 out of 10) with the respondents trusting health professionals and health officials for information on COVID-19. The majority of respondents were in favor of strict infection prevention policies to control the outbreak. Given our results, the public health/scientific leadership should be at the forefront of the COVID-19 response to promote trust.

negative: Predicting the outcomes of preterm neonates beyond the neonatal intensive care unit: What are we missing? ABSTRACT: Preterm infants are a population at high risk for mortality and adverse health outcomes. With recent improvements in survival to childhood, increasing attention is being paid to risk of long-term morbidity, specifically during childhood and young-adulthood. Although numerous tools for predicting the functional outcomes of preterm neonates have been developed in the past three decades, no studies have provided a comprehensive overview of these tools, along with their strengths and weaknesses. The purpose of this article is to provide an in-depth, narrative review of the current risk models available for predicting the functional outcomes of preterm neonates. A total of 32 studies describing 43 separate models were considered. We found that most studies used similar physiologic variables and standard regression techniques to develop models that primarily predict the risk of poor neurodevelopmental outcomes. With a recently expanded knowledge regarding the many factors that affect neurodevelopment and other important outcomes, as well as a better understanding of the limitations of traditional analytic methods, we argue that there is great room for improvement in creating risk prediction tools for preterm neonates. We also consider the ethical implications of utilizing these tools for clinical decision-making. IMPACT: Based on a literature review of risk prediction models for preterm neonates predicting functional outcomes, future models should aim for more consistent outcomes definitions, standardized assessment schedules and measurement tools, and consideration of risk beyond physiologic antecedents. Our review provides a comprehensive analysis and critique of risk prediction models developed for preterm neonates, specifically predicting functional outcomes instead of mortality, to reveal areas of improvement for future studies aiming to develop risk prediction tools for this population. To our knowledge, this is the first literature review and narrative analysis of risk prediction models for preterm neonates regarding their functional outcomes.

negative: Effect of early childhood development interventions implemented by primary care providers commencing in the neonatal period to improve cognitive outcomes in children aged 0-23 months: protocol for a systematic review and meta-analysis. BACKGROUND Impacts of early childhood development (ECD) interventions (such as fostering attachment and responsiveness through communication, play and stimulation) are well known. Globally, there is increasing recognition of the importance of the 'golden' minutes, hours and days after birth for infant health and development. However, only one systematic review has examined ECD interventions implemented in the neonatal period (0-27 days), and this review only assessed interventions implemented by specialised providers. Primary care providers have many potential contacts with mothers and infants throughout the neonatal period. However, it is unclear how many research studies or programmes have examined the effectiveness of ECD interventions commencing in the neonatal period and which methods were used. To date, there has been no systematic review of the effect of ECD interventions delivered by primary care providers commencing in the neonatal period. METHODS Our overall aim is to conduct a systematic review of the effect of ECD interventions implemented by primary care providers in the neonatal period. We will assess effects by timing and number ('dose') of contacts with primary care providers. Subgroup assessment will include effects in disadvantaged infants such as those born with low birth weight and to mothers with mental health disorders. We will also assess effects in low- and high-income countries and by type of care provider. The primary outcome is cognitive status in children aged 0-23 months as measured using standardised scales. Secondary outcomes include other child neurodevelopment domains (speech, language, fine motor, gross motor, social, emotional, behaviour, executive functioning, adaptive functioning) in children aged 0-23 months. Effects on maternal mental health will also be assessed between 0-23 months postpartum. Databases such as MEDLINE (OVID), PsycINFO (OVID), EMBASE (OVID), CINAHL, Cochrane Library, WHO databases and reference lists of papers will be searched for relevant articles. Only randomised controlled trials will be included. A narrative synthesis for all outcomes will be reported. Meta-analyses will be performed where exposures and outcomes are sufficiently homogeneous. Guidelines for PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols) will be followed. DISCUSSION This review appears to be the first to be conducted in this area. The findings will be an important resource for policymakers, primary care providers and researchers who work with young infants in primary care settings. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42019122021.

negative: When Stay-at-Home Orders Leave Victims Unsafe at Home: Exploring the Risk and Consequences of Intimate Partner Violence during the COVID-19 Pandemic The novel coronavirus pandemic (hereafter COVID-19) is likely to have unprecedented impacts on the incidence and impacts of crime and violence globally. This includes impacts to the risk, consequences, and decision-making of women experiencing violence by an intimate partner (hereafter IPV). Most importantly, the COVID-19 pandemic, and its impact on the risk of IPV is likely to differentially impact vulnerable populations, including minority women and those with long histories of victimization and mental health issues. This review paper explores the potential short- and long-term implications of COVID-19 on the risk of IPV, highlighting some of the most recent preliminary data. The economic impact of the COVID-19 pandemic, record levels of male unemployment, added stressors in the home, including the care and home schooling of children, and the social distancing measures required by the epidemiological response, may serve to undermine the decades of progress made in keeping women and children safe at home. Victim police reporting, help-seeking decisions, and social service utilization during the pandemic are likely to be impacted by stay-at-home orders and social distancing requirements. The paper concludes with a discussion of the implications for providing safety planning and self-care for victims and their children.

negative: The remaining unknowns: A determination of the current research priorities for COVID-19 by the global health research community

negative: Has mortality due to other causes increased during the Covid-19 pandemic? Early evidence from England and Wales Background: The Covid-19 pandemic has claimed many lives in the UK and globally. The objective of this paper is to study whether the novel coronavirus has also been associated with an increase in deaths in England and Wales for those who have not contracted the disease. Reasons behind this may include avoiding visits to hospitals or GPs, and the effects of the lockdown. Methods: I used weekly ONS data on the number of deaths that did not involve covid-19 over the period 2015-2020. Simply observing trends is not sufficient as spikes in deaths may occasionally occur. I thus followed a differences-in-differences econometric approach to study whether there was a relative increase in non-covid-19 deaths during the pandemic, compared to a control. As an additional approach, an interrupted time series model was also used. Results: Results suggest that there were an additional 531 non-covid-19 deaths in England and Wales since the outbreak of the pandemic, compared to what would have otherwise been expected [diff-in-diff interaction coeff: 531.11; 95%CI: 125.65 to 936.57]. This is confirmed by the interrupted time series model. Discussion: The health effects of covid-19 do not seem to be limited only to patients suffering from the disease, as the number of deaths for those who did not contract covid-19 has also demonstrated an absolute and relative increase. Analysing the cause of death for non-covid-19 deaths will shed light upon the reasons for the increase in such deaths and will help design appropriate policy responses to save lives.

negative: Associations between psychiatric disorders, COVID-19 testing probability and COVID-19 testing results: Findings from a population-based study Background The novel COVID-19 pandemic has affected over 2.4 million people worldwide. Little is known about COVID-19 testing rates and COVID-19 test outcomes in people with mental illness. We hypothesized that people with psychiatric disorders are less likely to undergo COVID-19 testing and more likely to test positive. Methods We used data on COVID-19 testing in the UK Biobank (UKB) cohort to compare the prevalence of COVID-19 testing and test outcomes among individuals with psychiatric disorders to those without such diagnoses. We further investigated associations of testing probability and outcome with psychiatric diagnostic categories. Outcomes Individuals with psychiatric disorders were overrepresented among the 1 474 UKB participants with test data: 23% of the COVID-19 test sample had a psychiatric diagnosis compared to 10% in the full cohort (p<0.0001). This overrepresentation persisted for each of the specific psychiatric disorders tested. Furthermore, individuals with a psychiatric disorder (p=0.01), particularly with substance use disorder (p<0.005), had negative test results significantly more often than individuals without psychiatric disorders. Sensitivity analyses confirmed our results. Interpretation In contrast with our hypotheses, UKB participants with psychiatric disorders have been tested for COVID-19 more frequently than individuals without a psychiatric history, pleading against the notion that limited health care access is preventing them from undergoing testing. Among those tested, test outcomes were more frequently negative for UKB participants with psychiatric disorders than in others, countering arguments that people with mental illness are more prone to contract the virus. Funding No external funding sources participated in any stage of the present study.

negative: Cognitive, Affective, and Behavioral Constructs of COVID-19 Health Beliefs: A Comparison Between Sexual Minority and Heterosexual Individuals in Taiwan This online survey study aimed to compare the cognitive, affective, and behavioral constructs of health beliefs related to coronavirus disease 2019 (COVID-19) between sexual minority and heterosexual individuals in Taiwan. In total, 533 sexual minority and 1421 heterosexual participants were recruited through a Facebook advertisement. The constructs pertaining to cognition (perceived relative susceptibility to COVID-19, perceived COVID-19 severity, having sufficient knowledge and information on COVID-19, and confidence in coping with COVID-19), affect (worry toward COVID-19), and behavior (adoption of health-protective behaviors) in relation to health beliefs about COVID-19 were compared between sexual minority and heterosexual participants. The results indicated that sexual minority participants had lower perceived susceptibility to COVID-19, greater self-confidence in coping with COVID-19, and lower worry about COVID-19 and were less likely to maintain good indoor ventilation and disinfect their household than heterosexual individuals. Sexual orientation is the modifying factor for the Health Belief Model in the COVID-19 pandemic and should be taken into consideration when medical professionals establish prevention programs for COVID-19.

negative: The psychological state and changes in the routine of the patients with rheumatic diseases during the coronavirus disease (COVID-19) outbreak in Turkey: a web-based cross-sectional survey We hypothesized that patients with rheumatic diseases (RD) would have increased psychological distress during the COVID-19 outbreak; therefore, assessed their psychological symptoms and changes in their routine. A web-based questionnaire survey was conducted in a cross-sectional design in three groups of participants: (1.) patients with RD, (2.) hospital workers, and (3.) high-school teachers/academic staff. Psychiatric status was evaluated using Hospital Anxiety and Depression Scale and Impact of Event Scale-Revised scale. Overall response rate was 34.7%. We studied 771 patients with RD, 535 hospital workers, and 917 teachers/academic staff. Most of the patients with RD were unwilling to go to the hospital (86%), while 22% discontinued their medications. Biological DMARDS were the most frequent drugs whose doses were altered. Only 4% were willing to take hydroxychloroquine for protection. Moreover, the frequency of anxiety (20%), depression (43%), and post-traumatic stress (28%) among patients with RD were found to be comparable to that found among the teachers/academic staff (23%, 43% and 29%, respectively), whereas significantly less than that observed among the hospital workers (40%, 62%, and 46%, respectively) (p < 0.001). Female gender, use of social media, having a comorbid disease, or a psychiatric disorder were found to be independently associated with psychiatric symptoms in total study population. The majority of the patients were unwilling to attend outpatient visits and one-fifth skipped or stopped their immunosuppressive agents. Psychiatric symptoms in patient’s and teacher’s populations were of considerable clinical concern, despite being significantly lower than that observed among the hospital workers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00296-020-04626-0) contains supplementary material, which is available to authorized users.

negative: SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes SARS-CoV-2 virus, the causative agent of the coronavirus infectious disease-19 (COVID-19), is taking the globe by storm, approaching 500,000 confirmed cases and over 21,000 deaths as of March 25, 2020. While under control in some affected Asian countries (Taiwan, Singapore, Vietnam), the virus demonstrated an exponential phase of infectivity in several large countries (China in late January and February and many European countries and the USA in March), with cases exploding by 30–50,000/day in the third and fourth weeks of March, 2020. SARS-CoV-2 has proven to be particularly deadly to older adults and those with certain underlying medical conditions, many of whom are of advanced age. Here, we briefly review the virus, its structure and evolution, epidemiology and pathogenesis, immunogenicity and immune, and clinical response in older adults, using available knowledge on SARS-CoV-2 and its highly pathogenic relatives MERS-CoV and SARS-CoV-1. We conclude by discussing clinical and basic science approaches to protect older adults against this disease.

negative: COVID-19 Datasets: A Survey and Future Challenges In December 2019, a novel virus named as COVID-19 emerged in the city of Wuhan, China. In early 2020, the COVID-19 virus spread in all continents of the world except Antarctica causing widespread infections and deaths due to its contagious characteristics and no medically proven treatment. The COVID-19 pandemic has been termed as most consequential global crisis after the World Wars. The first line of defense against the COVID-19 spread are the non-pharmaceutical measures like social distancing and personal hygiene. On the other hand, the medical service providers are the first responders for infected persons with severe symptoms of COVID-19. The great pandemic affecting billions of lives economically and socially has motivated the scientific community to come up with solutions based on computer-aided digital technologies for diagnosis, prevention, and estimation of COVID-19. Some of these efforts focus on statistical and Artificial Intelligence-based analysis of the available data concerning COVID-19. All of these scientific efforts necessitate that the data brought to service for the analysis should be open-source to promote the extension, validation, and collaboration of the work in the fight against the global pandemic. Our survey is motivated by the open-source efforts that can be mainly categorized as: (a) COVID-19 diagnosis from CT scans and X-ray images, (b) COVID-19 case reporting, transmission estimation, and prognosis from epidemiological, demographic, and mobility data, (c) COVID-19 emotional and sentiment analysis from social media, and (d) knowledge-based discovery and semantic analysis from the collection of scholarly articles covering COVID-19. We review and critically analyze works in these directions that are accompanied by open-source data and code. We hope that the article will provide the scientific community with an initiative to start open-source extensible and transparent research in the collective fight against COVID-19.

negative: COVID-19 severity is predicted by earlier evidence of accelerated aging With no known treatments or vaccine, COVID-19 presents a major threat, particularly to older adults, who account for the majority of severe illness and deaths. The age-related susceptibility is partly explained by increased comorbidities including dementia and type II diabetes. While it is unclear why these diseases predispose risk, we hypothesize that increased biological age, rather than chronological age, may be driving disease-related trends in COVID-19 severity with age. To test this hypothesis, we applied our previously validated biological age measure (PhenoAge) composed of chronological age and nine clinical chemistry biomarkers to data of 347,751 participants from a large community cohort in the United Kingdom (UK Biobank), recruited between 2006 and 2010. Other data included disease diagnoses (to 2017), mortality data (to 2020), and the UK national COVID-19 test results (to May 31, 2020). Accelerated aging 10-14 years prior to the start of the COVID-19 pandemic was associated with test positivity (OR=1.15 per 5-year acceleration, 95% CI: 1.08 to 1.21, p=3.2x10-6) and all-cause mortality with test-confirmed COVID-19 (OR=1.25, per 5-year acceleration, 95% CI: 1.09 to 1.44, p=0.002) after adjustment for demographics including current chronological age and pre-existing diseases or conditions. The corresponding areas under the curves were 0.669 and 0.803, respectively. Biological aging, as captured by PhenoAge, is a better predictor of COVID-19 severity than chronological age, and may inform risk stratification initiatives, while also elucidating possible underlying mechanisms, particularly those related to inflammaging.

negative: Laboratory tests and outcome for patients with COVID-19: A systematic review and meta-analysis BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (COVID-19) poses substantial challenges for health care systems. With a vastly expanding amount of publications on COVID-19, clinicians need evidence synthesis to produce guidance for handling patients with COVID-19. In this systematic review and meta-analysis, we examine which routine laboratory tests are associated with severe COVID-19 disease. CONTENT: PubMed (Medline), Scopus, and Web of Science were searched until the 22(nd) of March 2020 for studies on COVID-19. Eligible studies were original articles reporting on laboratory tests and outcome of patients with COVID-19. Data were synthesised and we conducted random effects meta-analysis and estimated mean difference (MD) and standard mean difference at biomarker level for disease severity. Risk of bias and applicability concern was evaluated using the Quality Assessment of Diagnostic Accuracy Studies -2. SUMMARY: 45 studies were included, of which 21 publications were used for the meta-analysis. Studies were heterogeneous, but had low risk of bias and applicability concern in terms of patient selection and reference standard. Severe disease was associated with higher white blood cell count (MD 1.28 x 10(9)/L), neutrophil count (MD 1.49 x 10(9)/L), C-reactive protein (MD 49.2 mg/L), lactate dehydrogenase (MD 196 U/L), D-dimer (SMD 0.58), and aspartate aminotransferase (MD 8.5 U/L), all p < 0.001. Furthermore, low lymphocyte count (MD -0.32 x 10(9)/L), platelet count (MD -22.4 x 10(9)/L), and haemoglobin (MD -4.1 g/L), all p < 0.001, were also associated with severe disease. In conclusion, several routine laboratory tests are associated with disease severity in COVID-19.

negative: Hospitalization and Mortality among Black Patients and White Patients with Covid-19 BACKGROUND: Many reports on coronavirus disease 2019 (Covid-19) have highlighted age- and sex-related differences in health outcomes. More information is needed about racial and ethnic differences in outcomes from Covid-19. METHODS: In this retrospective cohort study, we analyzed data from patients seen within an integrated-delivery health system (Ochsner Health) in Louisiana between March 1 and April 11, 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes Covid-19) on qualitative polymerase-chain-reaction assay. The Ochsner Health population is 31% black non-Hispanic and 65% white non-Hispanic. The primary outcomes were hospitalization and in-hospital death. RESULTS: A total of 3626 patients tested positive, of whom 145 were excluded (84 had missing data on race or ethnic group, 9 were Hispanic, and 52 were Asian or of another race or ethnic group). Of the 3481 Covid-19–positive patients included in our analyses, 60.0% were female, 70.4% were black non-Hispanic, and 29.6% were white non-Hispanic. Black patients had higher prevalences of obesity, diabetes, hypertension, and chronic kidney disease than white patients. A total of 39.7% of Covid-19–positive patients (1382 patients) were hospitalized, 76.9% of whom were black. In multivariable analyses, black race, increasing age, a higher score on the Charlson Comorbidity Index (indicating a greater burden of illness), public insurance (Medicare or Medicaid), residence in a low-income area, and obesity were associated with increased odds of hospital admission. Among the 326 patients who died from Covid-19, 70.6% were black. In adjusted time-to-event analyses, variables that were associated with higher in-hospital mortality were increasing age and presentation with an elevated respiratory rate; elevated levels of venous lactate, creatinine, or procalcitonin; or low platelet or lymphocyte counts. However, black race was not independently associated with higher mortality (hazard ratio for death vs. white race, 0.89; 95% confidence interval, 0.68 to 1.17). CONCLUSIONS: In a large cohort in Louisiana, 76.9% of the patients who were hospitalized with Covid-19 and 70.6% of those who died were black, whereas blacks comprise only 31% of the Ochsner Health population. Black race was not associated with higher in-hospital mortality than white race, after adjustment for differences in sociodemographic and clinical characteristics on admission.

negative: Knowledge and understanding among medical imaging professionals in India during the rapid rise of the covid-19 pandemic During the first week of March,2020 the surge of coronavirus disease (COVID-19) cases reached all over the globe with more than 100,000 cases. Healthcare national and international authorities have already initiated awareness and lockdown activities. A poor understanding of the disease among medical imaging professionals (MIPs) may result in rapid spread of infection. This study aimed to investigate the knowledge and understanding of MIPs about COVID-19. A cross-sectional, web-based study was conducted among MIPs about COVID- 19 during the fourth week of March 2020. An online sample of MIPs was successfully recruited via the authors’ networks in India using data collection tool – write google forms. A self-developed online KAP questionnaire was completed by the participants. The knowledge and understanding questionnaire consisted questions regarding the clinical characteristics and transmission routes of COVID-19. Assessment on practices towards COVID-19 included questions on techniques while imaging against COVID-19 suspected patients. Of 700 participants, a total of 550 MIPs completed the survey (response rate: 78.57%); 56.7% were males, 85.4.1% were aged 17–26 years, and most were undergraduates (77.6%) and postgraduates (17.1%). Regarding COVID-19, most of the participants answered correctly (95.5%) on symptoms, (84.4%) time interval for visible symptoms, (98.0%) transmission and (44%) airborne transmission respectively. A significant proportion of MIPs (36.4%) had poor knowledge about wearing multiple masks as an effective measure against coronavirus infection. Most of the respondents (48.5%) incorrectly considered X-ray as the reliable method of diagnosis for suspected COVID-19 patients. 44.6% of the respondents lacked knowledge about the steps involved in hand washing technique which is one of the most important safety practice methods in medical imaging to prevent spread of infection. Factors such as age and occupation were associated with inadequate knowledge and poor perception of COVID-19. As the current global threat of COVID-19 continues to emerge, it is crucial and critical to improve the knowledge and understanding of MIPs. Educational videos and live webinars are urgently needed to reach MIPs and further detailed studies are the need of the hour. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12553-020-00437-2) contains supplementary material, which is available to authorized users.

negative: Risk Factors Prediction, Clinical Outcomes, and Mortality of COVID-19 Patients Background: Preventing communicable diseases requires understanding the spread, epidemiology, clinical features, progression, and prognosis of the disease. Early identification of risk factors and clinical outcomes might help to identify critically ill patients, provide proper treatment and prevent mortality. Methods: We conducted a prospective study in patients with flu-like symptoms referred to the imaging department of a tertiary hospital in IRAN between 3 March 2020 and 8 April 2020. Patients with COVID-19 were followed up to check their health condition after two months. The categorical data between groups were analyzed by Fisher exact test and continuous data by Wilcoxon Rank-Sum Test. Findings: 319 patients (mean age 45.48 years, 177 women) were enrolled. Fever, dyspnea, weakness, shivering, C-reactive protein (CRP), fatigue, dry cough, anorexia, anosmia, ageusia, dizziness, sweating and age were the most important symptoms of COVID-19 infection. Traveling in past three months, asthma, taking corticosteroids, liver disease, rheumatological disease, cough with sputum, eczema, conjunctivitis, tobacco use, and chest pain did not have any relationship with COVID-19. Interpretation: Finding clinical symptoms for early diagnosis of COVID-19 is a critical part of prevention. These symptoms can help in the assessment of disease progression. To the best of our knowledge, some of the effective features on the mortality due to COVID-19 are investigated for the first time in this research. Funding: None

negative: Hemophagocytic lymphohistiocytosis: a review inspired by the COVID-19 pandemic Hemophagocytic syndrome (HPS) or hemophagocytic lymphohistiocytosis (HLH) is an acute and rapidly progressive systemic inflammatory disorder characterized by cytopenia, excessive cytokine production, and hyperferritinemia. Common clinical manifestations of HLH are acute unremitting fever, lymphadenopathy, hepatosplenomegaly, and multiorgan failure. Due to a massive cytokine release, this clinical condition is considered as a cytokine storm syndrome. HPS has primary and acquired (secondary, reactive) forms. Its primary form is mostly seen in childhood and caused by various mutations with genetic inheritance and, therefore, is called familial HLH. Secondary HLH may be caused in the presence of an underlying disorder, that is, secondary to a malignant, infectious, or autoimmune/autoinflammatory stimulus. This paper aims to review the pathogenesis and the clinical picture of HLH, and its severe complication, the cytokine storm, with a special emphasis on the developed classification criteria sets for rheumatologists, since COVID-19 infection has clinical symptoms resembling those of the common rheumatologic conditions and possibly triggers HLH. MED-LINE/Pubmed was searched from inception to April 2020, and the following terms were used for data searching: “hemophagocytic syndrome” OR “macrophage activation syndrome” OR “hemophagocytic lymphohistiocytosis”, OR “cytokine storm”. Finally, AND “COVID-19” was included in this algorithm. The selection is restricted to the past 5 years and limited numbers of earlier key references were manually selected. Only full-text manuscripts, published in an English language peer-reviewed journal were included. Manuscript selection procedure and numbers are given in Fig. 2. Briefly, the database search with the following terms of “Hemophagocytic syndrome” OR “Macrophage activation syndrome” OR “Hemophagocytic lymphohistiocytosis” OR “Cytokine storm” yielded 6744 results from inception to April 2020. The selection is restricted to the past 5 years and only limited numbers of earlier key references were selected, and this algorithm resulted in 3080 manuscripts. The addition of (AND “COVID-19”) resulted in 115 publications of which 47 studies, together with four sections of an online book were used in the final review. No statistical method was used. HLH is triggered by genetic conditions, infections, malignancies, autoimmune-autoinflammatory diseases, and some drugs. In COVID-19 patients, secondary HLH and cytokine storm may be responsible for unexplained progressive fever, cytopenia, ARDS, neurological and renal impairment. Differentiation between the primary and secondary forms of HLH is utterly important, since primary form of HLH requires complicated treatments such as hematopoietic stem cell transplantation. Further studies addressing the performance of HScore and other recommendations in the classification of these patients is necessary.

negative: Follow-up study on pulmonary function and radiological changes in critically ill patients with COVID-19

negative: AI4COVID-19: AI Enabled Preliminary Diagnosis for COVID-19 from Cough Samples via an App Inability to test at scale has become Achille's heel in humanity's ongoing war against COVID-19 pandemic. An agile, scalable and cost-effective testing, deployable at a global scale, can act as a game changer in this war. To address this challenge, building on the promising results of our prior work on cough-based diagnosis of a motley of respiratory diseases, we develop an Artificial Intelligence (AI)-based test for COVID-19 preliminary diagnosis. The test is deployable at scale through a mobile app named AI4COVID-19. The AI4COVID-19 app requires 2-second cough recordings of the subject. By analyzing the cough samples through an AI engine running in the cloud, the app returns a preliminary diagnosis within a minute. Unfortunately, cough is common symptom of over two dozen non-COVID-19 related medical conditions. This makes the COVID-19 diagnosis from cough alone an extremely challenging problem. We solve this problem by developing a novel multi-pronged mediator centered risk-averse AI architecture that minimizes misdiagnosis. At the time of writing, our AI engine can distinguish between COVID-19 patient coughs and several types of non-COVID-19 coughs with over 90% accuracy. AI4COVID-19's performance is likely to improve as more and better data becomes available. This paper presents a proof of concept to encourage controlled clinical trials and serves as a call for labeled cough data. AI4COVID-19 is not designed to compete with clinical testing. Instead, it offers a complementing tele-testing tool deployable anytime, anywhere, by anyone, so clinical-testing and treatment can be channeled to those who need it the most, thereby saving more lives.

negative: Sexual and reproductive health (SRH): a key issue in the emergency response to the coronavirus disease (COVID- 19) outbreak The novel coronavirus disease (COVID-19) outbreak was first declared in China in December 2019, and WHO declared the pandemic on 11 March 2020. A fast-rising number of confirmed cases has been observed in all continents, with Europe at the epicentre of the outbreak at this moment. Sexual and reproductive health (SRH) and rights is a significant public health issue during the epidemics. The novel coronavirus (SARS-CoV-2) is new to humans, and only limited scientific evidence is available to identify the impact of the disease COVID-19 on SRH, including clinical presentation and outcomes of the infection during pregnancy, or for persons with STI/HIV-related immunosuppression. Beyond the clinical scope of SRH, we should not neglect the impacts at the health system level and disruptions or interruptions in regular provision of SRH services, such as pre- and postnatal checks, safe abortion, contraception, HIV/AIDS and sexually transmitted infections. Furthermore, other aspects merit attention such as the potential increase of gender-based violence and domestic abuse, and effects of stigma and discrimination associated with COVID-19 and their effects on SRH clients and health care providers. Therefore, there is an urgent need for the scientific community to generate sound clinical, epidemiological, and psycho-social behavioral links between COVID-19 and SRH and rights outcomes.

negative: Vulnerable Children in a Dual Epidemic. Two epidemics-Covid-19 and opioid use disorder (OUD) -are creating short- and long-term mental and physical health risks for vulnerable children and adolescents. Information about the risks to children from exposure to the coronavirus is still fragmentary, but even many healthy children are not getting appropriate health care, such as vaccinations or monitoring of developmental milestones during the Covid-19 pandemic. Children living in poverty are at heightened risk. Youngsters who are already dealing with OUD in their families-2.2 million as of 2017-face serious consequences stemming from trauma and stress. Although not officially designated by the Centers for Disease Control and Prevention as "adverse childhood experiences" ("ACEs"), these situations meet the CDC's criteria for inclusion, such as death or separation from a parent. It is important to recognize and meet the needs of all these children now and not just when the long-term consequences become apparent.

negative: Exploring Opportunities for Household-Level Chronic Care Management Using Linked Electronic Health Records of Adults and Children: A Retrospective Cohort Study. OBJECTIVE Linking electronic health records (EHR) of pediatric and adult patients living in the same household has the potential to improve chronic care management efficiencies by facilitating the delivery of services to multiple household members at once. However, little is known about relationship between the chronic medical (CM) and behavioral health (CBH) of adults and children living in common households. METHODS EHR data for children were linked to the EHR data of adults living at the same address during the same time in a retrospective cohort study from 2006 to 2014 to evaluate associations between adult and child CM and CBH conditions within a Boston safety-net primary care patient sample. RESULTS Of the 13,845 included children, 61.6% lived with at least one adult with ≥ 1 CM or CBH condition. Compared to children living with an adult(s) without a chronic condition, children living with an adult with a CM or CBH condition had a respective 16.2% and 18.1% increased likelihood of having a chronic condition themselves, with multiple adult chronic conditions in adults increasing children's likelihood. CONCLUSIONS FOR PRACTICE We found a positive association between the chronic diseases of adult and child household members. Given the clustering of child and adult chronic disease within households, using EHR data to support the care management needs of multiple members of households may be a promising approach to improving child and adult health in safety-net settings.

negative: Parental Burnout and Child Maltreatment During the COVID-19 Pandemic The novel coronavirus (COVID-19) has spread across the United States, resulting in significant changes in almost all aspects daily life. These changes place parents at increased risk for parental burnout. Parental burnout is a chronic condition resulting from high levels of parenting-related stress due to a mismatch between the demands of parenting and the resources available for parents to meet those demands. Research on parental burnout has suggested that parents who experience burnout are more likely to engage in child abuse and neglect, placing children at risk for detrimental short- and long-term outcomes. The purpose of this paper is to review the concept of parental burnout, discuss parental burnout in the context of the current COVID-19 pandemic, and focus specifically on the effects of child maltreatment. Implications for practitioners will be discussed.

negative: COVID-19 and nonalcoholic fatty liver disease: two intersecting pandemics BACKGROUND: Initial evidence from China suggests that most vulnerable subjects to COVID-19 infection suffer from pre-existing illness, including metabolic abnormalities. The pandemic characteristics and high-lethality rate of COVID-19 infection have raised concerns about interactions between virus pathobiology and components of the metabolic syndrome. METHODS: We harmonized the information from the recent existing literature on COVID-19 acute pandemic and mechanisms of damage in non-alcoholic fatty liver disease (NAFLD), as an example of chronic (non-communicable) metabolic pandemic. RESULTS: COVID-19 patients are more fragile with underlying metabolic illness, including hypertension, cardiovascular disease, type 2 diabetes, chronic lung diseases (e.g., asthma, chronic obstructive pulmonary disease, and emphysema), and metabolic syndrome. During metabolic abnormalities, expansion of metabolically active fat ("overfat condition") parallels chronic inflammatory changes, development of insulin resistance, and accumulation of fat in configuring NAFLD. The deleterious interplay of inflammatory pathways chronically active in NAFLD and acutely in COVID-19 patients, can explain liver damage in a subgroup of patients, and might condition a worse outcome in metabolically-compromised NAFLD patients. In a subgroup of NAFLD patients, the underlying liver fibrosis might represent an additional and independent risk factor for severe COVID-19 illness, irrespective of metabolic comorbidities. CONCLUSIONS: NAFLD can play a role in the outcome of COVID-19 illness due to frequent association with comorbidities. Initial evidences suggest that increased liver fibrosis in NAFLD might affect COVID-19 outcome. In addition, long-term monitoring of post-COVID-19 NAFLD patients is advisable, to document further deterioration of liver damage. Further studies are required in this field.

negative: EEG findings in acutely ill patients investigated for SARS‐CoV‐2/COVID‐19: A small case series preliminary report OBJECTIVE: Acute encephalopathy may occur in COVID‐19‐infected patients. We investigated whether medically indicated EEGs performed in acutely ill patients under investigation (PUIs) for COVID‐19 report epileptiform abnormalities and whether these are more prevalent in COVID‐19 positive than negative patients. METHODS: In this retrospective case series, adult COVID‐19 inpatient PUIs underwent EEGs for acute encephalopathy and/or seizure‐like events. PUIs had 8‐channel headband EEGs (Ceribell; 20 COVID‐19 positive, 6 COVID‐19 negative); 2 more COVID‐19 patients had routine EEGs. Overall, 26 Ceribell EEGs, 4 routine and 7 continuous EEG studies were reviewed. EEGs were interpreted by board‐certified clinical neurophysiologists (n = 16). EEG findings were correlated with demographic data, clinical presentation and history, and medication usage. Fisher's exact test was used. RESULTS: We included 28 COVID‐19 PUIs (30‐83 years old), of whom 22 tested positive (63.6% males) and 6 tested negative (33.3% male). The most common indications for EEG, among COVID‐19‐positive vs COVID‐19‐negative patients, respectively, were new onset encephalopathy (68.2% vs 33.3%) and seizure‐like events (14/22, 63.6%; 2/6, 33.3%), even among patients without prior history of seizures (11/17, 64.7%; 2/6, 33.3%). Sporadic epileptiform discharges (EDs) were present in 40.9% of COVID‐19‐positive and 16.7% of COVID‐19‐negative patients; frontal sharp waves were reported in 8/9 (88.9%) of COVID‐19‐positive patients with EDs and in 1/1 of COVID‐19‐negative patient with EDs. No electrographic seizures were captured, but 19/22 COVID‐19‐positive and 6/6 COVID‐19‐negative patients were given antiseizure medications and/or sedatives before the EEG. SIGNIFICANCE: This is the first preliminary report of EDs in the EEG of acutely ill COVID‐19‐positive patients with encephalopathy or suspected clinical seizures. EDs are relatively common in this cohort and typically appear as frontal sharp waves. Further studies are needed to confirm these findings and evaluate the potential direct or indirect effects of COVID‐19 on activating epileptic activity.

negative: Pre-existing liver disease is associated with poor outcome in patients with SARS CoV2 infection; The APCOLIS Study (APASL COVID-19 Liver Injury Spectrum Study) BACKGROUND AND AIMS: COVID-19 is a dominant pulmonary disease, with multisystem involvement, depending upon comorbidities. Its profile in patients with pre-existing chronic liver disease (CLD) is largely unknown. We studied the liver injury patterns of SARS-Cov-2 in CLD patients, with or without cirrhosis. METHODS: Data was collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19. RESULTS: Altogether, 228 patients [185 CLD without cirrhosis and 43 with cirrhosis] were enrolled, with comorbidities in nearly 80%. Metabolism associated fatty liver disease (113, 61%) and viral etiology (26, 60%) were common. In CLD without cirrhosis, diabetes [57.7% vs 39.7%, OR = 2.1 (1.1-3.7), p = 0.01] and in cirrhotics, obesity, [64.3% vs. 17.2%, OR = 8.1 (1.9-38.8), p = 0.002] predisposed more to liver injury than those without these. Forty three percent of CLD without cirrhosis presented as acute liver injury and 20% cirrhotics presented with either acute-on-chronic liver failure [5 (11.6%)] or acute decompensation [4 (9%)]. Liver related complications increased (p < 0.05) with stage of liver disease; a Child-Turcotte Pugh score of 9 or more at presentation predicted high mortality [AUROC 0.94, HR = 19.2 (95 CI 2.3-163.3), p < 0.001, sensitivity 85.7% and specificity 94.4%). In decompensated cirrhotics, the liver injury was progressive in 57% patients, with 43% mortality. Rising bilirubin and AST/ALT ratio predicted mortality among cirrhosis patients. CONCLUSIONS: SARS-Cov-2 infection causes significant liver injury in CLD patients, decompensating one fifth of cirrhosis, and worsening the clinical status of the already decompensated. The CLD patients with diabetes and obesity are more vulnerable and should be closely monitored.

negative: Addressing the indirect effects of COVID-19 on the health of children and young people

negative: Children of COVID-19: pawns, pathfinders or partners? Countries throughout the world are counting the health and socioeconomic costs of the COVID-19 pandemic, including the strategies necessary to contain it. Profound consequences from social isolation are beginning to emerge, and there is an urgency about charting a path to recovery, albeit to a 'new normal' that mitigates them. Children have not suffered as much from the direct effects of COVID-19 infection as older adults. Still, there is mounting evidence that their health and welfare are being adversely affected. Closure of schools has been a critical component of social isolation but has a far broader impact than the diminution of educational opportunities, as important as these are. Reopening of schools is therefore essential to recovery, with some countries already tentatively implementing it. Children's interests are vital considerations in any recovery plan, but the question remains as to how to address them within the context of how society views children; should they be regarded as pawns, pathfinders or partners in this enterprise?

negative: Acute kidney injury in hospitalized children: consequences and outcomes Over the past decade, the nephrology and critical care communities have adopted a consensus approach to diagnosing acute kidney injury (AKI) and, as a result, we have seen transformative changes in our understanding of pediatric AKI epidemiology. The data regarding outcomes among neonates and children who develop AKI have become far more robust and AKI has been clearly linked with an increased need for mechanical ventilation, longer inpatient stays, and higher mortality. Though AKI was historically thought to be self-limited, we now know that renal recovery is far from universal, particularly when AKI is severe; the absence of recovery from AKI also carries longitudinal prognostic implications. AKI survivors, especially those without full recovery, are at risk for chronic renal sequelae including proteinuria, hypertension, and chronic kidney disease. This review comprehensively describes AKI-related outcomes across the entire pediatric age spectrum, using the most rigorous studies to identify the independent effects of AKI events.

negative: Psychosocial impact of COVID-19 BACKGROUND: Along with its high infectivity and fatality rates, the 2019 Corona Virus Disease (COVID-19) has caused universal psychosocial impact by causing mass hysteria, economic burden and financial losses. Mass fear of COVID-19, termed as “coronaphobia”, has generated a plethora of psychiatric manifestations across the different strata of the society. So, this review has been undertaken to define psychosocial impact of COVID-19. METHODS: Pubmed and GoogleScholar are searched with the following key terms- “COVID-19”, “SARS-CoV2”, “Pandemic”, “Psychology”, “Psychosocial”, “Psychitry”, “marginalized”, “telemedicine”, “mental health”, “quarantine”, “infodemic”, “social media” and” “internet”. Few news paper reports related to COVID-19 and psychosocial impacts have also been added as per context. RESULTS: Disease itself multitude by forced quarantine to combat COVID-19 applied by nationwide lockdowns can produce acute panic, anxiety, obsessive behaviors, hoarding, paranoia, and depression, and post-traumatic stress disorder (PTSD) in the long run. These have been fueled by an “infodemic” spread via different platforms social media. Outbursts of racism, stigmatization, and xenophobia against particular communities are also being widely reported. Nevertheless, frontline healthcare workers are at higher-risk of contracting the disease as well as experiencing adverse psychological outcomes in form of burnout, anxiety, fear of transmitting infection, feeling of incompatibility, depression, increased substance-dependence, and PTSD. Community-based mitigation programs to combat COVID-19 will disrupt children's usual lifestyle and may cause florid mental distress. The psychosocial aspects of older people, their caregivers, psychiatric patients and marginalized communities are affected by this pandemic in different ways and need special attention. CONCLUSION: For better dealing with these psychosocial issues of different strata of the society, psychosocial crisis prevention and intervention models should be urgently developed by the government, health care personnel and other stakeholders. Apt application of internet services, technology and social media to curb both pandemic and infodemic needs to be instigated. Psychosocial preparedness by setting up mental organizations specific for future pandemics is certainly necessary.

negative: Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19: A Living Systematic Review of Multiple Streams of Evidence BACKGROUND: Mechanical ventilation is used to treat respiratory failure in coronavirus disease 2019 (COVID-19). PURPOSE: To review multiple streams of evidence regarding the benefits and harms of ventilation techniques for coronavirus infections, including that causing COVID-19. (PROSPERO registration: CRD42020178187) DATA SOURCES: 21 standard, World Health Organization–specific and COVID-19–specific databases, without language restrictions, until 1 May 2020. STUDY SELECTION: Studies of any design and language comparing different oxygenation approaches in patients with coronavirus infections, including severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), or with hypoxemic respiratory failure. Animal, mechanistic, laboratory, and preclinical evidence was gathered regarding aerosol dispersion of coronavirus. Studies evaluating risk for virus transmission to health care workers from aerosol-generating procedures (AGPs) were included. DATA EXTRACTION: Independent and duplicate screening, data abstraction, and risk of bias assessment (GRADE for certainty of evidence and AMSTAR 2 for included systematic reviews). DATA SYNTHESIS: 123 studies were eligible (45 on COVID-19, 70 on SARS, 8 on MERS), but only 5 studies (1 on COVID-19, 3 on SARS, 1 on MERS) adjusted for important confounders. A study in hospitalized patients with COVID-19 reported slightly higher mortality with noninvasive ventilation (NIV) than with invasive mechanical ventilation (IMV), but 2 opposing studies, 1 in patients with MERS and 1 in patients with SARS, suggest a reduction in mortality with NIV (very low-certainty evidence). Two studies in patients with SARS report a reduction in mortality with NIV compared with no mechanical ventilation (low-certainty evidence). Two systematic reviews suggest a large reduction in mortality with NIV compared with conventional oxygen therapy. Other included studies suggest increased odds of transmission from AGPs. LIMITATION: Direct studies in COVID-19 are limited and poorly reported. CONCLUSION: Indirect and low-certainty evidence suggests that use of NIV, similar to IMV, probably reduces mortality but may increase the risk for transmission of COVID-19 to health care workers. PRIMARY FUNDING SOURCE: World Health Organization.

negative: Adolescent psychiatric disorders during the COVID-19 pandemic and lockdown The aim of this paper was to review the literature on adolescent psychiatric disorders related to the COVID-19 pandemic and lockdown. Stressful life events, extended home confinement, brutal grief, intrafamilial violence, overuse of the Internet and social media are factors that could influence the mental health of adolescents during this period. The COVID-19 pandemic could result in increased psychiatric disorders such as Post-Traumatic Stress, Depressive, and Anxiety Disorders, as well as grief-related symptoms. Adolescents with psychiatric disorders are at risk of a break or change in their care and management; they may experience increased symptoms. The COVID-19 pandemic and lockdown may have a negative impact on the mental health of adolescents, although there is still no data on the long term impact of this crisis. Adolescents’ individual, familial, and social vulnerability, as well as individual and familial coping abilities, are factors related to adolescent mental health in times of crisis. Adolescents are often vulnerable and require careful consideration by caregivers and healthcare system adaptations to allow for mental health support despite the lockdown. Research on adolescent psychiatric disorders in times of pandemics is necessary, as such a global situation could be prolonged or repeated.

negative: Physical child abuse demands increased awareness during health and socioeconomic crises like COVID-19. Background and purpose - Physical abuse of children, i.e., nonaccidental injury (NAI) including abusive head trauma (AHT) is experienced by up to 20% of children; however, only 0.1% are diagnosed. Healthcare professionals issue less than 20% of all reports suspecting NAI to the responsible authorities. Insufficient knowledge concerning NAI may partly explain this low percentage. The risk of NAI is heightened during health and socioeconomic crises such as COVID-19 and thus demands increased awareness. This review provides an overview and educational material on NAI and its clinical presentation.Methods - We combined a literature review with expert opinions of the senior authors into an educational paper aiming to help clinicians to recognize NAI and act appropriately by referral to multidisciplinary child protection teams and local authorities.Results - Despite the increased risk of NAI during the current COVID-19 crisis, the number of reports suspecting NAI decreased by 42% during the lockdown of the Danish society. Healthcare professionals filed only 17% of all reports of suspected child abuse in 2016.Interpretation - The key to recognizing and suspecting NAI upon clinical presentation is to be aware of inconsistencies in the medical history and suspicious findings on physical and paraclinical examination. During health and socioeconomic crises the incidence of NAI is likely to peak. Recognition of NAI, adequate handling by referral to child protection teams, and reporting to local authorities are of paramount importance to prevent mortality and physical and mental morbidity.

negative: Rhinoviruses, Allergic Inflammation, and Asthma Viral infections affect wheezing and asthma in children and adults of all ages. In infancy, wheezing illnesses are usually viral in origin, and children with more severe wheezing episodes are more likely to develop recurrent episodes of asthma and to develop asthma later in childhood. Children who develop allergen-specific immunoglobulin E (allergic sensitization), and those who wheeze with rhinoviruses (HRV) are at especially high risk for asthma. In older children and adults, HRV infections generally cause relatively mild respiratory illnesses and yet contribute to acute and potentially severe exacerbations in patients with asthma. These findings underline the importance of understanding the synergistic nature of allergic sensitization and infections with HRV in infants relative to the onset of asthma and in children and adults with respect to exacerbations of asthma. This review discusses clinical and experimental evidence of virus/allergen interactions and evaluates theories which relate immunologic responses to respiratory viruses and allergens to the pathogenesis and disease activity of asthma. Greater understanding of the relationship between viral respiratory infections, allergic inflammation, and asthma is likely to suggest new strategies for the prevention and treatment of asthma.

negative: The psychosocial effects of being quarantined following exposure to COVID-19: A qualitative study of Lebanese health care workers BACKGROUND: Since the outbreak of the novel Coronavirus (COVID-19), health care professionals in Lebanon have been diligently serving as the frontline of defense. In the light of challenging economic and political circumstances, putting their community wellbeing as a priority, and abiding by quarantine and strict infection control measures, health care professionals risk both their physical and mental wellbeing. OBJECTIVE: The aim of this study is to explore the psychosocial effects of being quarantined following exposure to COVID-19 among Lebanese health care professionals. METHOD: An exploratory qualitative research design was employed, where semi-structured interviews were carried out involving a sample of 13 Lebanese health care providers working at various COVID-19 units. RESULTS: The qualitative analysis has revealed four themes namely ‘Fears of contracting and spreading the virus’, ‘Conflict between professional duty and family obligation’, ‘Stigma of being infected’, and ‘Inadequate or inaccurate information’. CONCLUSION: COVID-19 quarantine has been posing intense psychological challenges among Lebanese health care workers which are worsened at times by the economic instability; thus, health care policymakers are urged to take proper action nationwide to alleviate longlisting implications and support the health care providers in fulfilling their mission.

negative: Perceived vulnerability to COVID-19 infection from event attendance: Results from Louisiana, USA, two weeks preceding the national emergency declaration In response to the mounting threat of COVID-19, we added questions to an ongoing food preference study held at Louisiana State University from March 3-12 of 2020. We asked 356 participants: (1) In your opinion, how likely is it that the spread of COVID-19 (the coronavirus) will cause a public health crisis in the United States? (2) How concerned are you that you will contract COVID-19 by attending events on campus? Participants' estimates of an impending national health crisis increased significantly during the study's second week (March 9-12) while concern about personally contracting COVID-19 from attending campus events increased only marginally during the study's final days. We find those expressing a higher likelihood of an impending national crisis were more concerned about contracting COVID-19 by attending campus events, suggesting a possible transmission from perceptions of national-level events to perceived personal vulnerability via local exposure. However, about 30% of participants perceived that COVID-19 would likely cause a public health crisis yet did not express concern about contracting COVID-19 from event attendance. These participants were significantly more likely to be younger students who agreed to participate in response to recruitment using same-day flyer distribution. Women expressed a higher likelihood of an emerging national health crisis, although they were not more concerned than men that attending campus events would result in virus contraction. Other groups (e.g., white, students younger than 25, highest income group) displayed similar concern about a national-level crisis, yet were significantly less concerned about contracting COVID-19 from attending campus events than others. Also, participants randomly assigned to information emphasizing the national impacts of food waste expressed significantly greater concern of contracting COVID-19 by attending campus events. These results provide some initial insight about how people perceived national and personal risks in the early stages of the COVID-19 crisis in Louisiana.

negative: What are the Underlying Transmission Patterns of COVID-19 Outbreak? – An Age-specific Social Contact Characterization Abstract Background COVID-19 has spread to 6 continents. Now is opportune to gain a deeper understanding of what may have happened. The findings can help inform mitigation strategies in the disease-affected countries. Methods In this work, we examine an essential factor that characterizes the disease transmission patterns: the interactions among people. We develop a computational model to reveal the interactions in terms of the social contact patterns among the population of different age-groups. We divide a city's population into seven age-groups: 0-6 years old (children); 7-14 (primary and junior high school students); 15-17 (high school students); 18-22 (university students); 23-44 (young/middle-aged people); 45-64 years old (middle-aged/elderly people); and 65 or above (elderly people). We consider four representative settings of social contacts that may cause the disease spread: (1) individual households; (2) schools, including primary/high schools as well as colleges and universities; (3) various physical workplaces; and (4) public places and communities where people can gather, such as stadiums, markets, squares, and organized tours. A contact matrix is computed to describe the contact intensity between different age-groups for each of the four settings. By integrating the four contact matrices with the next-generation matrix, we quantitatively characterize the underlying transmission patterns of COVID-19 among different populations. Findings We focus our study on 6 representative cities in China: Wuhan, the epicenter of COVID-19, together with Beijing, Tianjin, Hangzhou, Suzhou, and Shenzhen, which are five major cities from three key economic zones. The results show that the social contact-based analysis can readily explain the underlying disease transmission patterns as well as the associated risks (including both confirmed and unconfirmed cases). In Wuhan, the age-groups involving relatively intensive contacts in households and public/communities are dispersedly distributed. This can explain why the transmission of COVID-19 in the early stage mainly took place in public places and families in Wuhan. We estimate that Feb. 11, 2020 was the date with the highest transmission risk in Wuhan, which is consistent with the actual peak period of the reported case number (Feb. 4-14). Moreover, the surge in the number of new cases reported on Feb. 12-13 in Wuhan can readily be captured using our model, showing its ability in forecasting the potential/unconfirmed cases. We further estimate the disease transmission risks associated with different work resumption plans in these cities after the outbreak. The estimation results are consistent with the actual situations in the cities with relatively lenient control policies, such as Beijing, and those with strict control policies, such as Shenzhen. Interpretation With an in-depth characterization of age-specific social contact-based transmission, the retrospective and prospective situations of the disease outbreak, including the past and future transmission risks, the effectiveness of different interventions, and the disease transmission risks of restoring normal social activities, are computationally analyzed and reasonably explained. The conclusions drawn from the study not only provide a comprehensive explanation of the underlying COVID-19 transmission patterns in China, but more importantly, offer the social contact-based risk analysis methods that can readily be applied to guide intervention planning and operational responses in other countries, so that the impact of COVID-19 pandemic can be strategically mitigated. Funding General Research Fund of the Hong Kong Research Grants Council; Key Project Grants of the National Science Foundation of China.

negative: COVID-19 in older adults The Consequences of Neoliberalism in the Current Pandemic The advent of the SARS-CoV-2 and COVID-19 pandemic has generated a lot of publications at a rapid pace We know that older adults disproportionately suffer the most severe of COVID outcomes Here we attempt to coalesce the key knowledge of SARS-CoV-2 biology to the disease and clinical care concepts in the context of older adults This article analyzes how the neoliberal policies, such as the politics of austerity (with considerable cuts to social policy expenditures including medical care and public health services) and the privatization of health services, imposed by many governments on both sides of the North Atlantic, considerably weakened the capacity of the response to the coronavirus pandemic in Italy, Spain, and the United States

negative: Evaluating the Mental Health Impacts of the COVID-19 Pandemic in Urban South Africa: Perceived Risk of COVID-19 Infection and Childhood Trauma Predict Adult Depressive Symptoms South Africa’s national lockdown introduced serious threats to public mental health in a society where one in three individuals develop a psychiatric disorder during their life. We aimed to evaluate the mental health impacts of the COVID-19 pandemic using a mixed methods design. This longitudinal study drew from a preexisting sample of 957 adults living in Soweto, a major township near Johannesburg. Psychological assessments were administered across two waves: between August 2019-March 2020 and during the first six weeks of the lockdown (late March-early May 2020). Interviews on COVID-19 experiences were administered in the second wave. Multiple regression models examined relationships between perceived COVID-19 risk and depression. Full data on perceived COVID-19 risk, depression, and covariates were available in 221 adults. 14.5% of adults were at risk for depression. Higher perceived COVID-19 risk predicted greater depressive symptoms (p < 0.001) particularly among adults with histories of childhood trauma, though this effect was marginally significant (p = 0.062). Adults were two times more likely to experience significant depressive symptoms for every one unit increase in perceived COVID-19 risk (p = 0.016; 95% CI [1.14, 3.49]). Qualitative data identified potent experiences of anxiety, financial insecurity, fear of infection, and rumination. Higher perceived risk of COVID-19 infection is associated with greater depressive symptoms among adults with histories of childhood trauma during the first six weeks of quarantine. High rates of severe mental illness and low availability of mental healthcare amidst COVID-19 emphasize the need for immediate and accessible psychological resources in South Africa.

negative: Abstracts from the 11th International Congress of Behavioral Medicine

negative: Vulnerable Children in a Dual Epidemic Two epidemics-Covid-19 and opioid use disorder (OUD) -are creating short- and long-term mental and physical health risks for vulnerable children and adolescents. Information about the risks to children from exposure to the coronavirus is still fragmentary, but even many healthy children are not getting appropriate health care, such as vaccinations or monitoring of developmental milestones during the Covid-19 pandemic. Children living in poverty are at heightened risk. Youngsters who are already dealing with OUD in their families-2.2 million as of 2017-face serious consequences stemming from trauma and stress. Although not officially designated by the Centers for Disease Control and Prevention as "adverse childhood experiences" ("ACEs"), these situations meet the CDC's criteria for inclusion, such as death or separation from a parent. It is important to recognize and meet the needs of all these children now and not just when the long-term consequences become apparent.

negative: Pausing the Fight Against Malaria to Combat the COVID-19 Pandemic in Africa: Is the Future of Malaria Bleak? Malaria remains a major global health burden, killing hundreds of thousands annually, especially in sub-Saharan Africa. In 2019, a Phase IV Expanded Programme on Immunization (EPI)-linked malaria vaccine implementation was underway. However, in December 2019, a novel pneumonia condition termed coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with many clinical, epidemiological, and biological parallels to malaria, was reported in Wuhan, China. COVID-19 is spreading rapidly, and, as of the 3rd of June, 2020, more than 382,507 persons had died from COVID-19. Children under 5 years who suffer high malaria-attributable mortalities are largely asymptomatic for COVID-19. Considering that the malaria burden is highest in low-income tropical countries with little capacity to fund malaria control and eradication programs, the fight against malaria in these regions is likely to be hampered. Access to healthcare has generally been limited, while malaria interventions, such as seasonal malaria chemotherapy and distribution of insecticide-treated bed nets, have been suspended due to lockdowns. Likewise, the repurposing of antimalarials for treatment of COVID-19 shared symptoms and the shift in focus from the production of malaria rapid diagnostic tests (RDTs) to COVID-19 RDTs is a cause for concern in malaria-endemic regions. Children are less affected by the COVID-19 pandemic compared to the elderly. However, due to the fears of contracting SARS-CoV-2, the elderly who are worst affected by COVID-19 may not take children for malaria medication, resulting in high malaria-related mortalities among children. COVID-19 has disproportionately affected developed countries, threatening their donation capacity. These are likely to thwart malaria control efforts in low-income regions. Here, we present perspectives on the collateral impact of COVID-19 on malaria, especially in Africa.

negative: CSF neopterin, a useful biomarker in children presenting with influenza associated encephalopathy? Abstract Purpose Neurological complications of influenza cause significant disease in children. Central nervous system inflammation, the presumed mechanism of influenza-associated encephalopathy, is difficult to detect. Characteristics of children presenting with severe neurological complications of influenza, and potential biomarkers of influenza-associated encephalopathy are described. Methods A multi-center, retrospective case-series of children with influenza and neurological complications during 2017 was performed. Enrolled cases met criteria for influenza-associated encephalopathy or had status epilepticus. Functional outcome at discharge was compared between groups using the Modified Rankin Scale (mRS). Results There were 22 children with influenza studied of whom 11/22 had encephalopathy and 11/22 had status epilepticus. Only one child had a documented influenza immunization. The biomarker CSF neopterin was tested in 10/11 children with encephalopathy and was elevated in 8/10. MRI was performed in all children with encephalopathy and was abnormal in 8 (73%). Treatment of children with encephalopathy was with corticosteroids or intravenous immunoglobulin in 9/11 (82%). In all cases oseltamivir use was low (59%) while admission to the intensive care unit was frequent (14/22, 66%). Clinical outcome at discharge was moderate to severe disability (mRS score > 2) in the majority of children with encephalopathy (7/11, 64%), including one child who died. Children with status epilepticus recovered to near-baseline function in all cases. Conclusion Raised CSF neopterin was present in most cases of encephalopathy, and along with diffusion restriction on MRI, is a useful diagnostic biomarker. Lack of seasonal influenza vaccination represents a missed opportunity to prevent illness in children, including severe neurological disease.

negative: An investigation of district spatial variations of childhood diarrhoea and fever morbidity in Malawi Although diarrhoea and malaria are among the leading causes of child mortality and morbidity in Sub-Saharan Africa, few detailed studies have examined the patterns and determinants of these ailments in the most affected communities. In this paper, we investigate the spatial distribution of observed diarrhoea and fever prevalence in Malawi using individual data for 10,185 children from the 2000 Malawi Demographic and Health survey. We highlight inequalities in child health by mapping the residual district spatial effects using a geo-additive probit model that simultaneously controls for spatial dependence in the data and potential nonlinear effects of covariates. The residual spatial effects were modelled via a Bayesian approach. For both ailments, we were able to identify a distinct district pattern of childhood morbidity. In particular, the results suggest that children living in the capital city are less affected by fever, although this is not true for diarrhoea, where some urban agglomerations are associated with a higher childhood morbidity risk. The spatial patterns emphasize the role of remoteness as well as climatic, environmental, and geographic factors on morbidity. The fixed effects show that for diarrhoea, the risk of child morbidity appears to be lower among infants who are exclusively breastfed than among those who are mixed-fed. However, exclusive breastfeeding was not found to have a protective effect on fever. An important socio-economic factor for both diarrhoea and fever morbidity was parental education, especially maternal educational attainment. Diarrhoea and fever were both observed to show an interesting association with child's age. We were able to discern the continuous worsening of the child morbidity up to 8–12 months of age. This deterioration set in right after birth and continues, more or less linearly until 8–12 months, before beginning to decline thereafter. Independent of other factors, a separate spatial process produces district inequalities in child's health.

negative: Children's (in)visibility in social vulnerability and the impact of the novel coronavirus (COVID-19). OBJECTIVE To examine the impact of the infection by the novel coronavirus on Brazilian children in situation of social vulnerability based on the Millennium Sustainable Development Goals. METHOD Reflective study based on discursive formulation in three aspects: principles of the objectives and goals for the millennium sustainable development; impact of the pandemic on the health of children and their families living in social vulnerability; and the role of pediatric nursing in the care provided - limits and challenges. RESULTS In January 2020, the news of COVID 19 is released as a pandemic. In Brazil, children and families are still without access to basic rights, thereby increasing their risks of social vulnerability because of the quarantine. The nursing field has an important role in monitoring children and their families, offering guidance in search for solutions and preventing contamination. CONCLUSION There are still challenges to be overcome by the children and their families in situations of vulnerability against COVID-19.

negative: Infection-mediated asthma: etiology, mechanisms and treatment options, with focus on Chlamydia pneumoniae and macrolides Asthma is a chronic respiratory disease characterized by reversible airway obstruction and airway hyperresponsiveness to non-specific bronchoconstriction agonists as the primary underlying pathophysiology. The worldwide incidence of asthma has increased dramatically in the last 40 years. According to World Health Organization (WHO) estimates, over 300 million children and adults worldwide currently suffer from this incurable disease and 255,000 die from the disease each year. It is now well accepted that asthma is a heterogeneous syndrome and many clinical subtypes have been described. Viral infections such as respiratory syncytial virus (RSV) and human rhinovirus (hRV) have been implicated in asthma exacerbation in children because of their ability to cause severe airway inflammation and wheezing. Infections with atypical bacteria also appear to play a role in the induction and exacerbation of asthma in both children and adults. Recent studies confirm the existence of an infectious asthma etiology mediated by Chlamydia pneumoniae (CP) and possibly by other viral, bacterial and fungal microbes. It is also likely that early-life infections with microbes such as CP could lead to alterations in the lung microbiome that significantly affect asthma risk and treatment outcomes. These infectious microbes may exacerbate the symptoms of established chronic asthma and may even contribute to the initial development of the clinical onset of the disease. It is now becoming more widely accepted that patterns of airway inflammation differ based on the trigger responsible for asthma initiation and exacerbation. Therefore, a better understanding of asthma subtypes is now being explored more aggressively, not only to decipher pathophysiologic mechanisms but also to select treatment and guide prognoses. This review will explore infection-mediated asthma with special emphasis on the protean manifestations of CP lung infection, clinical characteristics of infection-mediated asthma, mechanisms involved and antibiotic treatment outcomes.

negative: Clinical recommendations on lung cancer management during the COVID‐19 pandemic Coronavirus disease 2019 (COVID‐19) is spreading worldwide, and has been declared as an international public health concern. Patients with lung cancer are highly susceptible to infection compared to healthy individuals because of systemic immunosuppression induced by malignancy and anticancer therapy. Furthermore, patients with cancer demonstrate poorer outcomes following infection. Hence, patients with lung cancer should be considered a priority group for COVID‐19 prevention. Furthermore, the routine treatment of patients with cancer has been affected during the COVID‐19 pandemic, and patients may not have been able to undergo timely and effective antitumor treatment, thereby indicating a poor prognosis. Here, we provide some suggestions for early identification of COVID‐19 and differential diagnosis in patients with lung cancer who have fever and respiratory symptoms. Our medical team also provide clinical recommendations on lung cancer management during the COVID‐19 pandemic, for carrying out meticulous and individualized clinical management of lung cancer patients and maximum protection to effectively prevent COVID‐19. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: This article provides suggestions for early identification of COVID‐19 and differential diagnosis in patients with lung cancer with fever and respiratory symptoms. WHAT THIS STUDY ADDS: This article makes clinical recommendations on lung cancer management during the COVID‐19 pandemic.

negative: Exploring Opportunities for Household-Level Chronic Care Management Using Linked Electronic Health Records of Adults and Children: A Retrospective Cohort Study OBJECTIVE: Linking electronic health records (EHR) of pediatric and adult patients living in the same household has the potential to improve chronic care management efficiencies by facilitating the delivery of services to multiple household members at once. However, little is known about relationship between the chronic medical (CM) and behavioral health (CBH) of adults and children living in common households. METHODS: EHR data for children were linked to the EHR data of adults living at the same address during the same time in a retrospective cohort study from 2006 to 2014 to evaluate associations between adult and child CM and CBH conditions within a Boston safety-net primary care patient sample. RESULTS: Of the 13,845 included children, 61.6% lived with at least one adult with ≥ 1 CM or CBH condition. Compared to children living with an adult(s) without a chronic condition, children living with an adult with a CM or CBH condition had a respective 16.2% and 18.1% increased likelihood of having a chronic condition themselves, with multiple adult chronic conditions in adults increasing children's likelihood. CONCLUSIONS FOR PRACTICE: We found a positive association between the chronic diseases of adult and child household members. Given the clustering of child and adult chronic disease within households, using EHR data to support the care management needs of multiple members of households may be a promising approach to improving child and adult health in safety-net settings.

negative: Childhood acute basilar artery thrombosis successfully treated with mechanical thrombectomy using stent retrievers: case report and review of the literature. INTRODUCTION Acute basilar artery occlusion (ABAO) is an infrequent but potentially fatal cause of strokes in both adults and children, and it is usually due to vertebral artery dissection (VAD). VAD has been found to be usually a consequence of traumatic vertebral artery injury. ABAO usually presents with symptoms of acute ischemic stroke (AIS) of the posterior circulation or transient ischemic attack (TIA). It may lead to death or long-term disability if not promptly recanalized. Basilar artery recanalization in children can be achieved safely and with excellent clinical outcome using endovascular thrombectomy with the new generation self-expanding and retrievable stents. CLINICAL PRESENTATION We report the case of a 23-month old baby that came to the emergency room of our hospital for progressive impairment of consciousness associated with widespread stiffness and plaintive cry, appeared after accidental fall from stroller. An emergency brain CT scan was obtained showing multiple infarction lesions in the brainstem and left cerebellum suggestive of acute stroke in posterior circulation territories. An MR scan with angiography and diffusion-weighted sequences confirmed the multiple infarction lesions and demonstrated poor representation of the flow signal at the V3 segment of the left vertebral artery and absent representation of the flow signal at the distal segment of the basilar artery suggestive of acute thrombotic occlusion. The patient was immediately referred to interventional neuroradiology unit, and digital subtraction angiography showed complete basilar artery occlusion and left vertebral artery dissection at extracranial V2-V3 segment. The patient underwent intra-arterial thrombectomy using stent retrievers and occlusion of the V2-V3 segment of the left vertebral artery. The patient survived and long-term outcome was excellent. CONCLUSIONS To our knowledge, only nine cases of ABAO in children treated with intra-arterial thrombectomy have been previously reported in the literature. In only three cases, the Solitaire stent was applied. Our case is the first case of basilar artery occlusion treated with Solitaire stent, in a child under 24 months. The reports that are available so far indicate that basilar artery recanalization in children can be achieved safely and with excellent clinical outcome using endovascular thrombectomy with the new generation self-expanding and retrievable stents.

negative: Review of Artificial Intelligence Techniques in Imaging Data Acquisition, Segmentation and Diagnosis for COVID-19 (This paper was submitted as an invited paper to IEEE Reviews in Biomedical Engineering on April 6, 2020.) The pandemic of coronavirus disease 2019 (COVID-19) is spreading all over the world. Medical imaging such as X-ray and computed tomography (CT) plays an essential role in the global fight against COVID-19, whereas the recently emerging artificial intelligence (AI) technologies further strengthen the power of the imaging tools and help medical specialists. We hereby review the rapid responses in the community of medical imaging (empowered by AI) toward COVID-19. For example, AI-empowered image acquisition can significantly help automate the scanning procedure and also reshape the workflow with minimal contact to patients, providing the best protection to the imaging technicians. Also, AI can improve work efficiency by accurate delination of infections in X-ray and CT images, facilitating subsequent quantification. Moreover, the computer-aided platforms help radiologists make clinical decisions, i.e., for disease diagnosis, tracking, and prognosis. In this review paper, we thus cover the entire pipeline of medical imaging and analysis techniques involved with COVID-19, including image acquisition, segmentation, diagnosis, and follow-up. We particularly focus on the integration of AI with X-ray and CT, both of which are widely used in the frontline hospitals, in order to depict the latest progress of medical imaging and radiology fighting against COVID-19.

negative: Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID): Study Design and Rationale BACKGROUND: As the COVID-19 pandemic developed, reports of neurological dysfunctions spanning the central and peripheral nervous systems have emerged. The spectrum of acute neurological dysfunctions may implicate direct viral invasion, para-infectious complications, neurological manifestations of systemic diseases, or co-incident neurological dysfunction in the context of high SARS-CoV-2 prevalence. A rapid and pragmatic approach to understanding the prevalence, phenotypes, pathophysiology and prognostic implications of COVID-19 neurological syndromes is urgently needed. METHODS: The Global Consortium to Study Neurological dysfunction in COVID-19 (GCS-NeuroCOVID), endorsed by the Neurocritical Care Society (NCS), was rapidly established to address this need in a tiered approach. Tier-1 consists of focused, pragmatic, low-cost, observational common data element (CDE) collection, which can be launched immediately at many sites in the first phase of this pandemic and is designed for expedited ethical board review with waiver-of-consent. Tier 2 consists of prospective functional and cognitive outcomes assessments with more detailed clinical, laboratory and radiographic data collection that would require informed consent. Tier 3 overlays Tiers 1 and 2 with experimental molecular, electrophysiology, pathology and imaging studies with longitudinal outcomes assessment and would require centers with specific resources. A multicenter pediatrics core has developed and launched a parallel study focusing on patients ages <18 years. Study sites are eligible for participation if they provide clinical care to COVID-19 patients and are able to conduct patient-oriented research under approval of an internal or global ethics committee. Hospitalized pediatric and adult patients with SARS-CoV-2 and with acute neurological signs or symptoms are eligible to participate. The primary study outcome is the overall prevalence of neurological complications among hospitalized COVID-19 patients, which will be calculated by pooled estimates of each neurological finding divided by the average census of COVID-19 positive patients over the study period. Secondary outcomes include: in-hospital, 30 and 90-day morality, discharge modified Rankin score, ventilator-free survival, ventilator days, discharge disposition, and hospital length of stay. RESULTS: In a one-month period (3/27/20–4/27/20) the GCS-NeuroCOVID consortium was able to recruit 71 adult study sites, representing 17 countries and 5 continents and 34 pediatrics study sites. CONCLUSIONS: This is one of the first large-scale global research collaboratives urgently assembled to evaluate acute neurological events in the context of a pandemic. The innovative and pragmatic tiered study approach has allowed for rapid recruitment and activation of numerous sites across the world—an approach essential to capture real-time critical neurological data to inform treatment strategies in this pandemic crisis.

negative: COVID‐19, food and nutrition insecurity and the wellbeing of children, pregnant and lactating women: A complex syndemic Globally, the COVID‐19 pandemic has already led to major increases in unemployment and is expected to lead to unprecedented increases in poverty and food insecurity, as well as poor health and nutrition outcomes. Families where young children, pregnant and lactating women live need to be protected against the ongoing protracted pandemic and the aftershocks that are very likely to follow for years to come. The future wellbeing of the vast majority of the world now depends on reconfiguringthe current ineffective food, nutrition, health and social protection systems to ensure food security for all. Because food, nutrition and social protection are intimately linked with health in a multidirectional way, it is essential that that we fully address global and local food, health care, and social protection systems and the inter‐relationship among them. Implementation science research will be needed to fill in the current major gaps. Not doing so will not only put the development of individuals at further risk, but also negatively impact on the development potential of entire nations and ultimately our Planet.

negative: Smoking, SARS-CoV-2 and COVID-19: A review of reviews considering implications for public health policy and practice INTRODUCTION: There has been significant speculation regarding the association between the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pathogen, coronavirus disease (COVID-19) and smoking. We provide an overview of the available literature regarding the association between smoking, risk of SARS-CoV-2 infection, and risk of severe COVID-19 and poor clinical outcomes, with the aim of informing public health policy and practice, particularly in England. METHODS: Publications were identified utilising a systematic search approach on PUBMED and Google Scholar. Publications presenting a systematic review or meta-analysis considering the association between smoking and SARS-COV-2 infection or COVID-19 outcomes were included. RESULTS: Eight studies were identified. One considered the relationship between smoking and the probability of SARS-CoV-2 infection, three considered the association between COVID-19 hospitalisation and smoking history, and six reviewed the association between smoking history and development of severe COVID-19. One study specifically investigated the risk of mortality. The studies considering risk of severe disease indicate that there is a significant association between COVID-19 and current or ever smoking. CONCLUSIONS: This is a rapidly evolving topic. Current analysis remains limited due to the quality of primary data, although, early results indicate an association between smoking and COVID-19 severity. We highly recommend public health messaging to continue focusing on smoking cessation efforts.

negative: Impact of the COVID-19 Outbreak on the Management of Patients with Cancer The coronavirus SARS-CoV-2 (COVID-19) outbreak is having a profound impact on the management of patients with cancer. In this review, we comprehensively investigate the various aspects of cancer care during the pandemic, taking advantage of data generated in Asia and Europe at the frontline of the COVID-19 pandemic spread. Cancer wards have been subjected to several modifications to protect patients and healthcare professionals from COVID-19 infection, while attempting to maintain cancer diagnosis, therapy, and research. In this setting, the management of COVID-19 infected patients with cancer is particularly challenging. We also discuss the direct and potential remote impacts of the global pandemic on the mortality of patients with cancer. As such, the indirect impact of the pandemic on the global economy and the potential consequences in terms of cancer mortality are discussed. As the infection is spreading worldwide, we are obtaining more knowledge on the COVID-19 pandemic consequences that are currently impacting and may continue to further challenge cancer care in several countries.

negative: A Longitudinal Study on the Mental Health of General Population during the COVID-19 Epidemic in China Abstract In addition to being a public physical health emergency, Coronavirus disease 2019 (COVID-19) affected global mental health, as evidenced by panic-buying worldwide as cases soared. Little is known about changes in levels of psychological impact, stress, anxiety and depression during this pandemic. This longitudinal study surveyed the general population twice - during the initial outbreak, and the epidemic's peak four weeks later, surveying demographics, symptoms, knowledge, concerns, and precautionary measures against COVID-19. There were 1738 respondents from 190 Chinese cities (1210 first-survey respondents, 861 second-survey respondents; 333 respondents participated in both). Psychological impact and mental health status were assessed by the Impact of Event Scale-Revised (IES-R) and the Depression, Anxiety and Stress Scale (DASS-21), respectively. IES-R measures PTSD symptoms in survivorship after an event. DASS -21 is based on tripartite model of psychopathology that comprise a general distress construct with distinct characteristics. This study found that there was a statistically significant longitudinal reduction in mean IES-R scores (from 32.98 to 30.76, p<0.01) after 4 weeks. Nevertheless, the mean IES-R score of the first- and second-survey respondents were above the cut-off scores (>24) for PTSD symptoms, suggesting that the reduction in scores was not clinically significant. During the initial evaluation, moderate-to-severe stress, anxiety and depression were noted in 8.1%, 28.8% and 16.5%, respectively and there were no significant longitudinal changes in stress, anxiety and depression levels (p>0.05). Protective factors included high level of confidence in doctors, perceived survival likelihood and low risk of contracting COVID-19, satisfaction with health information, personal precautionary measures. As countries around the world brace for an escalation in cases, Governments should focus on effective methods of disseminating unbiased COVID-19 knowledge, teaching correct containment methods, ensuring availability of essential services/commodities, and providing sufficient financial support.

negative: The epidemiology of respiratory infections in children()

negative: Using Partial Differential Equation with Google Mobility Data to Model COVID-19 in Arizona The outbreak of COVID-19 disrupts the life of many people in the world. The state of Arizona in the U.S. emerges as one of the country's newest COVID-19 hot spots. Accurate forecasting for COVID-19 cases will help governments to implement necessary measures and convince more people to take personal precautions to combat the virus. It is difficult to accurately predict the COVID-19 cases due to many human factors involved. This paper aims to provide a forecasting model for COVID-19 cases with the help of human activity data from the Google Community Mobility Reports. To achieve this goal, a specific partial differential equation (PDE) is developed and validated with the COVID-19 data from the New York Times at the county level in the state of Arizona in the U.S. The proposed model describes the combined effects of transboundary spread among county clusters in Arizona and human actives on the transmission of COVID-19. The results show that the prediction accuracy of this model is well acceptable (above 94\%). Furthermore, we study the effectiveness of human precautions such as wearing face masks and practicing social distancing on the decrease of COVID-19 cases at the local level. The localized analytical results can be used to help to slow down the spread of COVID-19 in Arizona. To the best of our knowledge, this work is the first attempt to apply PDE models on COVID-19 prediction with the Google Community Mobility Reports.

negative: Clinical features, diagnostics, and outcomes of patients presenting with acute respiratory illness: a comparison of patients with and without COVID-19 BACKGROUND: Emerging data on the clinical presentation, diagnostics, and outcomes of patients with COVID-19 have largely been presented as case series. Few studies have compared these clinical features and outcomes of COVID-19 to other acute respiratory illnesses. METHODS: We examined all patients presenting to an emergency department in San Francisco, California between February 3 and March 31, 2020 with an acute respiratory illness who were tested for SARS-CoV-2. We determined COVID-19 status by PCR and metagenomic next generation sequencing (mNGS). We compared demographics, comorbidities, symptoms, vital signs, and laboratory results including viral diagnostics using PCR and mNGS. Among those hospitalized, we determined differences in treatment (antibiotics, antivirals, respiratory support) and outcomes (ICU admission, ICU interventions, acute respiratory distress syndrome, cardiac injury). FINDINGS: In a cohort of 316 patients, 33 (10%) tested positive for SARS-CoV-2; 31 patients, all without COVID-19, tested positive for another respiratory virus (16%). Among patients with additional viral testing, no co-infections with SARS-CoV-2 were identified by PCR or mNGS. Patients with COVID-19 reported longer symptoms duration (median 7 vs. 3 days), and were more likely to report fever (82% vs. 44%), fatigue (85% vs. 50%), and myalgias (61% vs 27%); p<0.001 for all comparisons. Lymphopenia (55% vs 34%, p=0.018) and bilateral opacities on initial chest radiograph (55% vs. 24%, p=0.001) were more common in patients with COVID-19. Patients with COVID-19 were more often hospitalized (79% vs. 56%, p=0.014). Of 186 hospitalized patients, patients with COVID-19 had longer hospitalizations (median 10.7d vs. 4.7d, p<0.001) and were more likely to develop ARDS (23% vs. 3%, p<0.001). Most comorbidities, home medications, signs and symptoms, vital signs, laboratory results, treatment, and outcomes did not differ by COVID-19 status. INTERPRETATION: While we found differences in clinical features of COVID-19 compared to other acute respiratory illnesses, there was significant overlap in presentation and comorbidities. Patients with COVID-19 were more likely to be admitted to the hospital, have longer hospitalizations and develop ARDS, and were unlikely to have co-existent viral infections. These findings enhance understanding of the clinical characteristics of COVID-19 in comparison to other acute respiratory illnesses.

negative: Regional differences in reported Covid-19 cases show genetic correlations with higher socio-economic status and better health, potentially confounding studies on the genetics of disease susceptibility Background: In March 2020, England showed a rapid increase in Covid-19 cases. Susceptibility for infectious diseases like Covid-19 is likely to be partly genetic. Mapping the genetic susceptibility for Covid-19 outcomes may reveal biological mechanisms that could potentially aid in drug or vaccine developments. However, as the disease spreads unevenly across the country, regional allele frequency differences could become spuriously associated with disease prevalence. Methods: A regional genome-wide association study (RGWAS) was conducted in 396,042 individuals from England to investigate the association between 1.2 million genetic variants and regional differences in daily reported Covid-19 cases from March 1st to April 18th 2020. Results: The polygenic signal increases during the first weeks of March, peaking at March 13th with the measured genetic variants explaining ~3% of the variance, including two genome-wide significant loci. The explained variance starts to drop at the end of March and reaches almost zero on April 18th. The majority of this temporary polygenic signal is due to genes associated with higher educational attainment and better health. Conclusions: The temporary positive relationship between Covid-19 cases and regional socio-economic status (SES) at the beginning of the Covid-19 outbreak may reflect 1) a higher degree of international travelers, 2) more social contacts, and/or 3) better testing capacities in higher SES regions. These signals are in the opposite direction of expected disease risk increasing effects, which has the potential to cancel out signals of interest. Genetic association studies should be aware of the timing and location of cases as this can introduce interfering polygenic signals that reflect regional differences in genes associated with behavior.

negative: Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China: Wu C, Chen X, Cai Y, et al. JAMA Intern Med. doi:10.1001/jamainternmed.2020.0994.

negative: Defining Essential Services for Deaf and Hard of Hearing Children during the COVID-19 Pandemic. COVID-19 is a rapidly growing global pandemic caused by a novel coronavirus. With no vaccine or definitive treatment, public health authorities have recommended a strategy of "social distancing," reducing individual interaction, canceling elective procedures, and limiting nonessential services. Health care providers must determine what procedures are considered "elective," balancing risk of treatment delays with that of coronavirus exposure to patient, family, and providers. Given critical periods for language development and the long-term impact of auditory deprivation, some audiologic and otologic services should be considered essential. In this article, we describe the experience of a quaternary referral pediatric hospital in Seattle, the epicenter of COVID-19 in the United States, and share strategies for risk minimization employed by Seattle Children's Hospital. We hope that this work can be a reference for other centers continuing care for children who are deaf and hard of hearing during the COVID-19 and future resource-limiting crises.

negative: Should we wait or not? The preferable option for patients with stage IV oral cancer in COVID‐19 pandemic BACKGROUND: The coronavirus infection is rapidly spreading, putting a strain on health care services across the globe. Patients with oral cancer are susceptible often immunosuppressed due to the disease and/or the treatment received. METHODS: We performed a simulation of the currently available data using a multistate and hazards model to provide an objective model for counseling and decision making for health care workers. RESULTS: Stage IV patients with oral cancer who did not receive treatment had progression of disease and an increased mortality rate compared to patients who receive treatment but did not contract COVID‐19. The patients who received treatment and got affected with COVID‐19 had a far worse impact and higher mortality rate than all other groups. CONCLUSION: Isolation and deferring treatment for stage IV patients with oral cancer, so as to avoid hospital visits and contraction of COVID‐19, is an advisable strategy based on this model.

negative: COVID-19, school closures, and child poverty: a social crisis in the making

negative: Letter to the editor: Evidence on school closure and children’s social contact: useful for coronavirus disease (COVID-19)?

negative: Intimate Partner Violence Victimization and Perpetration among U.S. Adults during COVID-19: A Brief Report Importance: Anecdotal evidence such as increased calls to domestic violence (DV) hotlines across the globe suggest that there may be an increase of IPV prevalence in association with the COVID-19 outbreak; however, no study has investigated this phenomenon empirically. Objective: To evaluate the association between COVID-19 related conditions and recent use or experience of IPV (since the pandemic outbreak in the U.S). Design, Setting, and Participants: This cross-sectional study analyzed data collected online from a sample of noninstitutionalized adults (age 18+) in the U.S. (N=2,045). More than half of the sample self-identified as being in an intimate relationship at the time of the study. Main Outcomes and Measures: A four-item tool was used to assess IPV perpetration and victimization since the outbreak of COVID-19. The rapid tool inquired about two forms of IPV, psychological and physical. Participants self-reported demographic data and recent health histories, including COVID-19 tests results, related symptoms and degree of personal social distancing. We hypothesized that COVID-19 related factors would increase risks of IPV. Results: In this study, self-reported COVID-19 impacted respondents had an increased risk of IPV victimization and perpetration. Among those who reported having symptoms consistent with coronavirus, but were denied access to testing, psychological IPV victimization was 3 times greater than those who did not (Exp[B] =3.15, [1.19, 2.29] p <.05). For participants who reported testing positive to COVID-19, the odds of using psychological IPV (Exp[B] =3.24, [1.18, 8.89] p <.05) and physical IPV (Exp[B]=3.02, [1.12, 8.17] p <.05) against an intimate partner increased by more than 3 times. Conclusions and Relevance: Patient education and community outreach/health care system initiatives focused on IPV risk behaviors may help reduce the potential development of IPV. Continued surveillance is imperative to improve health and well-being along with effective intervention development and implementation.

negative: The burden, admission, and outcome of COVID-19 in Africa: protocol for a systematic review and meta-analysis Background: According to the World Health Organization (WHO), the outbreak of coronavirus disease in 2019 (COVID-19) has been declared as pandemic and public health emergency that infected more than 5 million people worldwide at the time of writing this protocol. Strong evidence for the burden, admission, and outcome of COVID-19 has not been published in Africa. Therefore, this protocol will be served as a guideline to conduct a systematic review and meta-analysis of the burden, admission, and outcome of COVID-19 in Africa. Methods: Published and unpublished studies on the burden, admission, and outcome of COVID-19 in Africa and written in any language will be included. Databases (PubMed / MEDLINE, Google Scholar, Google, EMBASE, Web of Science, Microsoft Academic, WHO COVID-19 database, Cochran Library, Africa Wide Knowledge, and Africa Index Medicus) from December 2019 to May 2020 will be searched. Two independent reviewers will select, screen, extract data, and assess the risk of bias. The proportion will be measured using a random-effects model. Subgroup analysis will be conducted to manage hetrogeinity. The presence of publication bias will be assessed using Egger's test and visual inspection of the funnel plots. This systematic and meta-analysis review protocol will be reported per the PRISMA-P guidelines. Conclusion: This systematic review and meta-analysis protocol will be expected to quantify the burden, admission, and outcome of COVID-19 in Africa. Systematic review registration: This protocol was submitted for registration with the International Prospective Register of Systematic Reviews (PROSPERO) in March 2020 and accepted with the registration number: CRD42020179321(https://www.crd.york.ac.uk/PROSPERO).

negative: Assessing racial and ethnic disparities using a COVID-19 outcomes continuum for New York State PURPOSE: Heightened COVID-19 mortality among Black non-Hispanic and Hispanic communities (relative to white non-Hispanic) is well established. This study aims to estimate the relative contributions to fatality disparities in terms of differences in SARS-CoV-2 infections, diagnoses, and disease severity. METHODS: We constructed COVID-19 outcome continua (similar to the HIV care continuum) for white non-Hispanic, Black non-Hispanic, and Hispanic adults in New York State. For each stage in the COVID-19 outcome continua (population, infection experience, diagnosis, hospitalization, fatality), we synthesized the most recent publicly-available data. We described each continuum using overall percentages, fatality rates, and relative changes between stages, with comparisons between race and ethnicity using risk ratios. RESULTS: Estimated per-population COVID-19 fatality rates were 0.03%, 0.18%, and 0.12% for white non-Hispanic, Black non-Hispanic, and Hispanic adults. The 3.48-fold disparity for Hispanic, relative to white, communities was explained by differences in infection-experience, whereas the 5.38-fold disparity for non-Hispanic Black, relative to white, communities was primarily driven by differences in both infection-experience and in the need for hospitalization, given infection. CONCLUSIONS: These findings suggest the most impactful stages upon which to intervene with programs and policies to build COVID-19 health equity.

negative: Impact of COVID -19 on children: special focus on the psychosocial aspect Although medical literature shows that children are minimally susceptible to 2019-Corona virus disease (COVID-19), they are hit the hardest by psychosocial impact of this pandemic. Being quarantined in homes and institutions may impose greater psychological burden than the physical sufferings caused by the virus. School closure, lack of outdoor activity, aberrant dietary and sleeping habits are likely to disrupt children's usual lifestyle and can potentially promote monotony, distress, impatience, annoyance and varied neuropsychiatric manifestations. Incidences of domestic violence, child abuse, adulterated online contents are on the rise. Children of single parent and frontline workers suffer unique problems. The children from marginalized communities are particularly susceptible to the infection and may suffer from extended ill-consequences of this pandemic, such as child labor, child trafficking, child marriage, sexual exploitation and death etc. Parents, pediatricians, psychologists, social workers, hospital authorities, government and non-governmental organizations have important roles to play to mitigate the psychosocial ill-effects of COVID-19 on children and adolescents. To provide the basic amenities, social security, medical care, and to minimize the educational inequities among the children of the different strata of the society are foremost priorities.

negative: Pulmonary exacerbations and clinical outcomes in a longitudinal cohort of infants and preschool children with cystic fibrosis BACKGROUND: Pulmonary exacerbations (PEx) in school aged children and adults with cystic fibrosis (CF) lead to increased morbidity and lung function decline. However, the effect of exacerbations in young children with CF is not fully understood. We sought to characterize the frequency and clinical impact of PEx in a pilot study of infants and pre-school aged children with CF. METHODS: Thirty young children with CF [median (range) 1.5 years (0.2–4.9)] were prospectively followed for 2 years. Exacerbation frequency (hospitalizations and outpatient antibiotic use) was determined. Chest radiographs were performed at enrollment and study completion and assigned a Brasfield score. Lung function at age 7 years was assessed in a subset of children. The association between PEx frequency, chest radiograph score, and lung function was determined using Spearman correlation coefficients and corresponding 95% confidence intervals. Correlations with an absolute magnitude of 0.3 or greater were considered clinically significant. RESULTS: Over 2 years, participants experienced a median of two PEx (range 0–13). Chest radiograph scores at enrollment and study completion were inversely associated with PEx frequency (R = −0.48 and R = −0.44, respectively). The association between frequency of PEx and lung function [forced expiratory volume in 1 s (FEV(1))] at age 7 years was small (R = 0.20). Higher forced vital capacity (FVC) at 7 years was associated with more frequent PEx during the study (R = 0.44). CONCLUSIONS: Children with worse chest radiograph scores had more frequent PEx over the subsequent 2 years, suggesting a group of patients at higher risk for PEx. Frequent PEx in infants and young children with CF were not associated with lower FEV(1) and FVC at 7 years, although spirometry in this age group may not be a sensitive marker of mild lung disease and disease progression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12890-017-0546-8) contains supplementary material, which is available to authorized users.

negative: Related Health Factors of Psychological Distress During the COVID-19 Pandemic in Spain Measures to prevent and contain the COVID-19 health crisis include population confinement, with the consequent isolation and interruption of their usual activities. The aim of the study is to analyse psychological distress during the COVID-19 pandemic. For this, a cross-sectional observational study with a sample of 4180 people over the age of 18 during quarantine was developed. Variables considered were sociodemographic variables, physical symptoms, health conditions, COVID-19 contact history and psychological adjustment. The data were collected through a self-developed questionnaire and the General Health Questionnaire (GHQ-12). Bivariate analyses were performed, including Chi-Squared test and Student’s T-test. Predictive ability was calculated through logistic regression. Results obtained showed a high level of psychological distress (72.0%), with a higher percentage in women and people of lower middle age. Statistically significant differences were found in the variable working situation (χ² = 63.139, p ≤ 0.001, V = 0.123) and living with children under the age of 16 (χ² = 7.393, p = 0.007, V = 0.042). The predictive variables with the highest weight were sex (OR = 1.952, 95% IC = (1.667, 2.286)), presence of symptoms (OR = 1.130, 95% CI = (1.074, 1.190)), and having had close contact with an individual with confirmed COVID-19 (OR = 1.241, 95% CI = (1.026, 1.500)). These results could enrich prevention interventions in public health and, in particular, in mental health in similar pandemic situations.

negative: 18F-Fluorocholine uptake matching CT lesions in the lungs of a patient clinically cured from COVID-19 syndrome

negative: COVID-19 Emergence and Social and Health Determinants in Colorado: A Rapid Spatial Analysis The aim of this rapid analysis was to investigate the spatial patterns of COVID-19 emergence across counties in Colorado. In the U.S. West, Colorado has the second highest number of cases and deaths, second only to California. Colorado is also reporting, like other states, that communities of color and low-income persons are disproportionately affected by COVID-19. Using GIS and correlation analysis, this study explored COVID-19 incidence and deaths from March 14 to April 8, 2020, with social determinants and chronic conditions. Preliminary results demonstrate that COVID-19 incidence intensified in mountain communities west of Denver and along the Urban Front Range, and evolved into new centers of risk in eastern Colorado. Overall, the greatest increase in COVID-19 incidence was in northern Colorado, i.e., Weld County, which reported the highest rates in the Urban Front Range. Social and health determinants associated with higher COVID-19-related deaths were population density and asthma, indicative of urban areas, and poverty and unemployment, suggestive of rural areas. Furthermore, a spatial overlap of high rates of chronic diseases with high rates of COVID-19 may suggest a broader syndemic health burden, where comorbidities intersect with inequality of social determinants of health.

negative: An International Review of Tobacco Use and the COVID-19 Pandemic: Examining Hospitalization, Asymptomatic Cases, and Severity Background and objectives: Since the World Health Organization (WHO) declared a public health emergency of imminent concern in March 2020, the novel coronavirus (SARS-CoV-2) and its related disease (COVID-19) has become a topic of much-needed research. This study primarily focused on what effect smoking had on hospitalization; however, asymptomaticity and severity were discussed. Data: Data was collected through searches on databases including PubMed and Google Scholar. Eligibility criteria included being RT-PCR verified and including smoking data. Discussion: This study found that smokers were significantly underrepresented in COVID-19 hospitalization on a purely epidemiological level in some areas, including China and Manhattan, but not others: Seattle, Greater New York City Area, and Italy. Furthermore, smokers were equally represented in asymptomatic populations, but smokers will likely experience a more severe manifestation of the disease if they are symptomatic. Further inquiry into possible mechanisms by which the observed epidemiological effect is necessary, as it has implications for recommendations on loosening restrictions on social distancing measures. Conclusions and Recommendations: This study recommends that smokers consider themselves to be at higher risk for COVID-19, as they may experience a more severe manifestation of the disease. Health care providers and policymakers should consider smokers at higher risk as well, as there is evidence to claim that smokers may contract a more severe form of COVID-19.

negative: Association of hypertension, diabetes, stroke, cancer, kidney disease, and high-cholesterol with COVID-19 disease severity and fatality: a systematic review Objective: To undertake a review and critical appraisal of published/preprint reports that offer methods of determining the effects of hypertension, diabetes, stroke, cancer, kidney issues, and high-cholesterol on COVID-19 disease severity. Data sources: Google Scholar, PubMed, COVID-19 Open Research Dataset: a resource of over 128,000 scholarly articles, including over 59,000 articles with full text related to COVID-19, SARS-CoV-2, and coronaviruses. Methods: A search was conducted by two authors independently on the freely available COVID-19 Open Research Dataset (CORD-19). We developed an automated search engine to screen a total of 59,000 articles in a few seconds. The search engine was built using a retrieval function that ranks a set of documents based on the query terms appearing in each document regardless of their proximity within the document. Filtering of the articles was then undertaken using keywords and questions, e.g. "Effects of diabetes on COVID/normal coronavirus/SARS-CoV-2/nCoV/COVID-19 disease severity, mortality?". The search terms were repeated for all the comorbidities considered in this paper. Additional articles were retrieved by searching via Google Scholar and PubMed. Findings: A total of 54 articles were considered for a full review. It was observed that diabetes, hypertension, and cholesterol levels possess an apparent relation to COVID-19 severity. Other comorbidities, such as cancer, kidney disease, and stroke, must be further evaluated to determine a strong relationship to the virus. Reports associating cancer, kidney disease, and stroke with COVID-19 should be carefully interpreted, not only because of the size of the samples, but also because patients could be old, have a history of smoking, or have any other clinical condition suggesting that these factors might be associated with the poor COVID-19 outcomes rather than the comorbidity itself. Such reports could lead many oncologists and physicians to change their treatment strategies without solid evidence and recommendations. Further research regarding this relationship and its clinical management is warranted. Additionally, treatment options must be examined further to provide optimal treatment and ensure better outcomes for patients suffering from these comorbidities. It should be noted that, whether definitive measurements exist or not, the care of patients as well as the research involved should be largely prioritized to tackle this deadly pandemic.

negative: Parents’ perceptions on physical activity for their children with autism spectrum disorders during the novel Coronavirus outbreak Considering that parents are one of the key figures in their child’s participation in physical activity, it is extremely important to examine parents’ perceptions and experiences of physical activity in order to protect children with Autism Spectrum Disorders (ASD) from the inactive life during the novel Coronavirus (COVID-19) outbreak and to include them in physical activities in the home environment. Although it is still a new subject, there is no research that addresses parents’ physical activity knowledge, needs and recommendations for the physical activity experiences of children with ASD during the COVID-19 outbreak, and offers solutions accordingly. Considering this gap in the literature, the aim of this qualitative study is to explore parents’ perceptions on physical activity for their children with ASD. Participants of the study were 10 parents with children with ASD, who participated in one-to-one semi-structured phone calls. Interview data were analyzed thematically. The analysis of the data revealed three main themes: 1) Possible benefits of physical activity during the COVID-19 outbreak, 2) Physical activity barriers during the COVID-19 outbreak, and 3) Recommendations for physical activity during the COVID-19 outbreak. The results revealed that parents thought that physical activities had a positive effect on the development areas of their children with ASD. It was determined that parents want to involve their children in physical activities in the home environment, but they have barriers that they need to overcome.

negative: The need for urogenital tract monitoring in COVID-19 Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2, which invades a cell through binding to the ACE2 receptor and TMPRSS2 priming. Patients with severe disease predominantly present with pneumonia-related symptoms. However, evidence suggests that COVID-19 infection also has implications for the urogenital tract. Thus, urogenital organs should be considered when treating COVID-19.

negative: COVID-19 and addiction BACKGROUND AND AIMS: 2019-coronavirus disease (COVID-19) is causing insurmountable psychosocial impact on the whole mankind. Marginalized community, particularly those with substance use disorders (SUD), are particularly vulnerable to contract the infection and also likely to suffer from greater psychosocial burden. This article analyses the intricate bi-directional relationship between COVID-19 and addiction. METHODS: Pubmed and Google Scholar are searched with the following key terms- “COVID-19”, “SARS-CoV2”, “Pandemic”, “Addiction”, “Opioid”, “Alcohol”, “Smoking”, “Addiction Psychiatry”, “Deaddiction”, “Substance use disorders”, “Behavioral addiction”. Few newspaper reports related to COVID-19 and addiction have also been added as per context. RESULTS: People with SUD are at greater risk of worse COVID-19 outcome. There is surge of addictive behaviors (both new and relapse) including behavioral addiction in this period. Withdrawal emergencies and death are also being increasingly reported. Addicted people are especially facing difficulties in accessing the healthcare services which are making them prone to procure drugs in illegal means. CONCLUSION: COVID-19 and addiction are the two pandemics which are on the verge of collision causing major public health threat. While every effort must be taken to make the public aware of deleterious effects of SUD on COVID-19 prognosis, the resumption of deaddiction services and easier accessibility of prescription drugs are needs of the hour.

negative: Personalized Risk–Benefit Ratio Adaptation of Breast Cancer Care at the Epicenter of COVID‐19 Outbreak Northern Italy has been one of the European regions reporting the highest number of COVID‐19 cases and deaths. The pandemic spread has challenged the National Health System, requiring reallocation of most of the available health care resources to treat COVID‐19‐positive patients, generating a competition with other health care needs, including cancer. Patients with cancer are at higher risk of developing critical illness after COVID‐19 infection. Thus, mitigation strategies should be adopted to reduce the likelihood of infection in all patients with cancer. At the same time, suboptimal care and treatments may result in worse cancer‐related outcome. In this article, we attempt to estimate the individual risk–benefit balance to define personalized strategies for optimal breast cancer management, avoiding as much as possible a general untailored approach. We discuss and report the strategies our Breast Unit adopted from the beginning of the COVID‐19 outbreak to ensure the continuum of the best possible cancer care for our patients while mitigating the risk of infection, despite limited health care resources. IMPLICATIONS FOR PRACTICE: Managing patients with breast cancer during the COVID‐19 outbreak is challenging. The present work highlights the need to estimate the individual patient risk of infection, which depends on both epidemiological considerations and individual clinical characteristics. The management of patients with breast cancer should be adapted and personalized according to the balance between COVID‐19‐related risk and the expected benefit of treatments. This work also provides useful suggestions on the modality of patient triage, the conduct of clinical trials, the management of an oncologic team, and the approach to patients’ and health workers’ psychological distress.

negative: Viral infections in allergy and immunology: How allergic inflammation influences viral infections and illness Viral respiratory tract infections are associated with asthma inception in early life and asthma exacerbations in older children and adults. Although how viruses influence asthma inception is poorly understood, much research has focused on the host response to respiratory viruses and how viruses can promote; or how the host response is affected by subsequent allergen sensitization and exposure. This review focuses on the innate interferon-mediated host response to respiratory viruses and discusses and summarizes the available evidence that this response is impaired or suboptimal. In addition, the ability of respiratory viruses to act in a synergistic or additive manner with TH2 pathways will be discussed. In this review we argue that these 2 outcomes are likely linked and discuss the available evidence that shows reciprocal negative regulation between innate interferons and TH2 mediators. With the renewed interest in anti-TH2 biologics, we propose a rationale for why they are particularly successful in controlling asthma exacerbations and suggest ways in which future clinical studies could be used to find direct evidence for this hypothesis.

negative: Double umbilical cord blood transplantation for children and adolescents Umbilical cord blood transplantation (UCBT) with two units has been conducted with promising results in adults to overcome the limitation of low cell numbers. In an attempt to improve the outcomes, double UCBT was performed in children and adolescents. Sixty-one patients, including 44 acute leukemia, and 17 other hematologic diseases, received double UCBT. Donor-type engraftment achieved in 82% of patients. Except one patient with persistent mixed chimerism of two units, other 49 patients showed dominancy of one unit and only the CFU-GM was significant factor influencing dominancy. The event-free survival (EFS) of leukemia and other hematologic disease were 59% and 53%, respectively, and the EFS of acute leukemia patients who received transplant in first or second CR (68.6%) was significantly better than in those with advanced disease (22.2%) (P = 0.007). Among the factors influencing outcomes, low cell dose difference between two units (TNC difference/TNC of large unit <15%) were associated with higher TRM, relapse, and lower EFS. Double UCBT was a promising modality of transplant in children and adolescence. However, engraftment and other results were not so satisfactory yet. To improve the outcomes, development of new selection guideline, probably including cell dose difference between two units and technology to enhance engraftment and reduce transplantation-related mortality are warranted.

negative: Varying Presentations and Favourable Outcomes of COVID-19 Infection in Children and Young Adults with Sickle Cell Disease: An Additional Case Series with Comparisons to Published Cases. Patients with sickle cell disease (SCD) are theoretically at greater risk for serious illness from COVID 19 due to the underlying pathophysiology of chronic inflammation with an increased risk of thrombosis, especially at the time of a vaso-occlusive event (1). Individuals living with SCD are also considered to be immunocompromised due to autoinfarction of their spleen or surgical splenectomy, often as a result of red cell splenic sequestration (2). In addition, patients with SCD often have comorbidities and secondary organ dysfunction that can put them at risk of significant morbidity and or mortality from the severe acute respiratory coronavirus 2 (SARS-CoV-2), and its subsequent disease COVID-19.

negative: Facing the COVID-19 outbreak in children with cancer Europe is now the epicenter of the COVID-19 outbreak. Many concerns have arisen about the management and treatment of children with cancer while researchers are wondering how to deal with this devastating pandemic. In view of the epidemiological and clinical characteristics of the COVID-19 outbreak, it is fundamental to stress that the behavior and hygiene rules adopted by children with cancer must be respected and implemented in order to continue to safeguard their health for the current pandemic.

negative: A compendium answering 150 questions on COVID‐19 and SARS‐CoV‐2 In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID‐19). This disease, caused by the severe acute respiratory syndrome‐related coronavirus 2 (SARS‐CoV‐2), has developed into a pandemic. To date it has resulted in ~6.5 million confirmed cases and caused almost 400,000 related deaths worldwide. Unequivocally, the COVID‐19 pandemic is the gravest health and socio‐economic crisis of our time. In this context, numerous questions have emerged in demand of basic scientific information and evidence‐based medical advice on SARS‐CoV‐2 and COVID‐19. Although the majority of the patients show a very mild, self‐limiting viral respiratory disease, many clinical manifestations in severe patients are unique to COVID‐19, such as severe lymphopenia and eosinopenia, extensive pneumonia, a “cytokine storm” leading to acute respiratory distress syndrome, endothelitis, thrombo‐embolic complications and multiorgan failure. The epidemiologic features of COVID‐19 are distinctive and have changed throughout the pandemic. Vaccine and drug development studies and clinical trials are rapidly growing at an unprecedented speed. However, basic and clinical research on COVID‐19‐related topics should be based on more coordinated high‐quality studies. This paper answers pressing questions, formulated by young clinicians and scientists, on SARS‐CoV‐2, COVID‐19 and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development and epidemiology. Over 140 questions were answered by experts in the field providing a comprehensive and practical overview of COVID‐19 and allergic disease.

negative: The cardiovascular burden of coronavirus disease 2019 (COVID-19) with a focus on congenital heart disease Abstract Coronavirus disease 2019 (COVID-19), caused by a novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first described in a cluster of patients presenting with pneumonia symptoms in Wuhan, China, in December of 2019. Over the past few months, COVID-19 has developed into a worldwide pandemic, with over 400,000 documented cases globally as of March 24, 2020. The SARS-CoV-2 virus is most likely of zoonotic origin, but has been shown to have effective human-to-human transmission. COVID-19 results in mild symptoms in the majority of infected patients, but can cause severe lung injury, cardiac injury, and death. Given the novel nature of COVID-19, no established treatment beyond supportive care exists currently, but extensive public-health measures to reduce person-to-person transmission of COVID-19 have been implemented globally to curb the spread of disease, reduce the burden on healthcare systems, and protect vulnerable populations, including the elderly and those with underlying medical comorbidities. Since this is an emerging infectious disease, there is, as of yet, limited data on the effects of this infection on patients with cardiovascular disease, particularly so for those with congenital heart disease. We summarize herewith the early experience with COVID-19 and consider the potential applicability to and implications for patients with cardiovascular disease in general and congenital heart disease in particular.

negative: Protecting children from iatrogenic harm during COVID19 pandemic Critical care management of patients with COVID‐19 has been influenced by a mixture of public, media and societal pressure, as well as clinical and anecdotal observations from many prominent researchers and key opinion leaders. These factors may have affected the principles of evidence‐based medicine and encouraged the widespread use of non‐tested pharmacological and aggressive respiratory support therapies, even in intensive care units (ICUs). The COVID‐19 pandemic has predominantly affected adult populations, while children appear to be relatively spared of severe disease. Notwithstanding, paediatric intensive care (PICU) clinicians may already have been influenced by changes in practices of adult ICUs, and these changes may pose unintended consequences to the vulnerable population in the PICU. In this article, we analyse several potential iatrogenic causes of the detrimental effects of the current pandemic to children and highlight the risks underlying a sudden change of clinical practice.

negative: Interpreting COVID-19 and Virtual Care Trends: Cohort Study BACKGROUND: The coronavirus disease (COVID-19) pandemic is rapidly spreading across the world. As of March 26, 2020, there are more than 500,000 cases and more than 25,000 deaths related to COVID-19, and the numbers are increasing by the hour. OBJECTIVE: The aim of this study was to explore the trends in confirmed COVID-19 cases in North Carolina, and to understand patterns in virtual visits related to symptoms of COVID-19. METHODS: We conducted a cohort study of confirmed COVID-19 cases and patients using an on-demand, statewide virtual urgent care center. We collected data from February 1, 2020, to March 15, 2020. Institutional Review Board exemption was obtained prior to the study. RESULTS: As of March, 18 2020, there were 92 confirmed COVID-19 cases and 733 total virtual visits. Of the total visits, 257 (35.1%) were related to COVID-19-like symptoms. Of the COVID-19-like visits, the number of females was 178 (69.2%). People in the age groups of 30-39 years (n=67, 26.1%) and 40-49 years (n=64, 24.9%) were half of the total patients. Additionally, approximately 96.9% (n=249) of the COVID-like encounters came from within the state of North Carolina. Our study shows that virtual care can provide efficient triaging in the counties with the highest number of COVID-19 cases. We also confirmed that the largest spread of the disease occurs in areas with a high population density as well as in areas with major airports. CONCLUSIONS: The use of virtual care presents promising potential in the fight against COVID-19. Virtual care is capable of reducing emergency room visits, conserving health care resources, and avoiding the spread of COVID-19 by treating patients remotely. We call for further adoption of virtual care by health systems across the United States and the world during the COVID-19 pandemic.

negative: Clinical outcomes in outpatient respiratory syncytial virus infection in immunocompromised children BACKGROUND: Immunocompromised patients are at high risk for morbidity and mortality due to respiratory syncytial virus (RSV) infection. Increasingly, pediatric patients with malignancy or undergoing transplantation are managed primarily as outpatients. Data regarding the clinical presentation and outcomes of RSV in the outpatient pediatric immunocompromised population are limited. METHODS: We performed a retrospective cohort study of children with hematologic malignancy or hematopoietic or solid organ transplant with laboratory‐confirmed RSV infection diagnosed as outpatients at an academic medical center between 2008 and 2013. RESULTS: Of 54 patients with RSV detected while outpatients, 15 (28%) were hospitalized, 7 (13%) received ribavirin, and one (2%) received intravenous immunoglobulin. One (2%) patient was critically ill, but there were no deaths due to RSV infection. Fever (P < 0·01) was associated with increased risk of hospitalization. CONCLUSIONS: Most immunocompromised children with RSV detected while outpatients did not require hospitalization or receive antiviral treatment. Potential studies of RSV therapies should consider inclusion of patients in an ambulatory setting.

negative: Hospital course and discharge criteria for children hospitalized with bronchiolitis BACKGROUND: For children hospitalized with bronchiolitis, there is uncertainty about the expected inpatient clinical course and when children are safe for discharge. OBJECTIVES: Examine the time to clinical improvement, risk of clinical worsening after improvement, and develop discharge criteria. DESIGN: Prospective multiyear cohort study. SETTING: Sixteen US hospitals. PARTICIPANTS: Consecutive hospitalized children age <2 years with bronchiolitis. MEASUREMENT: We defined clinical improvement using: (1) retraction severity, (2) respiratory rate, (3) room air oxygen saturation, and (4) hydration status. After meeting improvement criteria, children were considered clinically worse based on the inverse of ≥1 of these criteria or need for intensive care. RESULTS: Among 1916 children, the median number of days from onset of difficulty breathing until clinical improvement was 4 (interquartile range, 3–7.5 days). Of the total, 1702 (88%) met clinical improvement criteria, with 4% worsening (3% required intensive care). Children who worsened were age <2 months (adjusted odds ratio [AOR]: 3.51; 95% confidence interval [CI]: 2.07‐5.94), gestational age <37 weeks (AOR: 1.94; 95% CI: 1.13‐3.32), and presented with severe retractions (AOR: 5.55; 95% CI: 2.12‐14.50), inadequate oral intake (AOR: 2.54; 95% CI: 1.39‐4.62), or apnea (AOR: 2.87; 95% CI: 1.45‐5.68). Readmissions were similar for children who did and did not worsen. CONCLUSIONS: Although children hospitalized with bronchiolitis had wide‐ranging recovery times, only 4% worsened after initial improvement. Children who worsened were more likely to be younger, premature infants presenting in more severe distress. For children hospitalized with bronchiolitis, these data may help establish more evidence‐based discharge criteria, reduce practice variability, and safely shorten hospital length‐of‐stay. Journal of Hospital Medicine 2015;10:205–211. © 2015 Society of Hospital Medicine

negative: Antegrade cerebral perfusion at 25 °C for arch reconstruction in newborns and children preserves perioperative cerebral oxygenation and serum creatinine. BACKGROUND Antegrade cerebral perfusion (ACP) typically is used with deep hypothermia for cerebral protection during aortic arch reconstructions. The impact of ACP on cerebral oxygenation and serum creatinine at a more tepid 25 °C was studied in newborns and children. METHODS Between 2010 and 2014, 61 newborns and children (<5 years old) underwent aortic arch reconstruction using moderate hypothermia (25.0±0.9 °C) with ACP and a pH-stat blood gas management strategy. These included 44% Norwood-type operations, 30% isolated arch reconstructions, and 26% arch reconstructions with other major procedures. Median patient age at surgery was 9 days (range, 3 days-4.7 years). Cerebral oxygenation (NIRS) was monitored continuously perioperatively for 120 hours. Serum creatinine was monitored daily. RESULTS Median cardiopulmonary bypass (CPB) and cross clamp times were 181 minutes (range, 82-652 minutes) and 72 minutes (range, 10-364 minutes), respectively. ACP was performed at a mean flow rate of 46±6 mL/min/kg for a median of 48 minutes (range, 10-123 minutes). Cerebral and somatic NIRS were preserved intraoperatively and remained at baseline postoperatively during the first 120 hours. Peak postoperative serum creatinine levels averaged 0.7±0.3 mg/dL for all patients. There were 4 (6.6%) discharge mortalities. Six patients (9.8%) required ECMO support. Median postoperative length of hospital and intensive care unit (ICU) stay were 16 days(range, 4-104 days) and 9 days (range, 1-104 days), respectively. Two patients (3.3%) received short-term peritoneal dialysis for fluid removal, and none required hemodialysis. Three patients (4.9%) had an isolated seizure which resolved with medical therapy, and none had a neurologic deficit or stroke. CONCLUSIONS ACP at 25 °C preserved perioperative cerebral oxygenation and serum creatinine for newborns and children undergoing arch reconstruction. Early outcomes are encouraging, and additional study is warranted to assess the impact on late outcomes.

negative: Heightened risk of child maltreatment amid the COVID-19 pandemic can exacerbate mental health problems for the next generation. The spread of the COVID-19 disrupted ecological systems in which children develop, exacerbating threats to their safety and increasing their vulnerability to future psychopathology. Supports to reduce sources of stress for caregivers and protect children from threats to their safety are warranted. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

negative: SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes SARS-CoV-2 virus, the causative agent of the coronavirus infectious disease-19 (COVID-19), is taking the globe by storm, approaching 500,000 confirmed cases and over 21,000 deaths as of March 25, 2020. While under control in some affected Asian countries (Taiwan, Singapore, Vietnam), the virus demonstrated an exponential phase of infectivity in several large countries (China in late January and February and many European countries and the USA in March), with cases exploding by 30-50,000/day in the third and fourth weeks of March, 2020. SARS-CoV-2 has proven to be particularly deadly to older adults and those with certain underlying medical conditions, many of whom are of advanced age. Here, we briefly review the virus, its structure and evolution, epidemiology and pathogenesis, immunogenicity and immune, and clinical response in older adults, using available knowledge on SARS-CoV-2 and its highly pathogenic relatives MERS-CoV and SARS-CoV-1. We conclude by discussing clinical and basic science approaches to protect older adults against this disease.

negative: COVID-19 and type 1 diabetes: dealing with the difficult duo BACKGROUND: Coronavirus disease 2019 (COVID-19) has aroused global health concerns, particularly in relation to diabetes where it has been associated with poorer outcomes. The bulk of the evolving evidence in diabetes and COVID-19 relates to type 2 diabetes (T2D). Since there are a significant number of patients with type 1 diabetes (T1D) with unique concerns and challenges during the ongoing COVID-19 pandemic, we reviewed existing literature, relevant websites, and related guidelines to form this narrative review to help address key questions in this area. METHODS: We systematically searched the PubMed database up to May 31, 2020, and retrieved all the articles published on T1D and COVID-19. RESULTS: We found 18 relevant articles, each of which carried a part of the evidence regarding the risk of contracting COVID-19 in patients with T1D, effect of COVID-19 on development of T1D, outcomes in T1D with COVID-19, and special management issues in T1D in the light of COVID-19. These have been documented in the present review. CONCLUSION: COVID-19 with T1D presents special challenges. While the available evidence does shed some light, we need more evidence to deal with this difficult duo.

negative: Slums Are Not Places for Children to Live Vulnerabilities, Health Outcomes, and Possible Interventions

negative: Years of life lost due to the psychosocial consequences of COVID-19 mitigation strategies based on Swiss data BACKGROUND. The pandemic caused by coronavirus disease 2019 (COVID-19) has forced governments to implement strict social mitigation strategies to reduce the morbidity and mortality from acute infections. These strategies, however, carry a significant risk for mental health, which can lead to increased short-term and long-term mortality and is currently not included in modeling the impact of the pandemic. METHODS. We used years of life lost (YLL) as the main outcome measure, applied to Switzerland as an example. We focused on suicide, depression, alcohol use disorder, childhood trauma due to domestic violence, changes in marital status, and social isolation, as these are known to increase YLL in the context of imposed restriction in social contact and freedom of movement. We stipulated a minimum duration of mitigation of 3 months based on current public health plans. RESULTS. The study projects that the average person would suffer 0.205 YLL due to psychosocial consequence of COVID-19 mitigation measures. However, this loss would be entirely borne by 2.1% of the population, who will suffer an average of 9.79 YLL. CONCLUSIONS. The results presented here are likely to underestimate the true impact of the mitigation strategies on YLL. However, they highlight the need for public health models to expand their scope in order to provide better estimates of the risks and benefits of mitigation.

negative: COVID-19 Impacts on Child and Youth Anxiety and Depression: Challenges and Opportunities

negative: Appréhender le COVID-19 au fil de l’eau en tant que psychiatre d’enfant et d’adolescent Résumé Le COVID-19 est une maladie multi-organes liée à une infection par le virus SARS-CoV2 qui est devenue une pandémie au début de l’année 2020. Difficile de décrire autrement qu’en témoignant à chaud ce que cette pandémie implique pour un psychiatre d’enfants. Je propose de parcourir les principales questions éthiques qui se sont posées; de décrire comment mon équipe hospitalière s’est réorganisée pour faire face aux nouvelles demandes et questionnements, en particulier en ouvrant une unité dédiée aux personnes avec autisme et comportements défis atteints par le COVID-19; et d’aborder, dans un contexte de discussion nationale, comment la discipline a cherché à comprendre les conditions d’un certain bien-être pendant le confinement. Enfin, j’essaierai de terminer par des réflexions plus spéculatives concernant le déconfinement. Abstract COVID-19 is a multi-organ disease due to an infection with the SARS-CoV2 virus. It has become a pandemic in early 2020. The disease appears less devastating in children and adolescents. However, stress, quarantine and eventually mourning have major impacts on development. It is difficult to describe what this pandemic implies for a child psychiatrist, other than by giving a first-hand account. I propose to go through the main ethical questions that have arisen; to describe how my hospital team has reorganized itself to meet the new demands and questions, in particular by opening a unit dedicated to people with autism and challenging behaviors affected by COVID-19; and to address, in a context of national discussion, how the discipline has sought to understand the conditions of a certain well-being during quarantine. Finally, I will try to conclude with more speculative reflections on re-opening.

negative: COVID-19 health worries and anxiety symptoms among older adults: the moderating role of ageism A prominent feature of anxiety in late life is concerns regarding physical health. Anxiety symptoms among older adults have been connected with various psychological outcomes, including social isolation and loneliness. During the coronavirus disease 2019 (COVID-19) pandemic, many societies have demonstrated increased ageist attitudes, encouraging older adults to distance themselves from society. Accordingly, the current study examined the moderating role of COVID-19-related ageism in the connection between COVID-19 health worries and anxiety symptoms among older adults. Data were collected from 243 older adults (age range 60–92; M = 69.75, SD = 6.69), who completed scales assessing COVID-19-related health worries and ageism, as well as anxiety symptoms. The results demonstrated that both health worries and ageism were positively associated with anxiety symptoms. Moreover, the connection between health worries and anxiety symptoms was more pronounced among older adults with high ageism levels. The study highlights the vulnerability of older adults in general, and ageist older adults in particular, to the negative consequences of COVID-19-related health worries, and emphasizes the role of the increased ageist stance of society during the pandemic in this regard.

negative: Health Education for Parents During the COVID-19 OutbreakPublic 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 COVID-19 (Coronavirus disease 2019) 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, SARS (severe acute respiratory syndrome) and MERS (middle east respiratory syndrome) epidemics in Medline (via PubMed), 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. The potential bias of the studies was assessed by Joanna Briggs Institute Prevalence Critical Appraisal Tool. Results: Of 1067 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.

negative: Risk Factors for Mortality among COVID-19 Patients Abstract Aims COVID-19 is a current globalpandemic. However, comprehensive global data analyses for its mortality risk factors are lacking. The current investigation aimed to assess the predictors of death among COVID-19 patients from worldwide open access data. Methods A total of 828 confirmed cases of COVID-19 with definite outcomes were retrospectively identified from open access individual-level worldwide data. Univariate followed by multivariable regression analysis were used to evaluate the association between potential risk factors and mortality. Results Majority of the patients were males 59.1% located in Asia 69.3%. Based on the data, older age (adjusted odds ratio (aOR), 1.079; 95% confidence intervals (95% CI), 1.064-1.095 per year increase), males (aOR, 1.607; 95% CI, 1.002-2.576), patients with hypertension (aOR, 3.576; 95% CI, 1.694-7.548), diabetes mellitus (aOR, 12.234; 95% CI, 4.126-36.272), and patients located in America (aOR, 7.441; 95% CI, 3.546-15.617) were identified as the risk factors of mortality among COVID-19 patients. Conclusions Males, advanced age, hypertension patients, diabetes mellitus patients, and patients located in America were the independent risk factors of death among COVID-19 patients. Extra attention is required to be given to these factors and additional studies on the underlying mechanisms of these effects.

negative: Prevalence of obesity among adult inpatients with COVID-19 in France

negative: The experience of women infected by the COVID-19 during pregnancy in Brazil: a qualitative study protocol BACKGROUND: The Coronavirus disease (COVID-19) is highly infectious, with the recent World Health Organization decree confirming a global public health emergency. The outcomes related to maternal and fetal health among pregnant women infected with the virus are still poorly understood. The world population has been waiting for answers and remains constantly alert about the pandemic's progress. It is not yet known what impact this pandemic experience will have on the population's mental health, especially pregnant women. METHOD: We aim to understand and discuss the experiences of women who were infected by COVID-19 during pregnancy, in relation to the illness process, community relations, and social media influences. This is a qualitative study in which we will interview women who were infected by COVID-19 during pregnancy and received medical care from a tertiary university hospital specializing in women's health in Brazil. We will use the techniques of Semi-Directed Interviews of Open and In-depth Questions, socio-demographic and health data sheets, and Field Diaries. We will use purposive sampling and the criterion of theoretical saturation for its construction. The interviews will be conducted by phone or video call, with audio recorded for later transcription. The treatment of the data will be completed through Thematic Analysis and discussed in light of the Health Psychology framework, with the production of categories that answer the proposed research questions. DISCUSSION: It is expected that the results contribute to the understanding about the demands that come to the health professional of women infected by COVID-19 during pregnancy in a pandemic situation. INTRODUçãO: A doença causada pelo coronavírus (COVID-19) é altamente infecciosa, com a recente declaração da Organização Mundial de Saúde confirmando emergência global de saúde pública. Os desfechos relacionados a saúde materno-fetal entre gestantes infectadas pelo vírus ainda são pouco conhecidos. A população mundial tem aguardado respostas e se mantém constantemente em alerta sobre o progresso da pandemia. Ainda não se sabe qual será o impacto da experiência da pandemia sobre a saúde mental da população, especialmente entre mulheres grávidas. MéTODO: O objetivo deste estudo é compreender e discutir as experiências de mulheres infectadas pelo COVID-19 durante a gravidez, em relação ao processo de adoecimento, às relações comunitárias e a influência de mídias sociais. Este é um estudo qualitativo em que serão entrevistadas mulheres infectadas pelo COVID-19 durante a gestação, atendidas em um hospital universitário terciário especializado em saúde da mulher no Brasil. Serão usadas as técnicas de Entrevistas Semi-Dirigidas de Perguntas Abertas em Profundidade, ficha de dados sociodemográficos e de saúde e diários de campo. A amostra será selecionada intencionalmente, usando o critério de saturação teórica para a sua construção. As entrevistas serão conduzidas por telefone ou videoconferência, com áudio gravado para posterior transcrição. O tratamento dos dados seguirá a Análise Temática e os resultados serão discutidos sob conceitos de Psicologia da Saúde, com a produção de categorias que respondam as questões de pesquisa propostas. DISCUSSãO: Espera-se que os resultados contribuam para a compreensão de demandas emergentes entre profissionais de saúde para mulheres infectadas pelo COVID-19 durante a gestação em situação de pandemia.

negative: Rapid Implementation of an Adult COVID-19 Unit in a Children’s Hospital Objective To describe the rapid implementation of an adult coronavirus disease 2019 (COVID-19) unit using pediatric physician and nurse providers in a children’s hospital and to examine the characteristics and outcomes of the first 100 adult patients admitted. Study design We describe our approach to surge-in-place at a children’s hospital to meet the local demands of the COVID-19 pandemic. Instead of re-deploying pediatric providers to work with internist-led teams throughout a medical center, pediatric physicians and nurses organized and staffed a 40-bed adult COVID-19 treatment unit within a children’s hospital. We adapted internal medicine protocols, developed screening criteria to select appropriate patients for admission, and reorganized staffing and equipment to accommodate adult COVID-19 patients. We used patient counts and descriptive statistics to report sociodemographic, system, and clinical outcomes. Results The median patient age was 46 years; 69% were male. On admission, 78 (78%) required oxygen supplementation. During hospitalization, 13 (13%) eventually were intubated. Of the first 100 patients, 14 are still admitted to a medical unit, 6 are in the intensive care unit, 74 have been discharged, 4 died after transfer to the ICU, and 2 died on the unit. The median length of stay for discharged or deceased patients was 4 days (IQR 2,7). Conclusions Our pediatric team screened, admitted, and cared for hospitalized adults by leveraging the familiarity of our system, adaptability of our staff, and high-quality infrastructure. This experience may be informative for other healthcare systems that will be re-deploying pediatric providers and nurses to address a regional COVID-19 surge elsewhere.

negative: Responding to COVID19: What is happening for our vulnerable children and young people?

negative: Clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) and rheumatic disease: a comparative cohort study from a US 'hot spot' OBJECTIVE: To investigate differences in manifestations and outcomes of coronavirus disease 2019 (COVID-19) infection between those with and without rheumatic disease. METHODS: We conducted a comparative cohort study of patients with rheumatic disease and COVID-19 (confirmed by severe acute respiratory syndrome coronavirus 2 PCR), compared in a 1:2 ratio with matched comparators on age, sex and date of COVID-19 diagnosis, between 1 March and 8 April 2020, at Partners HealthCare System in the greater Boston, Massachusetts area. We examined differences in demographics, clinical features and outcomes of COVID-19 infection. The main outcomes were hospitalisation, intensive care admission, mechanical ventilation and mortality. RESULTS: We identified 52 rheumatic disease patients with COVID-19 (mean age, 63 years; 69% female) and matched these to 104 non-rheumatic disease comparators. The majority (39, 75%) of patients with rheumatic disease were on immunosuppressive medications. Patients with and without rheumatic disease had similar symptoms and laboratory findings. A similar proportion of patients with and without rheumatic disease were hospitalised (23 (44%) vs 42 (40%)), p=0.50) but those with rheumatic disease required intensive care admission and mechanical ventilation more often (11 (48%) vs 7 (18%), multivariable OR 3.11 (95% CI 1.07 to 9.05)). Mortality was similar between the two groups (3 (6%) vs 4 (4%), p=0.69). CONCLUSIONS: Patients with rheumatic disease and COVID-19 infection were more likely to require mechanical ventilation but had similar clinical features and hospitalisation rates as those without rheumatic disease. These findings have important implications for patients with rheumatic disease but require further validation.

negative: Leveraging parent-child interaction therapy and telehealth capacities to address the unique needs of young children during the COVID-19 public health crisis COVID-19 and related efforts to mitigate its spread have dramatically transformed the structure and predictability of modern childhood, resulting in growing concerns children may be particularly vulnerable to serious mental health consequences. Worldwide stay-at-home directives and emergency changes in healthcare policy and reimbursement have smoothed the trail for broad implementation of technology-based remote mental health services for children. Parent-Child Interaction Therapy (PCIT) is particularly well-positioned to address some of the most pressing child and parental needs that arise during stressful times, and telehealth formats of PCIT, such as Internet-delivered PCIT (iPCIT), have already been supported in controlled trials. This commentary explores PCIT implementation during the COVID-19 public health crisis and the challenges encountered in the move toward Internet-delivered services. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

negative: Age-dependent gender differences of COVID-19 in mainland China: comparative study BACKGROUND: The ongoing pandemic of novel coronavirus disease 2019 (COVID-19) is challenging global public health system. Sex-differences in infectious diseases are a common but neglected problem. METHODS: We used the national surveillance database of COVID-19 in mainland China to compared gender differences in attack rate (AR), proportion of severe and critical cases (PSCC) and case fatality rate (CFR) in relation to age, affected province, and onset-to-diagnosis interval. RESULTS: The overall AR was significantly higher in female population than in males (63.9 versus 60.5 per million persons; P ˂ .001). By contrast, PSCC and CFR were significantly lower among female patients (16.9% and 4.0%) than among males (19.5% and 7.2%), with ORs of 0.87 and 0.57, respectively (both P ˂ .001). The female-to-male differences were age-dependent, which were significant among people aged 50–69 years for AR, and in the patients of 30-years or older for both PSCC and CFR (all P ≤ .001). The AR, PSCC and CFR varied greatly from province to province. However, female-to-male differences in AR, PSCC and CFR were significant in the epicenter, Hubei province, where 82.2% confirmed cases and 97.4% deaths occurred. After adjusting for age, affected province and onset-to-diagnosis interval, the female-to-male difference in AR, PSCC and CFR remained significant in multivariate logistic regression analyses. CONCLUSIONS: We elucidate an age-dependent gender dimorphism for COVID-19, in which the females have higher susceptibility but lower severity and fatality. Further epidemiological and biological investigations are required to better understand the sex-specific differences for effective interventions.

negative: The outbreak of coronavirus disease in China: Risk perceptions, knowledge, and information sources among prenatal and postnatal women BACKGROUND: The COVID-19 pandemic has created anxiety among members of the public, including all women over the childbirth continuum, who are considered to be at a greater risk of contracting most infectious diseases. Understanding the perspectives of health care consumers on COVID-19 will play a crucial role in the development of effective risk communication strategies. This study aimed to examine COVID-19-related risk perceptions, knowledge, and information sources among prenatal and postnatal Chinese women during the initial phase of the COVID-19 pandemic. METHODS: A cross-sectional survey design was adopted, and a four-section online questionnaire was used to collect data. Using a social media platform, the online survey was administered to 161 participants during the outbreak of COVID-19 in Nanjing, China, in February 2020. RESULTS: The participants perceived their risk of contracting and dying from COVID-19 to be lower than their risk of contracting influenza, however many of them were worried that they might contract COVID-19. The participants demonstrated adequate knowledge about COVID-19. The three major sources from which they obtained information about COVID-19 were doctors, nurses/midwives, and the television, and they placed a high level of confidence in these sources. There was no significant relationship between the perceived risk of contracting COVID-19 and knowledge about this disease. CONCLUSION: The present findings offer valuable insights to healthcare professionals, including midwives, who serve on the frontline and provide care to pregnant women. Although the participants were adequately knowledgeable about COVID-19, they had misunderstood some of the recommendations of the World Health Organisation.

negative: Benefit-risk analysis of health benefits of routine childhood immunisation against the excess risk of SARS-CoV-2 infections during the Covid-19 pandemic in Africa Background: National immunisation programmes globally are at risk of suspension due to the severe health system constraints and physical distancing measures in place to mitigate the ongoing COVID-19 pandemic. Our aim is to compare the health benefits of sustaining routine childhood immunisation in Africa against the risk of acquiring SARS-CoV-2 infections through visiting routine vaccination service delivery points. Methods: We used two scenarios to approximate the child deaths that may be caused by immunisation coverage reductions during COVID-19 outbreaks. First, we used previously reported country-specific child mortality impact estimates of childhood immunisation for diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, pneumococcal, rotavirus, measles, meningitis A, rubella, and yellow fever (DTP3, HepB3, Hib3, PCV3, RotaC, MCV1, MCV2, MenA, RCV, YFV) to approximate the future deaths averted before completing five years of age by routine childhood vaccination during a 6-month Covid-19 risk period without catch-up campaigns. Second, we analysed an alternative scenario that approximates the health benefits of sustaining routine childhood immunisation to only the child deaths averted from measles outbreaks during the Covid-19 risk period. The excess number of infections due to additional SARS-CoV-2 exposure during immunisation visits assumes that contact reducing interventions flatten the outbreak curve during the Covid-19 risk period, that 60% of the population will have been infected by the end of that period, that children can be infected by either vaccinators or during transport and that upon child infection the whole household would be infected. Country specific household age structure estimates and age dependent infection fatality rates are then applied to calculate the number of deaths attributable to the vaccination clinic visits. We present benefit-risk ratios for routine childhood immunisation alongside 95% uncertainty range estimates from probabilistic sensitivity analysis. Findings: For every one excess Covid-19 death attributable to SARS-CoV-2 infections acquired during routine vaccination clinic visits, there could be 143 (38 - 576) deaths in children prevented by sustaining routine childhood immunisation in Africa. The benefit-risk ratio for the vaccinated children, siblings, parents or adult care-givers, and older adults in the households of vaccinated children are 58,000 (3,200 - 21,350,000), 52,000 (2,800 - 18,884,000), 2,000 (393 - 12,000), and 157 (41 - 652) respectively. In the alternative scenario that approximates the health benefits to only the child deaths averted from measles outbreaks, the benefit-risk ratio to the households of vaccinated children is 5 (1 - 21) under these highly conservative assumptions and if the risk to only the vaccinated children is considered, the benefit-risk ratio is 2,000 (131 - 839,000). Interpretation: Our analysis suggests that the health benefits of deaths prevented by sustaining routine childhood immunisation in Africa far outweighs the excess risk of Covid-19 deaths associated with vaccination clinic visits. However, there are other factors that must be considered for strategic decision making to sustain routine childhood immunisation in African countries during the Covid-19 pandemic. These include logistical constraints of vaccine supply chain problems caused by the Covid-19 pandemic, reallocation of immunisation providers to other prioritised health services, healthcare staff shortages caused by SARS-CoV-2 infections among the staff, decreased demand for vaccination arising from community reluctance to visit vaccination clinics for fear of contracting SARS-CoV-2 infections, and infection risk to healthcare staff providing immunisation services as well as to their households and onward SARS-CoV-2 transmission into the wider community.

negative: Improved survival outcome in SARs-CoV-2 (COVID-19) Acute Respiratory Distress Syndrome patients with Tocilizumab administration ABSTRACT Background: The novel human coronavirus, severe acute respiratory syndrome coronavirus-2 (SARs-CoV-2), was declared a global pandemic by the World Health Organization on March 11, 2020. Hence, there is an urgency to find effective treatment. Of those patients afflicted in the United States, many have required treatment with ventilator secondary to acute respiratory distress syndrome (ARDS). Data are needed regarding the benefit of treatment and prevention of the cytokine storms in COVID-19 patients with Tocilizumab. Methods: Clinical outcomes data for patients admitted to Orange Regional Medical Center with confirmed COVID-19 from Mar 15, 2020 to Apr 20, 2020 were identified through electronic health record chart review. We conducted a retrospective case-control study in confirmed COVID 19 positive patients with ARDS requiring mechanical ventilation and compared outcome in terms of mortality and length of stay amongst those who received Tocilizumab as treatment modality opposed to those that did not. Results: A total of 94 patients with COVID-19 ARDS were analyzed. 44 were in the study group and 50 in the control group. We tried to match both group as close as possible in terms of age, sex, BMI and HS score- calculated using inflammatory markers- ferritin, triglycerides, AST and fibrinogen. The median age was 55.5 years in the study group and 66 in the control group, difference was not statistically significant. Average HS score was 114 in the Tocilizumab group and 92 in the control group, difference was statistically significant with P<0.0001. Also, the patients in the study group had elevated levels of IL-6, triglycerides, AST, ferritin which were statistically significant with p < 0.0001 when compared to the control group. Length of stay was longer, average 17.9 days in the Tocilizumab. Survival rate was much lower at 48 % in the control group and 61.36 % in patients who received Tocilizumab with significant P value of < 0.00001. The number needed to treat (NNT) was 7.48, if we treat 8 patients with Tocilizumab, 1 will not die. Conclusions: Cytokine Release Syndrome (CRS) occurs in a large number of patients with severe COVID-19, which is also an important cause of death. IL- 6 is the key molecule of CRS, so IL-6R antagonist Tocilizumab may be of value in improving outcomes. In our study Tocilizumab group seemed to have improved survival outcome. Results have to be interpreted with caution since this is a retrospective study and mortality is affected by multiple, confounding factors. We await the results of ongoing randomized controlled trials to definitely answer the question of whether Tocilizumab improves survival in COVID-19 ARDS patients.

negative: COVID-19 and addiction BACKGROUND AND AIMS: 2019-coronavirus disease (COVID-19) is causing insurmountable psychosocial impact on the whole mankind. Marginalized community, particularly those with substance use disorders (SUD), are particularly vulnerable to contract the infection and also likely to suffer from greater psychosocial burden. This article analyses the intricate bi-directional relationship between COVID-19 and addiction. METHODS: Pubmed and Google Scholar are searched with the following key terms- "COVID-19", "SARS-CoV2", "Pandemic", "Addiction", "Opioid", "Alcohol", "Smoking", "Addiction Psychiatry", "Deaddiction", "Substance use disorders", "Behavioral addiction". Few newspaper reports related to COVID-19 and addiction have also been added as per context. RESULTS: People with SUD are at greater risk of worse COVID-19 outcome. There is surge of addictive behaviors (both new and relapse) including behavioral addiction in this period. Withdrawal emergencies and death are also being increasingly reported. Addicted people are especially facing difficulties in accessing the healthcare services which are making them prone to procure drugs by illegal means. CONCLUSION: COVID-19 and addiction are the two pandemics which are on the verge of collision causing major public health threat. While every effort must be taken to make the public aware of deleterious effects of SUD on COVID-19 prognosis, the resumption of deaddiction services and easier accessibility of prescription drugs are needs of the hour.

negative: Community-Acquired Pneumonia Hospitalization among Children with Neurologic Disorders Objective To describe and compare the clinical characteristics, outcomes, and etiology of pneumonia among children hospitalized with community-acquired pneumonia (CAP) with neurologic disorders, non-neurologic underlying conditions, and no underlying conditions. Study design Children <18 years old hospitalized with clinical and radiographic CAP were enrolled at 3 US children's hospitals. Neurologic disorders included cerebral palsy, developmental delay, Down syndrome, epilepsy, non-Down syndrome chromosomal abnormalities, and spinal cord abnormalities. We compared the epidemiology, etiology, and clinical outcomes of CAP in children with neurologic disorders with those with non-neurologic underlying conditions, and those with no underlying conditions using bivariate, age-stratified, and multivariate logistic regression analyses. Results From January 2010-June 2012, 2358 children with radiographically confirmed CAP were enrolled; 280 (11.9%) had a neurologic disorder (52.1% of these individuals also had non-neurologic underlying conditions), 934 (39.6%) had non-neurologic underlying conditions only, and 1144 (48.5%) had no underlying conditions. Children with neurologic disorders were older and more likely to require intensive care unit (ICU) admission than children with non-neurologic underlying conditions and children with no underlying conditions; similar proportions were mechanically ventilated. In age-stratified analysis, children with neurologic disorders were less likely to have a pathogen detected than children with non-neurologic underlying conditions. In multivariate analysis, having a neurologic disorder was associated with ICU admission for children ≥2 years of age. Conclusions Children with neurologic disorders hospitalized with CAP were less likely to have a pathogen detected and more likely to be admitted to the ICU than children without neurologic disorders.

negative: Pandemic controllability: a concept to guide a proportionate and flexible operational response to future influenza pandemics The 2009 H1N1 influenza pandemic posed challenges for governments worldwide. Strategies designed to limit community transmission, such as antiviral deployment, were largely ineffective due to both feasibility constraints and the generally mild nature of disease, resulting in incomplete case ascertainment. Reviews of national pandemic plans have identified pandemic impact, primarily linked to measures of transmissibility and severity, as a key concept to incorporate into the next generation of plans. While an assessment of impact provides the rationale under which interventions may be warranted, it does not directly provide an assessment on whether particular interventions may be effective. Such considerations motivate our introduction of the concept of pandemic controllability. For case-targeted interventions, such as antiviral treatment and post-exposure prophylaxis, we identify the visibility and transmissibility of a pandemic as the key drivers of controllability. Taking a case-study approach, we suggest that high-impact pandemics, for which control is most desirable, are likely uncontrollable with case-targeted interventions. Strategies that do not rely on the identification of cases may prove relatively more effective. By introducing a pragmatic framework for relating the assessment of impact to the ability to mitigate an epidemic (controllability), we hope to address a present omission identified in pandemic response plans.

negative: COVID-19 and children. From Luis Sepulveda to Madam Mim.

negative: Physical child abuse demands increased awareness during health and socioeconomic crises like COVID-19 Background and purpose - Physical abuse of children, i.e., nonaccidental injury (NAI) including abusive head trauma (AHT) is experienced by up to 20% of children; however, only 0.1% are diagnosed. Healthcare professionals issue less than 20% of all reports suspecting NAI to the responsible authorities. Insufficient knowledge concerning NAI may partly explain this low percentage. The risk of NAI is heightened during health and socioeconomic crises such as COVID-19 and thus demands increased awareness. This review provides an overview and educational material on NAI and its clinical presentation.Methods - We combined a literature review with expert opinions of the senior authors into an educational paper aiming to help clinicians to recognize NAI and act appropriately by referral to multidisciplinary child protection teams and local authorities.Results - Despite the increased risk of NAI during the current COVID-19 crisis, the number of reports suspecting NAI decreased by 42% during the lockdown of the Danish society. Healthcare professionals filed only 17% of all reports of suspected child abuse in 2016.Interpretation - The key to recognizing and suspecting NAI upon clinical presentation is to be aware of inconsistencies in the medical history and suspicious findings on physical and paraclinical examination. During health and socioeconomic crises the incidence of NAI is likely to peak. Recognition of NAI, adequate handling by referral to child protection teams, and reporting to local authorities are of paramount importance to prevent mortality and physical and mental morbidity.

negative: Does the protein corona take over the selectivity of molecularly imprinted nanoparticles? The biological challenges to recognition "Plastic antibodies" are nano-sized biomimetics prepared by the molecular imprinting technology, which have the robustness of polymers, but specificity and selectivity alike natural receptors making them ideal for analytical uses. The current challenge is to translate plastic antibodies to in vivo applications for diagnosis, drug delivery, theranostic, therefore it is crucial to evaluate the effect of the biological sample complexity on the selectivity and the formation of protein corona (PCs), which ultimately dictate the fate of circulating nanoparticles. A set (n = 4) of plastic antibodies (nanoMIPs) against different proteins was prepared. Quantitative (iBAC) shotgun proteomics permitted to define the PC composition of nanoMIPs in human plasma, the relative protein abundances, the correlation between PC and the plasma dilution. NanoMIPs showed >200 proteins PC, while ~150 proteins were found on controls, suggesting the imprinting process influences the nanoparticle's structure hence the protein uptake. NanoMIPs and controls shared the 44% of the PC, but PC iBAQ values on nanoMIPs were 10-100 times higher than controls, suggesting PC/nanoMIPs interactions were far stronger than PC/non imprinted particles. PCs were richer in small proteins and in immunoglobulins, indicating a defensive response, while the selectivity was negatively challenged in the crowded plasma sample. SIGNIFICANCE: The formation and the composition of the protein corona (PC) is key to decide the fate of nanoparticles when in vivo, therefore there is the strong need to study the composition of the PC. To enable and to support the translation of the use of plastic antibodies (nanoMIPs), prepared by means of the molecular imprinting technique, to the clinical practice and to in vivo uses, the present work evaluates the effects of the complexity of the biological sample (plasma) on nanoMIPs composed of highly crosslinked polyacrylamide and acrylamide derivatives. Proteomic study offers an in depth insight of the protein corona formed in plasma on nanoMIPs. A set of nanoMIPs synthesized and raised to recognize either small or large proteins was tested. The selection abilities of the nanoMIPs when placed in plasma at different dilutions was studied. Quantitative shotgun proteomics allowed to define the composition of the formed protein corona (PC) enabling to detail the protein compositions, the relative abundances, its correlation to the biological sample composition and the correlation between PC and nanoMIP's imprinted template. In plasma, all the nanoMIPs gained a PC composed of more than 200 proteins. Type of protein recruited for the corona, molecular weight and abundance in the PC were studied. The PC on the nanoMIPs appeared to be driven by the protein composition of the plasma, while the template protein, towards which a nanoMIP was imprinted and that was proven to have high affinity for, did not influence the PC.

negative: Exploring the Parent-Child Landscape Pattern after COVID-19 This article discusses the design of parent-child landscape space, in the 5-minute life circle, that is getting more and more attention in the late stage of the new coronavirus (COVID-19) By studying the theory and practice of current parent-child landscape design, combined with the age characteristics of children, it is proposed to divide the parent-child landscape site into 5 small landscape spaces At the same time, the design features and suggested landscape elements of these 5 landscape spaces are listed These 5 small landscape spaces can be enlarged or reduced according to the actual size of the site

negative: Perspective: Vitamin D deficiency and COVID‐19 severity – plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2, and thrombosis (R1) BACKGROUND: SARS‐CoV‐2 coronavirus infection ranges from asymptomatic through to fatal COVID‐19 characterised by a “cytokine storm” and lung failure. Vitamin D deficiency has been postulated as a determinant of severity. OBJECTIVES: To review the evidence relevant to vitamin D and COVID‐19 METHODS: Narrative review RESULTS: Regression modelling shows that more northerly countries in the Northern Hemisphere are currently (May 2020) showing relatively high COVID‐19 mortality, with an estimated 4.4% increase in mortality for each 1 degree latitude north of 28 degrees North (P=0.031) after adjustment for age of population. This supports a role for ultraviolet B acting via vitamin D synthesis. Factors associated with worse COVID‐19 prognosis include old age, ethnicity, male sex, obesity, diabetes and hypertension and these also associate with deficiency of vitamin D or its response. Vitamin D deficiency is also linked to severity of childhood respiratory illness. Experimentally, vitamin D increases the ratio of angiotensin converting enzyme 2 (ACE2) to ACE, thus increasing angiotensin II hydrolysis and reducing subsequent inflammatory cytokine response to pathogens and lung injury. CONCLUSIONS: Substantial evidence supports a link between vitamin D deficiency and COVID‐19 severity but it is all indirect. Community‐based placebo‐controlled trials of vitamin D supplementation may be difficult. Further evidence could come from study of COVID‐19 outcomes in large cohorts with information on prescribing data for vitamin D supplementation or assay of serum unbound 25(OH) vitamin D levels. Meanwhile vitamin D supplementation should be strongly advised for people likely to be deficient.

negative: Inactivated trivalent influenza vaccine is associated with lower mortality among Covid-19 patients in Brazil We analyzed data from 92,664 clinically and molecularly confirmed Covid-19 cases in Brazil to understand the potential associations between influenza vaccination and Covid-19 outcomes. Controlling for health facility of treatment, comorbidities as well as an extensive range of sociodemographic factors, we show that patients who received a recent influenza vaccine experienced on average 8% lower odds of needing intensive care treatment (95% CIs [0.86, 0.99]), 18% lower odds of requiring invasive respiratory support (0.74, 0.88) and 17% lower odds of death (0.75, 0.89). Large scale promotion of influenza vaccines seems advisable, especially in populations at high risk of severe SARS-CoV-2 infection.

negative: Using Insights from Behavioral Economics to Mitigate the Spread of COVID-19 The outbreak of 2019 coronavirus disease (COVID-19) has become a public health emergency of international concern. The number of COVID-infected individuals and related deaths continues to rise rapidly. Encouraging people to adopt and sustain preventive behaviors is a central focus of public health policies that seek to mitigate the spread of COVID-19. Public health policy needs improved methods to encourage people to adhere to COVID-19-preventive behaviors. In this paper, we introduce a number of insights from behavioral economics that help explain why people may behave irrationally during the COVID-19 pandemic. In particular, present bias, status quo bias, framing effect, optimism bias, affect heuristic, and herding behavior are discussed. We hope this paper will shed light on how insights from behavioral economics can enrich public health policies and interventions in the fight against COVID-19.

negative: Using Internet-Based Psychological Measurement to Capture the Deteriorating Community Mental Health Profile During COVID-19: Observational Study BACKGROUND: The coronavirus disease (COVID-19) is expected to have widespread and pervasive implications for mental health in terms of deteriorating outcomes and increased health service use, leading to calls for empirical research on mental health during the pandemic. Internet-based psychological measurement can play an important role in collecting imperative data, assisting to guide evidence-based decision making in practice and policy, and subsequently facilitating immediate reporting of measurement results to participants. OBJECTIVE: The aim of this study is to use an internet-based mental health measurement platform to compare the mental health profile of community members during COVID-19 with community members assessed before the pandemic. METHODS: This study uses an internet-based self-assessment tool to collect data on psychological distress, mental well-being, and resilience in community cohorts during (n=673) and prior to the pandemic (two cohorts, n=1264 and n=340). RESULTS: Our findings demonstrate significantly worse outcomes on all mental health measures for participants measured during COVID-19 compared to those measured before (P<.001 for all outcomes, effect sizes ranging between Cohen d=0.32 to Cohen d=0.81. Participants who demonstrated problematic scores for at least one of the mental health outcomes increased from 58% (n=197/340) before COVID-19 to 79% (n=532/673) during COVID-19, leading to only 21% (n=141) of measured participants displaying good mental health during the pandemic. CONCLUSIONS: The results clearly demonstrate deterioration in mental health outcomes during COVID-19. Although further research is needed, our findings support the serious mental health implications of the pandemic and highlight the utility of internet-based data collection tools in providing evidence to innovate and strengthen practice and policy during and after the pandemic.

negative: The impact of ethnicity on clinical outcomes in COVID-19: A systematic review BACKGROUND: The relationship between ethnicity and COVID-19 is uncertain. We performed a systematic review to assess whether ethnicity has been reported in patients with COVID-19 and its relation to clinical outcomes. METHODS: We searched EMBASE, MEDLINE, Cochrane Library and PROSPERO for English-language citations on ethnicity and COVID-19 (1(st) December 2019-15(th) May 2020). We also reviewed: COVID-19 articles in NEJM, Lancet, BMJ, JAMA, clinical trial protocols, grey literature, surveillance data and preprint articles on COVID-19 in MedRxiv to evaluate if the association between ethnicity and clinical outcomes were reported and what they showed. PROSPERO:180654. FINDINGS: Of 207 articles in the database search, five reported ethnicity; two reported no association between ethnicity and mortality. Of 690 articles identified from medical journals, 12 reported ethnicity; three reported no association between ethnicity and mortality. Of 209 preprints, 34 reported ethnicity – 13 found Black, Asian and Minority Ethnic (BAME) individuals had an increased risk of infection with SARS-CoV-2 and 12 reported worse clinical outcomes, including ITU admission and mortality, in BAME patients compared to White patients. Of 12 grey literature reports, seven with original data reported poorer clinical outcomes in BAME groups compared to White groups. INTERPRETATION: Data on ethnicity in patients with COVID-19 in the published medical literature remains limited. However, emerging data from the grey literature and preprint articles suggest BAME individuals are at an increased risk of acquiring SARS-CoV-2 infection compared to White individuals and also worse clinical outcomes from COVID-19. Further work on the role of ethnicity in the current pandemic is of urgent public health importance. FUNDING: NIHR

negative: Public perceptions of COVID-19 in Australia: perceived risk, knowledge, health-protective behaviours, and vaccine intentions Widespread and sustained engagement with health-protective behaviours (i.e., hygiene and distancing) is critical to successfully managing the COVID-19 pandemic. Evidence from previous emerging infectious disease outbreaks points to the role of perceived risk, worry, media coverage, and knowledge in shaping engagement with health-protective behaviours as well as vaccination intentions. The current study examined these factors in 2,174 Australian residents. An online survey was completed between 2-9 March 2020, at an early stage of the COVID-19 outbreak in Australia. Results revealed that two thirds of respondents were at least moderately worried about a widespread COVID-19 outbreak in Australia (which subsequently occurred). Worry about the outbreak and closely following media coverage were consistent predictors of health-protective behaviours (both over the previous month, and intended behaviours in the case of a widespread outbreak) as well as vaccination intentions. Health-behaviour engagement over the previous month was lower in some demographic groups, including males and younger individuals (18-29 age group). These was a substantial mismatch between respondents' expected symptoms of infection and emerging evidence that a meaningful proportion of people who contract the novel coronavirus will experience asymptomatic infection (i.e., they will not experience symptoms associated with COVID-19). Only 0.3% of those in the current study believed that they personally would not experience any symptoms if they were infected. Uncertainty and misconceptions about COVID-19 were common, including one third of respondents who reported being unsure whether people are likely have natural or existing immunity. There was also uncertainty around whether specific home remedies (e.g., vitamins, saline rinses) would offer protection, whether the virus could spread via the airborne route, and whether the virus was human made and deliberately released. Such misconceptions are likely to cause concern for members of the public. These results point to areas of uncertainty that could be usefully targeted by public education campaigns, as well as psychological and demographic factors associated with engagement with health-protective behaviours. These findings offer potential pathways for interventions to encourage health-protective behaviours to reduce the spread of COVID-19.

negative: Where have all the children gone? Decreases in paediatric emergency department attendances at the start of the COVID-19 pandemic of 2020

negative: Elevated troponin in patients with Coronavirus Disease 2019 (COVID-19): possible mechanisms Abstract Coronavirus disease 2019 (COVID-19) is a pandemic that has affected more than 1.8 million people worldwide, overwhelmed health care systems due to the high proportion of critical presentations, and resulted in over 100,000 deaths. Since the first data analyses in China, elevated cardiac troponin has been noted in a substantial proportion of patients, implicating myocardial injury as a possible pathogenic mechanism contributing to severe illness and mortality. Accordingly, high troponin levels are associated with increased mortality in patients with COVID-19. This brief review explores the available evidence regarding the association between COVID-19 and myocardial injury.

negative: The silent deaths of the elderly in long-term care facilities during the Covid-19 pandemic: The role of forensic pathology The Covid-19 pandemic is currently a major global public health problem. We know that the elderly and people with chronic diseases contract the infection more easily and they develop clinically more serious and often lethal forms. To date, the reasons for this have been generically attributed to old age and underlying diseases. Most Covid-19 deaths occurred in long-term care facilities because the residents are elderly people with chronic illness living in close contact. Therefore, facilities have become epidemic outbreaks. Forensic knowledge is very limited because an autopsy is rarely performed. Post-mortem investigations can help increase knowledge about Covid-19 and identify any undiagnosed pathologies in life. Therefore, forensic investigations play a role in protecting a frail population. Autopsies should be encouraged on elderly people who died of Covid-19.

negative: Transforming growth factor‐beta 1 in humidifier disinfectant‐associated children's interstitial lung disease BACKGROUND: Humidifier disinfectant‐associated children's interstitial lung disease has an unpredictable clinical course with a high morbidity and mortality. OBJECTIVES: To evaluate the differences in clinical findings between survivors and non‐survivors of humidifier disinfectant‐associated children's interstitial lung disease. To evaluate dynamic changes in serum cytokines related to inflammation and fibrosis in lung injury, and to determine whether these changes are predictive of survival in this disease. METHODS: We evaluated 17 children with humidifier disinfectant‐associated children's interstitial lung disease, from whom serum samples were obtained weekly during hospitalization. The severity of chest tomographic and lung pathologic findings was scored. Levels of several cytokines were measured in the serial serum samples. RESULTS: Seven of the 17 children were survivors. Compared to survivors, non‐survivors had greater ground‐glass attenuation on follow‐up chest tomography, higher admission neutrophil counts, and more macrophages on pathologic findings. Transforming growth factor‐beta 1 persisted at an elevated level (1,000–1,500 pg/ml) in survivors, whereas it decreased abruptly in non‐survivors. At the time of this decrease, non‐survivors had clinical worsening of their respiratory failure. Transforming growth factor‐beta 1 was positively correlated with PaO(2)/FiO(2) (r = 0.481, P < 0.0001). CONCLUSIONS: Non‐survivors exhibited more inflammatory clinical findings than survivors. Transforming growth factor‐beta 1 remained elevated in survivors, suggesting that it affected the clinical course of humidifier disinfectant‐associated children's interstitial lung disease. The prognosis of this lung disease may depend more on controlling excessive inflammation and repairing damaged lung than on fibrosis, and transforming growth factor‐beta 1 may play a key role in this process. Pediatr Pulmonol. 2016;51:173–182. © 2015 Wiley Periodicals, Inc.

negative: Addressing the indirect effects of COVID-19 on the health of children and young people.

negative: COVID-19 Impacts on Child and Youth Anxiety and Depression: Challenges and Opportunities.

negative: Smell and taste symptom‐based predictive model for COVID‐19 diagnosis BACKGROUND: The presentation of COVID‐19 overlaps with common influenza symptoms. There is limited data on whether a specific symptom or collection of symptoms may be useful to predict test positivity. METHODS: An anonymous electronic survey was publicized through social media to query participants with COVID‐19 testing. Respondents were questioned regarding 10 presenting symptoms, demographic information, comorbidities and COVID‐19 test results. Stepwise logistic regression was used to identify predictors for COVID positivity. Selected classifiers were assessed for prediction performance using receiver operating characteristic analysis (ROC). RESULTS: One‐hundred and forty‐five participants with positive COVID‐19 testing and 157 with negative results were included. Participants had a mean age of 39 years, and 214 (72%) were female. Smell or taste change, fever, and body ache were associated with COVID‐19 positivity, and shortness of breath and sore throat were associated with a negative test result (p<0.05). A model using all 5 diagnostic symptoms had the highest accuracy with a predictive ability of 82% in discriminating between COVID‐19 results. To maximize sensitivity and maintain fair diagnostic accuracy, a combination of 2 symptoms, change in sense of smell or taste and fever was found to have a sensitivity of 70% and overall discrimination accuracy of 75%. CONCLUSION: Smell or taste change is a strong predictor for a COVID‐19 positive test result. Using the presence of smell or taste change with fever, this parsimonious classifier correctly predicts 75% of COVID‐19 test results. A larger cohort of respondents will be necessary to refine classifier performance. This article is protected by copyright. All rights reserved

negative: A Nationwide Survey of Psychological Distress among Italian People during the COVID-19 Pandemic: Immediate Psychological Responses and Associated Factors The uncontrolled spread of the coronavirus disease 2019 (COVID-19) has called for unprecedented measures, to the extent that the Italian government has imposed a quarantine on the entire country. Quarantine has a huge impact and can cause considerable psychological strain. The present study aims to establish the prevalence of psychiatric symptoms and identify risk and protective factors for psychological distress in the general population. An online survey was administered from 18–22 March 2020 to 2766 participants. Multivariate ordinal logistic regression models were constructed to examine the associations between sociodemographic variables; personality traits; depression, anxiety, and stress. Female gender, negative affect, and detachment were associated with higher levels of depression, anxiety, and stress. Having an acquaintance infected was associated with increased levels of both depression and stress, whereas a history of stressful situations and medical problems was associated with higher levels of depression and anxiety. Finally, those with a family member infected and young person who had to work outside their domicile presented higher levels of anxiety and stress, respectively. This epidemiological picture is an important benchmark for identifying persons at greater risk of suffering from psychological distress and the results are useful for tailoring psychological interventions targeting the post-traumatic nature of the distress.

negative: Repurposing and reshaping of hospitals during the COVID-19 outbreak in South Korea Abstract During the extensive outbreak of coronavirus disease 2019 (COVID-19) in South Korea, many strategies in the hospital setting, such as stratified patient care, the assignment of hospitals/beds by a task force team, and the establishment of dedicated COVID-19 hospitals, dedicated COVID-19 emergency centers, COVID-19 community facilities, and respiratory care split hospitals, were adopted to mitigate community transmission and prevent nosocomial infection. Most of these strategies were used during the Middle East Respiratory syndrome outbreak and were applied again successfully during the COVID-19 outbreak. The reallocation of health care capacity, repurposing of hospitals, and close collaboration between the government and the health care committee might have been the key to successfully addressing the crisis of COVID-19 given the shortage of health care resources.

negative: Garden-based interventions and early childhood health: a protocol for an umbrella review. BACKGROUND Garden-based interventions have the potential to impact young children's health in a number of ways, including enhancing dietary intake, increasing outdoor physical activity, diversifying the gut microbiome, and promoting general wellbeing. A number of recent systematic reviews have either included or focused on garden-based interventions for young children. However, most prior reviews including young children only focus on one health outcome or one setting, making a full summary of prior research assessing the impact of garden-based interventions nonexistent. As such, this umbrella systematic review aims to synthesize the literature on health outcomes of garden-based interventions for young children. METHODS This protocol outlines the systematic steps we will take to conduct an umbrella review on health-related outcomes of garden-based interventions in children younger than 6 years of age. We will systematically search PubMed, PsycINFO, ERIC, CINAHL, Embase, Scopus, OVID-Agricola, and CAB Direct, including all systematic reviews and meta-analyses fitting the pre-determined inclusion/exclusion criteria. We will double screen at each phase of the review: title/abstract, full text, data extraction, and quality appraisal. We will assess the quality of included reviews using A Measurement Tool to Assess Systematic Reviews (AMSTAR 2). Based on the potential for stark variability in what how reviews report child health outcomes, we will analyze the reviews both narratively and quantitatively, reporting summary of findings tables and iteratively mapping the results. This protocol aligns with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols statement (PRISMA-P). DISCUSSION This umbrella review aims to summarize the role that garden-based interventions play in health promotion for young children. We will focus on a number of diverse child health outcomes in an effort to comprehensively synthesize the evidence to inform future garden-based interventions, research, and policy. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42019106848.

negative: Pediatric cancer research: Surviving COVID‐19 A diverse panel of pediatric cancer advocates and experts, whose collective experience spans the continuum of international academic medicine, industry, government research, and cancer advocacy, recently discussed challenges for pediatric cancer research in the context of coronavirus disease 2019 (COVID‐19). Specifically, this special report addresses the following focus areas: (a) the critical role that translational research has played in transforming pediatric cancer outcomes; (b) the current and potential future impact of COVID‐19 on pediatric cancer research; (c) target areas of COVID‐19 research that may have application in immunity, oncogenesis, and therapeutic discovery; and (d) future considerations and directions in maintaining pediatric cancer research during and after COVID‐19.

negative: Heightened risk of child maltreatment amid the COVID-19 pandemic can exacerbate mental health problems for the next generation The spread of the COVID-19 disrupted ecological systems in which children develop, exacerbating threats to their safety and increasing their vulnerability to future psychopathology. Supports to reduce sources of stress for caregivers and protect children from threats to their safety are warranted. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

negative: Considerations for Heart Failure Care During the Coronavirus Disease 2019 (COVID-19) Pandemic Abstract The coronavirus disease 2019 (COVID-19) pandemic has affected the care of patients with HF who contract COVID-19 as well as those without COVID-19 who have been impacted by the restructuring of health care delivery. Patients with HF and other cardiovascular comorbidities are at risk for severe disease and complications of infection. Similarly, COVID-19 has been demonstrated to cause myocarditis and may be implicated in new-onset cardiomyopathy. During this pandemic, special considerations are needed for patients with advanced HF, including those supported by durable left ventricular assist devices (LVADs) and heart transplant recipients. The purpose of this review is to summarize emerging data regarding the development of HF secondary to COVID-19, COVID-19 infection in patients with advanced HF, and the implications of the pandemic on care for non-infected patients with HF.

negative: Rhinovirus-induced bronchiolitis: Lack of association between virus genomic load and short-term outcomes

negative: Clinical Characteristics and Differential Clinical Diagnosis of Novel Coronavirus Disease 2019 (COVID-19) Novel Coronavirus Disease (COVID-19) has become a rapidly growing pandemic involving several nations. It is of serious concern and extreme challenge not only to the health personnel but also to the countries for containment. The causative organism is SARS-CoV-2, RNA virus of subgenus Sarbecovirus, similar to the SARS virus, and seventh member of the human coronavirus family responsible for this zoonotic infection. It binds to the human angiotensin converting enzyme (hACE-2) receptor and causes constitutional and respiratory symptoms. The major mode of transmission is human to human and the median incubation period is 4 days. The most common symptom as studied from various cohorts of COVID-19 patients are fever (83–98%) followed by fatigue (70%) and dry cough (59%); gastrointestinal symptoms are relatively uncommon differentiating it from SARS and MERS. Most of the SAR-CoV-2 infection are mild (80%) with a usual recovery period of 2 weeks. COVID-19 commonly affects males in the middle age and elderly age group, with highest case fatality (8–15%) among those aged >80 years. The disease begins with fever, dry cough, fatigue and myalgia progressing to dyspnoea and ARDS over 6 and 8 days post exposure, respectively. Underlying co-morbidities increase mortality in COVID-19. Poor prognostic factors are elderly, co-morbidities, severe lymphopaenia, high CRP and D-dimer >1 μg/L. The overall mortality rate ranges from 1.5 to 3.6%. COVID-19 has to be differentiated from other viral and bacterial pneumonias as they are more common among healthy adults. Despite constant and vigorous efforts by researchers and health agencies, we are far from containment, cure or prevention by vaccine; hence right information and stringent prevention and control measures are the only weapon in the armoury to combat the ongoing infection.

negative: Long‐term morbidity of respiratory viral infections during chemotherapy in children with leukaemia BACKGROUND: Respiratory viruses are a common cause of infection in immunosuppressed children undergoing cancer therapy. Pulmonary sequelae have been documented following respiratory viral infections (RVIs) in hematopoietic stem cell transplant (HSCT) recipients; however potential late effects in children undergoing nonmyeloablative chemotherapy have not been investigated. AIM: To evaluate the long‐term pulmonary morbidity of respiratory viral infections during chemotherapy in children with acute lymphoblastic leukemia (ALL). METHODS: Childhood ALL survivors, aged 7 to 18 years, greater than 6 months posttreatment were recruited. Exclusion criteria included HSCT or proven bacterial/fungal respiratory infection during treatment. Subjects were classified into “viral” or “control” groups according to retrospective medical records that documented the presence of laboratory‐proven RVIs during chemotherapy. Symptom questionnaires (Liverpool, ISAAC) and lung function testing (spirometry, plethysmography, diffusing capacity, forced oscillation technique to ATS/ERS standards) were then performed cross‐sectionally at the time of recruitment. RESULTS: Fifty‐four patients (31 viral, 23 control) were recruited: median (range) age 11.2 (7.2‐18.1) years, and at 4.9 (0.5‐13) years posttherapy. Abnormalities were detected in 17 (31%) individuals (8 viral, 9 control), with the most common being DLCO impairment (3 viral, 4 control) and reduced respiratory reactance at 5 Hz (5 viral, 6 control). Children with RVIs during chemotherapy reported more current respiratory symptoms, particularly wheeze (odds ratio [OR], 3.0; 95% confidence interval [CI]: 0.9‐10.0; P = .09) and cough (OR, 2.7; 95% CI: 0.8‐9.5; P = .11). No differences in lung function tests were observed between the two groups. CONCLUSIONS: Our study found children with RVIs during chemotherapy developed more long‐term respiratory symptoms than controls; however, differences did not reach statistical significance. No differences in static lung function were found between the two groups. Overall, pulmonary abnormalities and/or significant ongoing respiratory symptoms were detected in nearly a third of ALL survivors treated without HSCT. Larger, prospective studies are warranted to evaluate the etiology and clinical significance of these findings.

negative: Sepsis The health care provider faced with the management of a child with septic shock relies on a comprehensive understanding of the numerous disciplines embodied in the practice of pediatric critical care medicine. The child with septic shock may have simultaneous derangements in the function of virtually every system of the body including: cardiovascular, respiratory, immune, renal, coagulation, hepatic, metabolic and neurologic. The degree to which physiologic alterations are manifest in a given patient is variable and influenced by multiple host and non-host factors including: the developmental stage, the presence of co-morbidities, pathogen-related factors, and genetic influences on both the host inflammatory response as well as the response to pharmacologic agents, all combining to have a profound influence on outcome. The clinician must possess a systematic and multifaceted approach to these critically ill patients. The goal of this chapter is to provide a comprehensive description of the epidemiology, biology and pathophysiology (at both the cellular and organ level) of sepsis, as well as outlining the current principles of managing septic shock. It will be apparent that optimal management requires a strong working knowledge of cardiovascular physiology, infectious diseases, multiple organ interactions, immunity, coagulation, pharmacology, and the molecular biology of inflammation.

negative: Is the use of ACE inb/ARBs associated with higher in-hospital mortality in Covid-19 pneumonia patients? INTRODUCTION: The present research aimed to determine the relation between the use of angiotensin-converting enzyme inhibitors (ACE inh) and angiotensinogen receptor blockers (ARBs) and in-hospital mortality of hypertensive patients diagnosed with Covid-19 pneumonia. MATERIAL AND METHOD: In this retrospective study, we included 113 consecutive hypertensive patients admitted due to Covid-19 infection. In all patients, Covid-19 infection was confirmed with using reverse-transcription polymerase chain reaction. All patients were on ACE inh/ARBs or other antihypertensive therapy unless no contraindication was present. The primary outcome of the study was the in-hospital all-cause mortality. RESULTS: In total, 113 hypertensive Covid-19 patients were included, of them 74 patients were using ACE inh/ARBs. During in-hospital follow up, 30.9% [n = 35 patients] of patients died. The frequency of admission to the ICU and endotracheal intubation were significantly higher in patients using ACE inh/ARBs. In a multivariable analysis, the use of ACE inh/ARBs was an independent predictor of in-hospital mortality (OR: 3.66; 95%CI: 1.11-18.18; p= .032). Kaplan-Meir curve analysis displayed that patients on ACE inh/ARBs therapy had higher incidence of in-hospital death than those who were not. CONCLUSION: The present study has found that the use of ACE inh/ARBs therapy might be associated with an increased in-hospital mortality in patients who were diagnosed with Covid-19 pneumonia. It is likely that ACE inh/ARBs therapy might not be beneficial in the subgroup of hypertensive Covid-19 patients despite the fact that there might be the possibility of some unmeasured residual confounders to affect the results of the study.

negative: COVID-19: clinical issues from the Japan Surgical Society In this unprecedented COVID-19 pandemic, several key issues must be addressed to ensure safe treatment and prevent rapid spread of the virus and a consequential medical crisis. Careful evaluation of a patient’s condition is crucial for deciding the triage plan, based on the status of the disease and comorbidities. As functionality of the medical care system is greatly affected by the environmental situation, the treatment may differ according to the medical and infectious disease circumstances of the institution. Importantly, all medical staff must prevent nosocomial COVID-19 by minimizing the effects of aerosol spread and developing diagnostic and surgical procedures. Polymerase chain reaction (PCR) screening for COVID-19 infection, particularly in asymptomatic patients, should be encouraged as these patients are prone to postoperative respiratory failure. In this article, the Japan Surgical Society addresses the general principles of surgical treatment in relation to COVID-19 infection and advocates preventive measures against viral transmission during this unimaginable COVID-19 pandemic.

negative: Systematic review with meta‐analysis: liver manifestations and outcomes in COVID‐19 BACKGROUND: The incidence of elevated liver chemistries and the presence of the pre‐existing chronic liver disease (CLD) have been variably reported in COVID‐19. AIMS: To assess the prevalence of CLD, the incidence of elevated liver chemistries and the outcomes of patients with and without underlying CLD/elevated liver chemistries in COVID‐19. METHODS: A comprehensive search of electronic databases from 1 December 2019 to 24 April 2020 was done. We included studies reporting underlying CLD or elevated liver chemistries and patient outcomes in COVID‐19. RESULTS: 107 articles (n = 20 874 patients) were included for the systematic review. The pooled prevalence of underlying CLD was 3.6% (95% CI, 2.5‐5.1) among the 15 407 COVID‐19 patients. The pooled incidence of elevated liver chemistries in COVID‐19 was 23.1% (19.3‐27.3) at initial presentation. Additionally, 24.4% (13.5‐40) developed elevated liver chemistries during the illness. The pooled incidence of drug‐induced liver injury was 25.4% (14.2‐41.4). The pooled prevalence of CLD among 1587 severely infected patients was 3.9% (3%‐5.2%). The odds of developing severe COVID‐19 in CLD patients was 0.81 (0.31‐2.09; P = 0.67) compared to non‐CLD patients. COVID‐19 patients with elevated liver chemistries had increased risk of mortality (OR‐3.46 [2.42‐4.95, P < 0.001]) and severe disease (OR‐2.87 [95% CI, 2.29‐3.6, P < 0.001]) compared to patients without elevated liver chemistries. CONCLUSIONS: Elevated liver chemistries are common at presentation and during COVID‐19. The severity of elevated liver chemistries determines the outcome of COVID‐19. The presence of CLD does not alter the outcome of COVID‐19. Further studies are needed to analyse the outcomes of compensated and decompensated liver disease.

negative: SARS pandemic exposure impaired early childhood development: A lesson for COVID-19 Social and mental stressors associated with the COVID-19 pandemic may promote long-term effects on child development. However, reports aimed at identifying the relationship between pandemics and child health are limited. We conducted a retrospective study to evaluate the severe acute respiratory syndrome (SARS) pandemic in 2003 and its relationship to child development indicators using a representative sample across China. Our study involved longitudinal measurements of 14,647 children, 36% of whom (n = 5216) were born before or during the SARS pandemic. Cox models were utilized to examine the effects of SARS on preterm birth and four milestones of development: age to (1) walk independently, (2) say a complete sentence, (3) count from 0 to 10, and (4) undress him/herself for urination. Mixed effect models were utilized to associate SARS with birthweight, body weight and height. Our results show that experiencing SARS during early childhood was significantly associated with delayed milestones, with adjusted hazard ratios of 3.17 [95% confidence intervals (CI): 2.71, 3.70], 3.98 (3.50, 4.53), 4.96 (4.48, 5.49), or 5.57 (5.00, 6.20) for walking independently, saying a complete sentence, counting from 0 to 10, and undressing him/herself for urination, respectively. Experiencing SARS was also associated with reduced body weight. This effect was strongest for preschool children [a weight reduction of 4.86 (0.36, 9.35) kg, 5.48 (-0.56, 11.53) kg or 5.09 (-2.12, 12.30) kg for 2, 3, 4 year-olds, respectively]. We did not identify a significant effect of maternal SARS exposure on birthweight or gestational length. Collectively, our results showed that the SARS pandemic was associated with delayed child development and provided epidemiological evidence to support the association between infectious disease epidemics and impaired child health. These results provide a useful framework to investigate and mitigate relevant impacts from the COVID-19 pandemic.

negative: Clinical, virological and epidemiological characteristics of rhinovirus infections in early childhood: A comparison between non-hospitalised and hospitalised children Abstract Background Several studies have been published regarding the epidemiology and clinical significance of the different rhinovirus (RV) species (-A, -B and -C). However, data on RV types and the associations with clinical outcome in young children are limited. Here, we investigated the clinical, virological and epidemiological characteristics of RV infections in young children with mild or asymptomatic infection (non-hospitalised children) and in symptomatic young children admitted to the hospital. Objectives The aim of this study was to evaluate associations between different characteristics of RV infections and clinical outcome in young children. Study design RV-infected children were retrospectively selected from a Dutch birth cohort (EUROPA-study) and from hospitalised children admitted to the hospital because of respiratory symptoms. In total 120 RV-typed samples could be selected from 65 non-hospitalised and 49 hospitalised children between November 2009 and December 2012. Results RV-A was the predominant species in both study populations, followed closely by RV-C. RV-B was observed only sporadically. The distribution of the RV species was comparable in non-hospitalised and hospitalised children. In children with respiratory distress who required ICU-admission the distribution of RV species did not differ significantly from the non-hospitalised children. No predominant RV type was present in non-hospitalised nor hospitalised children. However, hospitalised children were younger, had more often an underlying illness, a higher RV load and more frequently a bacterial co-infection. Conclusions Clinical outcome of RV infected young children was not related to RV species or types, but may more likely be influenced by multiple (host-specific) factors.

negative: Impact of influenza-like illness and effectiveness of influenza vaccination in oncohematological children who have completed cancer therapy Abstract In order to evaluate the impact of influenza-like illness and the effectiveness of influenza vaccination in children with oncohematological disease who have completed cancer therapy, 182 children with a diagnosis of oncohematological disease were divided into two subgroups on the basis of the length of time off therapy (<6 months or 6–24 months) and randomised 1:1 to receive influenza vaccination or not. The controls were 91 otherwise healthy children unvaccinated against influenza. The results show that the clinical and socioeconomic impact of influenza-like illnesses and the effectiveness of influenza vaccination in oncohematological children who have completed cancer therapy are related to the length of the off therapy period, and seem to be significantly greater in those who have been off therapy for less than 6 months in comparison with healthy controls. This suggests that the administration of influenza vaccination should be strongly recommended only among oncohematological children who have been off therapy for less than 6 months.

negative: COVID-19 Abortion Bans and Their Implications for Public Health

negative: Posttraumatic Stress Symptoms and Associated Comorbidity During the COVID-19 Pandemic in Ireland: A Population-Based Study. The prevalence of posttraumatic stress disorder (PTSD) as it relates to individuals' experiences of the COVID-19 pandemic has yet to be determined. This study was conducted to determine rates of COVID-19-related PTSD in the Irish general population, the level of comorbidity with depression and anxiety, and the sociodemographic risk factors associated with COVID-19-related PTSD. A nationally representative sample of adults from the general population of the Republic of Ireland (N = 1,041) completed self-report measures of all study variables. The rate of COVID-19-related PTSD was 17.7% (n = 184), 95% CI [15.35%, 19.99%], and there was a high level of comorbidity with generalized anxiety (49.5%) and depression (53.8%). Meeting the diagnostic requirement for COVID-19-related PTSD was associated with younger age, male sex, living in a city, living with children, moderate and high perceived risk of COVID-19 infection, and screening positive for anxiety or depression. Posttraumatic stress symptoms related to the COVID-19 pandemic are common in the general population. Our results show that health professionals responsible for responding to the COVID-19 pandemic should expect to routinely encounter symptoms and concerns related to posttraumatic stress.

negative: Effects of resistance training on tendon mechanical properties and rapid force production in prepubertal children. Children develop lower levels of muscle force, and at slower rates, than adults. Although strength training in children is expected to reduce this differential, a synchronous adaptation in the tendon must be achieved to ensure forces continue to be transmitted to the skeleton with efficiency while minimizing the risk of strain-related tendon injury. We hypothesized that resistance training (RT) would alter tendon mechanical properties in children concomitantly with changes in force production characteristics. Twenty prepubertal children (age 8.9 ± 0.3 yr) were equally divided into control (nontraining) and experimental (training) groups. The training group completed a 10-wk RT intervention consisting of 2-3 sets of 8-15 plantar flexion contractions performed twice weekly on a recumbent calf-raise machine. Achilles tendon properties (cross-sectional area, elongation, stress, strain, stiffness, and Young's modulus), electromechanical delay (EMD; time between the onset of muscle activity and force), rate of force development (RFD; slope of the force-time curve), and rate of electromyographic (EMG) increase (REI; slope of the EMG time curve) were measured before and after RT. Tendon stiffness and Young's modulus increased significantly after RT in the experimental group only (∼29% and ∼25%, respectively); all other tendon properties were not significantly altered, although there were mean decreases in both peak tendon strain and strain at a given force level (14% and 24%, respectively; not significant) which may have implications for tendon injury risk and muscle fiber mechanics. A decrease of ∼13% in EMD was found after RT for the experimental group, which paralleled the increase in tendon stiffness (r = -0.59); however, RFD and REI were unchanged. The present data show that the Achilles tendon adapts to RT in prepubertal children and is paralleled by a change in EMD, although the magnitude of this change did not appear to be sufficient to influence RFD. These findings are of importance within the context of the efficiency and execution of movement.

negative: Is ethnicity linked to incidence or outcomes of covid-19?

negative: Effects of the COVID-19 Pandemic on Routine Pediatric Vaccine Ordering and Administration - United States, 2020. On March 13, 2020, the president of the United States declared a national emergency in response to the coronavirus disease 2019 (COVID-19) pandemic (1). With reports of laboratory-confirmed cases in all 50 states by that time (2), disruptions were anticipated in the U.S. health care system's ability to continue providing routine preventive and other nonemergency care. In addition, many states and localities issued shelter-in-place or stay-at-home orders to reduce the spread of COVID-19, limiting movement outside the home to essential activities (3). On March 24, CDC posted guidance emphasizing the importance of routine well child care and immunization, particularly for children aged ≤24 months, when many childhood vaccines are recommended.

negative: Intensivist-led care in the COVID-19 pandemic

negative: Middle East respiratory syndrome coronavirus in children The Middle East respiratory syndrome (MERS) is a new human disease caused by a novel coronavirus (CoV). The disease is reported mainly in adults. Data in children are scarce. The disease caused by MERS-CoV in children presents with a wide range of clinical manifestations, and it is associated with a lower mortality rate compared with adults. Poor outcome is observed mainly in admitted patients with medical comorbidities. We report a new case of MERS-CoV infection in a 9-month-old child complicated by severe respiratory symptoms, multi-organ dysfunction, and death. We reviewed the literature in an attempt to characterize the mode of presentation, the risk factors, and outcome of MERS-CoV infection in the pediatric population.

negative: Are hydroxychloroquine and chloroquine effective in the treatment of SARS-COV-2 (COVID-19)? Data sources The authors of this rapid review did not disclose which electronic databases were included in their literature search. The inclusion and exclusion criteria for the data sources are not reported in the manuscript.Study selection The authors included six studies on the effectiveness of hydroxychloroquine or chloroquine for the prevention and treatment of COVID-19 in humans. Studies comprised of two randomised controlled trials, two non-randomised trials both of which were non-blinded and open-label and one that was uncontrolled, a prospective cohort study and an interim report. The authors did not report details of any studies that were excluded.Data extraction and synthesis The data extraction methodology was not reported and it is unclear if the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were followed. Treatment regimens and the study outcomes were extracted where available and overall findings were presented in a table. There were no comparable outcome measures; therefore, results were deemed unsuitable to combine and no statistical analyses were carried out. A narrative synthesis of each study is presented.Results The results of the studies in this rapid review are difficult to quantify as each study had different outcome parameters. Due to the heterogeneity of the studies, results were not combined, and no statistical analysis was carried out. Narrative synthesis of each of the included studies identified important and significant limitations, precluding the studies from demonstrating a statistically significant difference in outcomes.Conclusions This review highlights the urgent need for more high quality evidence on the use of hydroxychloroquine and chloroquine in the prevention and treatment of COVID-19. The results of the studies included should be interpreted with caution due to the weak supporting data and numerous methodological limitations. The authors suggested that the studies be viewed as hypothesis-generating and should not be used in decision making around the recommendations and guidelines in the prevention and treatment of COVID-19. There are currently several ongoing randomised controlled trials looking at the effectiveness and efficacy of these drugs on COVID-19. It is hoped the outcome of these studies can help guide future recommendations and national guidelines.

negative: Transumbilical laparoscopically assisted extracorporeal appendectomy in children and young adults: A retrospective cohort study. BACKGROUND To compare surgical outcomes of pediatric patients aged 0-15 with acute appendicitis treated with single-port, transumbilical, extracorporeal laparoscopically assisted appendectomy (SP) with young adult patients aged 16-21. MATERIALS AND METHODS Single center retrospective chart review in patients 21 years and younger with a pre-operative diagnosis of appendicitis who underwent SP between January 2010 and December 2015. Patients were divided into two groups based on age. Operative time (OT), length of stay (LOS), cost, rates of conversion to standard three-port laparoscopic appendectomy (TP), and rates of infection were compared between the groups. RESULTS SP was performed in a total of 263 patients: 211 in pediatric patients aged 0-15 and 52 in patients aged 16-21. Age groups did not differ significantly on cost, LOS, operative time, rates of conversion to TP, or rates of infection. CONCLUSIONS SP has comparable surgical outcomes in adolescent, adult, and pediatric patients.

negative: The Impact of Respiratory Viral Infection on Wheezing Illnesses and Asthma Exacerbations The etiology and morbidity associated with asthma are thought to stem from both genetic factors and potentially modifiable environmental factors, such as viral infections.[1-7] Although it is unclear whether respiratory viral infections cause asthma, observational studies have demonstrated a high rate of asthma in children with a history of severe viral lower respiratory tract infections during infancy, and viruses are the associated with the majority of asthma exacerbations among both children and adults. This review will discuss the pathogens associated with virus-induced wheezing illnesses during infancy and early childhood, the association of bronchiolitis during infancy with an increased risk of childhood asthma, and the association of respiratory viruses with asthma exacerbations in older children and adults.

negative: Current smoking, former smoking, and adverse outcome among hospitalized COVID-19 patients: a systematic review and meta-analysis BACKGROUND: The purpose of this study was to examine the prevalence and effects of current smoking on adverse outcomes among hospitalized COVID-19 patients. METHODS: A systematic review of the literature (PubMed) identified 18 (from a total of 1398) relevant studies. Pooled current smoking prevalence was compared with the gender-adjusted and gender and age-adjusted, population-based expected prevalence by calculating prevalence odds ratio (POR). The association between current, compared with non-current and former, smoking and adverse outcome was examined. A secondary analysis was performed by including 12 pre-publications (30 studies in total). All analyses were performed using random-effects meta-analysis. RESULTS: Among 6515 patients, the pooled prevalence of current smoking was 6.8% [95% confidence interval (CI): 4.8–9.1%]. The gender-adjusted POR was 0.20 (95% CI: 0.16–0.25, p < 0.001), and the gender and age-adjusted POR was 0.24 (95% CI: 0.19–0.30, p < 0.001). Current smokers were more likely to have an adverse outcome compared with non-current smokers [odds ratio (OR): 1.53, 95%CI: 1.06–2.20, p = 0.022] but less likely compared with former smokers (OR: 0.42, 95% CI: 0.27–0.74, p = 0.003). When pre-publications were added (n = 10,631), the gender-adjusted POR was 0.27 (95% CI: 0.19–0.38, p < 0.001) and the gender and age-adjusted POR was 0.34 (95% CI: 0.24–0.48, p < 0.001). CONCLUSION: This meta-analysis of retrospective observational case series found an unexpectedly low prevalence of current smoking among hospitalized patients with COVID-19. Hospitalized current smokers had higher odds compared with non-current smokers but lower odds compared with former smokers for an adverse outcome. Smoking cannot be considered a protective measure for COVID-19. However, the hypothesis that nicotine may have a protective effect in COVID-19 that is partially masked by smoking-related toxicity and by the abrupt cessation of nicotine intake when smokers are hospitalized should be explored in laboratory studies and clinical trials using pharmaceutical nicotine products.

negative: Hyper Acute Demyelinating Encephalomyelitis of Childhood: A Rare Entity A young child with catastrophic neurological illness diagnosed as a rare variant of acute demyelinating encephalomyelitis (ADEM). She succumbed to her illness despite of aggressive and appropriate management. Malignant demyelinating encephalomyelitis should be considered in children who are refractory to the treatment of ADEM.

negative: Non-invasive estimation of cerebral perfusion pressure using transcranial Doppler ultrasonography in children with severe traumatic brain injury OBJECTIVE: To identify if cerebral perfusion pressure (CPP) can be non-invasively estimated by either of two methods calculated using transcranial Doppler ultrasound (TCD) parameters. DESIGN: Retrospective review of previously prospectively gathered data. SETTING: Pediatric intensive care unit in a tertiary care referral hospital. PATIENTS: Twenty-three children with severe traumatic brain injury (TBI) and invasive intracranial pressure (ICP) monitoring in place. INTERVENTIONS: TCD evaluation of the middle cerebral arteries was performed daily. CPP at the time of the TCD examination was recorded. For method 1, estimated cerebral perfusion pressure (CPPe) was calculated as: CPPe = MAP × (diastolic flow (Vd)/mean flow (Vm)) + 14. For method 2, critical closing pressure (CrCP) was identified as the intercept point on the x-axis of the linear regression line of blood pressure and flow velocity parameters. CrCP/CPPe was then calculated as MAP-CrCP. MEASUREMENTS AND MAIN RESULTS: One hundred eight paired measurements were available. Using patient averaged data, correlation between CPP and CPPe was significant (r = 0.78, p = < 0.001). However, on Bland-Altman plots, bias was 3.7 mmHg with 95% limits of agreement of − 17 to + 25 for CPPe. Using patient averaged data, correlation between CPP and CrCP/CPPe was significant (r = 0.59, p = < 0.001), but again bias was high at 11 mmHg with wide 95% limits of agreement of − 15 to + 38 mmHg. CONCLUSIONS: CPPe and CrCP/CPPe do not have clinical value to estimate the absolute CPP in pediatric patients with TBI.

negative: Management for patients with pediatric surgical disease during the COVID-19 epidemic

negative: Association of BMI and Obesity with Composite poor outcome in COVID-19 adult patients: A Systematic Review and Meta-Analysis Aim: This study aimed to evaluate the association between obesity and composite poor outcome in coronavirus disease 2019 (COVID-19) patients. Methods: We conducted a systematic literature search from PubMed and Embase database. We included all original research articles in COVID-19 adult patients and obesity based on classification of Body Mass Index (BMI) and composite poor outcome which consist of mortality, morbidity, admission of Intensive Care Unit (ICU), mechanical ventilation, Acute Respiratory Distress Syndrome (ARDS), and severe COVID-19. Results: Nine studies were included in meta-analysis with 6 studies presented BMI as continuous outcome and 3 studies presented BMI as dichotomous outcome (obese and non-obese). Most studies were conducted in China (55.5%) with remaining studies from French, Germany, and United States (US). COVID-19 patients with composite poor outcome had higher BMI with mean difference 0.55 kg/m2 (95% CI 0.07-1.03, P=0.02). BMI [≥]30 (obese) was associated with composite poor outcome with odds ratio 1.89 (95% CI 1.06-3.34, P=0.03). Multivariate meta-regression analysis by including three moderators: age, hypertension, and Diabetes Mellitus type 2 (DM type 2) showed the association between obesity and composite poor outcome was affected by age with regression coefficient =-0.06 and P=0.02. Subgroup analysis was not performed due to the limited number of studies for several outcomes. Conclusion: Obesity is a risk factor of composite poor outcome of COVID-19. On the other hand, COVID-19 patients with composite poor outcome have higher BMI. BMI is an important routine procedure that should be assessed in the management of COVID-19 patients and special attention should be given to patients with obesity. Keywords: Covid-19, Obesity, Body Mass Index

negative: COVID-19 Related Mortality: Is the BCG Vaccine Truly Effective? The coronavirus disease 2019 (COVID-19) pandemic has become a worldwide emergency. In the attempt to search for interventions that would improve outcomes, some studies have looked at the potential benefit of BCG vaccination. These past studies have found a statistically significant reduction in COVID-19 related mortality in countries with a current universal bacille Calmette-Guerin (BCG) vaccination policy. However, just as the authors themselves noted, the nature of ecological studies make them very prone to the presence of several confounders. This paper took into account demographic differences, economic differences and the different stages of the pandemic in each country; gathering data from publicly available sources. It was found that no statistically significant difference exists in mortality rates between countries with a current or prior BCG vaccination policy when compared to those that never had such a program. Nevertheless, the immunostimulatory potential of the BCG vaccine might still prove useful in the development of future vaccines or other prophylactic measures.

negative: Objective sensory and functional outcomes at the donor site following endoscopic-assisted sural nerve harvest. BACKGROUND The sural nerve is a common choice for a nerve graft. Understanding the potential morbidity associated with its harvest is important. In this study, we describe the objective sensory and functional outcomes associated with endoscopic sural nerve harvest from a combined paediatric and adult population. METHODS Data were collected prospectively from patients attending for follow-up between August 2015 and January 2016, who had previously undergone an endoscopic sural nerve graft harvest. Sensory loss was evaluated using a 5.07 Semmes-Weinstein monofilament. The lower extremity functional scale was used to evaluate the patients' lower limb function. Statistical comparison was made using the Student's t-test. RESULTS The outcomes from 46 sural nerve grafts were evaluated. The mean age of the patients was 18.1 years (range 4-45 years old). The mean time since surgery was 4.3 years. Those aged ≤18 years had a significantly smaller area of sensory loss (p = 0.003), which was not related to a difference in foot size. Those who had undergone surgery >6 months previously had a significantly smaller area of sensory loss than those who had undergone surgery <6 months ago (p = 0.0002). The mean lower extremity functional scale score was 78.7/80. CONCLUSION We demonstrated a significantly reduced post-harvest sensory deficit among a paediatric population compared to that seen in adults. Furthermore, sensory loss reduces with time. Despite the sensory loss resulting from sural nerve graft harvest, there is minimal loss of function. As such, the sural nerve continues to be an excellent donor for a nerve graft procedure.

negative: Covid-19, child and adolescent mental health – Croatian (in)experience The Covid-19 pandemic has caused unseen socio-economic changes all over the world, where enormous efforts are being made to preserve lives and maintain functional health systems. A secondary concern is to mitigate the severe economic consequences of the crisis. Different approaches have been adopted with varying outcomes and experiences. But regardless of the different approaches taken, one thing is common for all societies during this pandemic: fear and anxiety. This fear extends from concerns about the present situation, for the health and well-being of family members and loved ones from Covid-19 infection, to fears relating to how long the crisis will last, to the potential economic consequences of the pandemic (perhaps not seen in our lifetimes) and the ultimate fear of future uncertainty. Across the world, health systems are being faced with unprecedented challenges. At their core, these challenges are the same: how to beat Covid-19. Certainly, there are differences in how individual systems are organized and how they address the main issues arising from the pandemic while not forgetting the ongoing healthcare needs of the general population. In this paper, we share some perspectives from Croatia regarding Child and Adolescent Mental Health services (CAMHs) in these extraordinary circumstances. We give our personal insights on deficiencies in Child and Adolescent Mental Health Services prior to the arrival of Covid-19, which have contributed to difficulties in mitigating and managing the ongoing crisis.

negative: Analysis of Genetic Host Response Risk Factors in Severe COVID-19 Patients BACKGROUND Epidemiological studies indicate that as many as 20% of individuals who test positive for COVID-19 develop severe symptoms that can require hospitalization. These symptoms include low platelet count, severe hypoxia, increased inflammatory cytokines and reduced glomerular filtration rate. Additionally, severe COVID-19 is associated with several chronic co-morbidities, including cardiovascular disease, hypertension and type 2 diabetes mellitus. The identification of genetic risk factors that impact differential host responses to SARS-CoV-2, resulting in the development of severe COVID-19, is important in gaining greater understanding into the biological mechanisms underpinning life-threatening responses to the virus. These insights could be used in the identification of high-risk individuals and for the development of treatment strategies for these patients. METHODS As of June 6, 2020, there were 976 patients who tested positive for COVID-19 and were hospitalized, indicating they had a severe response to SARS-CoV-2. There were however too few patients with a mild form of COVID-19 to use this cohort as our control population. Instead we used similar control criteria to our previous study looking at shared genetic risk factors between severe COVID-19 and sepsis, selecting controls who had not developed sepsis despite having maximum co-morbidity risk and exposure to sepsis-causing pathogens. RESULTS Using a combinatorial (high-order epistasis) analysis approach, we identified 68 protein-coding genes that were highly associated with severe COVID-19. At the time of analysis, nine of these genes have been linked to differential response to SARS-CoV-2. We also found many novel targets that are involved in key biological pathways associated with the development of severe COVID-19, including production of pro-inflammatory cytokines, endothelial cell dysfunction, lipid droplets, neurodegeneration and viral susceptibility factors. CONCLUSION The variants we found in genes relating to immune response pathways and cytokine production cascades, were in equal proportions across all severe COVID-19 patients, regardless of their co-morbidities. This suggests that such variants are not associated with any specific co-morbidity, but are common amongst patients who develop severe COVID-19. Among the 68 severe COVID-19 risk-associated genes, we found several druggable protein targets and pathways. Nine are targeted by drugs that have reached at least Phase I clinical trials, and a further eight have active chemical starting points for novel drug development. Several of these targets were particularly enriched in specific co-morbidities, providing insights into shared pathological mechanisms underlying both the development of severe COVID-19, ARDS and these predisposing co-morbidities. We can use these insights to identify patients who are at greatest risk of contracting severe COVID-19 and develop targeted therapeutic strategies for them, with the aim of improving disease burden and survival rates.

negative: The COVID-19 Pandemic during the Time of the Diabetes Pandemic: Likely Fraternal Twins? An altered immune response to pathogens has been suggested to explain increased susceptibility to infectious diseases in patients with diabetes. Recent evidence has documented several immunometabolic pathways in patients with diabetes directly related to the COVID-19 infection. This also seems to be the case for prediabetic subjects with proinflammatory insulin resistance syndrome accompanied with prothrombotic hyperinsulinemic and dysglycemic states. Patients with frank hyperglycemia, dysglycemia and/or hyperinsulinemia develop systemic immunometabolic inflammation with higher levels of circulating cytokines. This deleterious scenario has been proposed as the underlying mechanism enhancing a cytokine storm-like hyperinflammatory state in diabetics infected with severe COVID-19 triggering multi-organ failure. Compared with moderately affected COVID-19 patients, diabetes was found to be highly prevalent among severely affected patients suggesting that this non-communicable disease should be considered as a risk factor for adverse outcomes. The COVID-19 pandemic mirrors with the diabetes pandemic in many pathobiological aspects. Our interest is to emphasize the ties between the immunoinflammatory mechanisms that underlie the morbidity and lethality when COVID-19 meets diabetes. This review brings attention to two pathologies of highly complex, multifactorial, developmental and environmentally dependent manifestations of critical importance to human survival. Extreme caution should be taken with diabetics with suspected symptoms of COVID-19 infection.

negative: Growing wealth and growing pains: child and adolescent psychiatry in Hong Kong, Malaysia and Singapore. OBJECTIVE Several Asian regions have undergone a dramatic transformation, some becoming very affluent. This paper aims to ascertain how countries that are becoming wealthy have dealt with child and adolescent mental health issues. METHOD Population health status, child and adolescent mental health services, child psychiatry training, the number of child psychiatrists and related matters were examined in Hong Kong, Malaysia and Singapore. RESULTS Hong Kong, Malaysia and Singapore are ethnically, religiously, socially and politically very different. In spite of considerable wealth and a growing recognition that mental health problems in the young are increasing, they face similar problems--lack of access to treatment due to a dearth of services and a lack of child psychiatrists (2.5, 0.5 and 2.8 per million people, respectively). CONCLUSIONS Because the number of child psychiatrists is so small, their ability to provide services, advocate, train, maintain a professional identity, and deal with future crises is very limited. Other rapidly developing countries can learn from this experience and should take action early to prevent a similar outcome.

negative: Impact of COVID -19 on children: special focus on the psychosocial aspect. Although medical literature shows that children are minimally susceptible to 2019-Corona virus disease (COVID-19), they are hit the hardest by psychosocial impact of this pandemic. Being quarantined in homes and institutions may impose greater psychological burden than the physical sufferings caused by the virus. School closure, lack of outdoor activity, aberrant dietary and sleeping habits are likely to disrupt children's usual lifestyle and can potentially promote monotony, distress, impatience, annoyance and varied neuropsychiatric manifestations. Incidences of domestic violence, child abuse, adulterated online contents are on the rise. Children of single parent and frontline workers suffer unique problems. The children from marginalized communities are particularly susceptible to the infection and may suffer from extended ill-consequences of this pandemic, such as child labor, child trafficking, child marriage, sexual exploitation and death etc. Parents, pediatricians, psychologists, social workers, hospital authorities, government and non-governmental organizations have important roles to play to mitigate the psychosocial ill-effects of COVID-19 on children and adolescents. To provide the basic amenities, social security, medical care, and to minimize the educational inequities among the children of the different strata of the society are foremost priorities.

negative: Mental health services for older adults in China during the COVID-19 outbreak

negative: COVID-Net: A Tailored Deep Convolutional Neural Network Design for Detection of COVID-19 Cases from Chest X-Ray Images The COVID-19 pandemic continues to have a devastating effect on the health and well-being of the global population. A critical step in the fight against COVID-19 is effective screening of infected patients, with one of the key screening approaches being radiology examination using chest radiography. Motivated by this and inspired by the open source efforts of the research community, in this study we introduce COVID-Net, a deep convolutional neural network design tailored for the detection of COVID-19 cases from chest X-ray (CXR) images that is open source and available to the general public. To the best of the authors' knowledge, COVID-Net is one of the first open source network designs for COVID-19 detection from CXR images at the time of initial release. We also introduce COVIDx, an open access benchmark dataset that we generated comprising of 13,975 CXR images across 13,870 patient patient cases, with the largest number of publicly available COVID-19 positive cases to the best of the authors' knowledge. Furthermore, we investigate how COVID-Net makes predictions using an explainability method in an attempt to not only gain deeper insights into critical factors associated with COVID cases, which can aid clinicians in improved screening, but also audit COVID-Net in a responsible and transparent manner to validate that it is making decisions based on relevant information from the CXR images. By no means a production-ready solution, the hope is that the open access COVID-Net, along with the description on constructing the open source COVIDx dataset, will be leveraged and build upon by both researchers and citizen data scientists alike to accelerate the development of highly accurate yet practical deep learning solutions for detecting COVID-19 cases and accelerate treatment of those who need it the most.

negative: Risk factors for a poor outcome among children admitted with clinically severe pneumonia to a university hospital in Rabat, Morocco Summary Objectives Data on prognostic factors among children with severe pneumonia are scarce in middle-income countries. We investigated prognostic factors for an adverse outcome among children admitted to the Hôpital d’Enfants de Rabat, Morocco with World Health Organization-defined clinically severe pneumonia (CSP). Methods Children aged 2–59 months admitted to the hospital and fulfilling the CSP definition were recruited into this 13-month prospective study. A poor prognosis was defined as death, a need for intensive care, or a Respiratory Index of Severity in Children (RISC) score ≥3. Multivariate logistic regression was performed to ascertain independent predictive factors for a poor prognosis. Results Of the 689 children included in this analysis, 55 (8.0%) required intensive care and 28 died (4.0%). Five hundred and two (72.8%) children were classified as having a good prognosis and 187 (27.2%) as having a poor prognosis. A history of prematurity (odds ratio (OR) 2.50, 95% confidence interval (CI) 1.24–5.04), of fever (OR 2.25, 95% CI 1.32–3.83), living in a house with smokers (OR 1.79, 95% CI 1.18–2.72), impaired consciousness (OR 10.96, 95% CI 2.88–41.73), cyanosis (OR 2.09, 95% CI 1.05–4.15), pallor (OR 2.27, 95% CI 1.34–3.84), having rhonchi on auscultation (OR 2.45, 95% CI 1.58–3.79), and human metapneumovirus infection (OR 2.13, 95% CI 1.13–4.02) were all independent risk factors for an adverse outcome, whereas a history of asthma (OR 0.46, 95% CI 0.25–0.84) was the only independent risk factor for a positive outcome. Conclusions The early identification of factors associated with a poor prognosis could improve management strategies and the likelihood of survival of Moroccan children with severe pneumonia.

negative: Risk Factors and Etiologies of Pediatric Acute Respiratory Distress Syndrome The risk factors for acute respiratory distress syndrome (ARDS) have been a focus for clinicians and researchers from the original description in 1967 to the most recent Pediatric Acute Lung Injury Consensus Conference (PALICC). Indeed, there are many comorbidities and risk factors that predispose a patient to develop pediatric ARDS (PARDS) including, but not limited to, immunodeficiency, weight extremes, genetics, and environmental factors. These are particularly important to investigators because accurate prediction of which patients are at greatest risk of PARDS – both the development of PARDS and worse clinical outcomes after PARDS has been established – is key to identifying the next generation of diagnostic techniques and preventative strategies. In addition to those risk factors, there are specific disease processes that lead to the development of PARDS, often divided into direct or pulmonary insults and indirect or extrapulmonary insults. Finally, beyond the clinically visible risk factors, researchers are attempting to identify novel biomarkers to uncover hidden phenotypes of PARDS and enrich the prognostication and prediction of patient outcomes. This chapter delves into each of these concepts.

negative: Inhaled corticosteroid use and risk COVID-19 related death among 966,461 patients with COPD or asthma: an OpenSAFELY analysis Background: Early descriptions of the coronavirus outbreak showed a lower prevalence of asthma and COPD than was expected for people diagnosed with COVID-19, leading to speculation that inhaled corticosteroids (ICS) may protect against infection with SARS-CoV-2, and development of serious sequelae. We evaluated the association between ICS and COVID-19 related death using linked electronic health records in the UK. Methods: We conducted cohort studies on two groups of people (COPD and asthma) using the OpenSAFELY platform to analyse data from primary care practices linked to national death registrations. People receiving an ICS were compared to those receiving alternative respiratory medications. Our primary outcome was COVID-19 related death. Findings: We identified 148,588 people with COPD and 817,973 people with asthma receiving relevant respiratory medications in the four months prior to 01 March 2020. People with COPD receiving ICS were at a greater risk of COVID-19 related death compared to those receiving a long-acting beta agonist (LABA) and a long-acting muscarinic antagonist (LAMA) (adjusted HR = 1.38, 95% CI = 1.08 - 1.75). People with asthma receiving high dose ICS were at an increased risk of death compared to those receiving a short-acting beta agonist (SABA) only (adjusted HR = 1.52, 95%CI = 1.08 - 2.14); the adjusted HR for those receiving low-medium dose ICS was 1.10 (95% CI = 0.82 - 1.49). Quantitative bias analyses indicated that an unmeasured confounder of only moderate strength of association with exposure and outcome could explain the observed associations in both populations. Interpretation: These results do not support a major role of ICS in protecting against COVID-19 related deaths. Observed increased risks of COVID-19 related death among people with COPD and asthma receiving ICS can be plausibly explained by unmeasured confounding due to disease severity.

negative: COVID-19 in Rheumatic Disease Patients on Immunosuppressive Agents OBJECTIVE: To analyze clinical characteristics and outcome of COVID-19 patients with underlying rheumatic diseases (RD) on immunosuppressive agents. METHOD: A case series of COVID-19 patients with RD on disease modifying anti-rheumatic drugs (DMARDs) were studied by a retrospective chart review. A literature search identified 9 similar studies of single cases and case series, which were also included. RESULTS: There were 4 COVID-19 inpatients with RD from our hospital, and the mean age was 57 ± 21 years. Two patients had a mild infection, and 2 developed severe COVID-19 related respiratory complications, including 1 patient on secukinumab requiring mechanical ventilation and 1 patient on rituximab developing viral pneumonia requiring supplemental oxygenation. All 4 patients had elevated acute phase reactants, 2 patients had mild COVID-19 with lymphopenia, and 2 patients had severe COVID-19 with normal lymphocyte counts, and high levels of IL-6. None of the patients exhibited an exacerbation of their underlying RD. In the literature, there were 9 studies of COVID-19 involving 197 cases of various inflammatory RD. Most patients were on DMARDs or biologics, of which TNFα inhibitors were most frequently used. Two tocilizumab users had a mild infection. Two patients were on rituximab with 1 severe COVID-19 requiring mechanical ventilation. Six patients were on secukinumab with 1 hospitalization. Of the total 201 cases, 12 died, with an estimated mortality of 5.9% CONCLUSION: Patients with RD are susceptible to COVID-19. Various DMARDs or biologics may affect the viral disease course differently. Patients on hydroxychloroquine, TNFα antagonists or tocilizumab may have a mild viral illness. Rituximab or secukinumab could worsen the viral disease. Further study is warranted.

negative: Impacts of school feeding on educational and health outcomes of school-age children and adolescents in low- and middle-income countries: protocol for a systematic review and meta-analysis. BACKGROUND School feeding programs are beneficial for the physical, mental, and psychosocial development of school-age children and adolescents, particularly those in low- and middle-income countries (LMICs). While school feeding programs are ubiquitous in LMICs, the specific benefits of school feeding programs are unclear. The aim of this systematic review and meta-analysis is to evaluate the impacts of school feeding programs on the educational and health outcomes of children and adolescents in LMICs. METHODS Rigorously designed interventional studies on the impacts of school feeding on nutritional and health outcomes of children and adolescents receiving primary or secondary education in LMICs will be included. The following information sources were used to identify relevant published or unpublished studies: MEDLINE, EMBASE, CINAHL, the Cochrane Library, and governmental or organizational websites. The risk of bias of randomized and non-randomized studies will be assessed using the Cochrane Risk of Bias tool and the ROBINS-I tool, respectively. Two reviewers will independently conduct the selection of studies, data extraction, and assessment of the risk of bias. A narrative synthesis of all the included studies will be provided. Meta-analyses will be performed whenever appropriate. Heterogeneity of effects will be assessed by I2, subgroup analyses, and meta-regression. The certainty of evidence for each outcome will be assessed using the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. DISCUSSION The design and implementation of school feeding programs in LMICs should be based on the understanding of the benefits of such programs. This work will provide a crucial evidence base for the educational and health benefits of school feeding on children and adolescents in LMICs. SYSTEMATIC REVIEW REGISTRATION This protocol was submitted for registration with the International Prospective Register of Systematic Reviews (PROSPERO) on November 18, 2019 (registration number: pending).

negative: Case-Initiated COVID-19 Contact Tracing Using Anonymous Notifications We discuss the concept of a participatory digital contact notification approach to assist tracing of contacts who are exposed to confirmed cases of coronavirus disease (COVID-19); the approach is simple and affordable for countries with limited access to health care resources and advanced technology. The proposed tool serves as a supplemental contract tracing approach to counteract the shortage of health care staff while providing privacy protection for both cases and contacts. This tool can be deployed on the internet or as a plugin for a smartphone app. Confirmed cases with COVID-19 can use this tool to provide contact information (either email addresses or mobile phone numbers) of close contacts. The system will then automatically send a message to the contacts informing them of their contact status, what this status means, the actions that should follow (eg, self-quarantine, respiratory hygiene/cough etiquette), and advice for receiving early care if they develop symptoms. The name of the sender of the notification message by email or mobile phone can be anonymous or not. The message received by the contact contains no disease information but contains a security code for the contact to log on the platform to retrieve the information.

negative: House Calls for Stem Cell Transplants During the COVID-19 Pandemic.

negative: Radiological and pulmonary function outcomes of children with SARS We examined the radiological and pulmonary function outcomes of children affected with severe acute respiratory syndrome (SARS) at 6 months from diagnosis. Twenty‐one female and 26 male Chinese patients (median age, 13.6 years; interquartile range, 9.9–16.0) were studied. In each subject, high‐resolution computed tomography (HRCT) of the thorax and pulmonary function were assessed. All children were asymptomatic and had a normal clinical examination. Mild pulmonary abnormalities were detected on HRCT in 16 (34.0%) subjects, including residual ground‐glass opacification (n = 5), air trapping (n = 8), and a combination of ground‐glass changes and air trapping (n = 3). The need for oxygen supplementation (P = 0.02) and lymphopenia during the course of illness (P = 0.012) were significant risk factors in predicting abnormal HRCT. There were no significant lung function differences between those with and without HRCT abnormalities. Despite complete clinical resolution, a considerable proportion of children affected with SARS had abnormal HRCT findings at 6 months. These abnormalities were more prevalent in those with severe disease. It is important that careful follow‐up be carried out to assess the clinical significance and persistence of such abnormalities. Pediatr Pulmonol. 2004; 38:427–433. © 2004 Wiley‐Liss, Inc.

negative: Macrophage activation syndrome in 13 children with systemic-onset juvenile idiopathic arthritis BACKGROUND: Macrophage activation syndrome (MAS) is a severe, potentially life-threatening condition induced by chronic rheumatic diseases, especially systemic-onset juvenile idiopathic arthritis (SoJIA) in childhood. This study aimed to analyze the clinical and laboratory characteristics of systemic-onset juvenile idiopathic arthritis (SoJIA) with macrophage activation syndrome (MAS) in 13 patients. METHODS: Clinical and laboratory data of 13 SoJIA patients with MAS treated in our hospital from January 2003 to October 2007 were analyzed. RESULTS: In the 13 patients, 9 were boys and 4 girls aged from 5 months to 12 years. Clinical manifestations were of no typical characteristics including persistent fever, anemia, arthritis, hepatosplenomegaly, lymph-adenopathy, dysfunction of the liver, abnormal fat metabolism, and hemophagocytic cells in the bone marrow. Two patients experienced acute respiratory distress syndrome, two had mutiorgan failure, and three died. The perforin A91V (NCBI:SNP rs35947132) gene in 6 patients was normal. Glucocorticoid and immunoimpressive therapy were effective in all patients and plasmapheresis used in one severe patient was also effective. CONCLUSIONS: MAS is a serious complication of JIA, especially systemic-onset juvenile idiopathic arthritis. It is essentially important to recognize and treat MAS earlier in order to lower the mortality.

negative: Asthma Asthma is the most common inflammatory disease of the lungs. The prevalence of asthma is increasing in many parts of the world that have adopted aspects of the Western lifestyle, and the disease poses a substantial global health and economic burden. Asthma involves both the large-conducting and the small-conducting airways, and is characterized by a combination of inflammation and structural remodelling that might begin in utero. Disease progression occurs in the context of a developmental background in which the postnatal acquisition of asthma is strongly linked with allergic sensitization. Most asthma cases follow a variable course, involving viral-induced wheezing and allergen sensitization, that is associated with various underlying mechanisms (or endotypes) that can differ between individuals. Each set of endotypes, in turn, produces specific asthma characteristics that evolve across the lifecourse of the patient. Strong genetic and environmental drivers of asthma interconnect through novel epigenetic mechanisms that operate prenatally and throughout childhood. Asthma can spontaneously remit or begin de novo in adulthood, and the factors that lead to the emergence and regression of asthma, irrespective of age, are poorly understood. Nonetheless, there is mounting evidence that supports a primary role for structural changes in the airways with asthma acquisition, on which altered innate immune mechanisms and microbiota interactions are superimposed. On the basis of the identification of new causative pathways, the subphenotyping of asthma across the lifecourse of patients is paving the way for more-personalized and precise pathway-specific approaches for the prevention and treatment of asthma, creating the real possibility of total prevention and cure for this chronic inflammatory disease. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrdp.2015.25) contains supplementary material, which is available to authorized users.

negative: Effect of the COVID‐19 pandemic on anxiety among children with cystic fibrosis and their mothers BACKGROUND: We aimed to evaluate anxiety among children with cystic fibrosis (CF) and their mothers related to the COVID‐19 pandemic. METHODS: A total of 45 patients with CF and their mothers were enrolled in the study together with 90 age‐matched healthy children and their mothers as a control group. The State and Trait Anxiety Inventory (STAI) was administered by teleconference with children aged 13–18 years old and their mothers. The STAI for children was administered with children aged 9–12 years. Results were compared with age‐matched healthy children and their mothers. The relationship between anxiety scores of children with CF and their mothers was evaluated by comparing with clinical data of children with CF. At the conclusion of the teleconference, mothers were asked whether their anxiety had changed as a result of the interview. RESULTS: It was found that healthy children aged 13–18 years had higher state anxiety scores than age‐matched children with CF. Mothers of children with CF had higher trait anxiety scores, especially those of children aged 0–12 years, than mothers of healthy children (p<0.05). For mothers of children with CF, state anxiety scores were higher among those whose children had chronic Pseudomonas infection (p<0.05). Most mothers of children with CF stated that their anxiety decreased following the interview. CONCLUSION: The COVID‐19 pandemic may increase anxiety among mothers of children with CF as well those with healthy children. However, COVID‐19 had no effect on the anxiety of children with CF. Informing parents of children with CF about COVID‐19 by teleconference may decrease anxiety. This article is protected by copyright. All rights reserved.

negative: COVID-19 , School Closings and Weight Gain. We found the publication on "COVID-19 Related School Closings and Risk of Weight Gain Among Children" to be interesting.1 Rundle et al. noted that "we anticipate that the COVID-19 pandemic will likely double out-of-school time this year for many children in the U.S. and will exacerbate the risk factors for weight gain associated with summer recess."1 In fact, there are several factors relating to nutritional status of the children. We would like to share observations from Thailand, the second country in the timeline of COVID-19.2 In Thailand, school aged children in rural areas where COVID-19 disease outbreak exists are usually underweight.3 Thus, school closing means the children have to live with poor parents adding to economic problems of the family.

negative: A 4 year prospective study to determine risk factors for severe community acquired pneumonia in children in southern China BACKGROUND: Pneumonia is the major cause of death under 5 years. With high CAP numbers in China and growing access to PICUs, factors associated with severe CAP need to be determined to optimize care. OBJECTIVE: To prospectively determine PICU CAP admission features and outcomes. METHODS: A 4 year prospective study of CAP aged 1 month to <14 years admitted to PICU, Children's Hospital Affiliated to Soochow University, China. All were managed in a standard manner. Clinical, laboratory, and imaging findings were collected systematically. All received antibiotics. RESULTS: Eight hundred ten (7%) of 10,836 CAP hospital admissions needed PICU. Seven hundred seven (87%) were enrolled. PICU CAP children were young (76% ≤ 12 months) and 33% had co‐morbid conditions; 21% congenital heart disease.21% required mechanical ventilation. The average length of PICU stay was 5 days (range, 3–27). The case fatality rate was 5.8%. Viruses were detected in 38%, RSV 24%; bacteria in 23%, Streptococcus pneumoniae 7%, Haemophilus influenza b 4%, Mycoplasma 11%. On single factor analysis, PICU admission respiratory rate >70/min, grunting/groaning, head nodding, cyanosis, and anemia were associated with respiratory failure and with fatality. On multivariate analysis only presence of congenital heart disease, Trisomy 21 and immunodeficiency correlated with fatality; not microbe nor PICU findings. CONCLUSIONS: Young age and underlying congenital heart disease were associated factors for PICU support in CAP in China. Early referral if altered sensorium, high respiratory rate, head nodding, grunting and anemia, and universal access to conjugated vaccines may decrease morbidity and mortality. Pediatr Pulmonol. 2013; 48:390–397. © 2012 Wiley Periodicals, Inc.

negative: Drinking to Cope with the Pandemic: The Unique Associations of COVID-19-Related Perceived Threat and Psychological Distress to Drinking Behaviors in American Men and Women The 2019 Coronavirus pandemic has brought about significant and unprecedented changes to the modern world, including stay-at-home orders, high rates of unemployment, and more than a hundred thousand deaths across the United States. Derived from the self-medication hypothesis, this research explored how perceived threat and psychological distress related to the COVID-19 pandemic are associated with drinking behavior among an American sample of adults. We also evaluated whether links between COVID-19-related perceived threat and psychological distress with drinking behavior are different for men and women. Participants (N=754; 50% women) completed an online Qualtrics Panels study between April 17(th) and 23(rd), 2020. Results suggested that psychological distress related to the COVID-19 pandemic was consistently related to alcohol use indices, and moderation results indicated this pattern was significant only among women for number of drinks consumed during the recent heaviest drinking occasion and number of drinks consumed on a typical evening. COVID-related distress’ link to frequency of drinking and heavy drinking episodes was not different for men and women. Our results suggest that continued monitoring, particularly among women, should be conducted as this pandemic continues to evolve to identify the long-term public health impacts of drinking to cope with COVID-19 distress.

negative: Asthma and COVID-19 in children: A systematic review and call for data RATIONALE: Whether asthma constitutes a risk factor for coronavirus disease-2019 (COVID-19) is unclear. Here, we aimed to assess whether asthma, the most common chronic disease in children, is associated with higher COVID-19 risk or severity in pediatric populations. METHODS: We performed a systematic literature search in three stages: first, we reviewed PubMed, EMBASE, and CINAHL for systematic reviews of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 in pediatric populations, and reviewed their primary articles; second, we searched PubMed for studies on COVID-19 or SARS-CoV-2 and asthma/wheeze, and evaluated whether the resulting studies included pediatric populations; third, we repeated the second search in BioRxiv.org and MedRxiv.org to find pre-prints that may have information on pediatric asthma. RESULTS: In the first search, eight systematic reviews were found, of which five were done in pediatric populations; none of the 67 primary studies included data on pediatric asthma as a comorbidity for COVID-19. In the second search, we found 34 results in PubMed, of which five reported asthma in adults, but none included data on children. In the third search, 25 pre-prints in MedRxiv included data on asthma, but none on children. We found one report by the US Centers for Disease Control and Prevention stating that 40/345 (~11.5%) children with data on chronic conditions had "chronic lung diseases including asthma," and one from a tertiary hospital in New York that reported asthma in 11/46 (~23.9%) children hospitalized for COVID-19. CONCLUSION: There is scarcely any data on whether childhood asthma (or other pediatric respiratory diseases) constitute risk factors for SARS-CoV-2 infection or COVID-19 severity. Studies are needed that go beyond counting the number of cases in the pediatric age range.

negative: Comment les enfants et adolescents avec le trouble déficit d’attention/hyperactivité (TDAH) vivent-ils le confinement durant la pandémie COVID-19 ? OBJECTIVES: During the COVID-19 pandemic, the French government has decided a general lockdown. This unprecedented situation has raised concerns about children's and adolescent's mental health. Children and adolescents diagnosed with attention deficit hyperactivity disorder (ADHD) may find this context of restrained activity particularly tricky. The objectives of our study are to gather information about the well-being and global life conditions of children and adolescents with ADHD during the COVID-19 outbreak in France. METHODS: We designed a survey including both open-ended questions and questionnaire items for parents of children and adolescents with ADHD. Parents responded to the following open-ended questions: 1) “How is your child doing since the lockdown?” 2) “How is life at home since the lockdown?” 3) “If you had a remote service provision with a mental health professional (e.g. by telephone or video technology), please share your thoughts and any suggestions with us” 4) “Please share any other items that you think are important about ADHD symptoms of your child and the lockdown situation”. This survey was posted on social media on the 6th of April and disseminated by French ADHD-parent and patient organizations. The present article reports the descriptive, qualitative and textometrical analyses of the survey. RESULTS: Between day 20 and 30 of lockdown, 538 parents responded to the survey, and we included 533 responses in the final analysis. The vast majority of responders were women 95 % (95 % CI 93,50; 97,18) with children whose mean age was 10,5 (95 % CI 7.58; 13.44). Since the lockdown, 34.71 % (95 % CI 30.70; 38.94) of children experienced a worsening in well-being, 34.33 % (95 % CI 30.34; 38.56) showed no significant changes and 30.96 % (95 % CI 27.09; 35.10) were doing better according to their parents. The thematic analysis showed that an improvement of their children's anxiety was one of the main topics addressed by parents. This improvement related to less school-related strain and flexible schedules that respected their children's rhythm. Improved self-esteem was another topic that parents linked with a lesser exposure of their children to negative feed-back. Parents repeatedly reported both inattention and hyperactivity/impulsivity. However, optimal lockdown life conditions seemed to compensate for the impact of ADHD symptoms (e.g. sufficient space at home, presence of a garden). Some parents reported worsening of general well-being in their children, and this manifested as oppositional/defiant attitudes and emotional outbursts. Parents also cited sleep problems and anxiety in this context. As regards everyday life during lock-down, at-home schooling was another major topic–parents described that their children struggled to complete school-related tasks and that teachers seemed to have forgotten about academic accommodations. The lockdown situation seems to have raised parents’ awareness of the role of inattention and ADHD symptoms in their children's learning difficulties. Due to potential selection biases, the results of our survey may not be generalizable to all children and adolescents with ADHD. The main strengths of this rapid survey-based study lies in the reactivity of the participants and the quality and diversity of their responses to the open-ended questions. CONCLUSIONS: According to their parents, most children and adolescents with ADHD experience stability or improvement of their well-being. An improvement in school-related anxiety and the flexible adjustment to the children's’ rhythms as well as parents’ increased awareness of the difficulties their children experience are among the key topics in parents’ descriptions.

negative: The Impact of COVID-19 Global Pandemic on Morbidity and Mortality of Liver Transplant Recipients Children and Adults: A Systematic Review of Case Series The pandemic of coronavirus disease 2019 (COVID-19) changed the surgical everyday practice overnight. Currently, the first articles reporting outcomes of liver transplant recipients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are published. The aim of the present study was to summarise the existing evidence of impact of COVID-19 global pandemic on liver transplant recipients. Electronic databases were searched in accordance with Preferred Reporting Items in Systematic Reviews and Meta-Analyses (PRISMA). Five studies were selected from a pool of 12 studies with a total of 854 liver transplant recipients of whom 700 were children and the rest 154 were adults. The present evidence, based on case reports and series demonstrated lower mortality in liver transplant recipients compared to general population.

negative: Protocol for the development and evaluation of a tool for predicting risk of short-term adverse outcomes due to COVID-19 in the general UK population Introduction: Novel coronavirus 2019 (COVID-19) has propagated a global pandemic with significant health, economic and social costs. Emerging emergence has suggested that several factors may be associated with increased risk from severe outcomes or death from COVID-19. Clinical risk prediction tools have significant potential to generate individualised assessment of risk and may be useful for population stratification and other use cases. Methods and analysis: We will use a prospective open cohort study of routinely collected data from 1205 general practices in England in the QResearch database. The primary outcome is COVID-19 mortality (in or out-of-hospital) defined as confirmed or suspected COVID-19 mentioned on the death certificate, or death occurring in a person with SARS-CoV-2 infection between 24th January and 30th April 2020. Our primary outcome in adults is COVID-19 mortality (including out of hospital and in hospital deaths). We will also examine COVID-19 hospitalisation in children. Time-to-event models will be developed in the training data to derive separate risk equations in adults (19-100 years) for males and females for evaluation of risk of each outcome within the 3-month follow-up period (24th January to 30th April 2020), accounting for competing risks. Predictors considered will include age, sex, ethnicity, deprivation, smoking status, alcohol intake, body mass index, pre-existing medical co-morbidities, and concurrent medication. Measures of performance (prediction errors, calibration and discrimination) will be determined in the test data for men and women separately and by ten-year age group. For children, descriptive statistics will be undertaken if there are currently too few serious events to allow development of a risk model. The final model will be externally evaluated in (a) geographically separate practices and (b) other relevant datasets as they become available. Ethics and dissemination: The project has ethical approval and the results will be submitted for publication in a peer-reviewed journal.

negative: Anticipating the impact of the COVID-19 pandemic on TB patients and TB control programmes The COVID-19 pandemic has currently overtaken every other health issue throughout the world. There are numerous ways in which this will impact existing public health issues. Here we reflect on the interactions between COVID-19 and tuberculosis (TB), which still ranks as the leading cause of death from a single infectious disease globally. There may be grave consequences for existing and undiagnosed TB patients globally, particularly in low and middle income countries (LMICs) where TB is endemic and health services poorly equipped. TB control programmes will be strained due to diversion of resources, and an inevitable loss of health system focus, such that some activities cannot or will not be prioritised. This is likely to lead to a reduction in quality of TB care and worse outcomes. Further, TB patients often have underlying co-morbidities and lung damage that may make them prone to more severe COVID-19. The symptoms of TB and COVID-19 can be similar, with for example cough and fever. Not only can this create diagnostic confusion, but it could worsen the stigmatization of TB patients especially in LMICs, given the fear of COVID-19. Children with TB are a vulnerable group especially likely to suffer as part of the "collateral damage". There will be a confounding of symptoms and epidemiological data through co-infection, as happens already with TB-HIV, and this will require unpicking. Lessons for COVID-19 could be learned from the vast experience of running global TB control programmes, while the astonishingly rapid and relatively well co-ordinated response to COVID-19 demonstrates how existing programmes could be significantly improved.

negative: Depression and loneliness during COVID-19 restrictions in the United States, and their associations with frequency of social and sexual connections Purpose: To estimate the prevalence of depression and loneliness during the US COVID-19 response, and examine their associations with frequency of social and sexual connections. Methods: We conducted an online cross-sectional survey of a nationally representative sample of American adults (n=1010), aged 18-94, running from April 10-20, 2020. We assessed depressive symptoms (CES-D-10 scale), loneliness (UCLA 3-Item Loneliness scale), and frequency of in-person and remote social connections (4 items, e.g. hugging family member, video chats) and sexual connections (4 items, e.g. partnered sexual activity, dating app use). Results: One-third of participants (32%) reported depressive symptoms, and loneliness was high [mean (SD): 4.4 (1.7)]. Those with depressive symptoms were more likely to be women, age 20-29, unmarried, and low-income. Frequent in-person connections were associated with lower depression and loneliness; frequent remote connections were not. Conclusions: Depression and loneliness were elevated during the early US COVID-19 response. Those who maintained frequent in-person, but not remote, social and sexual connections had better mental health outcomes. While COVID-19 social restrictions remain necessary, it will be critical to expand mental health services to serve those most at-risk and identify effective ways of maintaining social and sexual connections from a distance.

negative: Reflection on lower rates of COVID-19 in children: does childhood immunizations offer unexpected protection? The incidence of COVID-19 in children and teenagers is only about 2% in China. Children had mild symptoms and hardly infected other children or adults. It is worth considering that children are the most vulnerable to respiratory pathogens, but fatal SARS-like virus had not caused severe cases among them. According to the pathological studies of COVID-19 and SARS, a sharp decrease in T lymphocytes leads to the breakdown of the immune system. The cellular immune system of children differs from that of adults may be the keystone of atypical clinical manifestations or even covert infection. The frequent childhood vaccinations and repeated pathogens infections might be resulting in trained immunity of innate immune cells, immune fitness of adaptive immune cells or cross-protection of antibodies in the children. Therefore, due to lack of specific vaccine, some vaccines for tuberculosis, influenza and pneumonia may have certain application potential for the front-line health workers in the prevention and control of COVID-19. However, for high-risk susceptible populations, such as the elderly with basic diseases such as hypertension and diabetes, it is necessary to explore the acclimatization effect of the planned immune process on their immunity to achieve the trained immunity or immune fitness, so as to improve their own antiviral ability.

negative: Evidence for causal links between education and maternal and child health: systematic review. OBJECTIVE Numerous studies have documented an inverse association between years of schooling attained, particularly by women, and reduced maternal, infant and child mortality. However, if factors affecting educational attainment - many of which are unobservable, e.g. motivation and genetic endowment - also affect the likelihood of engaging in behaviours that enhance health, then assumed effects of schooling will be inflated in analyses that do not address this endogeneity. This systematic review assesses evidence for a causal link between education and maternal and child health in low and middle-income countries. METHODS Eligible studies controlled for observable and unobservable factors affecting both education and health. Reported effects were converted into partial correlations. When possible, we also conducted meta-analyses to estimate mean effects by outcome. RESULTS Of 4952 papers identified, 16 met the inclusion criteria. The 15 child health papers examined neonatal, infant and child mortality, stunting and wasting. Significant effects of education on infant and child health were observed for 30 of 33 models that did not account for endogeneity. In contrast, only 18 of 46 effects were significant in models that addressed endogeneity. Notably, for only one outcome -child mortality measured dichotomously -was the effect of maternal educational attainment significant in a meta-analysis. The one maternal morbidity paper found significant effects for the two preventable outcomes considered. CONCLUSION While we find evidence for a causal link between education and health, effects are weaker in models that address endogeneity compared to naïve models that do not account for unobservable factors affecting both education and health. Advances in women's educational outcomes have undoubtedly played a role in improving health in many settings; however, the effect is not as strong as some researchers and advocates have claimed.

negative: Partially-Latent Class Models (pLCM) for Case-Control Studies of Childhood Pneumonia Etiology In population studies on the etiology of disease, one goal is the estimation of the fraction of cases attributable to each of several causes. For example, pneumonia is a clinical diagnosis of lung infection that may be caused by viral, bacterial, fungal, or other pathogens. The study of pneumonia etiology is challenging because directly sampling from the lung to identify the etiologic pathogen is not standard clinical practice in most settings. Instead, measurements from multiple peripheral specimens are made. This paper introduces the statistical methodology designed for estimating the population etiology distribution and the individual etiology probabilities in the Pneumonia Etiology Research for Child Health (PERCH) study of 9; 500 children for 7 sites around the world. We formulate the scientific problem in statistical terms as estimating the mixing weights and latent class indicators under a partially-latent class model (pLCM) that combines heterogeneous measurements with different error rates obtained from a case-control study. We introduce the pLCM as an extension of the latent class model. We also introduce graphical displays of the population data and inferred latent-class frequencies. The methods are tested with simulated data, and then applied to PERCH data. The paper closes with a brief description of extensions of the pLCM to the regression setting and to the case where conditional independence among the measures is relaxed.

negative: Comparison of the clinical characteristics and outcomes of hospitalized adult COVID-19 and influenza patients: a prospective observational study Objective We compared the clinical characteristics, findings and outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19) or influenza to detect relevant differences. Methods From December 2019 to April 2020, we recruited all eligible hospitalized adults with respiratory infection to a prospective observational study at the HUS Jorvi Hospital, Finland. Influenza and SARS-CoV-2 infections were confirmed by RT-PCR. Follow-up lasted for at least 30 days from admission. Results We included 61 patients, of whom 28 were COVID-19 and 33 influenza patients with median ages of 53 and 56 years. Majority of both COVID-19 and influenza patients were men (61% vs 67%) and had at least one comorbidity (68% vs 85%). Pulmonary diseases and current smoking were less common among COVID-19 than influenza patients (5 [18%] vs 15 [45%], P=0.03 and 1 [4%] vs 10 [30%], P=0.008). In chest x-ray at admission, ground-glass opacities and consolidations were more frequent among COVID-19 than influenza patients (19 [68%] and 7 [21%], P < 0.001). Severe disease and intensive care unit (ICU) admission occurred more often among COVID-19 than influenza patients (26 [93%] vs 19 [58%], P=0.003 and 8 [29%] vs 2 [6%], P=0.034). COVID-19 patients were hospitalized longer than influenza patients (6 days [IQR 4-21] vs 3 [2-4], P<0.001). Conclusion Bilateral ground-glass opacities and consolidations in chest X-ray may help to differentiate COVID-19 from influenza. Hospitalized COVID-19 patients had more severe disease, required longer hospitalization and were admitted to ICU more often than influenza patients, which has important implications for public health policies.

negative: Ethical decision-making for children with neuromuscular disorders in the COVID-19 crisis. The sudden appearance and proliferation of COVID-19 has forced societies and governmental authorities across the world to confront the possibility of resource constraints when critical care facilities are overwhelmed by the sheer numbers of grievously ill patients. As governments and health care systems develop and update policies and guidelines regarding the allocation of resources, patients and families affected by chronic disabilities, including many neuromuscular disorders that affect children and young adults, have become alarmed at the possibility that they may be determined to have less favorable prognoses due to their underlying diagnoses and thus be assigned to lower priority groups. It is important for health care workers, policymakers, and government officials to be aware that the long term prognoses for children and young adults with neuromuscular disorders are often more promising than previously believed, due to a better understanding of the natural history of these diseases, benefits of multidisciplinary supportive care, and novel molecular therapies that can dramatically improve the disease course. Although the realities of a global pandemic have the potential to require a shift from our usual, highly individualistic standards of care to crisis standards of care, shifting priorities should nonetheless be informed by good facts. Resource allocation guidelines with the potential to affect children and young adults with neuromuscular disorders should take into account the known trajectory of acute respiratory illness in this population, and rely primarily on contemporary long-term outcome data.

negative: Clinical profile and outcome of swine flu in Indian children OBJECTIVE: To describe the clinical characteristics and outcome of Indian children infected with 2009 H1N1 influenza virus. STUDY DESIGN: Retrospective chart review. SETTING: Outpatient department and hospitalized patients in a tertiary care hospital. METHODS: Clinical details of 85 children (positive for the 2009 H1N1 virus infection tested by real-time reverse-transcriptase-polymerase-chain-reaction assay) were analyzed from medical charts. RESULTS: Of the 85 (55 boys) children positive for 2009 H1N1 virus infection, 64.7% were between 5 years to 16 years, and 35.3% were below 5 years age. The mean age of these children was 7.5±3.5 yr. Contact history was positive only in 22 (26%) cases. High grade fever was the most common symptom, followed by cough and rhinorrhea. Twenty-nine (34%) patients had an underlying co-morbid condition. Of the 34 patients who underwent chest radiography during evaluation, 18 children (52.9%) had findings consistent with lower respiratory tract infection. Antiviral therapy was initiated in 76 patients. Hospitalization was required in 30 (35.3%) children. Risk factors for hospitalization included underlying co-morbid condition, respiratory distress, vomiting, wheezing, diarrhea, hypotension and infiltrates/consolidation on chest radiograph. Mean length of hospitalization was 131±76 hours, irrespective of underlying disease. Three children developed Acute Respiratory Distress Syndrome and died. CONCLUSIONS: Clinical features and routine laboratory investigations in children with swine origin influenza were non-specific. Children with co-morbid condition, respiratory distress, vomiting, wheezing, diarrhea, hypotension and infiltrates/consolidation on chest radiograph were at higher risk of hospitalization.

negative: Differences in race and other state‐level characteristics and associations with mortality from COVID‐19 infection As reporting of COVID‐19 at the US state level has become more granular, many states have reported a higher proportion of deaths among African‐Americans. In our study, we assessed state level data on race, population density, age, obesity rates, insurance data, GDP, per capita healthcare resources (hospital‐beds/ventilators per‐capita), median household income and high‐school graduation rates. We report a higher death rate among states with a greater proportion of African‐American residents despite adjusting for case rates and state‐level factors. To the best of our knowledge this is the first study looking at state level data (from across the US) and mortality with COVID‐19. This article is protected by copyright. All rights reserved.

negative: Radiologist Reporting and Operational Management for Patients with Suspected COVID-19 Abstract Objective Evaluate adoption and outcomes of locally-designed reporting guidelines for patients with possible COVID-19. Methods We developed a departmental guideline for radiologists that specified reporting terminology and required communication for patients with imaging findings suggestive of COVID-19, based on patient test status and imaging indication. In this retrospective study, radiology reports completed 3/1/2020-5/3/2020 that mentioned COVID-19 were reviewed. Reports were divided into patients with known COVID-19, patients with “suspected” COVID-19 (having an order indication of respiratory or infectious signs or symptoms), and “unsuspected patients” (other order indications, e.g., trauma or non-chest pain). Primary outcome was percentage of COVID-19 reports using recommended terminology; secondary outcome was percentages of suspected and unsuspected patients diagnosed with COVID-19. Relationships between categorical variables were assessed with Fisher’s exact test. Results Among 77,400 total reports, 1,083 suggested COVID-19 based on imaging findings; 774 (71%) of COVID-19 reports used recommended terminology. Of 574 patients without known COVID-19 at time of interpretation, 345 (60%) were eventually diagnosed with COVID-19, including 61% (315/516) of suspected and 52% (30/58) of unsuspected patients. Nearly all (46/58) unsuspected patients were identified at CT. Discussion Radiologists rapidly adopted recommended reporting terminology for patients with suspected COVID-19. The majority of patients for whom radiologists raised concern for COVID-19 were subsequently diagnosed with the disease, including the majority of clinically unsuspected patients. Using unambiguous terminology and timely notification about previously unsuspected patients will become increasingly critical to facilitate COVID-19 testing and contact tracing as states begin to lift restrictions.

negative: COVID-19 Testing, Epidemic Features, Hospital Outcomes, and Household Prevalence, New York State—March 2020 BACKGROUND: The United States’ COVID-19 epidemic has grown extensively since February 2020, with substantial associated hospitalizations and mortality; New York State (NYS) has emerged as the national epicenter. We report on the extent of testing and test results during the month of March in NYS, along with risk factors, outcomes, and household prevalence among initial cases subject to in-depth investigations. METHODS: Specimen collection for COVID-19 testing was conducted in healthcare settings, community-based collection sites, and by home testing teams. Information on demographics, risk factors, and hospital outcomes of cases was obtained through epidemiological investigations and an electronic medical records match, and summarized descriptively. Active testing of initial case’s households enabled estimation of household prevalence. RESULTS: During March In NYS, outside of New York City, a total of 47,326 persons tested positive for SARS-CoV-2, out of 141,495 tests (33% test-positive), with the highest number of cases located in the metropolitan region counties. Among 229 initial cases diagnosed through March 12, by March 30 13% were hospitalized and 2% died. Testing conducted among 498 members of these case’s households found prevalent infection among 57%; excluding first-reported cases 38%. In these homes, we found a significant age gradient in prevalence, from 23% among those <5 years to 68% among those ≥65 years (p<.0001). CONCLUSIONS: New York State faced a substantial and increasing COVID-19 outbreak during March 2020. The earliest cases had high levels of infection in their households and by the end of the month, the risks of hospitalization and death were high.

negative: SARS-CoV-2 and Cancer: are they really partners in crime ? Abstract The outbreak of the SARS-CoV-2 pandemic has overwhelmed health care systems in many countries. The clinical presentation of the SARS-CoV-2 varies between a subclinical or flu-like syndrome to that of severe pneumonia with multi-organ failure and death. Initial reports have suggested that cancer patients may have a higher susceptibility to get infected by the SARS-CoV-2 virus but current evidence remains poor as it is biased by important confounders. Patients with ongoing or recent cancer treatment for advanced active disease, metastatic solid tumors and hematological malignancies are at higher risk of developing severe COVID-19 respiratory disease that requires hospitalization and have a poorer disease outcome compared to individuals without cancer. However it is not clear whether these are independent risk factors, or mainly driven by male gender, age, obesity, performance status, uncontrolled diabetes, cardiovascular disease and various other medical conditions. These often have a greater influence on the probability to die due to SARS-CoV-2 then cancer. Delayed diagnosis and suboptimal cancer management due to the pandemic results in disease upstaging and has considerable impact cancer on specific death rates. Surgery during the peak of the pandemic seems to increase mortality, but there is no convincing evidence that adjuvant systemic cancer therapy and radiotherapy are contraindicated, implicating that cancer treatment can be provided safely after individual risk/benefit assessment and some adaptive measures. Underlying immunosuppression, elevated cytokine levels, altered expression of the angiotensin converting enzyme (ACE-2) and TMPRSS2, and a prothrombotic status may fuel the effects of a SARS-CoV-2 in some cancer patients, but have the potential to be used as biomarkers for severe disease and therapeutic targets. The rapidly expanding literature on COVID-19 should be interpreted with care as it is often hampered by methodological and statistical flaws.

negative: Wheezing exacerbations in early childhood: evaluation, treatment, and recent advances relevant to the genesis of asthma Children who begin wheezing during early childhood are seen frequently by health care providers in primary care, in hospitals and emergency departments, and by allergists and pulmonologists. When young children, like the 2 year-old case presented here, are evaluated for wheezing, a frequent challenge for clinicians is to determine whether the symptoms represent transient, viral-induced wheezing, or whether sufficient risk factors are present to suspect that the child may experience recurrent wheezing and develop asthma. Most factors influencing prognosis are not mutually exclusive, are interrelated (i.e., cofactors), and often represent gene-environment interactions. Many of these risk factors have been, and continue to be, investigated in prospective studies in order to decipher their relative importance with the goal of developing new therapies and interventions in the future. The etiologies of wheezing in young children, diagnostic methods, treatment, prognostic factors, and potential targets for prevention of the development of asthma are discussed.

negative: Incomplete and late recovery of sudden olfactory dysfunction in COVID-19() INTRODUCTION: Sudden olfactory dysfunction is a new symptom related to COVID-19, with little data on its duration or recovery rate. OBJECTIVE: To characterize patients with sudden olfactory disfunction during the COVID-19 pandemic, especially their recovery data. METHODS: An online survey was conducted by the Brazilian Society of Otorhinolaryngology and Cervico-Facial Surgery, and Brazilian Academy of Rhinology, including doctors who assessed sudden olfactory dysfunction patients starting after February 1(st), 2020. RESULTS: 253 sudden olfactory dysfunction patients were included, of which 59.1% were females with median age of 36 years, with a median follow-up period of 31 days. 183 patients (72.3%) had been tested for COVID-19, and of those 145 (79.2%) tested positive. Patients that tested positive for COVID-19 more frequently showed non-specific inflammatory symptoms (89.7% vs. 73.7%; p = 0.02), a lower rate of total recovery of sudden olfactory dysfunction (52.6% vs. 70.3%; p = 0.05) and a longer duration to achieve total recovery (15 days vs. 10 days; p = 0.0006) than the ones who tested negative for COVID-19. Considering only positive-COVID-19 patients, individuals with sudden hyposmia completely recovered more often than the ones with sudden anosmia (68.4% vs. 50.0%; p = 0.04). CONCLUSION: Positive-COVID-19 patients with sudden olfactory dysfunction showed lower total recovery rate and longer duration than negative-COVID-19 patients. Additionally, total recovery was seen more frequently in positive-COVID-19 patients with sudden hyposmia than the ones with sudden anosmia.

negative: The impact of sex, gender and pregnancy on 2009 H1N1 disease Children and young adults of reproductive age have emerged as groups that are highly vulnerable to the current 2009 H1N1 pandemic. The sex of an individual is a fundamental factor that can influence exposure, susceptibility and immune responses to influenza. Worldwide, the incidence, disease burden, morbidity and mortality rates following exposure to the 2009 H1N1 influenza virus differ between males and females and are often age-dependent. Pregnancy and differences in the presentation of various risk factors contribute to the worse outcome of infection in women. Vaccination and antiviral treatment efficacy also vary in a sex-dependent manner. Finally, sex-specific genetic and hormonal differences may contribute to the severity of influenza and the clearance of viral infection. The contribution of sex and gender to influenza can only be determined by a greater consideration of these factors in clinical and epidemiological studies and increased research into the biological basis underlying these differences.

negative: The Mental Health Burden of the COVID-19 Pandemic on Physical Therapists We evaluated the mental health burden of coronavirus disease (COVID-19) on physical therapists, including their stress and anxiety levels, who were at risk of developing psychological distress and other mental health symptoms. A questionnaire survey was conducted with physical therapists of three university hospitals in South Korea on 10 April 2020. The questionnaires evaluated the presence of anxiety and depression in the respondents. Among the 65 physical therapists who completed our survey, 21 (32.3%) and 12 (18.5%) physical therapists reported having symptoms of anxiety and depression, respectively. If a physical therapist was living with a ≤6-year-old infant or child, the possibility of the presence of anxiety was significantly higher. The risk of depression among those who were in their 30 s and 50 s was significantly higher than among those in their 20 s. Thus, physical therapists living with a ≤6-year-old infant or child and those in their 30 s and 50 s need special attention.

negative: Management strategies for children with COVID-19: ESPR practical recommendations During the outbreak of the COVID-19 pandemic, guidelines have been issued by international, national and local authorities to address management and the need for preparedness. Children with COVID-19 differ from adults in that they are less often and less severely affected. Additional precautions required in the management of children address their increased radiosensitivity, need for accompanying carers, and methods for dealing with children in a mixed adult-paediatric institution. In this guidance document, our aim is to define a pragmatic strategy for imaging children with an emphasis on proven or suspected COVID-19 cases. Children suspected of COVID-19 should not be imaged routinely. Imaging should be performed only when expected to alter patient management, depending on symptoms, preexisting conditions and clinical evolution. In order to prevent disease transmission, it is important to manage the inpatient caseload effectively by triaging children and carers outside the hospital, re-scheduling nonurgent elective procedures and managing symptomatic children and carers as COVID-19 positive until proven otherwise. Within the imaging department one should consider conducting portable examinations with COVID-19 machines or arranging dedicated COVID-19 paediatric imaging sessions and performing routine nasopharyngeal swab testing before imaging under general anaesthesia. Finally, regular personal hygiene, appropriate usage of personal protective equipment, awareness of which procedures are considered aerosol generating and information on how to best disinfect imaging machinery after examinations should be highlighted to all staff members.

negative: COVID-19 and routine childhood immunization in Africa: leveraging systems thinking and implementation science to improve immunization system performance One of the routine health services that is being disrupted by coronavirus disease 2019 (COVID-19) in Africa is childhood immunization. This is because the immunization system relies on functioning health facilities and stable communities to be effective. Its disruption increases the risk of epidemics of vaccine-preventable diseases which can increase child mortality. Therefore, policymakers must quickly identify robust and context-specific strategies to rapidly scale-up routine immunization in order to mitigate the impact of COVID-19 on their national immunization performance. To achieve this, we propose a paradigm shift towards systems thinking and use of implementation science in immunization decision making. Systems thinking can inform a more nuanced and holistic understanding of the interrelationship that between COVID-19, its control strategies and childhood immunization. Tools like causal loop diagrams can be used to explicitly illustrate the systems structure by identifying the feedback loops. Once mapped and leverage points for interventions have been identified, implementation science can be used to guide the rapid uptake and utilization of multifaceted evidence-based innovations in complex practice settings. As Africa re-strategize for the post-2020 era, these emerging fields can contribute significantly in accelerating progress towards universal access to vaccines for all children on the continent despite COVID-19.

negative: Long-term outcomes of gastric electrical stimulation in children with gastroparesis. BACKGROUND Gastric electrical stimulation (GES) has been used in adults with gastroparesis. However its use has been limited in children. We describe the largest experience with GES in children with long-term outcomes. METHODS Data were collected on children who underwent GES over a 10-year period. Data regarding demographics, medical history, hospital course, and outcomes were collected and analyzed. Symptom scores (validated Likert scores) were compared using a paired Student's t test. RESULTS Overall, 97 patients underwent GES, and a majority were teenage Caucasian girls. Ninety-six had temporary GES (tGES), and 66 had improvement in their symptoms. A total of 67 underwent permanent implantation (pGES), and there was significant reduction in all individual symptoms (p<0.001) as well as the total symptom score (TSS) (p<0.0001) at 1, 6, 12, and >12 months. Recurrence of symptoms leading to device removal occurred in 7 cases. Forty-one patients had continued improvement in symptoms for over 12 months, with a mean follow-up of 3.5 years (range 1-9 years). CONCLUSIONS This study represents the largest experience of systematic application of GES in children. GES is a safe and effective therapy for selected children with intractable GP with continued symptomatic improvement at 1 year and beyond.

negative: What are the Underlying Transmission Patterns of COVID-19 Outbreak? - An Age-specific Social Contact Characterization Background: COVID-19 has spread to 6 continents. Now is opportune to gain a deeper understanding of what may have happened. The findings can help inform mitigation strategies in the disease-affected countries. Methods: In this work, we examine an essential factor that characterizes the disease transmission patterns: the interactions among people. We develop a computational model to reveal the interactions in terms of the social contact patterns among the population of different age-groups. We divide a city's population into seven age-groups: 0-6 years old (children); 7-14 (primary and junior high school students); 15-17 (high school students); 18-22 (university students); 23-44 (young/middle-aged people); 45-64 years old (middle-aged/elderly people); and 65 or above (elderly people). We consider four representative settings of social contacts that may cause the disease spread: (1) individual households; (2) schools, including primary/high schools as well as colleges and universities; (3) various physical workplaces; and (4) public places and communities where people can gather, such as stadiums, markets, squares, and organized tours. A contact matrix is computed to describe the contact intensity between different age-groups for each of the four settings. By integrating the four contact matrices with the next-generation matrix, we quantitatively characterize the underlying transmission patterns of COVID-19 among different populations. Findings: We focus our study on 6 representative cities in China: Wuhan, the epicenter of COVID-19, together with Beijing, Tianjin, Hangzhou, Suzhou, and Shenzhen, which are five major cities from three key economic zones. The results show that the social contact-based analysis can readily explain the underlying disease transmission patterns as well as the associated risks (including both confirmed and unconfirmed cases). In Wuhan, the age-groups involving relatively intensive contacts in households and public/communities are dispersedly distributed. This can explain why the transmission of COVID-19 in the early stage mainly took place in public places and families in Wuhan. We estimate that Feb. 11, 2020 was the date with the highest transmission risk in Wuhan, which is consistent with the actual peak period of the reported case number (Feb. 4-14). Moreover, the surge in the number of new cases reported on Feb. 12-13 in Wuhan can readily be captured using our model, showing its ability in forecasting the potential/unconfirmed cases. We further estimate the disease transmission risks associated with different work resumption plans in these cities after the outbreak. The estimation results are consistent with the actual situations in the cities with relatively lenient control policies, such as Beijing, and those with strict control policies, such as Shenzhen. Interpretation: With an in-depth characterization of age-specific social contact-based transmission, the retrospective and prospective situations of the disease outbreak, including the past and future transmission risks, the effectiveness of different interventions, and the disease transmission risks of restoring normal social activities, are computationally analyzed and reasonably explained. The conclusions drawn from the study not only provide a comprehensive explanation of the underlying COVID-19 transmission patterns in China, but more importantly, offer the social contact-based risk analysis methods that can readily be applied to guide intervention planning and operational responses in other countries, so that the impact of COVID-19 pandemic can be strategically mitigated. Funding: General Research Fund of the Hong Kong Research Grants Council; Key Project Grants of the National Science Foundation of China.

negative: Psychosocial and Behavioral Impact of COVID-19 in Autism Spectrum Disorder: An Online Parent Survey The 2019 coronavirus disease (COVID-19) outbreak could result in higher levels of psychological distress, especially among people suffering from pre-existing mental health conditions. Young individuals with autism spectrum disorders (ASD) are particularly at risk due to their vulnerability to unpredictable and complex changes. This study aimed to investigate the impact of the COVID-19 pandemic on ASD individuals, whether any pre-pandemic sociodemographic or clinical characteristics would predict a negative outcome, and to narratively characterize their needs. Parents and guardians of ASD individuals filled out an online survey consisting of 40 questions investigating socio-demographic and clinical characteristics of their children, impact of the COVID-19 outbreak on their wellbeing and needs to deal with the emergency. Data were available on 527 survey participants. The COVID-19 emergency resulted in a challenging period for 93.9% of families, increased difficulties in managing daily activities, especially free time (78.1%) and structured activities (75.7%), and, respectively, 35.5% and 41.5% of children presenting with more intense and more frequent behavior problems. Behavior problems predating the COVID-19 outbreak predicted a higher risk of more intense (odds ratio (OR) = 2.16, 95% confidence interval (CI) 1.42-3.29) and more frequent (OR = 1.67, 95% CI 1.13-2.48) disruptive behavior. Even though ASD children were receiving different types of support, also requiring specialist (19.1%) or emergency (1.5%) interventions in a relatively low proportion of cases, a number of needs emerged, including receiving more healthcare support (47.4%), especially in-home support (29.9%), as well as interventions to tackle a potentially disruptive quarantine (16.8%). The COVID-19 outbreak has undoubtedly resulted in increased difficulties among ASD individuals.

negative: Characteristics associated with spine injury on magnetic resonance imaging in children evaluated for abusive head trauma BACKGROUND: Spine injuries are increasingly common in the evaluation for abusive head trauma (AHT), but additional information is needed to explore the utility of spine MRI in AHT evaluations and to ensure an accurate understanding of injury mechanism. OBJECTIVE: To assess the incidence of spine injury on MRI in children evaluated for AHT, and to correlate spine MRI findings with clinical characteristics. MATERIALS AND METHODS: We identified children younger than 5 years who were evaluated for AHT with spine MRI. Abuse likelihood was determined a priori by expert consensus. We blindly reviewed spine MRIs and compared spinal injury, abuse likelihood, patient demographics, severity of brain injury, presence of retinal hemorrhages, and pattern of head injury between children with and without spine injury. RESULTS: Forty-five of 76 (59.2%) children had spine injury. Spine injury was associated with more severe injury (longer intensive care stays [P<0.001], lower initial mental status [P=0.01] and longer ventilation times [P=0.001]). Overall abuse likelihood and spine injury were not associated. Spinal subdural hemorrhage was the only finding associated with a combination of retinal hemorrhages (P=0.01), noncontact head injuries (P=0.008) and a diagnosis of AHT (P<0.05). Spinal subdural hemorrhage was associated with other spine injury (P=0.004) but not with intracranial hemorrhage (P=0.28). CONCLUSION: Spinal injury is seen in most children evaluated for AHT and might be clinically and forensically valuable. Spinal subdural hemorrhage might support a mechanism of severe acceleration/deceleration head injury and a diagnosis of AHT.

negative: Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms Abstract The coronavirus disease 19 (COVID-19) pandemic is a significant psychological stressor in addition to its tremendous impact on every facet of individuals’ lives and organizations in virtually all social and economic sectors worldwide. Fear of illness and uncertainty about the future precipitate anxiety- and stress-related disorders, and several groups have rightfully called for the creation and dissemination of robust mental health screening and treatment programs for the general public and front-line healthcare workers. However, in addition to pandemic-associated psychological distress, the direct effects of the virus itself (several acute respiratory syndrome coronavirus; SARS-CoV-2), and the subsequent host immunologic response, on the human central nervous system (CNS) and related outcomes are unknown. We discuss currently available evidence of COVID-19 related neuropsychiatric sequelae while drawing parallels to past viral pandemic-related outcomes. Past pandemics have demonstrated that diverse types of neuropsychiatric symptoms, such as encephalopathy, mood changes, psychosis, neuromuscular dysfunction, or demyelinating processes, may accompany acute viral infection, or may follow infection by weeks, months, or longer in recovered patients. The potential mechanisms are also discussed, including viral and immunological underpinnings. Therefore, prospective neuropsychiatric monitoring of individuals exposed to SARS-CoV-2 at various points in the life course, as well as their neuroimmune status, are needed to fully understand the long-term impact of COVID-19, and to establish a framework for integrating psychoneuroimmunology into epidemiologic studies of pandemics.

negative: Debate: COVID-19 and children in India The COVID-19 pandemic impact on children is a growing concern. The United Nations and its agencies (the World Health Organization and UNICEF), Indian Association For Child and Adolescent Mental Health and National Institute of Mental Health and Neuroscience in India warn about the broader impacts on children and call for urgent action to support the world's children amidst the pandemic which may have lasting consequences. The COVID-19 pandemic and unprecedented control measures to prevent its spread have disrupted nearly every aspect of children's lives - their health, development, learning, behaviour and their families' economic security, including protection from violence and abuse. Given this background, there is an urgent need for action through screening to minimize the mental health issues of children in India who constitute a substantial proportion of the population.

negative: COVID-19: a retrospective cohort study with focus on the over-80s and hospital-onset disease BACKGROUND: Data from the UK COVID-19 outbreak are emerging, and there are ongoing concerns about a disproportionate effect on ethnic minorities. There is very limited information on COVID-19 in the over-80s, and the rates of hospital-onset infections are unknown. METHODS: This was a retrospective cohort study from electronic case records of the first 450 patients admitted to our hospital with PCR-confirmed COVID-19, 77% of the total inpatient caseload to date. Demographic, clinical and biochemical data were extracted. The primary endpoint was death during the index hospital admission. The characteristics of all patients, those over 80 years of age and those with hospital-onset COVID-19 were examined. RESULTS: The median (IQR) age was 72 (56, 83), with 150 (33%) over 80 years old and 60% male. Presenting clinical and biochemical features were consistent with those reported elsewhere. The ethnic breakdown of patients admitted was similar to that of our underlying local population. Inpatient mortality was high at 38%. Patients over 80 presented earlier in their disease course and were significantly less likely to present with the typical features of cough, breathlessness and fever. Cardiac co-morbidity and markers of cardiac dysfunction were more common, but not those of bacterial infection. Mortality was significantly higher in this group (60% vs 28%, p < 0.001). Thirty-one (7%) patients acquired COVID-19 having continuously been in hospital for a median of 20 (14, 36) days. The peak of hospital-onset infections occurred at the same time as the overall peak of admitted infections. Despite being older and more frail than those with community-onset infection, their outcomes were no worse. CONCLUSIONS: Inpatient mortality was high, especially among the over-80s, who are more likely to present atypically. The ethnic composition of our caseload was similar to the underlying population. While a significant number of patients acquired COVID-19 while already in hospital, their outcomes were no worse.

negative: To what extent do children transmit SARS-CoV-2 virus?

negative: Hope and Homes for Children welcomes the new Lancet Group Commission

negative: Outcome of patients with cirrhosis requiring intensive care unit support: Prospective assessment of predictors of mortality Determinants of outcome and the utility of the Child-Pugh score and the acute physiology and chronic health evaluation (APACHE) II score as predictors of outcome were prospectively assessed in 54 consecutive patients with cirrhosis requiring intensive care unit (ICU) management. Overall mortality in the ICU was 43% (23/54). Child-Pugh scores did not differ between survivors or nonsurvivors (12.8 versus 12.3, P = 0.26), however APACHE II scores (P = 0.007), acute physiology scores (P = 0.006), and Karnofsky scores (P = 0.001) were significant predictors of outcome. By univariate analysis, requirement of mechanical ventilation analysis (P = 0.001), duration of mechanical ventilation (P = 0.001), pulmonary infiltrates (P = 0.0001), infections (P = 0.047), gastrointestinal bleeding (P = 0.005), and serum creatinine ≥1.5 mg/dl (P = 0.0005) were significantly associated with mortality. By logistic regression analysis only pulmonary infiltrates (P = 0.0001) and renal dysfunction (P = 0.041) were independent predictors of mortality. When controlled for the severity of illness (APACHE II scores), the mortality in patients with cirrhosis caused by alcohol was significantly lower than that in patients with liver disease not caused by alcohol (P = 0.01). Our study not only identified predictors of poor outcome in patients with cirrhosis requiring ICU care but also provided data that may have implications for optimal timing for transplantation.

negative: Asthma and the Coronavirus Disease 2019 Pandemic: A Literature Review Even though respiratory viruses are one of the most common triggers for asthma exacerbations, not all of these viruses affect patients equally. There is no strong evidence supporting that patients with asthma have a higher risk of becoming seriously ill from coronavirus disease 2019 (CO-VID-19), although recent reports from the USA and the UK suggest that asthma is much more common in children and adults with mild to severe COVID-19 than has previously been reported in Asia and in Europe. As in previous severe acute respiratory syndrome (SARS) outbreaks, patients with asthma, especially children, appear to be less susceptible to the coronavirus with a low rate of asthma exacerbations. A different expression of viral receptors and T2 inflammation can be responsible for different outcomes. Future studies focused on asthma and on other allergic disorders are needed to provide a greater understanding of the impact of underlying asthma and allergic inflammation on COVID-19 susceptibility and disease severity. However, for the moment, it is crucial that asthmatic patients maintain their controller medication, from inhaled corticosteroids to biologics, without making any dose adjustments on their own or stopping the medication. New data are emerging daily, rapidly updating our understanding of this novel coronavirus.

negative: Age differences in clinical features and outcomes in patients with COVID-19, Jiangsu, China: a retrospective, multi-center cohort study Objectives To determine the age-specific clinical presentations and incidence of adverse outcomes among patients with COVID-19 in Jiangsu, China. Design and setting This is a retrospective, multi-center cohort study performed at twenty-four hospitals in Jiangsu, China. Participants From January 10 to March 15, 2020, 625 patients with COVID-19 were involved. Results Of the 625 patients (median age, 46 years; 329 [52.6%] males), 37 (5.9%) were children (18 years or less), 261 (40%) young adults (19-44 years), 248 (39.7%) middle-aged adults (45-64 years), and 79 (12.6%) elderly (65 years or more). The incidence of hypertension, coronary heart disease, chronic obstructive pulmonary disease, and diabetes comorbidities increased with age (trend test, P < .0001, P = 0.0003, P < .0001, and P < .0001 respectively). Fever, cough, and shortness of breath occurred more commonly among older patients, especially the elderly, compared to children (Chi-square test, P = 0.0008, 0.0146, and 0.0282, respectively). The quadrant score and pulmonary opacity score increased with age (trend test, both P < .0001). Older patients had significantly more abnormal values in many laboratory parameters than younger patients. Elderly patients contributed the highest proportion of severe or critically-ill cases (33.0%, Chi-square test P < 0.001), intensive care unit (ICU) (35.4%, Chi-square test P < 0.001), and respiratory failure (31.6%, Chi-square test P = 0.0266), and longest hospital stay (21 days, ANOVA-test P < 0.001). Conclusions Elderly ([≥]65) patients with COVID-19 had the highest risk of severe or critical illness, intensive care use, respiratory failure, and the longest hospital stay, which may be due partly to that they had higher incidence of comorbidities and poor immune responses to COVID-19.

negative: COVID 19: Impacts and Implications for Pediatric Practice Since the rapid emergence of the novel coronavirus in December of 2019 and subsequent development of a global pandemic, clinicians around the world have struggled to understand and respond effectively and efficiently. With global response encompassing social, political, organizational, and economic realms, world leaders are struggling to keep pace with the rapid changes. Challenges within global healthcare system and the healthcare profession itself include rationing supplies and services within health care systems, many of which were stretched to the brink before this latest viral outbreak (American Hospital Association, 2020). Leaders are making policy decisions while balancing the slow and precise nature of science with the rapid and pressing need for life-saving information (Altmann, Douek, & Boyton, 2020). Shortcuts on research are occurring, including publishing papers with lack of peer review. Social media and lurid reporting bolster feelings of mistrust and panic-buying while burgeoning conspiracy theories commandeer national dialogue. This is a time in history to prioritize global health and thoughtful pandemic preparedness (Lancet, 2020). Pediatric Nurse Practitioners (PNPs) are ideally situated to be a trusted source of accurate health information for children. This continuing education article summarizes the latest evidence-based information on the rapidly developing coronavirus pandemic; equipping PNPs for clinical preparation and response. 1.. Distinguish risk factors for COVID-19-related morbidity and mortality and identify modes of transmission. 2.. Appraise appropriate COVID-19 testing parameters and procedures for children. 3.. Compare pediatric clinical presentation to adults with COVID-19 infection and recommend appropriate treatment measures. 4.. State appropriate infection-control measures to reduce transmission. 5.. Describe measures to reduce the risk of infection spread, mitigate adverse health effects in high-risk children, and to promote general health through preventive care.

negative: Disease and age‐related inequalities in paediatric research, funding and communication: lessons from the COVID‐19 pandemic COVID‐19 has already caused millions of infections, thousands of deaths and countless indirect and poorly estimated consequences on other diseases and the global economy. All ages are potentially susceptible, but the virus has had a lower direct impact on children, with fewer severe cases and low mortality rates. However, the reasons for this are still unclear and we cannot rule out children’s role in transmitting the disease. The serious impact that restrictive measures have had on children’s lives have not been fully considered. Because children are less affected by COVID‐19, the scientific community, health agencies and governments have not focused much attention on them during this pandemic.

negative: Systematic Review of Universal Resilience-Focused Interventions Targeting Child and Adolescent Mental Health in the School Setting. OBJECTIVE To examine the effect of universal, school-based, resilience-focused interventions on mental health problems in children and adolescents. METHOD Eligible studies were randomized controlled trials (RCTs) of universal, school-based interventions that included strategies to strengthen a minimum of 3 internal resilience protective factors, and included an outcome measure of mental health problems in children and adolescents aged 5 to 18 years. Six databases were searched from 1995 to 2015. Results were pooled in meta-analyses by mental health outcome (anxiety symptoms, depressive symptoms, hyperactivity, conduct problems, internalizing problems, externalizing problems, and general psychological distress), for all trials (5-18 years). Subgroup analyses were conducted by age (child: 5-10 years; adolescent: 11-18 years), length of follow-up (short: post-≤12 months; long: >12 months), and gender (narrative). RESULTS A total of 57 included trials were identified from 5,984 records, with 49 contributing to meta-analyses. For all trials, resilience-focused interventions were effective relative to a control in reducing 4 of 7 outcomes: depressive symptoms, internalizing problems, externalizing problems, and general psychological distress. For child trials (meta-analyses for 6 outcomes), interventions were effective for anxiety symptoms and general psychological distress. For adolescent trials (meta-analyses for 5 outcomes), interventions were effective for internalizing problems. For short-term follow-up, interventions were effective for 2 of 7 outcomes: depressive symptoms and anxiety symptoms. For long-term follow-up (meta-analyses for 5 outcomes), interventions were effective for internalizing problems. CONCLUSION The findings may suggest most promise for using universal resilience-focused interventions at least for short-term reductions in depressive and anxiety symptoms for children and adolescents, particularly if a cognitive-behavioral therapy-based approach is used. The limited number of trials providing data amenable for meta-analysis for some outcomes and subgroups, the variability of interventions, study quality, and bias mean that it is not possible to draw more specific conclusions. Identifying what intervention qualities (such as number and type of protective factor) achieve the greatest positive effect per mental health problem outcome remains an important area for future research. SYSTEMATIC REVIEW PROTOCOL AND REGISTRATION Systematic Review of Universal Resilience Interventions Targeting Child and Adolescent Mental Health in the School Setting; http://dx.doi.org/10.1186/s13643-015-0172-6; PROSPERO CRD42015025908.

negative: Changes in Solo and Partnered Sexual Behaviors during the COVID-19 Pandemic: Findings from a U.S. Probability Survey Background: Research demonstrates that pandemics adversely impact sexual and reproductive health (SRH), but few have examined their impact on participation in sex. We examined self-reported changes in solo and sexual behaviors in U.S. adults during early stages of the public health response to COVID-19. Methods: We conducted an online, nationally representative, cross-sectional survey of U.S. adults (N=1010; aged 18-94 years; 62% response rate) from April 10-20, 2020. We used weighted multinomial logistic regression to examine past month self-reported changes (decreased, stable or increased) in ten solo and partnered sexual behaviors. Predictor variables included: having children at home, past month depressive symptoms, (ACHA 3-item scale), past month loneliness (UCLA 3-Item Loneliness scale), COVID-19 protection behaviors (adapted 12-item scale), perceived COVID-19 consequences (adapted 10-item scale) and COVID-19 knowledge (adapted 10-item scale). Findings: Nearly half of all adults reported some kind of change, most commonly, a decrease, in their sexual behavior in the past month. Having elementary aged children at home, past month depressive symptoms and loneliness and enacting more COVID-19 protective behaviors were associated with both reduced partnered bonding behaviors, such as hugging, cuddling, holding hands and kissing, as well as reduced partnered sexual behaviors, such as oral sex, partnered genital touching and vaginal sex. Greater COVID19 risk perception and greater COVID19 knowledge were associated with mixed effects in behavior outcomes. Interpretations: Our data illustrate the very personal ways in which different pandemic-associated factors may create or inhibit opportunities for solo and partnered sex. The centrality of sexuality to health and well-being, even during pandemics, means that a critical piece of public health prevention and management responses should is ensuring that services and resource that support positive sexual decision making remain open and available.

negative: Transcranial Doppler ultrasound findings in children with moderate-to-severe traumatic brain injury following abusive head trauma PURPOSE: Abusive head trauma (AHT) is the leading cause of fatal head injuries for children under 2 years. The objective was to evaluate, using transcranial Doppler ultrasound (TCD), whether children with AHT have a similar neurovascular response to injury compared with children without AHT. METHODS: Retrospective sub-analysis of previously prospectively acquired data in a pediatric intensive care unit in a level 1 trauma hospital. TCD was performed daily until hospital day 8, discharge, or death. Neurologic outcome was assessed using the Glasgow Outcome Scale Extended (GOS-E Peds) at 1 month from initial injury. RESULTS: Sixty-nine children aged 1 day to 17 years with moderate-to-severe traumatic brain injury were enrolled. Fifteen children suffered AHT and 54 had no suspicion for AHT. Fifteen children with AHT underwent 80 serial TCD examinations; 54 children without AHT underwent 308 exams. After standardization for age and gender normative values, there was no statistically significant difference in mean cerebral blood flow velocity of the middle cerebral artery (V(MCA)) between children with and without AHT. There was no difference in the incidence of extreme cerebral blood flow velocity (CBFV, greater or less than 2 standard deviations from normative value) between groups. Within the AHT group, there were no statistically significant differences in V(MCA) between children with a favorable (GOS-E Peds 1–4) versus unfavorable neurologic outcome (GOS-E Peds 5–8). CONCLUSION: Children with AHT have no significant differences in V(MCA) or percentage of extreme CBFV in the middle cerebral artery compared to with those without AHT.

negative: The Unexpected Risks of COVID-19 on Asthma Control in Children Much is being learned about clinical outcomes for adult COVID-19 patients with underlying chronic conditions; however, there is less coverage on how the COVID-19 pandemic impacts the management of chronic medical conditions, such as asthma, in children and youth. Asthma is a common chronic medical condition in children that is uniquely susceptible to changes brought on by COVID-19. Sudden dramatic changes in the environment, medical practice, and medication use have altered the asthma management landscape with potential impacts on asthma outcomes. In this paper, we review how changes in transportation and travel patterns, school attendance, physical activity, and time spent indoors, along with changes in health care delivery since the start of the pandemic, all play a contributing role in asthma control in children. We review potentially important influences of asthma control in children during the COVID-19 pandemic worthy of further study.

negative: Considering how biological sex impacts immune responses and COVID-19 outcomes A male bias in mortality has emerged in the COVID-19 pandemic, which is consistent with the pathogenesis of other viral infections. Biological sex differences may manifest themselves in susceptibility to infection, early pathogenesis, innate viral control, adaptive immune responses or the balance of inflammation and tissue repair in the resolution of infection. We discuss available sex-disaggregated epidemiological data from the COVID-19 pandemic, introduce sex-differential features of immunity and highlight potential sex differences underlying COVID-19 severity. We propose that sex differences in immunopathogenesis will inform mechanisms of COVID-19, identify points for therapeutic intervention and improve vaccine design and increase vaccine efficacy.

negative: Rethinking ‘essential’ and ‘nonessential’: the developmental paediatrician’s COVID-19 response While terms such as ‘essential’ and ‘nonessential’ used amidst the COVID-19 pandemic may serve a practical purpose, they also pose a risk of obstructing our view of the harmful indirect health consequences of this crisis. SARS-CoV-2 cases and deaths in children are minimal compared to adults, but the pandemic impacts other ‘essential’ aspects of children’s health including child development and the associated areas of paediatric behaviour, mental health, and maltreatment. Alongside the management of severe SARS-CoV-2 cases in emergency rooms and intensive care units, continuing to care for children with developmental disabilities must also be concurrently championed as ‘essential’ during this crisis. The potentially devastating lifelong effects of the pandemic and isolation on an already vulnerable population demand that action be taken now. Video conferences and phone calls are ‘essential’ instruments we can use to continue to provide quality care for our patients.

negative: Lifestyle Risk Factors, Inflammatory Mechanisms, and COVID-19 Hospitalization: A Community-Based Cohort Study of 387,109 Adults in UK We conducted the first large-scale general population study on lifestyle risk factors (smoking, physical inactivity, obesity, and excessive alcohol intake) for COVID-19 using prospective cohort data with national registry linkage to hospitalisation. Participants were 387,109 men and women (56.4 ±8.8 yr; 55.1% women) residing in England from UK Biobank study. Physical activity, smoking, and alcohol intake, were assessed by questionnaire at baseline (2006-2010). Body mass index, from measured height and weight, was used as an indicator of overall obesity. Outcome was cases of COVID-19 serious enough to warrant a hospital admission from 16-March-2020 to 26-April-2020. There were 760 COVID-19 cases. After adjustment for age, sex and mutually for each lifestyle factor, physical inactivity (Relative risk, 1.32, 95% confidence interval, 1.10, 1.58), smoking (1.42;1.12, 1.79) and obesity (2.05 ;1.68, 2.49) but not heavy alcohol consumption (1.12; 0.93, 1.35) were all related to COVID-19. We also found a dose-dependent increase in risk of COVID-19 with less favourable lifestyle scores, such that participants in the most adverse category had 4-fold higher risk (4.41; 2.52 –7.71) compared to people with the most optimal lifestyle. C-reactive protein levels were associated with elevated risk of COVID-19 in a dose-dependent manner, and partly (10 – 16%) explained associations between adverse lifestyle and COVID-19. Based on UK risk factor prevalence estimates, unhealthy behaviours in combination accounted for up to 51% of the population attributable fraction of severe COVID-19. Our findings suggest that an unhealthy lifestyle synonymous with an elevated risk of non-communicable disease is also a risk factor for COVID-19 hospital admission, which might be partly explained by low grade inflammation. Adopting simple lifestyle changes could lower the risk of severe infection.

negative: Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis BACKGROUND: The prevalence and prognosis of digestive system involvement, including gastrointestinal symptoms and liver injury, in patients with COVID-19 remains largely unknown. We aimed to quantify the effects of COVID-19 on the digestive system. METHODS: In this systematic review and meta-analysis, we systematically searched PubMed, Embase, and Web of Science for studies published between Jan 1, 2020, and April 4, 2020. The websites of WHO, CDC, and major journals were also searched. We included studies that reported the epidemiological and clinical features of COVID-19 and the prevalence of gastrointestinal findings in infected patients, and excluded preprints, duplicate publications, reviews, editorials, single case reports, studies pertaining to other coronavirus-related illnesses, and small case series (<10 cases). Extracted data included author; date; study design; country; patient demographics; number of participants in severe and non-severe disease groups; prevalence of clinical gastrointestinal symptoms such as vomiting, nausea, diarrhoea, loss of appetite, abdominal pain, and belching; and digestive system comorbidities including liver disease and gastrointestinal diseases. Raw data from studies were pooled to determine effect estimates. FINDINGS: We analysed findings from 35 studies, including 6686 patients with COVID-19, that met inclusion criteria. 29 studies (n=6064) reported gastrointestinal symptoms in patients with COVID-19 at diagnosis, and the pooled prevalence of digestive system comorbidities was 4% (95% CI 2–5; range 0–15; I(2)=74%). The pooled prevalence of digestive symptoms was 15% (10–21; range: 2–57; I(2)=96%) with nausea or vomiting, diarrhoea, and loss of appetite being the three most common symptoms. The pooled prevalence of abnormal liver functions (12 studies, n=1267) was 19% (9–32; range 1–53; I(2)=96%). Subgroup analysis showed patients with severe COVID-19 had higher rates of gastrointestinal symptoms (odds ratio [OR] 1·60 [95% CI 1·09–2·36]; p=0·0020; I(2)=44%) and liver injury (2·20 [1·60–3·02]; p<0·00001; I(2)=36%) compared with those with non-severe disease. Patients in Hubei province, where the initial COVID-19 outbreak occurred, were more likely to present with abnormal liver functions (p<0·0001) compared with those outside of Hubei. Paediatric patients with COVID-19 had a similar prevalence of gastrointestinal symptoms to those of adult patients. 10% (95% CI 4–19; range 3–23; I(2)=97%) of patients presented with gastrointestinal symptoms alone without respiratory features. Patients who presented with gastrointestinal system involvement had delayed diagnosis (standardised mean difference 2·85 [95% CI 0·22–5·48]; p=0·030; I(2)=73%). Patients with gastrointestinal involvement had a higher prevalence of complication (OR 2·51 [95% CI 1·62–3·89]; p<0·0001; I(2)=0%). INTERPRETATION: Our study showed that digestive symptoms and liver injury are not uncommon in patients with COVID-19. Increased attention should be paid to the care of this unique group of patients. FUNDING: None.

negative: A geroscience perspective on COVID-19 mortality A novel coronavirus, SARS-CoV-2, emerged in December 2019, leading within a few months to a global pandemic. COVID-19, the disease caused by this highly contagious virus, can have serious health consequences, though risks of complications are highly age-dependent. Rates of hospitalization and death are less than 0.1% in children, but increase to 10% or more in older people. Moreover, at all ages, men are more likely than women to suffer serious consequences from COVID-19. These patterns are familiar to the geroscience community. The effects of age and sex on mortality rates from COVID-19 mirror the effects of aging on almost all major causes of mortality. These similarities are explored here, and underscore the need to consider the role of basic biological mechanisms of aging on potential treatment and outcomes of COVID-19.

negative: Taste and Smell Impairment in COVID-19: An AAO-HNS Anosmia Reporting Tool-Based Comparative Study OBJECTIVE: To identify the taste and smell impairment in coronavirus disease 2019 (COVID-19)–positive subjects and compare the findings with COVID-19–negative subjects using the American Academy of Otolaryngology–Head and Neck Surgery (AAO-HNS) Anosmia Reporting Tool. SETTING: Tertiary referral center/COVID-19 pandemic hospital. STUDY DESIGN: Comparative study. SUBJECTS AND METHODS: After power analysis, 128 subjects were divided into 2 groups according to real-time polymerase chain reaction (RT-PCR) COVID-19 testing results. Subjects were called via telephone, and the AAO-HNS Anosmia Reporting Tool was used to collect responses. RESULTS: The mean age of the study group was 38.63 ± 10.08 years. At the time of sampling, rhinorrhea was significantly high in the COVID-19–negative group, whereas those complaints described as “other” were significantly high in the COVID-19–positive group. There was a significant difference in the smell/taste impairment rates of the groups (n = 46% [71.9%] for the COVID-19–positive group vs n = 17 [26.6%] for the COVID-19–negative group, P = .001). For subjects with a smell impairment, anosmia rates did not differ between the groups. The rates of hyposmia and parosmia were significantly high in the COVID-19–positive group. For the subjects with taste impairment, ageusia rates did not differ between groups. The rate of hypogeusia and dysgeusia was significantly high in the COVID-19–positive group. Logistic regression analysis indicates that smell/taste impairment in COVID-19–positive subjects increases the odds ratio by 6.956 (95% CI, 3.16-15.29) times. CONCLUSION: COVID-19–positive subjects are strongly associated with smell/taste impairment.

negative: Survival of hospitalized COVID-19 patients in Northern Italy: a population-based cohort study by the ITA-COVID19 Network Background COVID19 case fatality rate in hospitalized patients varies across countries and studies, but reliable estimates specific for age, sex, and comorbidities are needed to design trials for COVID19 interventions. Aim of this study is to provide population-based survival curves of hospitalized COVID19 patients. Methods A cohort study was conducted in Lombardy, Veneto, and Reggio Emilia using COVID19 registries linked to hospital discharge databases containing patient clinical histories. All patients with positive SARS CoV 2 RTPCR test on oral/nasopharyngeal swabs hospitalized from 21st February to 21st April 2020 were identified. Kaplan Meier survival estimates were calculated at 14 and 30 days for death in any setting, stratifying by age, sex and Charlson Index. Findings Overall 42,926 hospitalized COVID19 patients were identified. Patients' median age was 69 years (IQR: 57; 79), 62.6% were males, 69.4% had a Charlson Index of 0. In total, 11,205 (26.1%) patients died over a median follow-up of 24 days (IQR: 10; 35). Survival curves showed that 22.0% of patients died within 14 days and 27.6% within 30 days of hospitalization. Survival was higher in younger patients and in females. Younger patients with comorbidities had a lower survival than older ones with comorbidities. Interpretation Over 27% of hospitalized COVID19 patients died within one month in three areas of Northern Italy that were heavily affected by SARS CoV 2 infection. Such a high fatality rate suggests that trials should focus on survival and have follow-up of at least one month.

negative: Should Schools Reopen Early or Late? - Transmission Dynamics of COVID-19 in Children

negative: Defining Essential Services for Deaf and Hard of Hearing Children during the COVID-19 Pandemic COVID-19 is a rapidly growing global pandemic caused by a novel coronavirus. With no vaccine or definitive treatment, public health authorities have recommended a strategy of "social distancing," reducing individual interaction, canceling elective procedures, and limiting nonessential services. Health care providers must determine what procedures are considered "elective," balancing risk of treatment delays with that of coronavirus exposure to patient, family, and providers. Given critical periods for language development and the long-term impact of auditory deprivation, some audiologic and otologic services should be considered essential. In this article, we describe the experience of a quaternary referral pediatric hospital in Seattle, the epicenter of COVID-19 in the United States, and share strategies for risk minimization employed by Seattle Children's Hospital. We hope that this work can be a reference for other centers continuing care for children who are deaf and hard of hearing during the COVID-19 and future resource-limiting crises.

negative: A Survey on Applications of Artificial Intelligence in Fighting Against COVID-19 The COVID-19 pandemic caused by the SARS-CoV-2 virus has spread rapidly worldwide, leading to a global outbreak. Most governments, enterprises, and scientific research institutions are participating in the COVID-19 struggle to curb the spread of the pandemic. As a powerful tool against COVID-19, artificial intelligence (AI) technologies are widely used in combating this pandemic. In this survey, we investigate the main scope and contributions of AI in combating COVID-19 from the aspects of disease detection and diagnosis, virology and pathogenesis, drug and vaccine development, and epidemic and transmission prediction. In addition, we summarize the available data and resources that can be used for AI-based COVID-19 research. Finally, the main challenges and potential directions of AI in fighting against COVID-19 are discussed. Currently, AI mainly focuses on medical image inspection, genomics, drug development, and transmission prediction, and thus AI still has great potential in this field. This survey presents medical and AI researchers with a comprehensive view of the existing and potential applications of AI technology in combating COVID-19 with the goal of inspiring researches to continue to maximize the advantages of AI and big data to fight COVID-19.

negative: Translating COVID-19 Evidence to Maximize Physical Therapists' Impact and Public Health Response Coronavirus disease 2019 (COVID-19) has sounded alarm bells throughout global health systems. Late May, 2020, over 100,000 COVID-19 related deaths were reported in the United State, the highest number of any country. This article describes COVID-19 as the next historical turning point in the physical therapy profession's growth and development. The profession has had over a 100-year tradition of responding to epidemics including poliomyelitis; two world wars and geographical regions experiencing conflicts and natural disasters; and the epidemic of noncommunicable diseases (NCDs). The evidence-based role of non-invasive interventions (non-pharmacologic/non-surgical) that hallmark physical therapist practice has emerged as being highly relevant today in addressing COVID-19 in two primary ways. First, despite some unique features, COVID-19 presents as acute respiratory distress syndrome (ARDS) in its severe acute stage. ARDS is well familiar to physical therapists in intensive care units. Body positioning and mobilization, prescribed based on comprehensive assessments/examinations, counter the negative sequelae of recumbency and bedrest; augment gas exchange and reduce airway closure, deconditioning and critical illness complications; and maximize long-term functional outcomes. Physical therapists have an indisputable role across the COVID-19 care continuum. Second, over 90% of individuals who contract and die from COVID-19 have co-morbidities, most notably cardiovascular disease, hypertension, chronic lung disease, type 2 diabetes mellitus, and obesity. Physical therapists need to redouble their efforts to address NCDs by assessing patients for risk factors and manifestations and institute evidence-based health education (smoking cessation, whole-food plant-based nutrition, weight control, physical activity/exercise), and/or support patients' efforts when these are managed by other professionals. Effective health education is a core competency for addressing risk of COVID-19 as well as NCDs. COVID-19 is a wake-up call to the profession, an opportunity to assert its role throughout the COVID-19 care continuum and augment public health initiatives by reducing the impact of the current pandemic.

negative: Vaginal delivery in SARS‐CoV‐2‐infected pregnant women in Northern Italy: a retrospective analysis OBJECTIVE: To report mode of delivery and immediate neonatal outcome in women infected with COVID‐19. DESIGN: Retrospective study. SETTING: Twelve hospitals in northern Italy. PARTICIPANTS: Pregnant women with COVID‐19‐confirmed infection who delivered. EXPOSURE: COVID 19 infection in pregnancy. METHODS: SARS‐CoV‐2‐infected women who were admitted and delivered from 1 to 20 March 2020 were eligible. Data were collected from the clinical records using a standardised questionnaire on maternal general characteristics, any medical or obstetric co‐morbidity, course of pregnancy, clinical signs and symptoms, treatment of COVID 19 infection, mode of delivery, neonatal data and breastfeeding. MAIN OUTCOME AND MEASURES: Data on mode of delivery and neonatal outcome. RESULTS: In all, 42 women with COVID‐19 delivered at the participating centres; 24 (57.1%, 95% CI 41.0–72.3) delivered vaginally. An elective caesarean section was performed in 18/42 (42.9%, 95% CI 27.7–59.0) cases: in eight cases the indication was unrelated to COVID‐19 infection. Pneumonia was diagnosed in 19/42 (45.2%, 95% CI 29.8–61.3) cases: of these, 7/19 (36.8%, 95% CI 16.3–61.6) required oxygen support and 4/19 (21.1%, 95% CI 6.1–45.6) were admitted to a critical care unit. Two women with COVID‐19 breastfed without a mask because infection was diagnosed in the postpartum period: their newborns tested positive for SARS‐Cov‐2 infection. In one case, a newborn had a positive test after a vaginal operative delivery. CONCLUSIONS: Although postpartum infection cannot be excluded with 100% certainty, these findings suggest that vaginal delivery is associated with a low risk of intrapartum SARS‐Cov‐2 transmission to the newborn. TWEETABLE ABSTRACT: This study suggests that vaginal delivery may be associated with a low risk of intrapartum SARS‐Cov‐2 transmission to the newborn.

negative: The impact of unplanned school closure on children's social contact: Rapid evidence review Background Emergency school closures are often used as public health interventions during infectious disease outbreaks in an attempt to minimise the spread of infection. However, if children continue to mix with others outside the home during the closures, these measures are unlikely to be effective. Objectives This review aimed to summarise existing literature on children's activities and contacts made outside the home during unplanned school closures. Methods We searched four databases from inception to February 2020 for relevant literature. Main findings were extracted. Results 3,343 citations were screened and 19 included in the review. Activities and social contacts appeared to decrease during closures but contact was still common. All studies reported children leaving the house or being looked after by non-household members. There was some evidence that older child age and parental disagreement with closure were predictive of children leaving the house, and mixed evidence regarding the relationship between infection status and leaving the home. Parental agreement with closure was generally high, but some parents disagreed due to perceived low risk of infection and practical issues regarding childcare and financial impact. Conclusions Evidence suggests that many children continue to leave the house and mix with others during school closures despite public health recommendations to avoid social contact. This review of behaviour during unplanned school closures could be used to improve infectious disease modelling.

negative: The TARGET cohort study protocol: a prospective primary care cohort study to derive and validate a clinical prediction rule to improve the targeting of antibiotics in children with respiratory tract illnesses BACKGROUND: Children with respiratory tract infections are the single most frequent patient group to make use of primary care health care resources. The use of antibiotics remains highly prevalent in young children, but can lead to antimicrobial resistance as well as reinforcing the idea that parents should re-consult for similar symptoms. One of the main drivers of indiscriminate antimicrobial use is the lack of evidence for, and therefore uncertainty regarding, which children are at risk of poor outcome. This paper describes the protocol for the TARGET cohort study, which aims to derive and validate a clinical prediction rule to identify children presenting to primary care with respiratory tract infections who are at risk of hospitalisation. METHODS/DESIGN: The TARGET cohort study is a large, multicentre prospective observational study aiming to recruit 8,300 children aged ≥3 months and <16 years presenting to primary care with a cough and respiratory tract infection symptoms from 4 study centres (Bristol, London, Oxford and Southampton). Following informed consent, symptoms, signs and demographics will be measured. In around a quarter of children from the Bristol centre, a single sweep, dual bacterial-viral throat swab will be taken and parents asked to complete a symptom diary until the child is completely well or for 28 days, whichever is sooner. A review of medical notes including clinical history, re-consultation and hospitalisations will be undertaken. Multivariable logistic regression will be used to identify the independent clinical predictors of hospitalisation as well as the prognostic significance of upper respiratory tract microbes. The clinical prediction rule will be internally validated using various methods including bootstrapping. DISCUSSION: The clinical prediction rule for hospitalisation has the potential to help identify a small group of children for hospitalisation and a much larger group where hospitalisation is very unlikely and antibiotic prescribing would be less warranted. This study will also be the largest natural history study to date of children presenting to primary care with acute cough and respiratory tract infections, and will provide important information on symptom duration, re-consultations and the microbiology of the upper respiratory tract.

negative: Sex and gender differences in the outcome of patients with COVID‐19 The SARS-CoV-2 pandemic is a new wave of emerging infections that the world is struggling with. There are many unanswered questions in this regard, including Gender-specific outcome in COVID-19. Gender and age are major risk factors for SARS-CoV-2 infection. In addition to the effect of these factors on the prevalence of SARS-CoV-2, the clinical outcome varies according to both of them. This article is protected by copyright. All rights reserved.

negative: Prevalence and outcomes of Guillain-Barré syndrome among pediatrics in Saudi Arabia: a 10-year retrospective study BACKGROUND: Guillain-Barré syndrome (GBS) is a progressive acute form of paralysis most probably secondary to an immune-mediated process. GBS among Saudis has been seldom investigated, which leaves both clinicians and researchers with scarcity in knowledge. Therefore, this study aims to assess the prevalence and clinical prognosis of GBS among pediatrics admitted with acute paralysis at a large healthcare facility in Riyadh, Saudi Arabia. METHODS: This retrospective study reviewed patients’ medical records between 2005 and 2015. Eligible cases were children (<14 years old) admitted to the hospital complaining of acute paralysis and later diagnosed with one form or variant of GBS. Pearson’s chi-square, Fisher’s exact test, and binary logistic regression were employed to analyze the collected data. RESULTS: The prevalence of GBS was 49%. The male-to-female ratio was 1.45:1. The mean ± standard deviation age was 7±3.7 years. There were 34 (69.4%) cases with progression to maximum paralysis in ≤2 weeks, while 15 (30.6%) cases occurred beyond 2 weeks. Males (n=24, 82.8%) were more likely to endure progression to maximum paralysis in ≤2 weeks after the disease onset, compared to females (n=10, 50%), P=0.014. All cases complaining of respiratory problems exhibited a progression to maximum paralysis in ≤2 weeks, compared to those with no respiratory problems, P=0.027. Residual paralysis at 60 days post disease onset was highly associated with GBS patients of age 8–14 years (n=15, 65.2%), compared to younger patients (n=8, 30.8%), P=0.016. Patients admitted in colder seasons (n=14, 63.6%) were more likely to suffer residual paralysis too, compared to those in warmer seasons (n=9, 33.3%), P=0.035. GBS cases who complained of facial weakness (n=9, 75%) and ocular abnormalities (n=10, 71.4%) were also more likely to endure residual paralysis at 60 days post disease onset, P=0.025 and P=0.03, respectively. CONCLUSION: Male gender could be a determinant of rapid progression to maximum paralysis, while the older age group in pediatrics is expected to endure residual paralysis at 60 days post disease onset. GBS can be accounted as a rare disease, especially in pediatrics, so confirmed cases should be investigated comprehensively for research purposes.

negative: The impact of vitamin D food fortification and health outcomes in children: a systematic review and meta-regression. OBJECTIVE Vitamin D (vitD) deficiency is a global childhood health problem. Food fortification is a promising strategy to curb vitD deficiency. We aimed to assess the effectiveness of utilizing vitD fortification in staple foods to improve 25hydroxyvitamin D (25(OH)D) concentration and to reduce the prevalence of vitD deficiency among healthy children. METHODS We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the use of vitD fortified food products compared to no fortification among healthy children aged 1-18 years old. We searched Medline, Embase, Global Health, and Cochrane (CENTRAL) databases from database inception until May 2019. Independently, six reviewers in pairs screened titles and abstracts, assessed the full text for eligibility, and performed data extraction and quality assessment. The primary outcome is the impact of fortification on 25(OH)D concentration. The secondary outcomes included the impact of fortification on the prevalence of vitD deficiency, school performance, cognitive function, school absences, infection rate, hospital admission length, and compliance with fortified food product consumption. RESULTS We identified 2229 articles. After assessing eligibility, 20 RCTs met the inclusion criteria. The eligible RCTs assessed the fortification of milk, cereal, juice, bread, yogurt, and cheese compared with no fortification. All RCTs, except for three, had a low risk of bias. Food fortification improved 25(OH)D concentration by a mean difference (MD) of 15.51 nmol/L (95% confidence interval (CI) 6.28, 24.74; I2 = 99%), which resulted in a mean increase of 3 nmol/l for every 100 IU of vitD, when adjusted for baseline 25(OH)D concentration and country latitude. Additionally, the prevalence of vitD deficiency decreased by a risk ratio of 0.53 (95% CI 0.41, 0.69; I2 = 95%), and cognitive function improved by a MD of 1.22 intelligence quotient (IQ) points (95% CI 0.65, 1.79; I2 = 0%). The overall evidence quality was high. CONCLUSION VitD food fortification is an effective way to improve 25(OH)D concentration, prevent vitD deficiency, and improve IQ levels. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42017057631.

negative: Characteristics and Mechanism of Liver Injury in 2019 Coronavirus Disease An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (2019 coronavirus disease, COVID-19) since December 2019, from Wuhan, China, has been posing a significant threat to global human health. The clinical features and outcomes of Chinese patients with COVID-19 have been widely reported. Increasing evidence has witnessed the frequent incident liver injury in COVID-19 patients, and it is often manifested as transient elevation of serum aminotransferases; however, the patients seldom have liver failure and obvious intrahepatic cholestasis, unless pre-existing advanced liver disease was present. The underlying mechanisms of liver injury in cases of COVID-19 might include psychological stress, systemic inflammation response, drug toxicity, and progression of pre-existing liver diseases. However, there is insufficient evidence for SARS-CoV-2 infected hepatocytes or virus-related liver injury in COVID-19 at present. The clinical, pathological and laboratory characteristics as well as underlying pathophysiology and etiology of liver injury in COVID-19 remain largely unclear. In this review, we highlight these important issues based on the recent developments in the field, for optimizing the management and treatment of liver injury in Chinese patients with COVID-19.

negative: Exploration of trends in the incidence and prevalence of childhood maltreatment and domestic abuse recording in UK primary care: a retrospective cohort study using ‘the health improvement network’ database OBJECTIVES: Describe the epidemiology of childhood maltreatment and domestic abuse (in women). DESIGN: Analysis of longitudinal records between 1 January 1995 to 31 December 2018. SETTING: UK primary care database: ‘The Health Improvement Network’ (THIN). PARTICIPANTS: 11 831 850 eligible patients from 787 contributing practices. Childhood maltreatment and domestic abuse (women only) were defined as the presence of a recorded Read code. OUTCOME MEASURES: The incidence rate (IR) and prevalence of childhood maltreatment (in children aged 0–18 years) and domestic abuse (in women aged over 18) between 1996 and 2017. An adjusted incidence rate ratio (aIRR) is given to examine the differences in IRs based on sex, ethnicity and deprivation. RESULTS: The age and gender breakdown of THIN has been previously reported to be representative of the UK population, however, there is substantial missing information on deprivation quintiles (<20%) and ethnicity (approximately 50%). The IR (IR 60.1; 95% CI 54.3 to 66.0 per 100 000 child years) and prevalence (416.1; 95% CI 401.3 to 430.9 per 100 000 child population) of childhood maltreatment rose until 2017. The aIRR was greater in patients from the most deprived backgrounds (aIRR 5.14; 95% CI 4.57 to 5.77 compared with least deprived) and from an ethnic minority community (eg, black aIRR 1.25; 1.04 to 1.49 compared with white). When examining domestic abuse in women, in 2017, the IR was 34.5 (31.4 to 37.7) per 100 000 adult years and prevalence 368.7 (358.7 to 378.7) per 100 000 adult population. Similarly, the IR was highest in the lowest socioeconomic class (aIRR 2.30; 2.71 to 3.30) and in ethnic minorities (South Asian aIRR 2.14; 1.92 to 2.39 and black aIRR 1.64; 1.42 to 1.89). CONCLUSION: Despite recent improvements in recording, there is still a substantial under-recording of maltreatment and abuse within UK primary care records, compared with currently existing sources of childhood maltreatment and domestic abuse data. Approaches must be implemented to improve recording and detection of childhood maltreatment and domestic abuse within medical records.

negative: Simulated Assessment of Pharmacokinetically Guided Dosing for Investigational Treatments of Pediatric Patients With Coronavirus Disease 2019. Importance Children of all ages appear susceptible to severe acute respiratory syndrome coronavirus 2 infection. To support pediatric clinical studies for investigational treatments of coronavirus disease 2019 (COVID-19), pediatric-specific dosing is required. Objective To define pediatric-specific dosing regimens for hydroxychloroquine and remdesivir for COVID-19 treatment. Design, Setting, and Participants Pharmacokinetic modeling and simulation were used to extrapolate investigated adult dosages toward children (March 2020-April 2020). Physiologically based pharmacokinetic modeling was used to inform pediatric dosing for hydroxychloroquine. For remdesivir, pediatric dosages were derived using allometric-scaling with age-dependent exponents. Dosing simulations were conducted using simulated pediatric and adult participants based on the demographics of a white US population. Interventions Simulated drug exposures following a 5-day course of hydroxychloroquine (400 mg every 12 hours × 2 doses followed by 200 mg every 12 hours × 8 doses) and a single 200-mg intravenous dose of remdesivir were computed for simulated adult participants. A simulation-based dose-ranging study was conducted in simulated children exploring different absolute and weight-normalized dosing strategies. Main Outcomes and Measures The primary outcome for hydroxychloroquine was average unbound plasma concentrations for 5 treatment days. Additionally, unbound interstitial lung concentrations were simulated. For remdesivir, the primary outcome was plasma exposure (area under the curve, 0 to infinity) following single-dose administration. Results For hydroxychloroquine, the physiologically based pharmacokinetic model analysis included 500 and 600 simulated white adult and pediatric participants, respectively, and supported weight-normalized dosing for children weighing less than 50 kg. Geometric mean-simulated average unbound plasma concentration values among children within different developmental age groups (32-35 ng/mL) were congruent to adults (32 ng/mL). Simulated unbound hydroxychloroquine concentrations in lung interstitial fluid mirrored those in unbound plasma and were notably lower than in vitro concentrations needed to mediate antiviral activity. For remdesivir, the analysis included 1000 and 6000 simulated adult and pediatric participants, respectively. The proposed pediatric dosing strategy supported weight-normalized dosing for participants weighing less than 60 kg. Geometric mean-simulated plasma area under the time curve 0 to infinity values among children within different developmental age-groups (4315-5027 ng × h/mL) were similar to adults (4398 ng × h/mL). Conclusions and Relevance This analysis provides pediatric-specific dosing suggestions for hydroxychloroquine and remdesivir and raises concerns regarding hydroxychloroquine use for COVID-19 treatment because concentrations were less than those needed to mediate an antiviral effect.

negative: COVID-19 gone bad: A new character in the spectrum of the hyperferritinemic syndrome? Abstract The severe form of COVID-19 share several clinical and laboratory features with four entities gathered under the term “hyperferritinemic syndrome” and including macrophage activation syndrome (MAS), adult-onset Still's disease (AOSD), catastrophic anti-phospholipid syndrome (CAPS) and septic shock. COVID-19 systemic inflammatory reaction and “hyperferritinemic syndromes” are all characterized by high serum ferritin and a life-threatening hyper-inflammation sustained by a cytokines storm which eventually leads to multi-organ failure. In this review, we analyze the possible epidemiological and molecular mechanisms responsible for hyper-inflammation in patients with severe COVID-19 and we underline the similarities between this condition and “hyperferritinemic syndromes” which would allow considering this entity as the fifth member of the spectrum of inflammatory conditions.

negative: Education, the science of learning, and the COVID-19 crisis In the COVID-19 crisis, the science of learning has two different responsibilities: first, to offer guidance about how best to deal with the impact of the current situation, including lockdown and home-schooling; and second, to consider bigger questions about what this large-scale educational experiment might mean for the future. The first part of this Viewpoint summarises advice for parents on mental health, and on becoming stand-in-teachers. The second part, taking the longer view, considers the potential negative impact of the COVID-19 crisis in increasing inequality in education; but also the potential positive impact of driving innovations in technology use for educating children.

negative: An increasing risk of family violence during the Covid-19 pandemic: Strengthening community collaborations to save lives Abstract Though necessary to slow the spread of the novel Coronavirus (Covid-19), actions such as social-distancing, sheltering in-place, restricted travel, and closures of key community foundations are likely to dramatically increase the risk for family violence around the globe. In fact many countries are already indicating a dramatic increase in reported cases of domestic violence. While no clear precedent for the current crisis exists in academic literature, exploring the impact of natural disasters on family violence reports may provide important insight for family violence victim-serving professionals. Improving collaborations between human welfare and animal welfare agencies, expanding community partnerships, and informing the public of the great importance of reporting any concerns of abuse are all critical at this time.

negative: Opinion of the Scientific Panel on Animal Health and Welfare (AHAW) on a request from the Commission related with animal health and welfare risks associated with the import of wild birds other than poultry into the European Union

negative: Epidemiological and Clinical Characteristics of Cases During the Early Phase of COVID-19 Pandemic: A Systematic Review and Meta-Analysis Background: On 29th December 2019, a cluster of cases displaying the symptoms of a “pneumonia of unknown cause” was identified in Wuhan, Hubei province of China. This systematic review and meta-analysis aims to review the epidemiological and clinical characteristics of COVID-19 cases in the early phase of the COVID-19 pandemic. Methods: The search strategy involved peer-reviewed studies published between 1st January and 11th February 2020 in Pubmed, Google scholar and China Knowledge Resource Integrated database. Publications identified were screened for their title and abstracts according to the eligibility criteria, and further shortlisted by full-text screening. Three independent reviewers extracted data from these studies, and studies were assessed for potential risk of bias. Studies comprising non-overlapping patient populations, were included for qualitative and quantitative synthesis of results. Pooled prevalence with 95% confidence intervals were calculated for patient characteristics. Results: A total of 29 publications were selected after full-text review. This comprised of 18 case reports, three case series and eight cross-sectional studies on patients admitted from mid-December of 2019 to early February of 2020. A total of 533 adult patients with pooled median age of 56 (95% CI: 49–57) and a pooled prevalence of male of 60% (95% CI: 52–68%) were admitted to hospital at a pooled median of 7 days (95% CI: 7–7) post-onset of symptoms. The most common symptoms at admission were fever, cough and fatigue, with a pooled prevalence of 90% (95% CI: 81–97%), 58% (95% CI: 47–68%), and 50% (95% CI: 29–71%), respectively. Myalgia, shortness of breath, headache, diarrhea and sore throat were less common with pooled prevalence of 27% (95% CI: 20–36%), 25% (95% CI: 15–35%), 10% (95% CI: 7–13%), 8% (95% CI: 5–13%), and 7% (95% CI: 1–15%), respectively. ICU patients had a higher proportion of shortness of breath at presentation, as well as pre-existing hypertension, cardiovascular disease and COPD, compared to non-ICU patients in 2 studies (n = 179). Conclusion: This study highlights the key epidemiological and clinical features of COVID-19 cases during the early phase of the COVID-19 pandemic.

negative: COVID-19 pharmacologic treatments for children: research priorities and approach to pediatric studies Clinical trials of pharmacologic treatments of coronavirus disease 2019 (COVID-19) are being rapidly designed and implemented in adults. Children are often not considered during development of novel treatments for infectious diseases until very late. Although children appear to have a lower risk compared to adults of severe COVID-19 disease, a substantial number of children globally will benefit from pharmacologic treatments. It will be reasonable to extrapolate efficacy of most treatments from adult trials to children. Pediatric trials should focus on characterizing a treatment’s pharmacokinetics, optimal dose and safety, across the age spectrum. These trials should use an adaptive design to efficiently add or remove arms in what will be a rapidly evolving treatment landscape, and should involve a large number of sites across the globe in a collaborative effort to facilitate efficient implementation. All stakeholders must commit to equitable access to any effective, safe treatment for children everywhere.

negative: Factors linked to changes in mental health outcomes among Brazilians in quarantine due to COVID-19 The 2020 COVID-19 pandemic is a crisis of global proportions with a significant impact on the country of Brazil. The aims of this investigation were to track changes and risk factors for mental health outcomes during state-mandated quarantine. Adults residing in Brazil (n = 360, 37.9 years of age, 68.9% female) were surveyed at the start of quarantine and 1 month later. Outcomes assessed included perceived stress, state anxiety and depression. Aside from demographics, behaviors and attitudes assessed included exercise, diet, use of tele-psychotherapy and number of COVID-19 related risk factors, such as perceived risk of COVID-19, information overload, and feeling imprisoned. Overall, all mental health outcomes worsened from Time 1 to time 2, although there was a significant gender x time interaction for stress. 9.7% of the sample reported stress above the clinical cut-off (2 SD above mean), while 8.0% and 9.4% were above this cutoff for depression and anxiety, respectively. In repeated measures analysis, female gender, worsening diet and excess of COVID-19 information was related to all mental health outcomes. Changes in diet for the worse were associated with increases in anxiety. Exercise frequency was clearly related to state anxiety (0 days/week > 6 days/week). Those who did aerobic exercise did not have any increase in depression. Use of tele-psychotherapy predicted lower levels of depression and anxiety. In multiple regression, anxiety was predicted by the greatest number of COVID-19 specific factors. In conclusion, mental health outcomes worsened for Brazilians during the first month of quarantine and these changes are associated with a variety of risk factors.

negative: The predictive value of FiO2 for outcome of children with respiratory syncytial virus-induced acute respiratory distress syndrome

negative: Comorbidity and its Impact on Patients with COVID-19 A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in Wuhan, China, in December 2019. Since then, the virus has made its way across the globe to affect over 180 countries. SARS-CoV-2 has infected humans in all age groups, of all ethnicities, both males and females while spreading through communities at an alarming rate. Given the nature of this virus, there is much still to be learned; however, we know that the clinical manifestations range from a common cold to more severe diseases such as bronchitis, pneumonia, severe acute respiratory distress syndrome (ARDS), multi-organ failure, and even death. It is believed that COVID-19, in those with underlying health conditions or comorbidities, has an increasingly rapid and severe progression, often leading to death. This paper examined the comorbid conditions, the progression of the disease, and mortality rates in patients of all ages, infected with the ongoing COVID-19 disease. An electronic literature review search was performed, and applicable data was then collected from peer-reviewed articles published from January to April 20, 2020. From what is known at the moment, patients with COVID-19 disease who have comorbidities, such as hypertension or diabetes mellitus, are more likely to develop a more severe course and progression of the disease. Furthermore, older patients, especially those 65 years old and above who have comorbidities and are infected, have an increased admission rate into the intensive care unit (ICU) and mortality from the COVID-19 disease. Patients with comorbidities should take all necessary precautions to avoid getting infected with SARS CoV-2, as they usually have the worst prognosis.

negative: Are hydroxychloroquine and chloroquine effective in the treatment of SARS-COV-2 (COVID-19)? Data sources The authors of this rapid review did not disclose which electronic databases were included in their literature search. The inclusion and exclusion criteria for the data sources are not reported in the manuscript. Study selection The authors included six studies on the effectiveness of hydroxychloroquine or chloroquine for the prevention and treatment of COVID-19 in humans. Studies comprised of two randomised controlled trials, two non-randomised trials both of which were non-blinded and open-label and one that was uncontrolled, a prospective cohort study and an interim report. The authors did not report details of any studies that were excluded. Data extraction and synthesis The data extraction methodology was not reported and it is unclear if the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were followed. Treatment regimens and the study outcomes were extracted where available and overall findings were presented in a table. There were no comparable outcome measures; therefore, results were deemed unsuitable to combine and no statistical analyses were carried out. A narrative synthesis of each study is presented. Results The results of the studies in this rapid review are difficult to quantify as each study had different outcome parameters. Due to the heterogeneity of the studies, results were not combined, and no statistical analysis was carried out. Narrative synthesis of each of the included studies identified important and significant limitations, precluding the studies from demonstrating a statistically significant difference in outcomes. Conclusions This review highlights the urgent need for more high quality evidence on the use of hydroxychloroquine and chloroquine in the prevention and treatment of COVID-19. The results of the studies included should be interpreted with caution due to the weak supporting data and numerous methodological limitations. The authors suggested that the studies be viewed as hypothesis-generating and should not be used in decision making around the recommendations and guidelines in the prevention and treatment of COVID-19. There are currently several ongoing randomised controlled trials looking at the effectiveness and efficacy of these drugs on COVID-19. It is hoped the outcome of these studies can help guide future recommendations and national guidelines.

negative: Characteristics and Clinical Outcomes of Adult Patients Hospitalized with COVID-19 - Georgia, March 2020. SARS-CoV-2, the novel coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in the United States during January 2020 (1). Since then, >980,000 cases have been reported in the United States, including >55,000 associated deaths as of April 28, 2020 (2). Detailed data on demographic characteristics, underlying medical conditions, and clinical outcomes for persons hospitalized with COVID-19 are needed to inform prevention strategies and community-specific intervention messages. For this report, CDC, the Georgia Department of Public Health, and eight Georgia hospitals (seven in metropolitan Atlanta and one in southern Georgia) summarized medical record-abstracted data for hospitalized adult patients with laboratory-confirmed* COVID-19 who were admitted during March 2020. Among 305 hospitalized patients with COVID-19, 61.6% were aged <65 years, 50.5% were female, and 83.2% with known race/ethnicity were non-Hispanic black (black). Over a quarter of patients (26.2%) did not have conditions thought to put them at higher risk for severe disease, including being aged ≥65 years. The proportion of hospitalized patients who were black was higher than expected based on overall hospital admissions. In an adjusted time-to-event analysis, black patients were not more likely than were nonblack patients to receive invasive mechanical ventilation† (IMV) or to die during hospitalization (hazard ratio [HR] = 0.63; 95% confidence interval [CI] = 0.35-1.13). Given the overrepresentation of black patients within this hospitalized cohort, it is important for public health officials to ensure that prevention activities prioritize communities and racial/ethnic groups most affected by COVID-19. Clinicians and public officials should be aware that all adults, regardless of underlying conditions or age, are at risk for serious illness from COVID-19.

negative: Clinical features, complications and atypical manifestations of children with severe forms of dengue hemorrhagic fever in South India OBJECTIVE: To review clinical features and outcome of children with severe forms of dengue hemorrhagic fever (DHF) presenting to a pediatric intensive care unit (PICU) with particular focus on clinical presentation and outcome. METHODS: Retrospective chart review of patients admitted to the Pediatric Intensive Care Unit (PICU) of a referral children's hospital in South India with DHF over 1.5 years (2001–January 2003). RESULTS: Of 858 patients with dengue fever/DHF admitted to the hospital during the study period, 109 cases with severe forms of disease required PICU admission, of which 9 patients died. 77 were under 5 years of age. The commonest indication for PICU admission was persistent shock (39 patients) followed by requirement for positive pressure ventilation in 29 patients (10 of whom had Acute Respiratory Distress Syndrome [ARDS]) and neurological symptoms in 24 patients. An important finding was the presence of diastolic dysfunction in 3 children. Six deaths of refractory shock included 4 who had ARDS and DIC and 2 who had shock with DIC 3 patients had abdominal compartment syndrome (ACS) has not been previously described in children with DSS and may lead to fluid refractory shock if not corrected. All patients had thrombocytopenia which was a defining feature of the syndrome, while 74 were also coagulopathic and 6 had severe fatal DIC. Hepatic dysfunction was more severe in children with prolonged shock, however, only a fifth of cases (5/24) with neurological manifestations were in shock. Other significant reasons for neurological presentation included cerebral edema, and encephalopathy secondary to hepatic dysfunction. 2 children had features of Acute Disseminated Encephalomyelitis (ADEM), previously only described in adults with dengue. CONCLUSION: It was found that complications such as DIC, diastolic dysfunction, abdominal compartment syndrome, ARDS and hepatic dysfunction were more frequent in severe established shock. However, most neurological events were unrelated to the perfusion status. Children referred late were harder to resuscitate. There were 9 PICU deaths (case fatality rate of 8.35%). Severe refractory shock, DIC, ARDS, hepatic failure and neurological manifestations singly or in combination were the commonest causes of death in the present study.

negative: Risk factors for adverse outcomes of Indigenous infants hospitalized with bronchiolitis BACKGROUND: Hospitalized bronchiolitis imposes a significant burden among infants, particularly among Indigenous children. Traditional or known risk factors for severe disease are well described, but there are limited data on risks for prolonged hospitalization and persistent symptoms. Our aims were to determine factors (clinical and microbiological) associated with (i) prolonged length of stay (LOS); (ii) persistent respiratory symptoms at 3 weeks; (iii) bronchiectasis up to ∼24 months post‐hospitalisation; and (iv) risk of respiratory readmissions within 6 months. METHODS: Indigenous infants hospitalized with bronchiolitis were enrolled at Royal Darwin Hospital between 2008 and 2013. Standardized forms were used to record clinical data. A nasopharyngeal swab was collected at enrolment to identify respiratory viruses and bacteria. RESULTS: The median age of 232 infants was 5 months (interquartile range 3–9); 65% male. On multivariate regression, our 12 point severity score (including accessory muscle use) was the only factor associated with prolonged LOS but the effect was modest (+3.0 hr per point, 95%CI: 0.7, 5.1, P = 0.01). Presence of cough at 3 weeks increased the odds of bronchiectasis (OR 3.0, 95%CI: 1.1, 7.0, P = 0.03). Factors associated with respiratory readmissions were: previous respiratory hospitalization (OR 2.3, 95%CI: 1.0, 5.4, P = 0.05) and household smoke (OR 2.6, 95%CI: 1.0, 6.3, P = 0.04). CONCLUSION: Increased severity score is associated with prolonged LOS in Indigenous children hospitalized with bronchiolitis. As persistent symptoms at 3 weeks post‐hospitalization are associated with future diagnosis of bronchiectasis, optimising clinical care beyond hospitalization is needed to improve long‐term respiratory outcomes for infants at risk of respiratory disease. Pediatr Pulmonol. 2016;51:613–623. © 2015 Wiley Periodicals, Inc.

negative: Assessing capacity to social distance and neighborhood-level health disparities during the COVID-19 pandemic The COVID-19 pandemic has yielded disproportionate impacts on communities of color in New York City (NYC). Researchers have noted that social disadvantage may result in limited capacity to socially distance, and consequent disparities. Here, we investigate the role of neighborhood social disadvantage on the ability to socially distance, infections, and mortality. We combine Census Bureau and NYC open data with SARS-CoV-2 testing data using supervised dimensionality-reduction with Bayesian Weighted Quantile Sums regression. The result is a ZIP code-level index with relative weights for social factors facilitating infection risk. We find a positive association between neighborhood social disadvantage and infections, adjusting for the number of tests administered. Neighborhood infection risk is also associated with capacity to socially isolate, as measured by NYC subway data. Finally, infection risk is associated with COVID-19-related mortality. These analyses support that differences in capacity to socially isolate is a credible pathway between disadvantage and COVID-19 disparities.

negative: Disease and age-related inequalities in paediatric research, funding and communication: lessons from the COVID-19 pandemic COVID-19 has already caused millions of infections, thousands of deaths and countless indirect and poorly estimated consequences on other diseases and the global economy. All ages are potentially susceptible, but the virus has had a lower direct impact on children, with fewer severe cases and low mortality rates. However, the reasons for this are still unclear and we cannot rule out children's role in transmitting the disease. The serious impact that restrictive measures have had on children's lives have not been fully considered. Because children are less affected by COVID-19, the scientific community, health agencies and governments have not focused much attention on them during this pandemic.

negative: Long-term outcomes after pediatric splenectomy. BACKGROUND Splenectomy is performed frequently for various and primarily hematologic indications in children and adolescents. We analyzed the long-term outcome after splenectomy (median, 8.7 years) focusing on sepsis, portal vein thrombosis (PVT), and retained accessory spleen. METHODS In total, 141 consecutive children after open (n = 89; 63%) or laparoscopic (n = 52; 37%) splenectomy from 1991 to 2010 were followed up through nationwide registries for septic infections, PVT, and causes of death. Sixty-six patients (58% of survivors) answered a structured questionnaire on infections, abdominal symptoms, and general health, and 64 (laparoscopic n = 26, open n = 38) consented to ultrasonography of the portal venous system. RESULTS Median operation age was 8.8 years (range, 1.0-22). Reoperations were required for bleeding after open procedures (n = 1) and retained accessory spleen after laparoscopic procedures (n = 3). Postsplenectomy sepsis occurred after a median of 1.7 years (range, 0.2-5.9) in 11 patients (8%), of whom 10 had an underlying immunodeficiency. No cases of PVT were observed, although the median portal vein flow was 1,130 mL/min (range, 440-2200) and diameter was 9.9 mm (range, 7-15) at a median follow-up of 9.5 years (range, 2.0-22) after splenectomy. Twenty-seven patients (19%) died after 8.7 years (0.03-23.00). The most common cause of death was the underlying malignancy (n = 15), with sepsis being an additional cause of death in 5 patients. CONCLUSION Postsplenectomy sepsis was associated almost exclusively with an underlying immunodeficiency with a high mortality rate. No PVT was observed. The overall risk of retained accessory spleen was around 7%, and was slightly greater after laparoscopic operation.

negative: COVID-19: What to do if you're worried about a child Social distancing has become the new normal for many of us in our efforts to slow the spread of COVID-19 (Coronavirus) and protect our national healthcare service during the global crisis Adjusting to such an unfamiliar routine and, for many, being isolated from colleagues, friends and family at a time like this can be overwhelming, especially when it comes to essential matters such as safeguarding However, it's important to remember that you are not alone, and if you do find yourself worried about a child or vulnerable adult, there are steps you can take to reach out and safely share your concerns

negative: The Role of Chest Imaging in Patient Management during the COVID-19 Pandemic: A Multinational Consensus Statement from the Fleischner Society With more than 900,000 confirmed cases worldwide and nearly 50,000 deaths during the first three months of 2020, the COVID-19 pandemic has emerged as an unprecedented healthcare crisis. The spread of COVID-19 has been heterogeneous, resulting in some regions having sporadic transmission and relatively few hospitalized patients with COVID-19 and others having community transmission that has led to overwhelming numbers of severe cases. For these regions, healthcare delivery has been disrupted and compromised by critical resource constraints in diagnostic testing, hospital beds, ventilators, and healthcare workers who have fallen ill to the virus exacerbated by shortages of personal protective equipment. While mild cases mimic common upper respiratory viral infections, respiratory dysfunction becomes the principal source of morbidity and mortality as the disease advances. Thoracic imaging with chest radiography (CXR) and computed tomography (CT) are key tools for pulmonary disease diagnosis and management, but their role in the management of COVID-19 has not been considered within the multivariable context of the severity of respiratory disease, pre-test probability, risk factors for disease progression, and critical resource constraints. To address this deficit, a multidisciplinary panel comprised principally of radiologists and pulmonologists from 10 countries with experience managing COVID-19 patients across a spectrum of healthcare environments evaluated the utility of imaging within three scenarios representing varying risk factors, community conditions, and resource constraints. Fourteen key questions, corresponding to 11 decision points within the three scenarios and three additional clinical situations, were rated by the panel based upon the anticipated value of the information that thoracic imaging would be expected to provide. The results were aggregated, resulting in five main and three additional recommendations intended to guide medical practitioners in the use of CXR and CT in the management of COVID-19.

negative: The experience on COVID-19 and cancer from an oncology hub institution in Milan, Lombardy Region Abstract The rapid outbreak of the SARS-CoV-2 related disease (COVID-19) has spread rapidly to a pandemic proportion, increasing the demands on health systems for the containment and management of COVID-19. Cancer has been reported as a major risk factor for adverse outcomes of and death from COVID-19. We extracted data from the World Health Organization’s progress reports and from the Italian Council of Medicine. In addition, we retrieved clinical data on cancer patients with confirmed COVID-19 in our Institution. As of April 2nd, 2020, 110 574 COVID-19 cases and 13 157 deaths have been described in Italy, representing a global share of 5.1% and 28.9% for incidence and mortality, respectively. In Italy, we report the analysis of the Italian Medical Council on 909 patients who died from COVID-19, of whom 16.5% were cancer patients. The population was enriched with subjects with multiple co-morbid non-communicable diseases, with less than 1% of the population presenting no co-morbid conditions. At the patient level, we identified nine patients referred to our department in the last two months who were receiving standard of care or experimental medications in the curative and palliative settings. The median age was 68 years (range: 42–79 years), and patients carried a median of one co-morbid condition (0–2); two out of nine patients presented with severe COVID-19 presentation, and were receiving inpatient care. None of the patients receiving immunotherapy experienced severe adverse outcomes, and four patients were discharged with complete reversal of the clinical syndrome and SARS-CoV-2 clearance. Learning from the experience of countries with a high burden, efforts must be made to assure the access of cancer patients to treatments, prioritizing the cancer health interventions based on their intrinsic value, and limiting the exposure to an unacceptable risk of infection for both health providers and patients. Any significant work in the design and implementation of health system actions, including in clinical care, must be framed as an initiative under the Global Response Agenda and through a community approach, with the intention of pursuing common goals to tackle COVID-19 and cancer, as ‘One Community’ working for ‘One Health’s.

negative: [The impact of Covid-19 pandemic on breastfeeding and birth care. The importance of recovering good practices.] The SARS-CoV-2 pandemic has had a major impact on birth care and lactation The lack of knowledge regarding the transmission mechanisms and the potential risks for the mother and the newborn, even when the vertical transmission of the virus has not been demonstrated, has led to the abandonment of practices such as skin-to-skin and the early initiation of breastfeeding (BF), which offer great benefits for maternal and child health Taking into account the available scientific evidence and the protective effect of BF, the World Health Organization (WHO), and other organisms recommend, in cases of suspected or confirmed SARS-CoV-2 infection of the mother, maintaining mother-child contact and BF, adopting preventive measure procedures to minimize the risk of contagion These measures include hand hygiene, before and after contact with the newborn and the use of a mask If a temporary separation of mother and child is required, it is recommended to feed the newborn with expressed breast milk The presence of IgA antibodies against SARS-CoV-2 has been confirmed in the milk of infected women, so BF could reduce the clinical impact of the disease in the infant, if it becomes infected

negative: Challenges and burden of the Coronavirus 2019 (COVID-19) pandemic for child and adolescent mental health: a narrative review to highlight clinical and research needs in the acute phase and the long return to normality BACKGROUND: The coronavirus disease 2019 (COVID-19) is profoundly affecting life around the globe. Isolation, contact restrictions and economic shutdown impose a complete change to the psychosocial environment in affected countries. These measures have the potential to threaten the mental health of children and adolescents significantly. Even though the current crisis can bring with it opportunities for personal growth and family cohesion, disadvantages may outweigh these benefits. Anxiety, lack of peer contact and reduced opportunities for stress regulation are main concerns. Another main threat is an increased risk for parental mental illness, domestic violence and child maltreatment. Especially for children and adolescents with special needs or disadvantages, such as disabilities, trauma experiences, already existing mental health problems, migrant background and low socioeconomic status, this may be a particularly challenging time. To maintain regular and emergency child and adolescent psychiatric treatment during the pandemic is a major challenge but is necessary for limiting long-term consequences for the mental health of children and adolescents. Urgent research questions comprise understanding the mental health effects of social distancing and economic pressure, identifying risk and resilience factors, and preventing long-term consequences, including—but not restricted to—child maltreatment. The efficacy of telepsychiatry is another highly relevant issue is to evaluate the efficacy of telehealth and perfect its applications to child and adolescent psychiatry. CONCLUSION: There are numerous mental health threats associated with the current pandemic and subsequent restrictions. Child and adolescent psychiatrists must ensure continuity of care during all phases of the pandemic. COVID-19-associated mental health risks will disproportionately hit children and adolescents who are already disadvantaged and marginalized. Research is needed to assess the implications of policies enacted to contain the pandemic on mental health of children and adolescents, and to estimate the risk/benefit ratio of measures such as home schooling, in order to be better prepared for future developments.

negative: COVID-19 Preparedness in a Neonatal Unit at a Tertiary Hospital in Johannesburg, South Africa Background: The novel coronavirus disease 2019 (COVID-19) pandemic has spread to South Africa and poses an infection risk in pregnant women and their newborns, as well as health-care workers and other patients. Objective: To discuss the implementation of international and local recommendations, and any additional actions undertaken at our Neonatal Unit in order to prepare for COVID-19. Discussion: Standard precautions in order to prepare a facility and its personnel to safely care for COVID-19 patients as outlined by the World Health Organization procedures have been implemented. Further actions undertaken in our Neonatal Unit included the creation of standard operating procedures, increased communication between neonatal and obstetric teams, limiting staff exposure, the creation of disposable resuscitation boxes to attend deliveries, reallocation of a triage area in the high care ward to an isolation area for sick newborns of suspected or confirmed maternal COVID-19 cases, staff training on personal protective equipment procedures and initiation of an online resources portal for neonatal staff. Conclusion: A rational approach to suspected cases and infection control in-line with local and international guidelines as well as ongoing education should diminish anxiety amongst health-care professionals and provide the best possible care to patients. South Africa is a low-to-middle income country, and the lack of resources available means we cannot increase our capacity, staffing numbers or available equipment. Yet, we must be as prepared, adaptable and efficient as possible to maximize the resources and equipment we have available to us.

negative: The impact of influenza infection on young children, their family and the health care system BACKGROUND: Influenza is a major cause of respiratory illness in young children. Assessing the impact of infection on children and the community is required to guide immunisation policies. OBJECTIVES: To describe the impact of laboratory‐proven influenza in young children and to compare its impact with that of other respiratory viruses on the child, their family and the health care system. METHODS: Preschool children presenting for care or admission to a tertiary paediatric hospital during the 2008‐2014 influenza seasons were tested for respiratory virus by polymerase chain reaction and culture. Parental surveys were used to determine the impact of infection on illness duration, medication use, absenteeism and health service utilisation. Multivariate regression analyses were used to assess the impact of influenza and to evaluate the association between influenza status and outcomes. RESULTS: Among 1191 children assessed, 238 had influenza. Among children with influenza, 87.8% were administered antipyretics and 40.9% antibiotics. 28.6% had secondary complications. 65.4% of children missed school/day care, and 53.4% of parents missed work. When influenza and other viruses were compared, significant differences were noted including duration of illness (influenza: 9.54 days, other viruses: 8.50 days; P = 0.005) and duration of absenteeism for both the child (23.1 vs 17.3 hours; P = 0.015) and their parents (28.5 vs 22.7 hours; P = 0.012). CONCLUSIONS: Influenza infection in young children has a significant impact on medication use, absenteeism and the use of health care service. Significant differences are identified when compared with other ILI. These data demonstrate that influenza prevention strategies including immunisation are likely to have wide and significant impacts.

negative: Mental Health Status of the General Population during the COVID-19 Pandemic: A Cross-sectional National Survey in Japan The ongoing COVID-19 pandemic may have detrimental mental health consequences. However, as yet, there is limited understanding of its impact on the mental health of the general population. The aim of this study is to examine the mental health of the Japanese general population by conducting the first systematic survey during the pandemic (N=1,000), with a particular focus on identifying the most vulnerable groups. Results from logistic regression analyses showed that the mental health of young and middle-aged individuals was significantly worse than that of older individuals during the pandemic. There was also some indication that individuals who were not currently working were significantly more likely to report a high level of anxiety and depressive symptoms. Part-time and temporary contract-based workers were also more likely to suffer from anxiety disorder. Our results highlight that monitoring the mental health of younger and economically vulnerable individuals may be especially important. In addition, they also indicate that population mental health might not only be affected by the direct health consequences of COVID-19, but also by the economic ramifications of the pandemic.

negative: COVID-19 and myocarditis: What do we know so far? COVID-19 has been declared a global pandemic by the World Health Organization and is responsible for hundreds of thousands of deaths worldwide. COVID-19 is caused by SARS-CoV-2, and common clinical symptoms include fever, cough, sore throat, headache, and fatigue. Myocardial injury is relatively common in COVID-19, accounting for 7-23% of cases, and is associated with a higher morbidity and mortality. There is a discrepancy in the literature about myocarditis as the etiology of myocardial injury in COVID-19; although many anecdotal reports of myocarditis have been noted, there are only a handful of case reports in the literature about myocarditis related to COVID-19. This review summarizes the most up-to-date literature around the association between COVID-19 and myocarditis and gives clinicians a practical framework about the clinical manifestations, diagnostic tools and treatment options currently available. Importantly, this review will heighten suspicion for myocarditis as an etiology of myocardial injury in COVID-19 patients, therefore improving clinical outcomes and encouraging shared clinical decision-making. This will also open the door for further research to build around this review. Emergent treatment options for COVID-19 are in clinical trials and may be of benefit to COVID-19 patients with myocarditis in addition to current guideline-based recommendations.

negative: Poor Outcome of Acute Respiratory Infection in Young Children with Underlying Health Condition in Brazil Summary Objectives It is well established that respiratory viruses are an important cause of hospitalizations in young children worldwide, but data are limited on the contribution of specific viruses to severe illness in South America. We describe clinical and laboratory findings from prospective surveillance for acute respiratory infections at a tertiary hospital in São Paulo, Brazil. Methods We screened children < 2 years old with acute respiratory tract infections admitted to an urban tertiary hospital for respiratory viruses from March 2008 through February 2010, using polymerase chain reaction assays. Results Respiratory viruses were identified in 378 (53%) of the 715 samples analyzed. Respiratory syncytial virus was the most commonly identified virus (52%), followed by adenovirus (27%) and Human metapneumovirus (12%). More than one virus was identified in 19% of specimens. Almost half of the samples (46%) were from children with underlying health conditions. We demonstrated that compared to the previously healthy group, those with comorbidities had a worse outcome in terms of severity, with prolonged hospital stay and more need of intensive care. Conclusion Identification of this high-risk population along with strategies for fast diagnosis might each help to reduce morbidity and mortality in this group.

negative: The diagnostic value of detecting sudden smell loss among asymptomatic COVID-19 patients in early stage: The possible early sign of COVID-19 IMPORTANCE: The newly emerged coronavirus disease 19 (COVID-19), is threatening the world. Olfactory or gustatory dysfunction is reported as one of the symptoms worldwide. As reported so far, different clinical features have been reported according to outbreak sites and gender; most of the patients, who complained of anosmia or hyposmia, were Europeans. We had a fast review for novel articles about COVID-19 infection and olfactory function. OBSERVATIONS: Rapid reviews for COVID-19 or other viral infection and olfactory and/or gustatory dysfunctions were done in this review. Up to date, a lot of reports have shown that olfactory dysfunction is related to viral infections but no exact mechanism, clinical course, and definite treatment have been discovered, which is also same in COVID-19. In general, intranasal steroid (INS) and oral steroid for short time help improve the recovery of the olfactory function in case of olfactory dysfunction after virus infection. Considering severe respiratory complications and immunocompromised state of COVID-19, the use of steroid should be limited and cautious because we do not have enough data to support the usage of steroid to treat olfactory dysfunction in the clinical course of COVID-19. CONCLUSIONS AND RELEVANCE: In the days of pandemic COVID-19, we should keep in mind that olfactory dysfunctions, even without other upper respiratory infection or otolaryngologic symptoms, might be the early signs of COVID-19.

negative: COVID-19 in persons with haematological cancers Infection with SARS-CoV-2, the cause of coronavirus infectious disease–19 (COVID-19), has caused a pandemic with >850,000 cases worldwide and increasing. Several studies report outcomes of COVID-19 in predominately well persons. There are also some data on COVID-19 in persons with predominately solid cancer but controversy whether these persons have the same outcomes. We conducted a cohort study at two centres in Wuhan, China, of 128 hospitalised subjects with haematological cancers, 13 (10%) of whom developed COVID-19. We also studied 226 health care providers, 16 of whom developed COVID-19 and 11 of whom were hospitalised. Co-variates were compared with the 115 subjects with haematological cancers without COVID-19 and with 11 hospitalised health care providers with COVID-19. There were no significant differences in baseline co-variates between subjects with haematological cancers developing or not developing COVID-19. Case rates for COVID-19 in hospitalised subjects with haematological cancers was 10% (95% Confidence Interval [CI], 6, 17%) compared with 7% (4, 12%; P = 0.322) in health care providers. However, the 13 subjects with haematological cancers had more severe COVID-19 and more deaths compared with hospitalised health care providers with COVID-19. Case fatality rates were 62% (32, 85%) and 0 (0, 32%; P = 0.002). Hospitalised persons with haematological cancers have a similar case rate of COVID-19 compared with normal health care providers but have more severe disease and a higher case fatality rate. Because we were unable to identify specific risk factors for COVID-19 in hospitalised persons with haematological cancers, we suggest increased surveillance and possible protective isolation.

negative: COVID-19 Related School Closings and Risk of Weight Gain Among Children. The COVID-19 pandemic is causing substantial morbidity and mortality, straining health care systems, shutting down economies, and closing school districts. While it is a priority to mitigate its immediate impact, we want to call attention to the pandemic's longer-term effect on children's health: COVID-19, via these school closures, may exacerbate the epidemic of childhood obesity and increase disparities in obesity risk. In many areas of the U.S., the COVID-19 pandemic has closed schools and some of these school systems are not expected to re-open this school year. The experiences in Hong Kong, Taiwan and Singapore suggest that social distancing orders, if lifted after short periods, will have to be periodically re-instated to control COVID-19 flare ups. In short, we anticipate that the COVID-19 pandemic will likely double out-of-school time this year for many children in the U.S. and will exacerbate the risk factors for weight gain associated with summer recess.

negative: BCG VACCINES MAY NOT REDUCE COVID-19 MORTALITY RATES The reason for the observed country-wise variability in incidence and severity of the COVID-19 outcome remains unknown. Few recent studies have suggested a positive protective correlation of the BCG vaccination policy of the countries with the observed COVID-19 severity. The current study was undertaken to reassess the existing data as of 4th April 2020. The incidence rates (cases per million population), Case Fatality Rates (CFR) and inherently more robust Infection Fatality Rates (IFR) were calculated across countries accounting for about 99% COVID-19 deaths. The initial scrutiny suggested a weaker association with BCG vaccination policy or BCG coverage, so positivity to the Tuberculin Sensitivity Test (TST)/ Interferon Gamma Release Assay (IGRA) as a measure of the potential protective effect of the resident populations exposure to Mycobacterium spp. whether from BCG vaccination or as a result of exposure to environmental mycobacteria was analyzed. The incidence rates (the number of cases per million population) decreased with an increase in % LTBI (TST/IGRA positivity) for the analyzed countries with R2 =0.6343, suggesting an exponentially negative covariation. However, the covariation of CFR estimates that ranged from 0.29% to 12.25 % (average 5.39%) among countries, was tenuous. Interim estimates of IFR (i-IFR), a more dependable measure for such studies, for the best and worst-case scenarios, i.e., i-IFR-l and i-IFR-h, predict on an average 20.57% to 30.15 % COVID-19 fatality rates globally, but individual country estimates display huge variation. Among countries accounting for 92.14% deaths (11 countries; top 20% countries included in current study) the estimate for lowest IFRs (i-IFR-l=4.16 (China) & i-IFR-h=4.61 (China)) and highest IFRs (i-IFR-l=96.39% (UK); & i-IFR-h=96.54% (UK)) displayed huge difference (average for the group: CFR=6.8 ± 3.6%; i-IFR-l=34.97 ± 30.55%; & i-IFR-h=44.20 ± 29.08%). Currently, the worst affected countries Italy (CFR=12.25%; i-IFR-l=42.63%; i-IFR-h=48.69%) and Spain (CFR=9.39%; i-IFR-l=26.85%; i-IFR-h=36.60%) would seemingly cope with COVID-19 better than UK, Netherlands and USA while the countries Germany (CFR=1.40%; i-IFR-l=4.93%; i-IFR-h=17.49%) and Switzerland (CFR=3.01%; i-IFR-l=10.87%; i-IFR-h=16.23%) along with China could fare the best. The rest of the 80% countries (accounting for 6.74% deaths), seemed to have reduced mortality (CFR=2.45 ± 2.01; i-IFR-l= 30.62 ± 28.24%; i-IFR-h=40.99 ± 30.47%) with associated high % LTBI (17.28 ± 8.87) than top 20% countries. The inherent issues in the data set (e.g., heterogeneity, non-random sampling, different criteria of sampling and reporting, access to health care, genetic composition, underlying co-morbidities, etc) need to be taken into account for making informed decisions.

negative: Rapid Systematic Review: The Impact of Social Isolation and Loneliness on the Mental Health of Children and Adolescents in the Context of COVID-19 OBJECTIVE: Disease containment of COVID-19 has necessitated widespread social isolation. We aimed to establish what is known about how loneliness and disease containment measures impact on the mental health in children and adolescents. METHOD: For this rapid review, we searched MEDLINE, PSYCHINFO, and Web of Science for articles published between 01/01/1946 and 03/29/2020. 20% of articles were double screened using pre-defined criteria and 20% of data was double extracted for quality assurance. RESULTS: 83 articles (80 studies) met inclusion criteria. Of these, 63 studies reported on the impact of social isolation and loneliness on the mental health of previously healthy children and adolescents (n=51,576; mean age 15.3) 61 studies were observational; 18 were longitudinal and 43 cross sectional studies assessing self-reported loneliness in healthy children and adolescents. One of these studies was a retrospective investigation after a pandemic. Two studies evaluated interventions. Studies had a high risk of bias although longitudinal studies were of better methodological quality. Social isolation and loneliness increased the risk of depression, and possibly anxiety at the time loneliness was measured and between 0.25 to 9 years later. Duration of loneliness was more strongly correlated with mental health symptoms than intensity of loneliness. CONCLUSION: Children and adolescents are probably more likely to experience high rates of depression and probably anxiety during and after enforced isolation ends. This may increase as enforced isolation continues. Clinical services should offer preventative support and early intervention where possible and be prepared for an increase in mental health problems.

negative: Impact of school closures for COVID-19 on the US health-care workforce and net mortality: a modelling study BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is leading to social (physical) distancing policies worldwide, including in the USA. Some of the first actions taken by governments are the closing of schools. The evidence that mandatory school closures reduce the number of cases and, ultimately, mortality comes from experience with influenza or from models that do not include the effect of school closure on the health-care labour force. The potential benefits from school closures need to be weighed against costs of health-care worker absenteeism associated with additional child-care obligations. In this study, we aimed to measure child-care obligations for US health-care workers arising from school closures when these are used as a social distancing measure. We then assessed how important the contribution of health-care workers would have to be in reducing mortality for their absenteeism due to child-care obligations to undo the benefits of school closures in reducing the number of cases. METHODS: For this modelling analysis, we used data from the monthly releases of the US Current Population Survey to characterise the family structure and probable within-household child-care options of US health-care workers. We accounted for the occupation within the health-care sector, state, and household structure to identify the segments of the health-care workforce that are most exposed to child-care obligations from school closures. We used these estimates to identify the critical level at which the importance of health-care labour supply in increasing the survival probability of a patient with COVID-19 would undo the benefits of school closures and ultimately increase cumulative mortality. FINDINGS: Between January, 2018, and January, 2020, the US Current Population Survey included information on more than 3·1 million individuals across 1·3 million households. We found that the US health-care sector has some of the highest child-care obligations in the USA, with 28·8% (95% CI 28·5-29·1) of the health-care workforce needing to provide care for children aged 3-12 years. Assuming non-working adults or a sibling aged 13 years or older can provide child care, 15·0% (14·8-15·2) of the health-care workforce would still be in need of child care during a school closure. We observed substantial variation within the health-care system. We estimated that, combined with reasonable parameters for COVID-19 such as a 15·0% case reduction from school closings and 2·0% baseline mortality rate, a 15·0% decrease in the health-care labour force would need to decrease the survival probability per percent health-care worker lost by 17·6% for a school closure to increase cumulative mortality. Our model estimates that if the infection mortality rate of COVID-19 increases from 2·00% to 2·35% when the health-care workforce declines by 15·0%, school closures could lead to a greater number of deaths than they prevent. INTERPRETATION: School closures come with many trade-offs, and can create unintended child-care obligations. Our results suggest that the potential contagion prevention from school closures needs to be carefully weighted with the potential loss of health-care workers from the standpoint of reducing cumulative mortality due to COVID-19, in the absence of mitigating measures. FUNDING: None.

negative: The impact of school reopening on the spread of COVID-19 in England Background: In the UK, cases of COVID-19 have been declining since mid-April and there is good evidence to suggest that the effective reproduction number has dropped below 1, leading to a multi-phase relaxation plan for the country to emerge from lockdown. As part of this staggered process, primary schools are scheduled to partially reopen on 1st June. Evidence from a range of sources suggests that children are, in general, only mildly affected by the disease and have low mortality rates, though there is less certainty regarding children's role in transmission. Therefore, there is wide discussion on the impact of reopening schools. Methods: We compare eight strategies for reopening primary and secondary schools in England from 1st June, focusing on the return of particular year groups and the associated epidemic consequences. This is assessed through model simulation, modifying a previously developed dynamic transmission model for SARS-CoV-2. We quantify how the process of reopening schools affected contact patterns and anticipated secondary infections, the relative change in R according to the extent of school reopening, and determine the public health impact via estimated change in clinical cases and its sensitivity to decreases in adherence post strict lockdown. Findings: Whilst reopening schools, in any form, results in more mixing between children, an increase in R and hence transmission of the disease, the magnitude of that increase can be low dependent upon the age-groups that return to school and the behaviour of the remaining population. We predict that reopening schools in a way that allows half class sizes or that is focused on younger children is unlikely to push R above one, although there is noticeable variation between the regions of the country. Given that older children have a greater number of social contacts and hence a greater potential for transmission, our findings suggest reopening secondary schools results in larger increases in case burden than only reopening primary schools; reopening both generates the largest increase and could push R above one in some regions. The impact of less social-distancing in the rest of the population, generally has far larger effects than reopening schools and exacerbates the impacts of reopening. Discussion: Our work indicates that any reopening of schools will result in increased mixing and infection amongst children and the wider population, although the opening of schools alone is unlikely to push the value of R above one. However, impacts of other recent relaxations of lockdown measures are yet to be quantified, suggesting some regions may be closer to the critical threshold that would lead to a growth in cases. Given the uncertainties, in part due to limited data on COVID-19 in children, school reopening should be carefully monitored. Ultimately, the decision about reopening classrooms is a difficult trade-off between increased epidemiological consequences and the emotional, educational and developmental needs of children.

negative: Cardiovascular Complications in Patients with COVID-19: Consequences of Viral Toxicities and Host Immune Response PURPOSE OF REVIEW: Coronavirus disease of 2019 (COVID-19) is a cause of significant morbidity and mortality worldwide. While cardiac injury has been demonstrated in critically ill COVID-19 patients, the mechanism of injury remains unclear. Here, we review our current knowledge of the biology of SARS-CoV-2 and the potential mechanisms of myocardial injury due to viral toxicities and host immune responses. RECENT FINDINGS: A number of studies have reported an epidemiological association between history of cardiac disease and worsened outcome during COVID infection. Development of new onset myocardial injury during COVID-19 also increases mortality. While limited data exist, potential mechanisms of cardiac injury include direct viral entry through the angiotensin-converting enzyme 2 (ACE2) receptor and toxicity in host cells, hypoxia-related myocyte injury, and immune-mediated cytokine release syndrome. Potential treatments for reducing viral infection and excessive immune responses are also discussed. SUMMARY: COVID patients with cardiac disease history or acquire new cardiac injury are at an increased risk for in-hospital morbidity and mortality. More studies are needed to address the mechanism of cardiotoxicity and the treatments that can minimize permanent damage to the cardiovascular system.

negative: Pre-existing liver disease is associated with poor outcome in patients with SARS CoV2 infection; The APCOLIS Study (APASL COVID-19 Liver Injury Spectrum Study) BACKGROUND AND AIMS: COVID-19 is a dominant pulmonary disease, with multisystem involvement, depending upon comorbidities. Its profile in patients with pre-existing chronic liver disease (CLD) is largely unknown. We studied the liver injury patterns of SARS-Cov-2 in CLD patients, with or without cirrhosis. METHODS: Data was collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19. RESULTS: Altogether, 228 patients [185 CLD without cirrhosis and 43 with cirrhosis] were enrolled, with comorbidities in nearly 80%. Metabolism associated fatty liver disease (113, 61%) and viral etiology (26, 60%) were common. In CLD without cirrhosis, diabetes [57.7% vs 39.7%, OR = 2.1 (1.1–3.7), p = 0.01] and in cirrhotics, obesity, [64.3% vs. 17.2%, OR = 8.1 (1.9–38.8), p = 0.002] predisposed more to liver injury than those without these. Forty three percent of CLD without cirrhosis presented as acute liver injury and 20% cirrhotics presented with either acute-on-chronic liver failure [5 (11.6%)] or acute decompensation [4 (9%)]. Liver related complications increased (p < 0.05) with stage of liver disease; a Child-Turcotte Pugh score of 9 or more at presentation predicted high mortality [AUROC 0.94, HR = 19.2 (95 CI 2.3–163.3), p < 0.001, sensitivity 85.7% and specificity 94.4%). In decompensated cirrhotics, the liver injury was progressive in 57% patients, with 43% mortality. Rising bilirubin and AST/ALT ratio predicted mortality among cirrhosis patients. CONCLUSIONS: SARS-Cov-2 infection causes significant liver injury in CLD patients, decompensating one fifth of cirrhosis, and worsening the clinical status of the already decompensated. The CLD patients with diabetes and obesity are more vulnerable and should be closely monitored. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12072-020-10072-8) contains supplementary material, which is available to authorized users.

negative: Provision of Pediatric Immunization Services During the COVID-19 Pandemic: an Assessment of Capacity Among Pediatric Immunization Providers Participating in the Vaccines for Children Program - United States, May 2020 Recent reports suggest that routine childhood immunization coverage might have decreased during the coronavirus disease 2019 (COVID-19) pandemic (1,2). To assess the capacity of pediatric health care practices to provide immunization services to children during the pandemic, a survey of practices participating in the Vaccines for Children (VFC) program was conducted during May 12-20, 2020. Data were weighted to account for the sampling design; thus, all percentages reported are weighted. Among 1,933 responding practices, 1,727 (89.8%) were currently open; 1,397 (81.1%) of these reported offering immunization services to all of their patients. When asked whether the practice would likely be able to accommodate new patients to assist with provision of immunization services through August, 1,135 (59.1%) respondents answered affirmatively. These results suggest that health care providers appear to have the capacity to deliver routinely recommended childhood vaccines, allowing children to catch up on vaccines that might have been delayed as a result of COVID-19-related effects on the provision of or demand for routine well child care. Health care providers and immunization programs should educate parents on the need to return for well-child and immunization visits or refer patients to other practices, if they are unable to provide services (3).

negative: ENT manifestation in COVID-19 patients OBJECTIVE: to detect, analyze and discuss the different ear nose throat (ENT) manifestations those were reported in COVID19 positive patients in the reviewed and published literatures. METHODS: We performed a search in the PubMed databases, Web of Science, LILACS, MEDLINE, SciELO, and Cochrane Library using the keywords; COVID-19, Novel coronavirus, corona, 2019-nCoV, SARS-CoV-2, ENT, ear, nose, throat, otorhinolaryngology, ORL, pharynx, ORL, smell, larynx, different ENT related symptoms. We reviewed published and peer reviewed studies that reported the ENT manifestations in COVID-19 laboratory-confirmed positive patients. RESULTS: within the included 1773 COVID-19 laboratory-confirmed positive patients, the most common ENT manifestations of COVID-19 were sore throat (11.3%) and headache (10.7%). While the other reported ENT manifestations were pharyngeal erythema (5.3%), nasal congestion (4.1%), runny nose or rhinorrhea (2.1%), upper respiratory tract infection (URTI) (1.9%), and tonsil enlargement (1.3%). CONCLUSION: ENT manifestations for COVID-19 are not common as fever and cough. But, a universal questionnaire using well-defined COVID-19 manifestations is needed to make the COVID-19 data precisely defined, complete and homogenous.

negative: Recommendations on management of gynecological malignancies during the COVID-19 pandemic: perspectives from Chinese gynecological oncologists The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 has rapidly spread globally. Cancer patients are at a higher risk of being infected with the coronavirus and are more likely to develop severe complications, as compared to the general population. The increasing spread of COVID-19 presents challenges for the clinical care of patients with gynecological malignancies. Concerted efforts should be put into managing gynecological malignancies in an orderly manner by strictly implementing the measures that are specifically developed for controlling the spread of COVID-19. We have drafted Recommendations on Management of Gynecological Malignancies during the COVID-19 Pandemic based on our experience on controlling COVID-19 pandemic in China. We recommend that patients with gynecological malignancies should be managed in hierarchical and individualized manners in combination with local conditions related to COVID-19. Medical care decision should be balanced between controlling COVID-19 pandemic spread and timely diagnosis and treatment for gynecologic oncology patients.

negative: Hydroxychloroquine-azithromycin for COVID-19 – Warranted or dangerous?

negative: The non-specific and sex-differential effects of vaccines The textbook view of vaccination is that it functions to induce immune memory of the specific pathogen components of the vaccine, leading to a quantitatively and qualitatively better response if the host is exposed to infection with the same pathogen. However, evidence accumulated over the past few decades increasingly suggests that vaccines can also have non-specific effects on unrelated infections and diseases, with important implications for childhood mortality particularly in low-income settings. Furthermore, many of these non-specific effects, as well as the pathogen-specific effects, of vaccines show differences between the sexes. Here, members of the Optimmunize consortium discuss the evidence for and potential mechanisms of non-specific and sex-differential effects of vaccines, as well as their potential policy implications. Given that the non-specific effects of some vaccines are now being tested for their ability to protect against COVID-19, the authors also comment on the broader implications of these trials.

negative: Pediatric Modification of the Medically Necessary, Time-Sensitive Scoring System for Operating Room Procedure Prioritization During the COVID-19 Pandemic BACKGROUND: The COVID-19 pandemic forced surgeons to reconsider concepts of “elective” surgery. Perceptions regarding the time-sensitivity and medical necessity of a procedure have taken on greater significance during the pandemic. The evolving ethical and clinical environment requires reappraisal of perioperative factors such as personal protective equipment conservation; limiting the risk of exposure to COVID-19 for patients, families, and health care workers; preservation of hospital beds and intensive care unit resources; and minimizing COVID-19 related perioperative risk to patients. STUDY DESIGN: A scaffold for the complex decision-making required for prioritization of Medically Necessary, Time Sensitive (MeNTS) surgeries was developed for adult patients by colleagues at The University of Chicago(i). Although adult MeNTS scoring can be applied across adult surgical specialties, some variables were irrelevant in a pediatric population. Pediatric manifestations of chronic diseases and congenital anomalies were not accounted for. In order to account for the unique challenges children face, we modified the adult MeNTS system for use across pediatric subspecialties. RESULTS: This Pediatric MeNTS (pMeNTS) scoring system was applied to 101 cases both performed and deferred between March 23(rd) and April 19(th), 2020, at The University of Chicago Comer Children’s Hospital. The pMeNTS scores provides a safe, equitable, transparent, and ethical strategy to prioritize children’s surgical procedures. CONCLUSIONS: This process is adaptable to individual institutions, and we project it will be useful during the acute phase of the pandemic (maximal limitations) as well as the anticipated recovery phase.

negative: Neonatal Resuscitation and Postresuscitation Care of Infants Born to Mothers with Suspected or Confirmed SARS-CoV-2 Infection The first case of novel coronavirus disease of 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was reported in November2019. The rapid progression to a global pandemic of COVID-19 has had profound medical, social, and economic consequences. Pregnant women and newborns represent a vulnerable population. However, the precise impact of this novel virus on the fetus and neonate remains uncertain. Appropriate protection of health care workers and newly born infants during and after delivery by a COVID-19 mother is essential. There is some disagreement among expert organizations on an optimal approach based on resource availability, surge volume, and potential risk of transmission. The manuscript outlines the precautions and steps to be taken before, during, and after resuscitation of a newborn born to a COVID-19 mother, including three optional variations of current standards involving shared-decision making with parents for perinatal management, resuscitation of the newborn, disposition, nutrition, and postdischarge care. The availability of resources may also drive the application of these guidelines. More evidence and research are needed to assess the risk of vertical and horizontal transmission of SARS-CoV-2 and its impact on fetal and neonatal outcomes. KEY POINTS: · The risk of vertical transmission is unclear; transmission from family members/providers to neonates is possible.. · Optimal personal-protective-equipment (airborne vs. droplet/contact precautions) for providers is crucial to prevent transmission.. · Parents should be engaged in shared decision-making with options for rooming in, skin-to-skin contact, and breastfeeding..

negative: COVID-19 and Individual Genetic Susceptibility/Receptivity: Role of ACE1/ACE2 Genes, Immunity, Inflammation and Coagulation. Might the Double X-chromosome in Females Be Protective against SARS-CoV-2 Compared to the Single X-Chromosome in Males? In December 2019, a novel severe acute respiratory syndrome (SARS) from a new coronavirus (SARS-CoV-2) was recognized in the city of Wuhan, China. Rapidly, it became an epidemic in China and has now spread throughout the world reaching pandemic proportions. High mortality rates characterize SARS-CoV-2 disease (COVID-19), which mainly affects the elderly, causing unrestrained cytokines-storm and subsequent pulmonary shutdown, also suspected micro thromboembolism events. At the present time, no specific and dedicated treatments, nor approved vaccines, are available, though very promising data come from the use of anti-inflammatory, anti-malaria, and anti-coagulant drugs. In addition, it seems that males are more susceptible to SARS-CoV-2 than females, with males 65% more likely to die from the infection than females. Data from the World Health Organization (WHO) and Chinese scientists show that of all cases about 1.7% of women who contract the virus will die compared with 2.8% of men, and data from Hong Kong hospitals state that 32% of male and 15% of female COVID-19 patients required intensive care or died. On the other hand, the long-term fallout of coronavirus may be worse for women than for men due to social and psychosocial reasons. Regardless of sex- or gender-biased data obtained from WHO and those gathered from sometimes controversial scientific journals, some central points should be considered. Firstly, SARS-CoV-2 has a strong interaction with the human ACE2 receptor, which plays an essential role in cell entry together with transmembrane serine protease 2 (TMPRSS2); it is interesting to note that the ACE2 gene lays on the X-chromosome, thus allowing females to be potentially heterozygous and differently assorted compared to men who are definitely hemizygous. Secondly, the higher ACE2 expression rate in females, though controversial, might ascribe them the worst prognosis, in contrast with worldwide epidemiological data. Finally, several genes involved in inflammation are located on the X-chromosome, which also contains high number of immune-related genes responsible for innate and adaptive immune responses to infection. Other genes, out from the RAS-pathway, might directly or indirectly impact on the ACE1/ACE2 balance by influencing its main actors (e.g., ABO locus, SRY, SOX3, ADAM17). Unexpectedly, the higher levels of ACE2 or ACE1/ACE2 rebalancing might improve the outcome of COVID-19 in both sexes by reducing inflammation, thrombosis, and death. Moreover, X-heterozygous females might also activate a mosaic advantage and show more pronounced sex-related differences resulting in a sex dimorphism, further favoring them in counteracting the progression of the SARS-CoV-2 infection.

negative: Association of chemosensory dysfunction and Covid‐19 in patients presenting with influenza‐like symptoms BACKGROUND: Rapid spread of the SARS‐CoV‐2 virus and concern for viral transmission by ambulatory patients with minimal to no symptoms underline the importance of identifying early or subclinical symptoms of Covid‐19 infection. Two such candidate symptoms include anecdotally reported loss of smell and taste. Understanding the timing and association of smell/taste loss in Covid‐19 may help facilitate screening and early isolation of cases. METHODS: A single‐institution, cross‐sectional study evaluating patient‐reported symptoms with a focus on smell and taste was conducted using an internet‐based platform on adult subjects who underwent testing for Covid‐19. Logistic regression was employed to identify symptoms associated with Covid‐19 positivity. RESULTS: A total of 1480 patients with influenza‐like symptoms underwent Covid‐19 testing between March 3 through 29, 2020. Our study captured 59 of 102 (58%) Covid‐19‐positive patients and 203 of 1378 (15%) Covid‐19‐negative patients. Smell and taste loss were reported in 68% (40/59) and 71% (42/59) of Covid‐19‐positive subjects, respectively, compared to 16% (33/203) and 17% (35/203) of Covid‐19‐negative patients (p<0.001). Smell and taste impairment were independently and strongly associated with Covid‐19‐positivity (anosmia: adjusted odds ratio [aOR] 10.9, 95%CI:5.08‐23.5; ageusia: aOR 10.2 95%CI:4.74‐22.1); whereas, sore throat was associated with Covid‐19‐negativity (aOR 0.23, 95%CI:0.11‐0.50). Of patients who reported Covid‐19‐associated loss of smell, 74% (28/38) reported resolution of anosmia with clinical resolution of illness. CONCLUSIONS: In ambulatory individuals with influenza‐like symptoms, chemosensory dysfunction was strongly associated with Covid‐19 infection and should be considered when screening symptoms. Most will recover chemosensory function within weeks paralleling resolution of other disease‐related symptoms. This article is protected by copyright. All rights reserved

negative: Identifying novel factors associated with COVID-19 transmission and fatality using the machine learning approach The COVID-19 virus has infected millions of people and resulted in hundreds of thousands of deaths worldwide. By using the logistic regression model, we identified novel critical factors associated with COVID19 cases, death, and case fatality rates in 154 countries and in the 50 U.S. states. Among numerous factors associated with COVID-19 risk, we found that the unitary state system was counter-intuitively positively associated with increased COVID-19 cases and deaths. Blood type B was a protective factor for COVID-19 risk, while blood type A was a risk factor. The prevalence of HIV, influenza and pneumonia, and chronic lower respiratory diseases was associated with reduced COVID-19 risk. Obesity and the condition of unimproved water sources were associated with increased COVID-19 risk. Other factors included temperature, humidity, social distancing, smoking, and vitamin D intake. Our comprehensive identification of the factors affecting COVID-19 transmission and fatality may provide new insights into the COVID-19 pandemic and advise effective strategies for preventing and migrating COVID-19 spread.

negative: Health-education to prevent COVID-19 in schoolchildren: a call to action BACKGROUND: There is currently considerable international debate around school closures/openings and the role of children in the transmission of coronavirus disease 2019 (COVID-19). Whilst evidence suggests that children are not impacted by COVID-19 as severely as adults, little is still known about their transmission potential, and with a lot of asymptomatic cases they may be silent transmitters (i.e. infectious without showing clinical signs of disease), albeit at a lower level than adults. In relation to this, it is somewhat concerning that in many countries children are cared for, or are often in close contact with, older individuals such as grandparents ─ the age group most at risk of acquiring serious respiratory complications resulting in death. MAIN TEXT: We emphasise that in the absence of a vaccine or an effective therapeutic drug, preventive measures such as good hygiene practices ─ hand washing, cough etiquette, disinfection of surfaces and social distancing represent the major (in fact only) weapons that we have against COVID-19. Accordingly, we stress that there is a pressing need to develop specific COVID-19 prevention messages for schoolchildren. CONCLUSION: An entertainment education intervention for schoolchildren systematically implemented in schools would be highly effective and fill this need. With such measures in place there would be greater confidence around the opening of schools.

negative: COVID-19 PICU guidelines: for high- and limited-resource settings. Fewer children than adults have been affected by the COVID-19 pandemic, and the clinical manifestations are distinct from those of adults. Some children particularly those with acute or chronic comorbidities are likely to develop critical illness. Recently, a Multisystem Inflammatory Syndrome (MIS-C) has been described in children with these patients often requiring care in the Pediatric ICU. An international collaboration was formed to review the available evidence and develop evidence-based guidelines for the care of critically ill children with SARS-CoV-2 infection. Where the evidence was lacking, those gaps were replaced with consensus-based guidelines. This process has generated 44 recommendations related to pediatric COVID-19 patients presenting with respiratory distress or failure, sepsis or septic shock, cardiopulmonary arrest, MIS-C, or those requiring adjuvant therapies, or ECMO. Evidence to explain the milder disease patterns in children and the potential to use repurposed antiviral drugs, anti-inflammatory or antithrombotic therapies are also described. Brief summaries of pediatric SARS-CoV-2 infection in different regions of the world are included since few registries are capturing these data globally. These guidelines seek to harmonize the standards and strategies for intensive care that critically ill children with COVID-19 receive across the world. IMPACT: At the time of publication, this is the latest evidence for managing critically ill children infected with SARS-CoV-2.Referring to these guidelines can decrease the morbidity and potentially the mortality of children effected by COVID-19 and its sequalae.These guidelines can be adapted to both high- and limited-resource settings.

negative: Why Are Children With Bronchiolitis At Risk Of Urinary Tract Infections? Viral respiratory infections are frequently eliminated from human bodies without any sequelae. Secondary serious bacterial infection (SBI) in children with acute bronchiolitis has been an apprehension expressed by health care providers. Several published studies have shown an association between acute bronchiolitis and secondary bacterial infection, including urinary tract infections (UTI). However, the proposed mechanism by which a virus can induce UTIs is not yet known. The aim of this commentary is to update the current evidence of risk of UTI in children with bronchiolitis. We present several clinical studies related to the topic as well as a brief review of the potential pathophysiology of secondary infections that could present with viral respiratory illness.

negative: Optimal Conditions for the Control Problem Associated to a Biomedical Process This paper considers a mathematical model of infectious disease of SIS type. We will analyze the problem of minimizing the cost of diseases trough medical treatment. Mathematical modeling of this process leads to an optimal control problem with a finite horizon. The necessary conditions for optimality are given. Using the optimality conditions we prove the existence, uniqueness and stability of the steady state for a differential equations system.

negative: A predictive model and scoring system combining clinical and CT characteristics for the diagnosis of COVID-19 OBJECTIVES: To develop a predictive model and scoring system to enhance the diagnostic efficiency for coronavirus disease 2019 (COVID-19). METHODS: From January 19 to February 6, 2020, 88 confirmed COVID-19 patients presenting with pneumonia and 80 non-COVID-19 patients suffering from pneumonia of other origins were retrospectively enrolled. Clinical data and laboratory results were collected. CT features and scores were evaluated at the segmental level according to the lesions’ position, attenuation, and form. Scores were calculated based on the size of the pneumonia lesion, which graded at the range of 1 to 4. Air bronchogram, tree-in-bud sign, crazy-paving pattern, subpleural curvilinear line, bronchiectasis, air space, pleural effusion, and mediastinal and/or hilar lymphadenopathy were also evaluated. RESULTS: Multivariate logistic regression analysis showed that history of exposure (β = 3.095, odds ratio (OR) = 22.088), leukocyte count (β = − 1.495, OR = 0.224), number of segments with peripheral lesions (β = 1.604, OR = 1.604), and crazy-paving pattern (β = 2.836, OR = 2.836) were used for establishing the predictive model to identify COVID-19-positive patients (p < 0.05). In this model, values of area under curve (AUC) in the training and testing groups were 0.910 and 0.914, respectively (p < 0.001). A predicted score for COVID-19 (PSC-19) was calculated based on the predictive model by the following formula: PSC-19 = 2 × history of exposure (0–1 point) − 1 × leukocyte count (0–2 points) + 1 × peripheral lesions (0–1 point) + 2 × crazy-paving pattern (0–1 point), with an optimal cutoff point of 1 (sensitivity, 88.5%; specificity, 91.7%). CONCLUSIONS: Our predictive model and PSC-19 can be applied for identification of COVID-19-positive cases, assisting physicians and radiologists until receiving the results of reverse transcription–polymerase chain reaction (RT-PCR) tests. KEY POINTS: • Prediction of RT-PCR positivity is crucial for fast diagnosis of patients suspected of having coronavirus disease 2019 (COVID-19). • Typical CT manifestations are advantageous for diagnosing COVID-19 and differentiation of COVID-19 from other types of pneumonia. • A predictive model and scoring system combining both clinical and CT features were herein developed to enable high diagnostic efficiency for COVID-19.

negative: Health impacts of parental migration on left-behind children and adolescents: a systematic review and meta-analysis. BACKGROUND Globally, a growing number of children and adolescents are left behind when parents migrate. We investigated the effect of parental migration on the health of left behind-children and adolescents in low-income and middle-income countries (LMICs). METHODS For this systematic review and meta-analysis we searched MEDLINE, Embase, CINAHL, the Cochrane Library, Web of Science, PsychINFO, Global Index Medicus, Scopus, and Popline from inception to April 27, 2017, without language restrictions, for observational studies investigating the effects of parental migration on nutrition, mental health, unintentional injuries, infectious disease, substance use, unprotected sex, early pregnancy, and abuse in left-behind children (aged 0-19 years) in LMICs. We excluded studies in which less than 50% of participants were aged 0-19 years, the mean or median age of participants was more than 19 years, fewer than 50% of parents had migrated for more than 6 months, or the mean or median duration of migration was less than 6 months. We screened studies using systematic review software and extracted summary estimates from published reports independently. The main outcomes were risk and prevalence of health outcomes, including nutrition (stunting, wasting, underweight, overweight and obesity, low birthweight, and anaemia), mental health (depressive disorder, anxiety disorder, conduct disorders, self-harm, and suicide), unintentional injuries, substance use, abuse, and infectious disease. We calculated pooled risk ratios (RRs) and standardised mean differences (SMDs) using random-effects models. This study is registered with PROSPERO, number CRD42017064871. FINDINGS Our search identified 10 284 records, of which 111 studies were included for analysis, including a total of 264 967 children (n=106 167 left-behind children and adolescents; n=158 800 children and adolescents of non-migrant parents). 91 studies were done in China and focused on effects of internal labour migration. Compared with children of non-migrants, left-behind children had increased risk of depression and higher depression scores (RR 1·52 [95% CI 1·27-1·82]; SMD 0·16 [0·10-0·21]), anxiety (RR 1·85 [1·36-2·53]; SMD 0·18 [0·11-0·26]), suicidal ideation (RR 1·70 [1·28-2·26]), conduct disorder (SMD 0·16 [0·04-0·28]), substance use (RR 1·24 [1·00-1·52]), wasting (RR 1·13 [1·02-1·24]) and stunting (RR 1·12 [1·00-1·26]). No differences were identified between left-behind children and children of non-migrants for other nutrition outcomes, unintentional injury, abuse, or diarrhoea. No studies reported outcomes for other infectious diseases, self-harm, unprotected sex, or early pregnancy. Study quality varied across the included studies, with 43% of studies at high or unclear risk of bias across five or more domains. INTERPRETATION Parental migration is detrimental to the health of left-behind children and adolescents, with no evidence of any benefit. Policy makers and health-care professionals need to take action to improve the health of these young people. FUNDING Wellcome Trust.

negative: Respiratory outcomes of late preterm infants of mothers with early and late onset preeclampsia OBJECTIVE: To study the effect of early and late onset preeclampsia (EOPE, LOPE, respectively) on outcomes of late preterm infants. STUDY DESIGN: Cohort study of late preterm infants admitted to a tertiary care NICU from January 2014–July 2015. Outcomes of late preterm infants of EOPE mothers were compared with the next late preterm infant of a LOPE mother and the next two late preterm infants of normotensive non-PE mothers. Primary outcome comprised use of continuous positive airway pressure, mechanical ventilation and/or surfactant in the 24 h after birth. RESULTS: Compared to normotensives (n = 131), adjusted odds ratio (AORs) of the primary outcome was higher in the EOPE (n = 64) and LOPE (n = 65) groups but reached statistical significance only in the EOPE group, AORs 12.9, 95% CI 3.5–37 and 2.7, 95% CI 0.95–8.1, respectively. CONCLUSIONS: Compared to late preterm infants of normotensive and LOPE mothers, infants of mothers with EOPE have significantly higher respiratory morbidity.

negative: Frequently asked questions regarding SARS-CoV-2 in cancer patients—recommendations for clinicians caring for patients with malignant diseases Since early 2020, the SARS-CoV-2 pandemic has a massive impact on health care systems worldwide. Patients with malignant diseases are assumed to be at increased risk for a worse outcome of SARS-CoV-2 infection, and therefore, guidance regarding prevention and management of the infection as well as safe administration of cancer-therapy is required. Here, we provide recommendations for the management of patients with malignant disease in the times of COVID-19. These recommendations were prepared by an international panel of experts and then consented by the EHA Scientific Working Group on Infection in Hematology. The primary aim is to enable clinicians to provide optimal cancer care as safely as possible, since the most important protection for patients with malignant disease is the best-possible control of the underlying disease.

negative: Personal exposure to nitrogen dioxide (NO2) and the severity of virus-induced asthma in children Summary Background A link between exposure to the air pollutant nitrogen dioxide (NO2) and respiratory disease has been suggested. Viral infections are the major cause of asthma exacerbations. We aimed to assess whether there is a relation between NO2 exposure and the severity of asthma exacerbations caused by proven respiratory viral infections in children. Methods A cohort of 114 asthmatic children aged between 8 and 11 years recorded daily upper and lower respiratory-tract symptoms, peak expiratory flow (PEF), and measured personal NO2 exposures every week for up to 13 months. We took nasal aspirates during reported episodes of upper respiratory-tract illness and tested for infection by common respiratory viruses and atypical bacteria with RT-PCR assays. We used generalised estimating equations to assess the relation between low (<7·5 μg/m3), medium (7·5–14 μg/m3), and high (>14 μg/m3) tertiles of NO2 exposure in the week before or after upper respiratory-tract infection and the severity of asthma exacerbation in the week after the start of an infection. Findings One or more viruses were detected in 78% of reported infection episodes, and the medians of NO2 exposure were 5 (IQR 3·6–6·3), 10 (8·7–12·0), and 21 μg/m3 (16·8–42·9) for low, medium, and high tertiles, respectively. There were significant increases in the severity of lower respiratory-tract symptom scores across the three tertiles (0·6 for all viruses [p=0·05] and >2 for respiratory syncytial virus [p=0·01]) and a reduction in PEF of more than 12 L/min for picornavirus (p=0·04) for high compared with low NO2 exposure before the start of the virus-induced exacerbation. Interpretation High exposure to NO2 in the week before the start of a respiratory viral infection, and at levels within current air quality standards, is associated with an increase in the severity of a resulting asthma exacerbation.

negative: Transcriptomic Similarities and Differences in Host Response between SARS-CoV-2 and Other Viral Infections COVID-19 is a pandemic that shares certain clinical characteristics with other acute viral infections. Here, we studied the whole-blood transcriptomic host response to SARS-CoV-2 and compared it with other viral infections to understand similarities and differences in host response. Using RNAseq we profiled peripheral blood from 24 healthy controls and 62 prospectively enrolled patients with community-acquired lower respiratory tract infection by SARS-Cov-2 within the first 24 hours of hospital admission. We also compiled and curated 23 independent studies that profiled 1,855 blood samples from patients with one of six viruses (influenza, RSV, HRV, ebola, Dengue, and SARS-CoV-1). We show gene expression changes in peripheral blood in patients with COVID-19 versus healthy controls are highly correlated with changes in response to other viral infections (r=0.74, p<0.001). However, two genes, ACO1 and ATL3, show significantly opposite changes between conditions. Pathway analysis in patients with COVID-19 or other viral infections versus healthy controls identified similar pathways including neutrophil activation, innate immune response, immune response to viral infection, and cytokine production for over-expressed genes. Conversely, for under-expressed genes, pathways indicated repression of lymphocyte differentiation and T cell activation. When comparing transcriptome profiles of patients with COVID-19 directly with those with other viral infections, we found 114 and 302 genes were over- or under-expressed, respectively, during COVID-19. Pathways analysis did not identify any significant pathways in these genes, suggesting novel responses to further study. Statistical deconvolution using immunoStates found that M1 macrophages, plasmacytoid dendritic cells, CD14+ monocytes, CD4+ T cells, and total B cells showed change consistently in the same direction across all viral infections including COVID-19. Those that increased in COVID-19 but decreased in non-COVID-19 viral infections were CD56bright NK cells, M2 macrophages, and total NK cells. The concordant and discordant responses mapped out here provide a window to explore the pathophysiology of COVID-19 versus other viral infections and show clear differences in signaling pathways and cellularity as part of the host response to SARS-CoV-2.

negative: Contingent reflections on coronavirus and priorities for educational planning and development The COVID-19 pandemic has dramatically shifted education and development priorities. The tragic death toll and high rates of morbidity across many countries are an unprecedented setback and a calamity for those affected physically and mentally. The economic and social effects of lockdowns, loss of production and business confidence, and global recession will cast a long shadow over education systems. Despite the 435 million items that Google already indexes under “COVID-19 education”, many things remain unknown. No one has a clear idea of how the current pandemic will unravel over anything but the short term. The challenge is to strengthen the mechanisms to separate evidence from opinion and to balance popularism with speaking truth to power—especially when political systems can find it difficult to distinguish fact from convenient fiction. This paper advances ten propositions that will shape policy dialogue and whatever iteration of the Sustainable Development Goals is needed to ensure they remain fit for purpose. Testing these propositions over the next year will open the door to an evidence-based approach to reconstruction and sustainable development and juxtapose immediate concerns of the present with aspirations for the future. More than ever the need is to see beyond the exigencies of COVID-19 and act to secure the educational gains of the recent past. UNESCO and other development agencies can play a key role in sharing how to manage revitalised and resilient learning systems that allow the community of practice to stay focussed on development that is economically, socially, medically, and educationally sustainable. Spaceship Earth has to be secured for future generations through the knowledge, skill and attitudes of its crew and passengers. Seriously revisiting SDG4, its targets and indicators, and its relationships with other SDGs, would be a start.

negative: What do children die from in India today?

negative: School closure, COVID‐19 and lunch programme: Unprecedented undernutrition crisis in low‐middle income countries The coronavirus disease 2019 pandemic has affected nearly 70% of children and teenagers around the world due to school closure policies. School closure is implemented widely in order to prevent viral transmission and its impact on the broader community, based on preliminary recommendations and evidence from influenza. However, there is debate with regard to the effectiveness of school closures. Growing evidence suggests that a child's SARS‐CoV‐2 infection is often mild or asymptomatic and that children may not be major SARS‐CoV‐2 transmitters; thus, it is questionable if school closures prevent transmission significantly. This question is important as a majority of children in low‐ and middle‐income countries depend on free school meals; unexpected long‐term school closure may adversely impact nutrition and educational outcomes. Food insecurity is expected to be higher during the pandemic. In this viewpoint, we argue for a more thorough exploration of potential adverse impacts of school closures in low‐ and middle‐income countries and recommend actions to ensure that the health and learning needs of vulnerable populations are met in this time of crisis.

negative: How COVID-19 Deepens Child Oral Health Inequities ABSTRACT The fallout from COVID-19 will reveal the depth and range of social, economic, and political disparities faced by U.S. families and children. Those same injustices, magnified and worsened by COVID-19, are also responsible for perpetuating child oral health disparities.

negative: Behavioural change towards reduced intensity physical activity is disproportionately prevalent among adults with serious health issues or self-perception of high risk during the UK COVID-19 lockdown. Importance: There are growing concerns that the UK COVID-19 lockdown has reduced opportunities to maintain health through physical activity, placing individuals at higher risk of chronic disease and leaving them more vulnerable to severe sequelae of COVID-19. Objective: To examine whether the UK's lockdown measures have had disproportionate impacts on intensity of physical activity in groups who are, or who perceive themselves to be, at heightened risk from COVID-19. Designs, Setting, Participants: UK-wide survey of adults aged over 20, data collected between 2020-04-06 and 2020-04-22. Exposures: Self-reported doctor-diagnosed obesity, hypertension, type I/II diabetes, lung disease, cancer, stroke, heart disease. Self-reported disabilities and depression. Sex, gender, educational qualifications, household income, caring for school-age children. Narrative data on coping strategies. Main Outcomes and Measures: Change in physical activity intensity after implementation of UK COVID-19 lockdown (self-reported). Results: Most (60%) participants achieved the same level of intensity of physical activity during the lockdown as before the epidemic. Doing less intensive physical activity during the lockdown was associated with obesity (OR 1.21, 95% CI 1.02-1.41), hypertension (OR 1.52, 1.33-1.71), lung disease (OR 1.31,1.13-1.49), depression (OR 2.02, 1.82-2.22) and disability (OR 2.34, 1.99-2.69). Participants who reduced their physical activity intensity also had higher odds of being female, living alone or having no garden, and more commonly expressed sentiments about personal or household risks in narratives on coping. Conclusions and relevance: Groups who reduced physical activity intensity included disproportionate numbers of people with either heightened objective clinical risks or greater tendency to express subjective perceptions of risk. Policy on exercise for health during lockdowns should include strategies to facilitate health promoting levels of physical activity in vulnerable groups, including those with both objective and subjective risks.

negative: Post-operative outcomes after cleft palate repair in syndromic and non-syndromic children: a systematic review protocol. BACKGROUND There is a lack of high-level evidence on the surgical management of cleft palate. An appreciation of the differences in the complication rates between different surgical techniques and timing of repair is essential in optimizing cleft palate management. METHOD A comprehensive electronic database search will be conducted on the complication rates associated with cleft palate repair using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. Two independent reviewers with expertise in cleft pathology will screen all appropriate titles, abstracts, and full-text publications prior to deciding whether each meet the predetermined inclusion criteria. The study findings will be tabulated and summarized. The primary outcomes will be the rate of palatal fistula, the incidence and severity of velopharyngeal insufficiency, and the rate of maxillary hypoplasia with different techniques and also the timing of the repair. A meta-analysis will be conducted using a random effects model. DISCUSSION The evidence behind the optimal surgical approach to cleft palate repair is minimal, with no gold standard technique identified to date for a certain type of cleft palate. It is essential to appreciate how the complication rates differ between each surgical technique and each time point of repair, in order to optimize the management of these patients. A more critical evaluation of the outcomes of different cleft palate repair methods may also provide insight into more effective surgical approaches for different types of cleft palates.

negative: The impacts of unstructured nature play on health in early childhood development: A systematic review. BACKGROUND Nature play is growing in popularity as children's play spaces are transforming from traditional playgrounds into more nature-based play spaces with considerable financial and resource investment from government bodies. This has resulted in the re-development of children's play spaces to incorporate more natural elements such as trees, plants and rocks. Despite this, it is unclear whether there is empirical evidence to support claims that play in nature is beneficial for child health and development. AIM To conduct a systematic review examining the impacts of nature play on the health and developmental outcomes of children aged 2-12 years. METHODS Seven electronic databases were searched (MEDLINE, ERIC, Embase, PsycINFO, The Cochrane Library, The Joanna Briggs Institute and Emcare) from inception to July/August 2018 (search updated July/August 2019). The Inclusion criteria were children aged 2-12 years with no health/developmental conditions. The exposure/intervention of interest was unstructured, free play in nature. Critical appraisal of included studies was conducted using the McMaster Critical Appraisal Tool. Descriptive synthesis was then undertaken using the NHMRC FORM Framework. RESULTS Out of 2927 articles identified, 16 studies met the inclusion criteria. The nature play exposure/intervention was heterogeneously described, and a plethora of outcome measures were used. Nature play had consistent positive impacts on physical activity outcomes and cognitive play behaviours (imaginative and dramatic play). However, there remain some concerns regarding the quality of the evidence base, heterogeneity in intervention description and parameters in the outcome measures used. CONCLUSIONS While the positive impacts of nature play were encouraging in terms of physical activity and cognitive development, nature play stakeholders should focus on producing a universal definition for nature play, the development of standardised outcome measures and the conduct of robust research designs. Implications of these findings suggest the need for the development of standardised guidelines to inform practice and policy in the design of children's play spaces in different contexts.

negative: Public health initiatives from hospitalized patients with COVID-19, China BACKGROUND: Since December 2019, when it first occurred in Wuhan, China, coronavirus disease 2019 (COVID-19) has spread rapidly worldwide via human-to-human transmission. We aimed to describe the epidemiological and demographic features of COVID-19 outside Wuhan. METHODS: A single-center case series of 136 consecutive (from January 16 to February 17, 2020) patients with confirmed COVID-19 hospitalized in The First People's Hospital of Jingzhou, China, was retrospectively analyzed. Outcomes were followed up until February 19, 2020. RESULTS: Of the 136 patients (median age, 49 years; interquartile range [IQR], 33-63 years; range, 0.3-83 years), 91 (67%) had been to Wuhan or contacted persons from Wuhan. Forty-five (33.1%) were familial clusters. The median incubation period was 6 days (IQR: 4-11 days). All children had an exact exposure history, family members with COVID-19, and "Mild/Moderate" symptoms at admission. Among the 64 elderly patients, 14 (21.9%) had no exposure history, and 43 (67.2%) had a chronic illness. All 11 (8.1%) "Severe/very severe" illness at onset cases and 5 (3.7%) fatal cases were elderly patients. The duration from symptom onset to admission was positively correlated with the duration from symptom onset to endpoint. Overall, patients with a longer incubation period had more severe outcomes. CONCLUSION: As high-risk susceptible groups, strong protection should be implemented for children and the elderly. Universal screening should be performed for people with a clear exposure history, even lacking apparent symptoms. Given the rapid progression of COVID-19, people should be admitted quickly following symptom onset.

negative: Preparing Children for Pandemics COVID-19 has given us a food for thought that whether we are prepared for such pandemics or not. Developed nations may say that they have enough resources to tackle such situations, but when it comes to the physical and emotional security of the children, even they have to think manifolds because preparing children for such pandemics need lot of effort and apt planning. The purpose of this chapter is to reflect issues related to children during any infectious disease outbreak like COVID-19. Adults are mature enough to control their emotions and can act patiently, but immature minds are always perplexed and act in a very clingy way when some adverse situation is thrown to them. Children are ardent observers and act according to the reactions of the folks around them. It is difficult for them to conceal their behavior, and it is difficult for parents as well to manage their anxiety levels. During crisis period when social distancing and refrained outdoor activities have brought our children into a knotty situation, it is necessary that we understand their fears and myths, try to resolve their concerns in a polite way and strengthen their minds. At this stage the role of parents, teachers, educational institutes, social media, and international children’s organizations need to be redefined. The importance of the decisions taken by the governing bodies should be explained to the children in an effective way, so that they do not panic and reflect a brave attitude. UNICEF in collaboration with international health support systems and departments has a major role to play. Appropriate planning for preparing the children for pandemics has to be incorporated in our system, so that any future crisis can be dealt in an easier way. Schools colleges and other educational institutes should execute immunization and hygiene and health practices in advance to promote prevention.

negative: Mental health in chronic disease patients during the COVID-19 quarantine in Greece OBJECTIVE: To investigate the effect of the time spent on quarantine on distress, anxiety, depression, and somatization of chronic disease patients during the COVID-19 quarantine in Greece and the differences in these parameters between healthy individuals and chronic disease patients. METHOD: The sample consisted of 943 healthy individuals and 163 patients (respiratory, autoimmune, cardiovascular, endocrine, patients with other diseases, and patients with more than one disease) completing sociodemographic assessments as well as the 4-Dimensional Symptom Questionnaire (4DSQ) during March 30, 2020 to May 3, 2020. Pearson's correlation was used to search for the association between time spent on quarantine and the 4DSQ subscales (distress, anxiety, depression, and somatization). Independent sample T-test and Glass's Δ were used for differences between healthy individuals and chronic disease patients in these subscales, an analysis also carried out between healthy individuals and all patient subgroups. RESULTS: No statistically significant correlations were noted between the 4DSQ subscales and the quarantine duration, both for the patient and the healthy individuals’ group. Chronic disease patients had significantly higher levels of distress (p = 0.001, Δ = 0.28) and somatization (p = 0.000, Δ = 0.47), but not there were no significant differences in anxiety (p = 0.098, Δ = 0.14) and depression (p = 0.052, Δ = 0.19). Concerning head-to-head comparisons between the healthy individuals’ group and each patient group, significantly higher scores in distress were found only for patients with respiratory diseases (p = 0.028, Δ = 0.42). Regarding somatization, significantly higher scores were noted for the healthy individuals’ group compared with patients with autoimmune diseases (p = 0.010, Δ = 0.62), respiratory diseases (p = 0.027, Δ = 0.42), other diseases (p = 0.003, Δ = 0.55), and more than one disease (p = 0.012, Δ = 0.60). No statistically significant differences were found in anxiety and depression. SIGNIFICANCE OF RESULTS: The results of this study indicate that interventional programs for chronic disease patients during quarantine should focus on distress and somatization, not on anxiety and depression. Respiratory patients might have more supportive care needs compared with patients with other diseases.

negative: Outcome Risk Factors during Respiratory Infections in a Paediatric Ward in Antananarivo, Madagascar 2010–2012 BACKGROUND: Acute respiratory infections are a leading cause of infectious disease-related morbidity, hospitalisation and mortality among children worldwide, and particularly in developing countries. In these low-income countries, most patients with acute respiratory infection (ARI), whether it is mild or severe, are still treated empirically. The aim of the study was to evaluate the risk factors associated with the evolution and outcome of respiratory illnesses in patients aged under 5 years old. MATERIALS AND METHODS: We conducted a prospective study in a paediatric ward in Antananarivo from November 2010 to July 2012 including patients under 5 years old suffering from respiratory infections. We collected demographic, socio-economic, clinical and epidemiological data, and samples for laboratory analysis. Deaths, rapid progression to respiratory distress during hospitalisation, and hospitalisation for more than 10 days were considered as severe outcomes. We used multivariate analysis to study the effects of co-infections. RESULTS: From November 2010 to July 2012, a total of 290 patients were enrolled. Co-infection was found in 192 patients (70%). Co-infections were more frequent in children under 36 months, with a significant difference for the 19–24 month-old group (OR: 8.0). Sixty-nine percent (230/290) of the patients recovered fully and without any severe outcome during hospitalisation; the outcome was scored as severe for 60 children and nine patients (3%) died. Risk factors significantly associated with worsening evolution during hospitalisation (severe outcome) were admission at age under 6 months (OR = 5.3), comorbidity (OR = 4.6) and low household income (OR = 4.1). CONCLUSION: Co-mordidity, low-income and age under 6 months increase the risk of severe outcome for children infected by numerous respiratory pathogens. These results highlight the need for implementation of targeted public health policy to reduce the contribution of respiratory diseases to childhood morbidity and mortality in low income countries.

negative: Effectiveness of Family-Based Behavior Change Interventions on Obesity-Related Behavior Change in Children: A Realist Synthesis Effective treatment interventions for childhood obesity involve parents, are multicomponent and use behavior change strategies, but more information is needed on the mechanisms influencing behavioral outcomes and the type of parental involvement that is efficacious in behavioral treatment interventions with school-age children. This review aimed to understand key characteristics of programs that contribute to dietary and physical activity behavioral outcomes, and through which key mechanisms. This was a systematic review with narrative synthesis following PRISMA guidelines and realist analysis using RAMESES guidelines to explain outcome patterns and influence of parental involvement. Overall, the findings contribute to understanding the complex relationship between family barriers to behavior change, strategies employed in treatment interventions and behavioral outcomes. Implications for enhancing future policy and practice include involving parents in goal setting, motivational counselling, role modeling, and restructuring the physical environment to promote mutual empowerment of both parents and children, shared value and whole-family ownership in which intrinsic motivation and self-efficacy are implicit. These characteristics were associated with positive dietary and physical activity behavior change in children and may be useful considerations for the design and implementation of future theory-based treatment interventions to encourage habitual healthy diet and physical activity to reduce childhood obesity.

negative: Children and adolescents in the CoVid-19 pandemic: Schools and daycare centers are to be opened again without restrictions. The protection of teachers, educators, carers and parents and the general hygiene rules do not conflict with this In the opinion of the medical societies of hygiene and pediatrics undersigning the present statement, the analyses published to date regarding transmission of SARS-CoV-2 and the course of CoVid-19 show that children play a much less significant role in the spread of the virus than do adults. According to the findings available to date, not only do children and adolescents less frequently fall ill with CoVid-19, they also generally become less severely ill than do adults. The vast majority of infections in children and adolescents are asymptomatic or oligosymptomatic. Even the first analyses from China demonstrated that children and adolescents play a subordinate role in the transmission of the virus – not only to other children and adolescents, but also to adults. Taking into account regional infection rates and available resources, daycare centers, kindergartens and elementary schools promptly should be reopened. For children, this should be possible without excessive restrictions, such as clustering into very small groups, implementation of barrier precautions, maintaining appropriate distance from others or wearing masks. A factor more decisive than individual group size is the issue of sustaining the constancy of respective group members and the avoidance of intermixing. Children can be taught basic rules of hygiene such as handwashing and careful hygiene behavior when coming into contact with others during mealtimes and/or when using sanitary facilities. Independent of the prevention measures implemented for children and adolescents, the protection of teachers, educators and caregivers is crucial, (e.g., the maintenance of appropriate distance from others, use of medical masks, situation-dependent hand disinfection, when necessary, supported by regular pool testing). Children over the age of 10 and adolescents up to school graduation age are more capable of actively understanding and conforming to specific hygiene rules. For this group, maintaining appropriate distance from others (1.5 meters), wearing a mouth-and-nose protection (whenever they are not sitting in their assigned classroom seats) and consistent education regarding the basic rules of infection prevention may provide increased options for normalizing teaching activities. Children and adolescents suspected of infection with SARS-CoV-2 should be tested immediately in order to either confirm or rule out such an infection. Evidence of individual infections in children or students must not automatically lead to the closure of the entire daycare center or school. A detailed analysis of the chain of infection is a prerequisite for a balanced approach to infection control. The opening of schools and children’s facilities should be accompanied by specifically structured, model surveillance studies that further clarify outstanding questions about infectious disease events and hygiene control. These prospective, concomitant examinations will be essential for the purpose of evaluating and verifying the effectiveness of the required hygiene measures.

negative: Extrapulmonary and atypical clinical presentations of COVID‐19 The novel coronavirus (SARS‐CoV2) has led to outbreak of multiple cases of pneumonia in Wuhan city in December 2019. The disease caused by this virus was named coronavirus disease 2019 or “COVID‐19”, which was declared by WHO as a global pandemic in March 2020. It typically presents with respiratory symptoms and febrile illness. However, there are few reported extrapulmonary and atypical presentations, such as haemoptysis, cardiac, neurological, gastrointestinal, ocular and cutaneous manifestations, as well as venous and arterial thrombosis. Lack of awareness of these presentations might lead to misdiagnosis, delayed diagnosis and isolation of suspected patients which increases the risk of transmission of infection between patients and doctors. All these issues will be discussed in this review. This article is protected by copyright. All rights reserved.

negative: Knowledge, attitudes, and practices towards COVID-19 among Chinese residents during the rapid rise period of the COVID-19 outbreak: a quick online cross-sectional survey Unprecedented measures have been adopted to control the rapid spread of the ongoing COVID-19 epidemic in China. People's adherence to control measures is affected by their knowledge, attitudes, and practices (KAP) towards COVID-19. In this study, we investigated Chinese residents' KAP towards COVID-19 during the rapid rise period of the outbreak. An online sample of Chinese residents was successfully recruited via the authors' networks with residents and popular media in Hubei, China. A self-developed online KAP questionnaire was completed by the participants. The knowledge questionnaire consisted of 12 questions regarding the clinical characteristics and prevention of COVID-19. Assessments on residents' attitudes and practices towards COVID-19 included questions on confidence in winning the battle against COVID-19 and wearing masks when going out in recent days. Among the survey completers (n=6910), 65.7% were women, 63.5% held a bachelor degree or above, and 56.2% engaged in mental labor. The overall correct rate of the knowledge questionnaire was 90%. The majority of the respondents (97.1%) had confidence that China can win the battle against COVID-19. Nearly all of the participants (98.0%) wore masks when going out in recent days. In multiple logistic regression analyses, the COVID-19 knowledge score (OR: 0.75-0.90, P<0.001) was significantly associated with a lower likelihood of negative attitudes and preventive practices towards COVID-2019. Most Chinese residents of a relatively high socioeconomic status, in particular women, are knowledgeable about COVID-19, hold optimistic attitudes, and have appropriate practices towards COVID-19. Health education programs aimed at improving COVID-19 knowledge are helpful for Chinese residents to hold optimistic attitudes and maintain appropriate practices. Due to the limited sample representativeness, we must be cautious when generalizing these findings to populations of a low socioeconomic status.

negative: The Impact of Coronavirus Disease 2019 Pandemic on U.S. and Canadian PICUs There are limited reports of the impact of the coronavirus disease 2019 pandemic focused on U.S. and Canadian PICUs. This hypothesis-generating report aims to identify the United States and Canadian trends of coronavirus disease 2019 in PICUs. DESIGN AND SETTING: To better understand how the coronavirus disease 2019 pandemic was affecting U.S. and Canadian PICUs, an open voluntary daily data collection process of Canadian and U.S. PICUs was initiated by Virtual Pediatric Systems, LLC (Los Angeles, CA; http://www.myvps.org) in mid-March 2020. Information was made available online to all PICUs wishing to participate. A secondary data collection was performed to follow-up on patients discharged from those PICUs reporting coronavirus disease 2019 positive patients. MEASUREMENTS AND MAIN RESULTS: To date, over 180 PICUs have responded detailing 530 PICU admissions requiring over 3,467 days of PICU care with 30 deaths. The preponderance of cases was in the eastern regions. Twenty-four percent of the patients admitted to the PICUs were over 18 years old. Fourteen percent of admissions were under 2 years old. Nearly 60% of children had comorbidities at admission with the average length of stay increasing by age and by severity of comorbidity. Advanced respiratory support was necessary during 67% of the current days of care, with 69% being conventional mechanical ventilation. CONCLUSIONS: PICUs have been significantly impacted by the pandemic. They have provided care not only for children but also adults. Patients with coronavirus disease 2019 have a high frequency of comorbidities, require longer stays, more ventilatory support than usual PICU admissions. These data suggest several avenues for further exploration.