SARS-CoV-2 infection in technology-dependent children: a multicenter case series.

PURPOSE: The objective of this study was to describe the clinical course and outcomes in children with technology dependence (TD) hospitalized with SARS-CoV-2 infection. METHODS: Seventeen pediatric hospitals (15 Canadian and one each in Iran and Costa Rica) included children up to 17 years of age admitted February 1, 2020, through May 31, 2021, with detection of SARS-CoV-2. For those with TD, data were collected on demographics, clinical course and outcome. RESULTS: Of 691 children entered in the database, 42 (6%) had TD of which 22 had feeding tube dependence only, 9 were on supplemental oxygen only, 3 had feeding tube dependence and were on supplemental oxygen, 2 had a tracheostomy but were not ventilated, 4 were on non-invasive ventilation, and 2 were on mechanical ventilation prior to admission. Three of 42 had incidental SARS-CoV-2 infection. Two with end-stage underlying conditions were transitioned to comfort care and died. Sixteen (43%) of the remaining 37 cases required increased respiratory support from baseline due to COVID-19 while 21 (57%) did not. All survivors were discharged home. CONCLUSION: Children with TD appear to have an increased risk of COVID-19 hospitalization. However, in the absence of end-stage chronic conditions, all survived to discharge.

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study.

Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2-11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75-1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58-1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91-1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70-1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11-0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50-0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38-0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45-0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health.

Neurological involvement in hospitalized children with SARS-CoV-2 infection: a multinational study.

BACKGROUND AND OBJECTIVES: Neurological involvement associated with SARS-CoV-2 infection is increasingly recognized. However, the specific characteristics and prevalence in pediatric patients remain unclear. The objective of this study was to describe the neurological involvement in a multinational cohort of hospitalized pediatric patients with SARS-CoV-2. METHODS: This was a multicenter observational study of children <18 years of age with confirmed SARS-CoV-2 infection or multisystemic inflammatory syndrome (MIS-C) and laboratory evidence of SARS-CoV-2 infection in children, admitted to 15 tertiary hospitals/healthcare centers in Canada, Costa Rica, and Iran February 2020-May 2021. Descriptive statistical analyses were performed and logistic regression was used to identify factors associated with neurological involvement. RESULTS: One-hundred forty-seven (21%) of 697 hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Headache (n = 103), encephalopathy (n = 28), and seizures (n = 30) were the most reported. Neurological signs/symptoms were significantly associated with ICU admission (OR: 1.71, 95% CI: 1.15-2.55; p = 0.008), satisfaction of MIS-C criteria (OR: 3.71, 95% CI: 2.46-5.59; p < 0.001), fever during hospitalization (OR: 2.15, 95% CI: 1.46-3.15; p < 0.001), and gastrointestinal involvement (OR: 2.31, 95% CI: 1.58-3.40; p < 0.001). Non-headache neurological manifestations were significantly associated with ICU admission (OR: 1.92, 95% CI: 1.08-3.42; p = 0.026), underlying neurological disorders (OR: 2.98, 95% CI: 1.49-5.97, p = 0.002), and a history of fever prior to hospital admission (OR: 2.76, 95% CI: 1.58-4.82; p < 0.001). DISCUSSION: In this study, approximately 21% of hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Future studies should focus on pathogenesis and long-term outcomes in these children.

Multisystem Inflammatory Syndrome in Children in Western Countries? Decreasing Incidence as the Pandemic Progresses?: An Observational Multicenter International Cross-sectional Study.

BACKGROUND: SARS-CoV-2 variations as well as immune protection after previous infections and/or vaccination may have altered the incidence of multisystemic inflammatory syndrome in children (MIS-C). We aimed to report an international time-series analysis of the incidence of MIS-C to determine if there was a shift in the regions or countries included into the study. METHODS: This is a multicenter, international, cross-sectional study. We collected the MIS-C incidence from the participant regions and countries for the period July 2020 to November 2021. We assessed the ratio between MIS-C cases and COVID-19 pediatric cases in children <18 years diagnosed 4 weeks earlier (average time for the temporal association observed in this disease) for the study period. We performed a binomial regression analysis for 8 participating sites [Bogotá (Colombia), Chile, Costa Rica, Lazio (Italy), Mexico DF, Panama, The Netherlands and Catalonia (Spain)]. RESULTS: We included 904 cases of MIS-C, among a reference population of 17,906,432 children. We estimated a global significant decrease trend ratio in MIS-C cases/COVID-19 diagnosed cases in the previous month ( P < 0.001). When analyzing separately each of the sites, Chile and The Netherlands maintained a significant decrease trend ( P < 0.001), but this ratio was not statistically significant for the rest of sites. CONCLUSIONS: To our knowledge, this is the first international study describing a global reduction in the trend of the MIS-C incidence during the pandemic. COVID-19 vaccination and other factors possibly linked to the virus itself and/or community transmission may have played a role in preventing new MIS-C cases.

Multisystem Inflammatory Syndrome in Children (MIS-C) temporally related to COVID-19: the experience at a pediatric reference hospital in Colombia.

OBJECTIVE: This study aimed to describe the clinical characteristics and the different phenotypes of children with multisystem inflammatory syndrome in children (MIS-C) temporally related to COVID-19 and to evaluate the risk conditions that favored a greater severity of the disease during a 12-month period at a pediatric reference hospital in Colombia. METHODS: A 12-month retrospective observational study of children under the age of 18 years who met criteria for MIS-C. RESULTS: A total of 28 children presented MIS-C criteria. The median age was 7 years. Other than fever (100%) (onset 4 days prior to admission), the most frequent clinical features were gastrointestinal (86%) and mucocutaneous (61%). Notably, 14 (50%) children had Kawasaki-like symptoms. The most frequent echocardiographic abnormalities were pericardial effusion (64%), valvular involvement (68%), ventricular dysfunction (39%), and coronary artery abnormalities (29%). In addition, 75% had lymphopenia. All had at least one abnormal coagulation test. Most received intravenous immunoglobulin (89%), glucocorticoids (82%), vasopressors (54%), and antibiotics (64%). Notably, 61% had a more severe form of the disease and were admitted to an intensive care unit (median 4 days, mean 6 days); the severity predictors were patients with the inflammatory/MIS-C phenotype (OR 26.5; 95%CI 1.40-503.7; p=0.029) and rash (OR 14.7; 95%CI 1.2-178.7; p=0.034). Two patients had macrophage activation syndrome. CONCLUSIONS: Coronary artery abnormalities, ventricular dysfunction, and intensive care unit admission were frequent, which needs to highlight the importance of early clinical suspicion.

Predictors of severe illness in children with multisystem inflammatory syndrome after SARS-CoV-2 infection: a multicentre cohort study.

BACKGROUND: SARS-CoV-2 infection can lead to multisystem inflammatory syndrome in children (MIS-C). We sought to investigate risk factors for admission to the intensive care unit (ICU) and explored changes in disease severity over time. METHODS: We obtained data from chart reviews of children younger than 18 years with confirmed or probable MIS-C who were admitted to 15 hospitals in Canada, Iran and Costa Rica between Mar. 1, 2020, and Mar. 7, 2021. Using multivariable analyses, we evaluated whether admission date and other characteristics were associated with ICU admission or cardiac involvement. RESULTS: Of 232 children with MIS-C (median age 5.8 yr), 130 (56.0%) were male and 50 (21.6%) had comorbidities. Seventy-three (31.5%) patients were admitted to the ICU but none died. We observed an increased risk of ICU admission among children aged 13-17 years (adjusted risk difference 27.7%, 95% confidence interval [CI] 8.3% to 47.2%), those aged 6-12 years (adjusted risk difference 25.2%, 95% CI 13.6% to 36.9%) or those with initial ferritin levels greater than 500 µg/L (adjusted risk difference 18.4%, 95% CI 5.6% to 31.3%). Children admitted to hospital after Oct. 31, 2020, had numerically higher rates of ICU admission (adjusted risk difference 12.3%, 95% CI -0.3% to 25.0%) and significantly higher rates of cardiac involvement (adjusted risk difference 30.9%, 95% CI 17.3% to 44.4%). At Canadian sites, the risk of ICU admission was significantly higher for children admitted to hospital between December 2020 and March 2021 than those admitted between March and May 2020 (adjusted risk difference 25.3%, 95% CI 6.5% to 44.0%). INTERPRETATION: We observed that age and higher ferritin levels were associated with more severe MIS-C. We observed greater severity of MIS-C later in the study period. Whether emerging SARS-CoV-2 variants pose different risks of severe MIS-C needs to be determined.

Risk factors for severe PCR-positive SARS-CoV-2 infection in hospitalised children

Objective To identify risk factors for severe disease in children hospitalised for SARS-CoV-2 infection. Design Multicentre retrospective cohort study. Setting 18 hospitals in Canada, Iran and Costa Rica from 1 February 2020 to 31 May 2021. Patients Children<18 years of age hospitalised for symptomatic PCR-positive SARS-CoV-2 infection, including PCR-positive multisystem inflammatory syndrome in children (MIS-C). Main outcome measure Severity on the WHO COVID-19 Clinical Progression Scale was used for ordinal logistic regression analyses. Results We identified 403 hospitalisations. Median age was 3.78 years (IQR 0.53–10.77). At least one comorbidity was present in 46.4% (187/403) and multiple comorbidities in 18.6% (75/403). Eighty-one children (20.1%) met WHO criteria for PCR-positive MIS-C. Progression to WHO clinical scale score ≥6 occurred in 25.3% (102/403). In multivariable ordinal logistic regression analyses adjusted for age, chest imaging findings, laboratory-confirmed bacterial and/or viral coinfection, and MIS-C diagnosis, presence of a single (adjusted OR (aOR) 1.90, 95% CI 1.13 to 3.20) or multiple chronic comorbidities (aOR 2.12, 95% CI 1.19 to 3.79), obesity (aOR 3.42, 95% CI 1.76 to 6.66) and chromosomal disorders (aOR 4.47, 95% CI 1.25 to 16.01) were independent risk factors for severity. Age was not an independent risk factor, but different age-specific comorbidities were associated with more severe disease in age-stratified adjusted analyses: cardiac (aOR 2.90, 95% CI 1.11 to 7.56) and non-asthma pulmonary disorders (aOR 3.07, 95% CI 1.26 to 7.49) in children<12 years old and obesity (aOR 3.69, 1.45–9.40) in adolescents≥12 years old. Among infants<1 year old, neurological (aOR 10.72, 95% CI 1.01 to 113.35) and cardiac disorders (aOR 10.13, 95% CI 1.69 to 60.54) were independent predictors of severe disease. Conclusion We identified risk factors for disease severity among children hospitalised for PCR-positive SARS-CoV-2 infection. Comorbidities predisposing children to more severe disease may vary by age. These findings can potentially guide vaccination programmes and treatment approaches in children.

Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination in Children with a History of Multisystem Inflammatory Syndrome in Children: An International Survey.

The optimal severe acute respiratory syndrome coronavirus 2 vaccine strategy for patients with a history of multisystem inflammatory syndrome in children (MIS-C) is unclear. We performed an international survey (32 countries) and found substantial variations in vaccine policies. Respondents did not report relapses of MIS-C or other severe inflammatory side effects after severe acute respiratory syndrome coronavirus 2 vaccination in 273 patients with a history of MIS-C.

Multisystem Inflammatory Syndrome Temporally Related to COVID-19 in Children From Latin America and the Caribbean Region: A Systematic Review With a Meta-Analysis of Data From Regional Surveillance Systems.

Background: With the emergence of the COVID-19 pandemic, increasing numbers of cases of the multisystem inflammatory syndrome in children (MIS-C) have been reported worldwide; however, it is unclear whether this syndrome has a differential pattern in children from Latin America and the Caribbean (LAC). We conducted a systematic review and meta-analysis to analyze the epidemiological, clinical, and outcome characteristics of patients with MIS-C in LAC countries. Methods: A systematic literature search was conducted in the main electronic databases and scientific meetings from March 1, 2020, to June 30, 2021. Available reports on epidemiological surveillance of countries in the region during the same period were analyzed. Results: Of the 464 relevant studies identified, 23 were included with 592 patients with MIS-C from LAC. Mean age was 6.6 years (IQR, 6-7.4 years); 60% were male. The most common clinical manifestations were fever, rash, and conjunctival injection; 59% showed Kawasaki disease. Pool proportion of shock was 52%. A total of 47% of patients were admitted to the pediatric intensive care unit (PICU), 23% required mechanical ventilation, and 74% required vasoactive drugs. Intravenous gamma globulin alone was administered in 87% of patients, and in combination with steroids in 60% of cases. Length of hospital stay was 10 days (IQR, 9-10) and PICU stay 5.75 (IQR, 5-6). Overall case fatality ratio was 4% and for those hospitalized in the PICU it was 7%. Conclusion: Limited information was available on the clinical outcomes. Improvements in the surveillance system are required to obtain a better epidemiologic overview in the region.

Thrombosis and hemorrhage experienced by hospitalized children with SARS-CoV-2 infection or MIS-C: Results of the PICNIC registry.

INTRODUCTION: Coagulopathy and thrombosis associated with SARS-CoV-2 infection are well defined in hospitalized adults and leads to adverse outcomes. Pediatric studies are limited. METHODS: An international multicentered (n = 15) retrospective registry collected information on the clinical manifestations of SARS-CoV-2 and multisystem inflammatory syndrome (MIS-C) in hospitalized children from February 1, 2020 through May 31, 2021. This sub-study focused on coagulopathy. Study variables included patient demographics, comorbidities, clinical presentation, hospital course, laboratory parameters, management, and outcomes. RESULTS: Nine hundred eighty-five children were enrolled, of which 915 (93%) had clinical information available; 385 (42%) had symptomatic SARS-CoV-2 infection, 288 had MIS-C (31.4%), and 242 (26.4%) had SARS-CoV-2 identified incidentally. Ten children (1%) experienced thrombosis, 16 (1.7%) experienced hemorrhage, and two (0.2%) experienced both thrombosis and hemorrhage. Significantly prevalent prothrombotic comorbidities included congenital heart disease (p-value .007), respiratory support (p-value .006), central venous catheter (CVC) (p = .04) in children with primary SARS-CoV-2 and in those with MIS-C included respiratory support (p-value .03), obesity (p-value .002), and cytokine storm (p = .012). Comorbidities prevalent in children with hemorrhage included age >10 years (p = .04), CVC (p = .03) in children with primary SARS-CoV-2 infection and in those with MIS-C encompassed thrombocytopenia (p = .001) and cytokine storm (p = .02). Eleven patients died (1.2%), with no deaths attributed to thrombosis or hemorrhage. CONCLUSION: Thrombosis and hemorrhage are uncommon events in children with SARS-CoV-2; largely experienced by those with pre-existing comorbidities. Understanding the complete spectrum of coagulopathy in children with SARS-CoV-2 infection requires ongoing research.

Multisystem Inflammatory Syndrome Temporally Related to COVID-19 in Children From Latin America and the Caribbean Region: A Systematic Review With a Meta-Analysis of Data From Regional Surveillance Systems

Background With the emergence of the COVID-19 pandemic, increasing numbers of cases of the multisystem inflammatory syndrome in children (MIS-C) have been reported worldwide;however, it is unclear whether this syndrome has a differential pattern in children from Latin America and the Caribbean (LAC). We conducted a systematic review and meta-analysis to analyze the epidemiological, clinical, and outcome characteristics of patients with MIS-C in LAC countries. Methods A systematic literature search was conducted in the main electronic databases and scientific meetings from March 1, 2020, to June 30, 2021. Available reports on epidemiological surveillance of countries in the region during the same period were analyzed. Results Of the 464 relevant studies identified, 23 were included with 592 patients with MIS-C from LAC. Mean age was 6.6 years (IQR, 6–7.4 years);60% were male. The most common clinical manifestations were fever, rash, and conjunctival injection;59% showed Kawasaki disease. Pool proportion of shock was 52%. A total of 47% of patients were admitted to the pediatric intensive care unit (PICU), 23% required mechanical ventilation, and 74% required vasoactive drugs. Intravenous gamma globulin alone was administered in 87% of patients, and in combination with steroids in 60% of cases. Length of hospital stay was 10 days (IQR, 9–10) and PICU stay 5.75 (IQR, 5–6). Overall case fatality ratio was 4% and for those hospitalized in the PICU it was 7%. Conclusion Limited information was available on the clinical outcomes. Improvements in the surveillance system are required to obtain a better epidemiologic overview in the region.

Factors Associated With Hospitalization or Intensive Care Admission in Children With COVID-19 in Latin America.

Background: Limited data is available from low-middle and upper-middle income countries of the factors associated with hospitalization or admission to pediatric intensive care unit (PICU) for children with COVID-19. Objective: To describe the factors associated with hospitalization or PICU admission of children with COVID-19 in Latin America. Method: Multicenter, analytical, retrospective study of children reported from 10 different Latin American countries to the Latin-American Society of Pediatric Infectious Diseases (SLIPE-COVID) research network from June 1, 2020, and February 28, 2021. Outpatient or hospitalized children <18 years of age with COVID-19 confirmed by polymerase chain reaction or antigen detection from the nasopharynx were included. Children with multisystem inflammatory syndrome in children (MIS-C) were excluded. Associations were assessed using univariate and multivariable logistic regression models. Results: A total of 1063 children with COVID-19 were included; 500 (47%) hospitalized, with 419 (84%) to the pediatric wards and 81 (16%) to the ICU. In multivariable analyses, age <1 year (Odds Ratio [OR] 1.78; 95% CI 1.08-2.94), native race (OR 5.40; 95% CI 2.13-13.69) and having a co-morbid condition (OR 5.3; 95% CI 3.10-9.15), were associated with hospitalization. Children with metabolic or endocrine disorders (OR 4.22; 95% CI 1.76-10.11), immune deficiency (1.91; 95% CI 1.05-3.49), preterm birth (OR 2.52; 95% CI 1.41-4.49), anemia at presentation (OR 2.34; 95% CI 1.28-4.27), radiological peribronchial wall thickening (OR 2.59; 95% CI 1.15-5.84) and hypoxia, altered mental status, seizures, or shock were more likely to require PICU admission. The presence of pharyngitis (OR 0.34; 95% CI 0.25-0.48); myalgia (OR 0.47; 95% CI 0.28-0.79) or diarrhea (OR 0.38; 95% CI 0.21-0.67) were inversely associated with hospital admission. Conclusions: In this data analysis reported to the SLIPE research network in Latin America, infants, social inequalities, comorbidities, anemia, bronchial wall thickening and specific clinical findings on presentation were associated with higher rates of hospitalization or PICU admission. This evidence provides data for prioritization prevention and treatment strategies for children suffering from COVID-19.

Infants hospitalized for acute COVID-19: disease severity in a multicenter cohort study.

Age is the most important determinant of COVID-19 severity. Infectious disease severity by age is typically J-shaped, with infants and the elderly carrying a high burden of disease. We report on the comparative disease severity between infants and older children in a multicenter retrospective cohort study of children 0 to 17 years old admitted for acute COVID-19 from February 2020 through May 2021 in 17 pediatric hospitals. We compare clinical and laboratory characteristics and estimate the association between age group and disease severity using ordinal logistic regression. We found that infants comprised one-third of cases, but were admitted for a shorter period (median 3 days IQR 2-5 versus 4 days IQR 2-7), had a lower likelihood to have an increased C-reactive protein, and had half the odds of older children of having severe or critical disease (OR 0.50 (95% confidence interval 0.32-0.78)).    Conclusion: When compared to older children, there appeared to be a lower threshold to admit infants but their length of stay was shorter and they had lower odds than older children of progressing to severe or critical disease. What is Known: • A small proportion of children infected with SARS-CoV-2 require hospitalization for acute COVID-19 with a subgroup needing specialized intensive care to treat more severe disease. • For most infectious diseases including viral respiratory tract infections, disease severity by age is J-shaped, with infants having more severe disease compared to older children. What is New: • One-third of admitted children for acute COVID-19 during the first 14 months of the pandemic were infants. • Infants had half the odds of older children of having severe or critical disease.

Treatment of Multisystem Inflammatory Syndrome in Children.

BACKGROUND: Evidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2. METHODS: We performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation. RESULTS: Data were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups. CONCLUSIONS: We found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue. (Funded by the European Union's Horizon 2020 Program and others; BATS ISRCTN number, ISRCTN69546370.).

Acute Abdomen and Appendicitis in 1010 Pediatric Patients With COVID-19 or MIS-C: A Multinational Experience from Latin America.

BACKGROUND: To date, there are only sporadic reports of acute abdomen and appendicitis in children with coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C). METHODS: Children 17 years of age or younger assessed in 5 Latin American countries with a diagnosis of microbiologically confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and children fulfilling MIS-C definition were included. For children with acute abdomen, we investigate main radiologic patterns, surgical treatment and intraoperative findings, outcomes. FINDINGS: One-thousand ten children were enrolled. Forty-two children (4.2%) had a clinical diagnosis of acute abdomen. Four (9.5%) were diagnosed with MIS-C and did not undergo surgery. The remaining 38 children (3.8%) underwent abdominal surgery due to suspected appendicitis, 34 of them (89.7%) had an intraoperative diagnosis of acute appendicitis (AA), while 4 of them had nonsurgical findings. Eight children died (0.8%), none of them being diagnosed with appendicitis. Children with AA were significantly older than those without (P < 0.0001). Children with complicated appendicitis had more frequently fever (85.7% vs. 60%), intestinal distension on the abdominal radiograph (7.1% vs. none), leukocytosis (85.7% vs. 40%) and high levels of C-reactive protein (35.7% vs. 5%), although differences were not statistically significant. CONCLUSIONS: Our study showed that children may present with acute abdomen during COVID-19 or MIS-C, which is not always associated with intraoperative findings of appendicitis, particularly in case of MIS-C. Further studies are needed to better characterize children with acute abdomen during COVID-19 or MIS-C, to avoid delay in diagnosis of surgical conditions and at the same time, minimize unnecessary surgical approaches.

The Fifth International Neonatal and Maternal Immunization Symposium (INMIS 2019): Securing Protection for the Next Generation.

Despite significant progress in reaching some milestones of the United Nations Sustainable Development Goals, neonatal and early infant morbidity and mortality remain high, and maternal health remains suboptimal in many countries. Novel and improved preventative strategies with the potential to benefit pregnant women and their infants are needed, with maternal and neonatal immunization representing effective approaches. Experts from immunology, vaccinology, infectious diseases, clinicians, industry, public health, and vaccine-related social sciences convened at the 5th International Neonatal and Maternal Immunization Symposium (INMIS) in Vancouver, Canada, from 15 to 17 September 2019. We critically evaluated the lessons learned from recent clinical studies, presented cutting-edge scientific progress in maternal and neonatal immunology and vaccine development, and discussed maternal and neonatal immunization in the broader context of infectious disease epidemiology and public health. Focusing on practical aspects of research and implementation, we also discussed the safety, awareness, and perception of maternal immunization as an existing strategy to address the need to improve maternal and neonatal health worldwide. The symposium provided a comprehensive scientific and practical primer as well as an update for all those with an interest in maternal and neonatal infection, immunity, and vaccination. The summary presented here provides an update of the current status of progress in maternal and neonatal immunization.

BCG Scar Local Skin Inflammation as a Novel Reaction Following mRNA COVID-19 Vaccines in Two International Healthcare Workers.

Bacillus Calmette-Guérin (BCG) local scar inflammatory reactions have been mostly associated with Kawasaki disease in children and less commonly with other viral infections (i.e., measles). BCG scar inflammation associated with or following vaccine administration has only been reported with the influenza vaccine. We describe the first reports in the literature of local BCG inflammation following two different available messenger ribonucleic acid (mRNA) anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) vaccines (mRNA-1273, and BNT162b2) in two young healthy physicians, one from Costa Rica, and another from the United States of America, with normal cell blood counts, flow cytometries, and negative for human immunodeficiency virus (HIV). In both cases, BCG scar inflammation appeared after 24 hours of vaccination of the second dose, without signs of reaction on the injection site, and resolved within four days. Dermoscopic findings in one case showed arborizing and comma-shaped vessels. Pharmacovigilance surveillance of BCG scar reactions following coronavirus disease 2019 (COVID-19) vaccines should be considered particularly in countries where BCG is part of their national immunization programs.

Epidemiological and clinical profile between influenza A and B virus in Costa Rican children.

OBJECTIVE: We aimed to evaluate the clinical and epidemiological behavior of influenza type A versus type B and analyze if there was any correlation or differences between the characteristics of both groups. METHODS: An observational, retrospective, descriptive, and population-based study based of children who were hospitalized at the only national pediatric hospital of Costa Rica from January 1, 2010 to December 31, 2018 and had a confirmed influenza virus infection. RESULTS: 336 patients were analyzed. Mean age was 35,6 ± 36,7 months (3,0 ± 3,1 years). The only significant variables at 25% in relation to influenza type A or B virus were: sex, month of diagnosis, fever, vomiting, cough, use of antibiotics and admission to the PICU. The hospitalization rate at our hospital increased between the months of October to December, with a higher percentage of cases in November and December, which reveals that the "real peak" in our population begins between 3 to 4 months after the end of the vaccination campaign. Patients with influenza A virus had a 2.5 times greater risk of being admitted to the PICU. Mortality rate was 0.6% and 0% among influenza A and B children, respectively. CONCLUSIONS: Variables in which a causality was found with type A or B virus were: admission to the PICU, month of diagnosis, and cough. However, influenza B clinical behavior continues to be unpredictable.