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

Summary 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.

The COVID-19 Sentinel Schools Network of Catalonia (CSSNC) project: Associated factors to prevalence and incidence of SARS-CoV-2 infection in educational settings during the 2020-2021 academic year.

The Sentinel Schools project was designed to monitor and evaluate the epidemiology of COVID-19 in Catalonia, gathering evidence for health and education policies to inform the development of health protocols and public health interventions to control of SARS-CoV-2 infection in schools. The aim of this study was to estimate the prevalence and incidence of SARS-CoV-2 infections and to identify their determinants among students and staff during February to June in the academic year 2020-2021. We performed two complementary studies, a cross-sectional and a longitudinal component, using a questionnaire to collect nominal data and testing for SARS-CoV-2 detection. We describe the results and perform a univariate and multivariate analysis. The initial crude seroprevalence was 14.8% (95% CI: 13.1-16.5) and 22% (95% CI: 18.3-25.8) for students and staff respectively, and the active infection prevalence was 0.7% (95% CI: 0.3-1) and 1.1% (95% CI: 0.1-2). The overall incidence for persons at risk was 2.73 per 100 person-month and 2.89 and 2.34 per 100 person-month for students and staff, respectively. Socioeconomic, self-reported knowledge, risk perceptions and contact pattern variables were positively associated with the outcome while sanitary measure compliance was negatively associated, the same significance trend was observed in multivariate analysis. In the longitudinal component, epidemiological close contact with SARS-CoV-2 infection was a risk factor for SARS-CoV-2 infection while the highest socioeconomic status level was protective as was compliance with sanitary measures. The small number of active cases detected in these schools suggests a low transmission among children in school and the efficacy of public health measures implemented, at least in the epidemiological scenario of the study period. The major contribution of this study was to provide results and evidence that help analyze the transmission dynamic of SARS-CoV-2 and evaluate the associations between sanitary protocols implemented, and measures to avoid SARS-CoV-2 spread in schools.

Health and Vaccination Status of Unaccompanied Minors After Arrival in a European Border Country: A Cross-sectional Study (2017-2020).

BACKGROUND: Unaccompanied and separated children (UASC) are a high-risk group for infectious diseases and information on their vaccination status is scarce. Different approaches are used to screen newly arrived minors in Europe. The aim of this study was to describe the health status and serological protection against different vaccine-preventable diseases among UASC to inform public health decision-making. METHODS: Retrospective study of all UASC seen at an international health reference center in Barcelona (Spain) between January 2017 and February 2020. Screening results were analyzed using binary logistic regression with adjustment for symptoms, geographic origin, and time since arrival. RESULTS: We studied 289 UASC (88.9% males; median age, 17 years). At least one infection was diagnosed in 136 minors (47.1%). There was a high prevalence of intestinal parasites (22.8%), latent tuberculosis infection (22.5%), and hepatitis B (5.2%), even in asymptomatic individuals, and especially among UASC from sub-Saharan Africa (odds ratio, 2.5; 95% confidence interval, 1.5-4.0, P < 0.001). We did not observe a significant association between clinical symptoms and the presence of infection or differences in the prevalence of different infections according to number of months since arrival. Protection against hepatitis B virus (36%), measles (80%), and varicella (83%) was suboptimal. CONCLUSIONS: Our results highlight the importance of screening and vaccination programs for UASC arriving in Europe, especially border countries. Protocols should be adjusted according to geographic origin. Absence of symptoms does not necessarily rule out infection, highlighting the importance of screening in asymptomatic minors. These programs are a public health priority and should not be neglected during the current COVID-19 pandemic.

Unravelling the role of the mandatory use of face covering masks for the control of SARS-CoV-2 in schools: a quasi-experimental study nested in a population-based cohort in Catalonia (Spain).

OBJECTIVE: To assess the effectiveness of mandatory use of face covering masks (FCMs) in schools during the first term of the 2021-2022 academic year. DESIGN: A retrospective population-based study. SETTING: Schools in Catalonia (Spain). POPULATION: 599 314 children aged 3-11 years attending preschool (3-5 years, without FCM mandate) and primary education (6-11 years, with FCM mandate). STUDY PERIOD: From 13 September to 22 December 2021 (before Omicron variant). INTERVENTIONS: A quasi-experimental comparison between children in the last grade of preschool (5 years old), as a control group, and children in year 1 of primary education (6 years old), as an interventional group. MAIN OUTCOME MEASURES: Incidence of SARS-CoV-2, secondary attack rates (SARs) and effective reproductive number (R*). RESULTS: SARS-CoV-2 incidence was significantly lower in preschool than in primary education, and an increasing trend with age was observed. Six-year-old children showed higher incidence than 5 year olds (3.54% vs 3.1%; OR 1.15 (95% CI 1.08 to 1.22)) and slightly lower but not statistically significant SAR (4.36% vs 4.59%; incidence risk ratio 0.96 (95% CI 0.82 to 1.11)) and R* (0.9 vs 0.93; OR 0.96 (95% CI 0.87 to 1.09)). Results remained consistent using a regression discontinuity design and linear regression extrapolation approaches. CONCLUSIONS: We found no significant differences in SARS-CoV-2 transmission due to FCM mandates in Catalonian schools. Instead, age was the most important factor in explaining the transmission risk for children attending school.

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.

Fever without source as the first manifestation of SARS-CoV-2 infection in infants less than 90 days old.

Fever without source (FWS) in infants is a frequent cause of consultation at the emergency department, and the emergence of SARS-CoV-2 could affect the approach to those infants. The aim of this study is to define the clinical characteristics and rates of bacterial coinfections of infants < 90 days with FWS as the first manifestation of SARS-CoV-2 infection. This is a cross-sectional study of infants under 90 days of age with FWS and positive SARS-CoV2 PCR in nasopharyngeal swab/aspirate, attended at the emergency departments of 49 Spanish hospitals (EPICO-AEP cohort) from March 1 to June 26, 2020. Three hundred and thirty-three children with COVID-19 were included in EPICO-AEP. A total of 67/336 (20%) were infants less than 90 days old, and 27/67(40%) presented with FWS. Blood cultures were performed in 24/27(89%) and were negative in all but one (4%) who presented a Streptococcus mitis bacteremia. Urine culture was performed in 26/27(97%) children and was negative in all, except in two (7%) patients. Lumbar puncture was performed in 6/27(22%) cases, with no growth of bacteria. Two children had bacterial coinfections: 1 had UTI and bacteremia, and 1 had UTI. C-reactive was protein over 20 mg/L in two children (one with bacterial coinfection), and procalcitonin was normal in all. One child was admitted to the pediatric intensive care unit because of apnea episodes. No patients died.Conclusion: FWS was frequent in infants under 90 days of age with SARS-CoV-2 infection. Standardized markers to rule out bacterial infections remain useful in this population, and the outcome is generally good. What is Known: • Fever without source (FWS) in infants is a common cause of consultation at the emergency department, and young infants have a higher risk of serious bacterial infections (SBI). • The emergence of the new coronavirus SARS-CoV-2 could affect the approach to young infants with FWS in the emergency department. management of those children is a challenge because information about bacterial coinfection and prognosis is scarce. What is New: • SARS-CoV-2 infection should be ruled out in young infants (< 90 days of age) with FWS in areas with community transmission. • Bacterial coinfection rarely coexists in those infants. • Inflammatory markers were not increased in children without bacterial coinfection. • Outcome is good in most patients.