Severe Bacterial Infection Initially Misdiagnosed as MIS-C: Caution Needed.

Working in the era of the novel coronavirus disease 2019 can predispose to cognitive bias. We present a case of life-threatening bacterial infection misdiagnosed as multisystem inflammatory syndrome in children. While multisystem inflammatory syndrome in children-related myocardial dysfunction is now a well-recognized complication of coronavirus disease 2019, a rigorous differential diagnosis approach, notably for infectious etiologies, is paramount.

Impact of COVID-19 pandemic on access to online therapeutic education programs for children with sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a lifelong disease for which outcomes may be influenced by patients' self-care knowledge. Therapeutic education (TPE) is a patient-centered teaching instrument based on patient's adaptative processes and needs. TPE was developed in the Paris area by a pediatric health network using interactive face-to-face meetings. The COVID-19 pandemic has impacted the TPE modalities by promoting online training. Our aims were to evaluate the accessibility of patients with SCD to online TPE. METHODS: We compared sessions of TPE before and after the onset of the pandemic: the number of sessions, performed face-to-face or online, individual or in a group. We also recorded the number of participants in each session and their age, school level, and department in France. FINDINGS: We observed an increase in the total number of trained children, but participation varied greatly according to the geographical area of residence, with a decrease from 22.4% to 4.9% in the proportion of attendees living in the most socio-economically deprived French departments. DISCUSSION: Online TPE is feasible for patients with SCD but with unequal access according to socio-economic status. APPLICATION TO PRACTICE: Access to TPE needs to be improved for patients living in socially disadvantaged areas.

A monocyte/dendritic cell molecular signature of SARS-CoV-2-related multisystem inflammatory syndrome in children with severe myocarditis.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is generally milder than in adults, but a proportion of cases result in hyperinflammatory conditions often including myocarditis. METHODS: To better understand these cases, we applied a multiparametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. Plasma cytokine and chemokine levels and blood cellular composition were measured, alongside gene expression at the bulk and single-cell levels. FINDINGS: The most severe forms of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 that resulted in myocarditis were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomics analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis characterized by sustained nuclear factor κB (NF-κB) activity and tumor necrosis factor alpha (TNF-α) signaling and associated with decreased gene expression of NF-κB inhibitors. We also found a weak response to type I and type II interferons, hyperinflammation, and response to oxidative stress related to increased HIF-1α and Vascular endothelial growth factor (VEGF) signaling. CONCLUSIONS: These results provide potential for a better understanding of disease pathophysiology. FUNDING: Agence National de la Recherche (Institut Hospitalo-Universitaire Imagine, grant ANR-10-IAHU-01; Recherche Hospitalo-Universitaire, grant ANR-18-RHUS-0010; Laboratoire d'Excellence ''Milieu Intérieur," grant ANR-10-LABX-69-01; ANR-flash Covid19 "AIROCovid" and "CoVarImm"), Institut National de la Santé et de la Recherche Médicale (INSERM), and the "URGENCE COVID-19" fundraising campaign of Institut Pasteur.

Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children.

Importance: Multisystem inflammatory syndrome in children (MIS-C) is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but the optimal therapeutic strategy remains unknown. Objective: To compare intravenous immunoglobulins (IVIG) plus methylprednisolone vs IVIG alone as initial therapy in MIS-C. Design, Setting, and Participants: Retrospective cohort study drawn from a national surveillance system with propensity score-matched analysis. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the World Health Organization definition were included. The study started on April 1, 2020, and follow-up ended on January 6, 2021. Exposures: IVIG and methylprednisolone vs IVIG alone. Main Outcomes and Measures: The primary outcome was persistence of fever 2 days after the introduction of initial therapy or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit. The primary analysis involved propensity score matching with a minimum caliper of 0.1. Results: Among 181 children with suspected MIS-C, 111 fulfilled the World Health Organization definition (58 females [52%]; median age, 8.6 years [interquartile range, 4.7 to 12.1]). Five children did not receive either treatment. Overall, 3 of 34 children (9%) in the IVIG and methylprednisolone group and 37 of 72 (51%) in the IVIG alone group did not respond to treatment. Treatment with IVIG and methylprednisolone vs IVIG alone was associated with lower risk of treatment failure (absolute risk difference, -0.28 [95% CI, -0.48 to -0.08]; odds ratio [OR], 0.25 [95% CI, 0.09 to 0.70]; P = .008). IVIG and methylprednisolone therapy vs IVIG alone was also significantly associated with lower risk of use of second-line therapy (absolute risk difference, -0.22 [95% CI, -0.40 to -0.04]; OR, 0.19 [95% CI, 0.06 to 0.61]; P = .004), hemodynamic support (absolute risk difference, -0.17 [95% CI, -0.34 to -0.004]; OR, 0.21 [95% CI, 0.06 to 0.76]), acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, -0.18 [95% CI, -0.35 to -0.01]; OR, 0.20 [95% CI, 0.06 to 0.66]), and duration of stay in the pediatric intensive care unit (median, 4 vs 6 days; difference in days, -2.4 [95% CI, -4.0 to -0.7]). Conclusions and Relevance: Among children with MIS-C, treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course. Study interpretation is limited by the observational design.

COVID-19-Related Fatalities and Intensive-Care-Unit Admissions by Age Groups in Europe: A Meta-Analysis.

Objectives: Precise international estimates of the age breakdown of COVID-19-related deaths and intensive-care-unit (ICU) admissions are lacking. We evaluated the distribution of COVID-19-related fatalities and ICU admissions by age groups in Europe. Materials and methods: On April 6, 2020, we systematically reviewed official COVID-19-related data from 32 European countries. We included countries that provided data regarding more than 10 COVID-19-related deaths stratified by age according to pre-specified age groups (i.e., <40, 40-69, ≥70 years). We used random-effects meta-analysis to summarize the data. Results: Thirteen European countries were included in the review, for a total of 31,864 COVID-19-related deaths (range: 27-14,381 per country). In the main meta-analysis (including data from Germany, Hungary, Italy, The Netherlands, Portugal, Spain, Switzerland; 21,522 COVID-19-related fatalities), the summary proportions of individuals <40, 40-69, and ≥70 years old among all COVID-19-related deaths were 0.1% (0.0-0.2; I 2 28.6%), 13.0% (10.8-15.4; I 2 91.5%), and 86.6% (84.2-88.9; I 2 91.5%), respectively. ICU data were available for four countries (France, Greece, Spain, Sweden). The summary proportions of individuals around <40-50, around 40-69, and around ≥60-70 years old among all COVID-19-related ICU admissions were 5.4% (3.4-7.8; I 2 89.0%), 52.6% (41.8-63.3; I 2 98.1%), and 41.8% (32.0-51.9; I 2 99%), respectively. Conclusions: People under 40 years old represent a small fraction of most severe COVID-19 cases in Europe. These results may help health authorities respond to public concerns and guide future physical distancing and mitigation strategies. Specific measures to protect older people should be considered.

Distinctive Features of Kawasaki Disease Following SARS-CoV-2 Infection: a Controlled Study in Paris, France.

BACKGROUND: An outbreak of multisystem inflammatory syndrome in children, including Kawasaki disease (KD), emerged during COVID-19 pandemic. We explored whether Kawasaki-like disease (KD), when associated with confirmed SARS-CoV-2 infection, has specific characteristics. METHODS: We included children and adolescents with KD criteria admitted in the department of general pediatrics of a university hospital in Paris, France, between January 1, 2018, and May 26, 2020. The incidence of KD was compared between the outbreak and a pre-outbreak control period (January 1, 2018, to April 25). Characteristics of patients with positive SARS-CoV-2 testing (KD-SARS-CoV-2) were compared to those of the pre-outbreak period (classic KD). RESULTS: A total of 30 and 59 children with KD were admitted during the outbreak and pre-outbreak periods, respectively (incidence ratio 13.2 [8.3-21.0]). During the outbreak, 23/30 (77%) children were diagnosed as KD-SARS-CoV-2. When compared with patients with classic KD, those with KD-SARS-CoV-2 were more frequently of sub-Saharan African ancestry (OR 4.4 [1.6-12.6]) and older (median 8.2 vs. 4.0 years, p < 0.001), had more often initial gastrointestinal (OR 84 [4.9-1456]) and neurological (OR 7.3 [1.9-27.7] manifestations, and shock syndrome (OR 13.7 [4.2-45.1]). They had significantly higher CRP and ferritin levels. Noticeably, they had more frequently myocarditis (OR 387 [38-3933]). CONCLUSIONS: Children and adolescents with KD-SARS-CoV-2 have specific features when compared with those with classic KD. These findings should raise awareness and facilitate the study of their pathogenesis.

Association between SARS-CoV-2 infection and Kawasaki-like multisystem inflammatory syndrome: a retrospective matched case-control study, Paris, France, April to May 2020.

We assessed the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and Kawasaki disease (KD)-like multisystem inflammatory syndrome in a retrospective case-control study in France. RT-PCR and serological tests revealed SARS-CoV-2 infection in 17/23 cases vs 11/102 controls (matched odds ratio: 26.4; 95% confidence interval: 6.0-116.9), indicating strong association between SARS-CoV-2 infection and KD-like illness. Clinicians should keep a high level of suspicion for KD-like illness during the COVID-19 pandemic.

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.