Neurological manifestations of Kawasaki disease and multisystem inflammatory syndrome in children associated with COVID-19: A comparison of two different clinical entities.

Kawasaki disease (KD) is one of the most frequent idiopathic vasculitis in children, affecting medium- and small-sized vessels. Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 has recently emerged as a new systemic hyperinflammatory condition affecting children some weeks after an acute COVID-19 infection. KD and MIS-C share different aspects and differ in many others: patients affected by MIS-C are usually older, with prominent gastrointestinal manifestations, diffuse adenopathy, extensive conjunctivitis, myocardial damage, leukopenia, and thrombocytopenia at the laboratory exams. Both conditions can present neurological complications. The aim of this manuscript is to provide a narrative review of neurological involvement in KD and MIS-C. A comprehensive review literature has been performed, and the main clinical features have been analyzed, contributing to neurological differential diagnosis.

Neurological manifestations of Kawasaki disease and multisystem inflammatory syndrome in children associated with COVID-19: A comparison of two different clinical entities

Kawasaki disease (KD) is one of the most frequent idiopathic vasculitis in children, affecting medium- and small-sized vessels. Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 has recently emerged as a new systemic hyperinflammatory condition affecting children some weeks after an acute COVID-19 infection. KD and MIS-C share different aspects and differ in many others: patients affected by MIS-C are usually older, with prominent gastrointestinal manifestations, diffuse adenopathy, extensive conjunctivitis, myocardial damage, leukopenia, and thrombocytopenia at the laboratory exams. Both conditions can present neurological complications. The aim of this manuscript is to provide a narrative review of neurological involvement in KD and MIS-C. A comprehensive review literature has been performed, and the main clinical features have been analyzed, contributing to neurological differential diagnosis

Acute cardiac compromission in patients with MIS-C

Background and Aim: Multisystem inflammatory syndrome in chil-dren (MIS-C) is a late manifestation of SARS-CoV-2 infection. Cardiac involvement is common and presents as ventricular dys-function, shock, and coronary anomalies. The aim of the study is evaluate the influence of cardiac disfunction on clinical presen-tations and outcomes in a single center. Method(s): A retrospective study on patients diagnosed with MIS-C and referred to Buzzi Children's Hospital in Milan from November 2020 to February 2021. Patients were treated with intravenous immunoglobulins, corticosteroids and anti-throm-botic prophylaxis, in respect to our approved multidisciplinary protocol. According to the admission cardiac left ventricular ejec-tion fraction (LVEF), the patients were divided into group A (LVEF lt;45%) and group B (LVEF >=45%). Result(s): We collected 32 consecutive patients. Group A included 10 patients (9M/1F, aged 13 years [IQR 5-15]), and group B included 22 patients (15M/7M, aged 9 years [IQR 7-13]). At the presentation, significant differences were observed among shock (group A 6/10 vs group B 2/22, plt;0.01), gastrointestinal involvement (9/10 vs 11/22, p = 0.04) and duration of fever (5.3 vs 6.9 days, p = 0.02). All patients in group A required inten-sive care hospitalization (10/10 vs 12/22, p = 0.01). Interestingly, despite good cardiac function, two patients in group B presented with shock, probably due to vasoplegic/distributive cardiocircula-tory impairment secondary to the inflammatory state. Among biochemistry parameters, leukocytes, neutrophils, and CRP were significantly worse in group A (p = 0.001, p = 0.001 and p = 0.008, respectively). Pathological level of troponin T and NTproBNP were detected in all patients in group A and also in 33% and 77% of group B;with statistically significant higher median values in group A (Troponin T 72 [40-243] ng/L vs 22 [8-49] ng/L, p = 0.01;NTproBNP 14825 [11340-17810] ng/L vs 5921 [1114-11243] ng/L, p = 0.01). In group A, mitral regurgitation was more frequent (plt;0.01) and one patient had transient left main coronary dilation (Boston z-score +2.39). At the discharge, cardiac function normalized in all patients. Total length of hospital stay and cardiac recovery time were not statistically different between groups. Conclusion(s): If correctly diagnosed and early treated, all the MIS-C patients completely recovered, regardless of the initial cardiac involvement.

CHARACTERIZATION of HIV and SARS-CoV-2 COINFECTION: ROLE of IL-10

Background: Interaction between HIV and SARS-CoV-2 infection has not yet been fully characterized. To this purpose, an in-vitro HIV/SARS-CoV-2 coinfection assay was set up. Furthermore, the results obtained in the in-vitro model were verified in a cohort of HIV/SARS-CoV-2 coinfected young individuals. Methods: We designed an in-vitro SARS-CoV-2/HIV coinfection. We challenged PBMCs derived from 10 healthy volunteers with 1 ng/1×106 cells of HIV-1BaL and subsequently co-cultured them with a human lung epithelial cell line (CaLu3) infected with SARS-CoV-2 at 0.015 MOI. At 96 hours post HIV-1 infection, both PBMCs and CaLu3 cells were harvested for mRNA expression and proteomic analysis. Furthermore, we enrolled 85 ART-treated HIV-vertically transmitted patients (mean age 22.4 years) followed at the Unit of Pediatric Infectious Diseases, Sacco Hospital in Milan, Italy. Real-time PCR was performed to detect SARS-CoV-2 and plasma samples were tested for anti-SARS-CoV-2-specific IgG (Euroimmun Kit). The subjects who contracted SARS-CoV-2 infection (H+/S+) were compared to the HIV-positive, SARS-CoV-2 negative ones (H+/S-) and to a cohort of SARS-CoV-2 positive, HIV-negative age-matched patients (H-/S+, mean age 22.8 years). We evaluated mRNA expression of factors involved in the anti-viral immune response on PBMCs upon stimulation with SARS-CoV-2 antigens (Quantigene Plex assay) and secreted cytokines/chemokines on plasma (Multiplex Cytokine Array). Results: We observed a significant reduction of SARS-CoV-2 replication on CaLu3 cells when exposed to HIV-pre-infected PBMCs in-vitro. IL-10 expression and production were significantly higher in the coinfected condition, in both CaLu3 cells and PBMCs. The upregulation of IL-10 was associated to higher expression levels of STAT3. In the HIV-vertically transmitted cohort, 4 out of 85 subjects contracted SARS-CoV-2 infection (H+/S+). All H+/S+ patients were asymptomatic. Similarly to the data obtained in-vitro, a significant increase in both expression and production of IL-10 emerged in comparison to H+/S-and H-/S+. Conclusion: In-vitro, a dampening in SARS-CoV-2 replication, along with a higher IL-10 mRNA expression and production, have been observed in the HIV/SARS-CoV-2 coinfected condition. Presumably, IL-10 exerted its activity through the STAT3 pathway. These results were confirmed in HIV/SARS-CoV-2 coinfected subjects in which an upregulation of IL-10 was observed. Our data might be useful defining HIV/SARS-CoV-2 coinfected young individuals pathogenesis.

SARS-COV-2: Its implications in the paediatric population

By the end of December 2019 there was an outbreak of polmonitis of a new coronavirus named SARS-CoV-2. Until now there have been 76,727 cases, 2,247 deaths and 18,562 healed patients in China and less than 1,200 cases in the rest of the world. Few data are available regarding the epidemiology and the clinical manifestations in the paediatric population, nonetheless the virus seems to be affecting this population way less severely than the adults. This data may be due to an understatement of children's involvement, since they seem to have very scarce symptoms. The question that arises is: Can those mildly symptomatic or asymptomatic paediatric cases infect others therefore enhancing the virus transmission?.

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.