Project description:Data on COVID-19 vaccine acceptability among parents of children with multisystem inflammatory syndrome (MIS-C) are limited. In this cohort of children with MIS-C, enrolled in the Swissped RECOVERY trial (NCT04826588), comparing intravenous immunoglobulins or methylprednisolone, who, in accordance with Swiss guidelines, were recommended for SARS-CoV-2 vaccination, 65% (73/112) of parents reported being vaccinated against SARS-CoV-2 before the MIS-C, while 70% were vaccinated after the MIS-C episode of their child. None of the children were vaccinated before the occurrence of the MIS-C, and only 9% (5/56) received the COVID-19 vaccine after the MIS-C. The predominant barriers to COVID-19 vaccination were concerns over potential side effects and insufficient support from their doctors. This emphasizes the crucial role of health care providers in promoting COVID-19 vaccination among children.
Project description:While fewer cases of severe Coronavirus Disease 2019 (COVID-19) are reported globally in children, a small proportion of SARS-CoV-2 infected children develop a novel pediatric febrile entity called multisystem inflammatory syndrome in children (MIS-C) that develops 2 to 5 weeks after initial SARS-CoV-2 exposure. MIS-C primarily effects male children and children of Hispanic or black descent. MIS-C manifests as a severe and uncontrolled inflammatory response with multiorgan involvement. A hyperinflammatory state is evidenced by clinical makers of inflammation including high levels of C-reactive protein (CRP), ferritin, and D-dimers, and an increased expression of pro-inflammatory cytokines. Children often present with persistent fever, severe gastrointestinal symptoms, cardiovascular manifestations, respiratory symptoms and neurological symptoms6-11,13. Cardiovascular manifestations include hypotension, shock, cardiac dysfunction, myocarditis and pericardial effusion. In the united states, admission to the intensive care unit occurs in approximately 58% of cases. To understand disease pathogenesis of MIS-C and proteins associated with the severe form of disease we performed proteomics analysis of serum or plasma samples. We collected serum from healthy children (SARS-CoV-2 negative, n=20), mild MIS-C (non-ICU, n=5) and severe MIS-C (ICU, n = 20) patients. MIS-C definition and diagnosis was performed according to CDC guidelines. Healthy adult serum (n = 4) was also used for reference ranges quality control and we obtained plasma samples from Kawasaki Disease (KD; n=7) patients that were recruited before the Coronavirus Disease 2019 (COVID-19) pandemic.
Project description:In a subset of children and adolescents, SARS-CoV-2 infection leads to multisystem inflammatory syndrome in children (MIS-C), a severe hyperinflammatory shock occurring 4-8 weeks post-infection. MIS-C is characterized by a specific expansion of TCRVβ21.3+ T-cells and systemic hyperinflammation, with an unclear pathogenesis. Here, we show that acute MIS-C exhibits impaired reactivation of virus-specific memory T cells due to elevated TGF-β levels, mirroring severe COVID-19 in adults. Functionally, the impaired T-cell cytotoxicity is accompanied by TGF-β-response signatures and reduced antigen-presentation capabilities of monocytes, reversible by TGF-β blockade. MIS-C TCRVβ21.3+ T cells resemble Epstein-Barr Virus (EBV)-reactive T cells, displaying enhanced capability in eliminating EBV-infected B cells. Clinically, active MIS-C correlates with TGF-β-induced defects in T-cell cytotoxicity, elevated EBV seroprevalence, and EBV-reactivation. Our findings establish a connection between SARS-CoV-2 infection and COVID-19 sequelae in children, where reduced T-cell cytotoxicity induced by SARS-CoV-2-triggered TGF-β overproduction leads to EBV-reactivation and contributes to hyperinflammation.
Project description:Parents' awareness of malocclusion and the appropriate timing to seek orthodontic consultation for their children has a substantial impact on children's orthodontic treatment. This cross-sectional study aims to investigate parents' awareness of malocclusion and orthodontic consultation of their children and the influence of parents' demographics on their awareness level. An electronic survey collected information about participants' demographics and awareness about malocclusion and orthodontic consultation of children. A total of 473 parents living in Jeddah, Saudi Arabia, participated in the study. The average awareness level among parents was moderate (3.09 ± 1.4). Male gender and unemployment were associated with low orthodontic awareness levels relative to moderate awareness (OR = 3.3, 95% CI = 1.8-5.8 and OR = 2.1, 95% CI = 1.1-3.8, respectively). Former or current orthodontic treatment was associated with high awareness levels (OR = 3.9, 95% CI = 2.4-6.5). There is still a need to raise the awareness of Saudi parents about malocclusion and orthodontic consultations for their children. Orthodontic awareness-raising campaigns should be designed to include fathers and parents with low socioeconomic status. The findings of this study also suggest that orthodontists can enhance their patient's awareness of malocclusion and orthodontic consultation for their children.
Project description:BackgroundEvidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2.MethodsWe 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.ResultsData 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.ConclusionsWe 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.).
Project description:ObjectiveTo describe the similarities and differences in the evaluation and treatment of multisystem inflammatory syndrome in children (MIS-C) at hospitals in the US.Study designWe conducted a cross-sectional survey from June 16 to July 16, 2020, of US children's hospitals regarding protocols for management of patients with MIS-C. Elements included characteristics of the hospital, clinical definition of MIS-C, evaluation, treatment, and follow-up. We summarized key findings and compared results from centers in which >5 patients had been treated vs those in which ≤5 patients had been treated.ResultsIn all, 40 centers of varying size and experience with MIS-C participated in this protocol survey. Overall, 21 of 40 centers required only 1 day of fever for MIS-C to be considered. In the evaluation of patients, there was often a tiered approach. Intravenous immunoglobulin was the most widely recommended medication to treat MIS-C (98% of centers). Corticosteroids were listed in 93% of protocols primarily for moderate or severe cases. Aspirin was commonly recommended for mild cases, whereas heparin or low molecular weight heparin were to be used primarily in severe cases. In severe cases, anakinra and vasopressors frequently were recommended; 39 of 40 centers recommended follow-up with cardiology. There were similar findings between centers in which >5 patients vs ≤5 patients had been managed. Supplemental materials containing hospital protocols are provided.ConclusionsThere are many similarities yet key differences between hospital protocols for MIS-C. These findings can help healthcare providers learn from others regarding options for managing MIS-C.
Project description:Incomplete childhood immunization against communicable diseases is a major concern and vaccine hesitancy remains a hurdle to overcome in primary vaccination programs. This study was to examine the parents' vaccine knowledge, awareness and hesitancy in relation to their children's immunization status. A cross-sectional questionnaire study design was used. The parents who brought their children for immunization visit or follow-up at four public health clinics located in Sandakan district were invited to participate in this survey. Informed consent was obtained before each participant completed a hard copy of self-administered questionnaire in either English or Malay versions. Of 405 parents responded, they generally had good knowledge and awareness of vaccines, only a small percentage (6.8%) of parents were found vaccine hesitant. There were significant differences in vaccine knowledge and awareness in those from different education levels and employment status; similarly, these two factors also significantly affected the vaccine hesitancy among the parents. The parents' knowledge score was found to be moderately associated with their awareness (r = 0.551, p < 0.01) and inversely correlated to vaccine hesitancy (r = -0.397, p < 0.01). Most of the children (n = 376, 92.8%) in the study were immunized. The children's immunization status was significantly associated with the parents' education level (p = 0.025). There was also a significant difference in the total vaccine knowledge scores between the groups of parents with different child immunization status (p = 0.05). This study revealed that parents with higher education had a better knowledge of vaccinations, were less vaccine hesitant and were more likely to ensure that their children complete the recommended course of immunization. It is crucial to ensure parents are well-informed about the safety and efficacy of vaccines so that the children are protected from communicable diseases by the child vaccination program.
Project description:Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection1,2, yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of samples from patients with MIS-C to identify a distinct set of host proteins targeted by patient autoantibodies including a particular autoreactive epitope within SNX8, a protein involved in regulating an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed antibody responses from patients with MIS-C to the complete SARS-CoV-2 proteome and found enriched reactivity against a distinct domain of the SARS-CoV-2 nucleocapsid protein. The immunogenic regions of the viral nucleocapsid and host SNX8 proteins bear remarkable sequence similarity. Consequently, we found that many children with anti-SNX8 autoantibodies also have cross-reactive T cells engaging both the SNX8 and the SARS-CoV-2 nucleocapsid protein epitopes. Together, these findings suggest that patients with MIS-C develop a characteristic immune response to the SARS-CoV-2 nucleocapsid protein that is associated with cross-reactivity to the self-protein SNX8, demonstrating a mechanistic link between the infection and the inflammatory syndrome, with implications for better understanding a range of post-infectious autoinflammatory diseases.
Project description:BackgroundUnderstanding 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.MethodsWe 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.ResultsWe 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%).ConclusionsMultisystem 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.).