cord-030192-ebsh62ll	2020	
cord-035239-5zdjxtm7	2020	title: A Rare Presentation of Multi-System Inflammatory Disease in Children Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) This article reports a rare presentation of multi-system inflammatory disease in a previously healthy 16-month-old male who fully recovered with minimal residual cardiac insufficiency upon discharge. Since April 2020, multiple reports emerged from Europe and later from New York of multi-system inflammatory disease in children (MIS-C) presenting with different clinical patterns that occur from one to six weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the pediatric age group [1] [2] [3] [4] [5] [6] [7] [8] . Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic Characteristics, cardiac involvement, and outcomes of multisystem inflammatory disease of childhood (MIS-C) associated with SARS-CoV-2 infection COVID-19 associated Multisystem Inflammatory Syndrome in Children (MIS-C) guidelines; a Western New York approach Cardiac MRI of children with multisystem inflammatory syndrome (MIS-C) associated with COVID-19: case series
cord-271186-82q22u6i	2020	In their review discussing the effects of Severe Acute Respiratory Syndrome Coronavirus-2 (SARSin children and adolescents, Loke, Berul and Harahsheh highlight the overlapping features between Kawasaki disease (KD) and the recently described inflammatory syndrome called Multisystem Inflammatory Syndrome in Children (MIS-C) [1] . Although in children with MIS-C, the inflammatory response may sometimes be associated with transitory respiratory impairment, this feature is more prominent in adults with COVID-19, who may even require venous-venous extracorporeal membrane oxygenation (V-V ECMO) support. However, notwithstanding the existence of considerable observational data on the use of ECMO for influenza A (H1N1) and Middle East Respiratory Syndrome (MERS) coronavirus-related ARDS, the real utility of ECMO in adult COVID-19 patients with respiratory failure is uncertain and remains under investigation [15] . In conclusion, SARS-CoV-2 may generate an inflammatory syndrome in both adults and children, albeit with several different characteristics and consequences. Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease
cord-271662-h281jgcb	2020	
cord-274834-24v2b509	2020	Although the impact of SARS-CoV-2 infection in children is less clinically apparent, collecting high-quality biospecimens from infants, children, and adolescents in a standardized manner during the COVID-19 pandemic is essential to establish a biologic understanding of the disease in the pediatric population. METHODS: A COVID-19 biospecimen collection study was implemented with strategic enrollment guidelines to include patients seen in urgent care clinics and hospital settings, neonates born to SARS-CoV-2 infected mothers, and asymptomatic children. Specific questions that must be addressed revolve around the role children play in viral transmission, differences in pediatric viral susceptibility and immune responses, which could guide potential therapies for adults, the impact of maternal SARS-CoV-2 infection on fetal development, and factors driving the development of severe hyperinflammatory shock and cardiac damage seen in Multisystem Inflammatory Syndrome in Children (MIS-C). In order to capture the full range of SARS-CoV-2 infection in the pediatric population, a COVID-19 biospecimen collection study was designed and implemented, including patients seen in urgent care clinics and hospital settings, neonates born to SARS-CoV-2-infected mothers, and asymptomatic children.
cord-278672-pxzsntfg	2020	
cord-281948-xv7vuypd	2020	We included published or in press peer-reviewed cross-sectional, case series, and case reports providing clinical signs, imaging findings, and/or laboratory results of pediatric patients who were positive for COVID-19. Data collected included the type of article (e.g., case series), country of origin, number of pediatric patients, demographic information, and all clinical symptoms (e. Compared to that review and other COVID-19 pediatric systematic reviews, [18À21] this manuscript has several key advantages: (1) we summarize 131 studies that includes 7780 children from 26 different countries, (2) this report synthesizes underlying pediatric medical conditions and delineates bacterial and viral coinfections, (3) we quantitatively describe clinical symptoms and imaging findings, (4) herein, we conglomerate the mean and standard deviation of frequently used laboratory analytes in COVID-19 positive children, (5) our report presents antiviral therapies by specific agents, and (6) our systematic review offers a preliminary comparison of patients with/without MIS-C.
cord-293259-o51fnvuw	2020	Thus far, only a small number of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection have involved children, so that they have accounted for only 1-5% of total patients [2, [6] [7] [8] [9] [10] . Severe SARS-CoV-2 infection is characterized by a hyperproinflammatory response or cytokine storm state that results to acute respiratory distress syndrome (ARDS) and multisystem inflammatory syndrome (MIS). The search strategy was constructed based on searching terms 2019 novel coronavirus, COVID-19, SARS-CoV-2 with using and/or, also the terms of child, pediatric, newborn, infant, adolescence, adult, age, age groups, severity, epidemiology, prevalence, difference, immune system, etiology, reasons in title, abstract, and key words. The first results stem from some considerations that children have a less vigorous immune response to the virus than adults because the cytokine storm is thought to be important in the pathogenesis of severe SARS-CoV-2 infections [28] .
cord-293367-0fe62h2f	2020	Since its initial description in December 2019 in Wuhan China, coronavirus disease 2019 , caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly evolved into a worldwide pandemic affecting millions of lives.(1) Unlike adults, the vast majority of children with COVID-19 have mild symptoms. Reports in the literature and unpublished observations by members of the panel both note that some patients with MIS-C can decompensate rapidly; however, the risk factors that predispose patients to such severe and progressive illness have not been identified.(10, 13) Accordingly, children with abnormal vital signs, concerning physical examination findings, significantly elevated inflammatory markers, or signs of cardiac involvement will need to be admitted to the hospital for supportive care while Tier 2 testing is completed.
cord-293715-lipme817	2020	BACKGROUND: Multisystem Inflammatory Syndrome in Children (MIS-C) related to coronavirus disease-2019 (COVID-19) is an emergent syndrome affecting children globally in the wake of the SARS-CoV-2 pandemic. METHOD: This case describes a 14-year-old boy who developed prominent neuropsychiatric symptoms including delirium followed by impairments in executive functioning in the context of MIS-C with positive SARS-CoV-2 antibodies. The recent SARS-CoV-2 pandemic has been associated with emergence of a new syndrome referred to as Multisystem Inflammatory Syndrome in Children (MIS-C) related to coronavirus disease-2019 (COVID19) . Given the paucity of knowledge concerning this syndrome''s effect on the nervous system, the intent of this case report is to describe the neuropsychiatric symptoms in one 14-year-old boy presenting with multisystem inflammatory syndrome and positive SARS-CoV-2 antibodies. Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicenter cohort
cord-294729-c9f0iokr	2020	
cord-301868-ehck72z2	2020	title: Longitudinal Echocardiographic Assessment of Coronary Arteries and Left Ventricular Function Following Multisystem Inflammatory Syndrome in Children (MIS-C) On May 14, 2020, the Centers for Disease Control and Prevention (CDC) recognized this clinical complex as multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 and released a case definition based on clinical and laboratory criteria. [4] MIS-C patients come to medical attention with fever, elevated inflammatory markers, multisystem organ involvement (renal, gastrointestinal, neurologic, dermatologic, cardiac), with evidence of a current or recent SARS-CoV-2 infection or recent close contact with a known or suspected case of COVID-19. We sought to describe the echocardiographic manifestations of MIS-C including evolution of abnormalities of coronary artery dilation and ventricular systolic function over short-term follow-up after discharge from the hospital. Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 Infection: A Multiinstitutional Study from New York City
cord-308046-y9kui730	2020	This syndrome has been termed multisystem inflammatory syndrome in children (MIS-C), and is observed in association with the coronavirus disease 2019 (COVID-19). The majority of patients had a negative COVID PCR at the time of diagnosis, likely because the disease tends to present 4-6 weeks after the viral infection. Documented cutaneous findings reported in children with COVID-19 include non-specific maculopapular eruptions, followed by chilblain-like or pernio-like acral lesions, urticarial lesions, livedo reticularis, papulovesicular or varicella-like lesions, petechiae or dengue-like lesions, and erythema multiforme-like lesions. 19 Looking at all the thirteen-case series presented in Table 3 , the percentage of children diagnosed with MIS-C who developed mucocutaneous findings included: conjunctivitis 27% -93%, oral mucosal changes 25% -87%, eruption 47% -81%, and hand/feed erythema and edema 27% -68%. Multisystem Inflammatory Syndrome in Children (MIS-C) Related to COVID-19: A New York City Experience Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed Management
cord-313058-nrrl4kjc	2020	title: COVID-19 Associated Multisystem Inflammatory Syndrome in Children (MIS-C): a novel disease that mimics Toxic Shock Syndrome. As of mid-September, the novel severe acute respiratory syndrome coronavirus 2 26 (SARS-CoV-2) has infected more than 30 million people, resulting in approximately one 27 million deaths worldwide, including over 200,000 deaths in the USA alone. Exacerbation of the COVID-19 immune response manifested by extensive cytokines 33 release, called cytokine storm, may lead to multisystem inflammatory syndrome that is 34 fatal in 28% of cases 1 . Interestingly, SAg-induced TSS has been associated with long-term 94 neuropsychologic deficits in adults, including cognitive decline 10 , and we identified a 95 homology between the SAg motif of SARS-CoV-2 and neurotoxin-like sequences which 96 are able to bind the TCR 5 . Clinical 131 Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome 132 Temporally Associated With SARS-CoV-2
cord-314662-nem6dw34	2020	Initial reports surfaced in the UK [3] and Italy [4] , followed by New York and other parts of the U.S. Preliminary accounts of the features of this syndrome resemble those of known entities such as Kawasaki Disease (KD), toxic shock syndrome (TSS), and secondary hemophagocytic lymphohistiocytosis (SHLH)/macrophage activation syndrome (MAS). Early consultation of specialists to assist in management, such as intensive care, cardiology, rheumatology, infectious diseases, allergy/immunology, neurology Abbreviations: ALT, alanine transaminase; AST, aspartate transaminase; pro-BNP, pro-B-type natriuretic peptide; BUN, blood urea nitrogen; CRP, C-reactive protein; CT, computed tomography; ESR, erythrocyte sedimentation rate; GI, gastrointestinal; HLH, hemophagocytic lymphohistiocytosis; IL, interleukin; MIS-C, multisystem inflammatory syndrome in children; NK, natural killer; NP, nasopharyngeal; PT, prothrombin time; PTT, partial thromboplastin time; RT-PCR, reverse transcriptase polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
cord-315508-8bcpxo02	2020	Patients with SARS-Cov-2-associated multisystem inflammatory syndrome frequently presented with persistent fever, gastrointestinal symptoms, polymorphic rash, conjunctivitis, and mucosal changes. Notably, a subset of patients presents with hypotension and shock from either acute myocardial involvement or systemic hyperinflammation/vasodilation, frequently requiring intensive care admission, circulatory, and respiratory support (Tables 2 and 3 ) [4, 5, 8, 9, 13-20, 22-25, 27] . Possible causes of myocardial injury in adults with COVID-19 include acute myocarditis, hypoxic injury, ischemic injury caused by cardiac microvascular damage or coronary artery disease, right heart strain (acute cor pulmonale), stress cardiomyopathy (Takotsubo), and systemic inflammatory response syndrome [3, [34] [35] [36] [37] . Due to the scarce knowledge and the small number of reported cases so far, the management of patients with MIS-C has been largely based on expert opinion and extrapolated from KD treatment, adult experience with COVID-19, and other systemic inflammatory disorders in children. Cardiac MRI of children with multisystem inflammatory syndrome (MIS-C) associated with COVID-19: case series Eléonore
cord-317822-e4uhop4w	2020	A growing body of evidence from the UK, Europe and the USA suggests that a number of paediatric patients could present with fever, rash and shock with concomitant COVID-19 infection. Vital signs showed a temperature of 39.5 C, sinus tachycardia (165 beats/min), tachypnoea with normal Key Points 1 A growing body of evidence from the United Kingdom (UK), Europe, and the United States of America (USA) suggests that a number of paediatric patients could present with Kawasakilike symptoms such as fever, rash and shock with concomitant COVID-19 infection which has been referred to multisystem inflammatory syndrome in children (MIS-C). 2 The negative results of polymerase chain reaction (PCR) test for COVID-19 in a patient with high levels of serum IgG could suggest that the virus had been cleared and the presence of Kawasaki-like manifestations may be due to delayed immunemediated phenomenon caused by COVID-19.
cord-322435-c88tkbnz	2020	title: Mucocutaneous Disease and Related Clinical Characteristics in Hospitalized Children and Adolescents with COVID-19 and MIS-C Objective To characterize mucocutaneous disease and its relation to clinical course among hospitalized patients with COVID-19 and MIS-C. [1] [2] [3] [4] [5] In addition to fever and respiratory symptoms, pediatric patients infected with 74 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen in COVID-19, also 75 develop eruptions and mucositis. The purpose of this study was to estimate prevalence of integumentary findings in hospitalized 81 patients with COVID-19 and MIS-C, to characterize their morphologic patterns, to evaluate whether rash 82 Criteria for confirming the diagnosis of MIS-C included age <21 years, fever for ≥24 hours, clinically 89 severe illness requiring hospitalization, multisystem organ involvement, no alternative plausible 90 diagnosis, and exposure to a suspected or confirmed COVID-19 case or positive SARS-CoV-2 infection 91 by PCR/serology testing. Clinical and epidemiological features of 36 children 219 with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study
cord-336049-n3swuykg	2020	INTERPRETATION: Multisystem inflammatory syndrome is a new pediatric disease associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is dangerous and potentially lethal. However, in early May 2020, investigators from South Thames Retrieval Service in London, UK published a report describing eight severely ill pediatric patients presenting in hyperinflammatory shock with multiorgan involvement [6] Specifically, the children manifested with high fever, rash, conjunctivitis, peripheral edema, and gastrointestinal symptoms. We included patients with COVID-19 to reinforce to the healthcare community and public the differences in the clinical presentation, to highlight the degree of systemic inflammation in MIS-C, and to iterate the differences in treatment and outcome between the two diseases. Data collected from the studies included demographics, number of patients, signs and symptoms, laboratory markers, imaging results, medications, and outcomes. Cardiac MRI of children with multisystem inflammatory syndrome (MIS-C) associated with COVID-19: case series
cord-336144-e7hvp9wy	2020	
cord-339709-49q2xxkw	2020	Despite a low frequency of respiratory symptoms, cases of Multisystem Inflammatory 108 Syndrome (MIS) have been reported in children that were infected by SARS-CoV-2 or were in contact 109 with COVID-19 patients 14, 15 . We also analysed SARS-CoV-2 and seasonal HCoVs humoral responses of patients with MIS 122 regarding antibody targets and functional neutralizing activity. Our study is the first to analyse in depth 123 the typology of humoral responses to SARS-CoV-2 in children, and provides evidence that prior 124 infections by seasonal coronaviruses has no significant impact on SARS-CoV-2 infection or related MIS 125 disease in children. We compared the prevalence of anti-N and -S antibodies against the four seasonal HCoVs in a 220 subpopulation of children among the HOS-P (n=54), MIS-P (n=15) and CTL (n=118) groups (Figure 1) .
cord-344683-lr1xr2um	2020	An unbridled host immune response to SARS-CoV-2 infection likely underlies severe cases of the disease and has been labeled a "Cytokine Storm Syndrome". Infection with SARS-CoV-2, the etiologic agent of Coronavirus Disease 2019 (COVID19) , can lead to severe pneumonia, multi-organ failure, and death. Given the clinical and laboratory features, it is reasonable to consider MIS-C as a separate but related entity to the severe multi-organ dysfunction observed in patients with S-CSS (Figure 1 ). A second study showed pediatric patients with MIS-C exhibit distinct cytokine profiles from those with severe SARS-CoV-2 respiratory disease, exhibiting higher IL-10 and TNF [19] . What are the optimal clinical characteristics and biomarkers to identify and classify cases of MIS-C, S-CSS, and other diseases associated with Cytokine Storm Syndrome? Factors associated with death outcome in patients with severe coronavirus disease-19 (COVID-19): a case-control study Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS-CoV-2
cord-350401-suefuurq	2020	title: Multisystem inflammatory syndrome in children (MIS-C) during SARS-CoV-2 pandemic in Brazil: a multicenter, prospective cohort study()()() From March 25 to August 23, 2020, pediatric patients (age range: 1 month -19 years) were consecutively included if they met the CDC case definition[8] for MIS-C: 1) fever > 38.0°C for ≥ 24 hours (objective or subjective); 2) laboratory evidence of inflammation, including, but not limited to, one or more of the following: high values of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase (LDH), or interleukin 6 (IL-6); elevated neutrophils, reduced lymphocytes, and low albumin; 3) no alternative plausible diagnosis; 4) current or recent SARS-CoV-2 infection diagnosed by a positive reverse transcription polymerase chain reaction (RT-PCR) or positive serological tests (IgM, IgG or IgA), or exposure to a suspected or confirmed COVID-19 case within the four weeks prior to the onset of symptoms.
cord-351126-d6lfktf9	2020	
cord-351634-x1aw6gv2	2020	Multisystem inflammatory syndrome in children (MIS-C) affects a small percentage of pediatric patients infected with COVID-19 and is characterized by fever, laboratory evidence of inflammation, multisystem involvement, and severe illness necessitating hospitalization. 1,2 Despite a relatively benign clinical course for most, pediatric patients may rarely exhibit exaggerated immune responses that fall on a spectrum ranging from a mild febrile inflammatory state without multisystem involvement, to a moderate Kawasaki disease (KD)-like illness, to a severe multisystem inflammatory syndrome with shock. 3 Beginning in late April 2020, multisystem inflammatory syndrome in children (MIS-C) became an increasingly recognized hyperinflammatory phenotype in pediatric patients with evidence of COVID-19 infection. detailed 78 cases of pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), which is very similar to MIS-C but with a slightly less restrictive case definition, particularly patients may exhibit single organ system dysfunction and may or may not require hospitalization.
cord-354093-zdhfyotl	2020	This review focuses on cardiac involvement during COVID-19 infection and the multisystem inflammatory syndrome in children (MIS-C) [6, 7] . Cardiac involvement, which can manifest as acute myocardial injury with elevated plasma troponin concentration, acute coronary events, heart failure and arrhythmias is both common and associated with a higher morbidity and mortality in adults with COVID-19 [8] [9] [10] . Cardiac involvement during COVID-19 is not common in children who require pediatric intensive care unit (PICU) admission; use of inotropes was reported in 12 (25%) patients admitted to a North American PICU in a recent study [4] . Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19 Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 Clinical Guidance for Pediatric Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 and Hyperinflammation in COVID-19
cord-354608-1me3nopu	2020	By mid-August 2020, the World Health Organization reported over 23 million confirmed cases of infection with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), resulting in more than 710,000 death worldwide [1] . We review the current evidence of epidemiology, clinical presentation, treatment, and indirect health consequences of SARS-CoV-2 on children. In reports from countries that were severely affected early in course of the pandemic, children comprise 1-2% the diagnosed COVID-19 cases, underrepresented compared with other age groups [3, [13] [14] [15] . In summary, children at any age may be infected with SARS-CoV-2, with reduced frequency and severity compared with adults, although clear epidemiologic data is still missing. Characteristics and outcomes of children with coronavirus disease 2019 (COVID-19) infection admitted to US and Canadian Pediatric Intensive Care Units American College of Rheumatology Clinical Guidance for Pediatric Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) associated with SARS-CoV-2 and hyperinflammation in COVID-19.
cord-355636-mq7xb9d4	2020	Various surgical societies published guidelines which were not in favour of minimally invasive surgery (MIS) due to the perceived risk of virus spread from aerosolisation 2,3 . Guidelines have suggested caution with a perceived risk of virus spread through aerosol generating procedures (AGPs) including laparoscopy and robotic surgery. All patients for elective surgery were self-isolated for two weeks and had COVID-19 test performed 48 hours before the procedure. Emergency surgery patient underwent PCR COVID-19 test prior to their procedure where feasible. During the study period, there was no COVID-19 positive case reported amongst the patients in the MIS group or theatre staff. This data would suggest that, with appropriate screening of patients and protection of theatre staff as outlined, MIS is safe and feasible. Patients should not be denied the clear advantages of laparoscopic surgery over open surgery during the current COVID-19 pandemic.