Kawasaki Disease in the Time of COVID-19 and MIS-C - The International Kawasaki Disease Registry.

BACKGROUND: Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) and Kawasaki disease (KD) have overlapping clinical features. We compared demographics/clinical presentation, management, and outcomes of patients by evidence of prior SARS-CoV-2 infection. METHODS: The International KD Registry (IKDR) enrolled KD and MIS-C patients from sites from North, Central and South America, Europe, Asia and Middle East. Evidence of prior infection was defined as: Positive (+ve household contact or positive PCR/serology), Possible (suggestive clinical features of MIS-C and/or KD with negative PCR or serology but not both), Negative (negative PCR and serology and no known exposure), and Unknown (incomplete testing and no known exposure). RESULTS: Of 2345 enrolled patients SARS-CoV-2 status was Positive for 1541 (66%) patients, Possible 89 (4%), Negative 404 (17%) and Unknown for 311 (13%) patients. Clinical outcomes varied significantly between the groups, with more patients in the Positive/Possible groups presenting with shock, having admission to Intensive Care, receiving inotropic support, and having longer hospital stays. Regarding cardiac abnormalities, patients in the Positive/Possible groups had a higher prevalence of left ventricular dysfunction, while patients in the Negative and Unknown groups had more severe coronary artery abnormalities. results CONCLUSION: : There appears to be a spectrum of clinical features from MIS-C to KD with a great deal of heterogeneity, and one primary differentiating factor is evidence for prior acute SARS CoV2 infection/exposure. SARS-CoV-2 Positive/Possible patients had more severe presentations and required more intensive management, with a greater likelihood of ventricular dysfunction but less severe coronary artery adverse outcomes, in keeping with MIS-C.

Emerging Insights Into the Pathophysiology of Multisystem Inflammatory Syndrome Associated With COVID-19 in Children.

Multisystem inflammatory syndrome in children (MIS-C) has emerged as a rare delayed hyperinflammatory response to SARS-CoV-2 infection and causes severe morbidity in the pediatric age group. Although MIS-C shares many clinical similarities to Kawasaki disease (KD), important differences in epidemiologic, clinical, immunologic, and potentially genetic factors exist and suggest potential differences in pathophysiology and points to be explored and explained. Epidemiologic features include male predominance, peak age of 6 to12 years, and specific racial or ethnicity predilections. MIS-C is characterized by fever, prominent gastrointestinal symptoms, mucocutaneous manifestations, respiratory symptoms, and neurologic complaints, and patients often present with shock. Cardiac complications are frequent and include ventricular dysfunction, valvular regurgitation, pericardial effusion, coronary artery dilation and aneurysms, conduction abnormalities, and arrhythmias. Emerging evidence regarding potential immunologic mechanisms suggest that an exaggerated T-cell response to a superantigen on the SARS-CoV-2 spike glycoprotein-as well as the formation of autoantibodies against cardiovascular, gastrointestinal, and endothelial antigens-are major contributors to the inflammatory milieu of MIS-C. Further studies are needed to determine both shared and distinct immunologic pathway(s) that underlie the pathogenesis of MIS-C vs both acute SARS-CoV-2 infection and KD. There is evidence to suggest that the rare risk of more benign mRNA vaccine-associated myopericarditis is outweighed by a reduced risk of more severe MIS-C. In the current review, we synthesize the published literature to describe associated factors and potential mechanisms regarding an increased risk of MIS-C and cardiac complications, provide insights into the underlying immunologic pathophysiology, and define similarities and differences with KD.

COVID-19 Positive Versus Negative Complete Kawasaki Disease: A Study from the International Kawasaki Disease Registry.

To determine clinical differences for children with complete Kawasaki disease (KD) with and without evidence of preceding SARS-CoV-2 infection. From January 2020, contemporaneous patients with complete KD criteria were classified as either SARS-CoV-2 positive (KDCOVID+; confirmed household exposure, positive PCR and/or serology) or SARS-CoV-2 negative (KDCOVID-; negative testing and no exposure) and compared. Of 744 patients in the International Kawasaki Disease Registry, 52 were KDCOVID- and 61 were KDCOVID+. KDCOVID+ patients were older (median 5.5 vs. 3.7 years; p < 0.001), and all additionally met diagnostic criteria for multisystem inflammatory syndrome in children (MIS-C). They were more likely to have abdominal pain (60% vs. 35%; p = 0.008) and headache (38% vs. 10%; p < 0.001) and had significantly higher CRP, troponin, and BUN/creatinine, and lower hemoglobin, platelets, and lymphocytes. KDCOVID+ patients were more likely to have shock (41% vs. 6%; p < 0.001), ICU admission (62% vs. 10%; p < 0.001), lower left ventricular ejection fraction (mean lowest LVEF 53% vs. 60%; p < 0.001), and to have received inotropic support (60% vs. 10%; p < 0.001). Both groups received IVIG (2 doses in 22% vs. 18%; p = 0.63), but KDCOVID+ were more likely to have received steroids (85% vs. 35%; p < 0.001) and anakinra (60% vs. 10%; p = 0.002). KDCOVID- patients were more likely to have medium/large coronary artery aneurysms (CAA, 12% vs. 0%; p = 0.01). KDCOVID+ patients differ from KDCOVID-, have more severe disease, and greater evidence of myocardial involvement and cardiovascular dysfunction rather than CAA. These patients may be a distinct KD phenotype in the presence of a prevalent specific trigger.

Management of MIS-C (Multi-system Inflammatory Syndrome in Children): Decision-making regarding a new condition in the absence of clinical trial data.

Multisystem inflammatory syndrome in children (MIS-C) is a new illness that evolved during the COVID-19 pandemic with initial reports of severe disease including use of extracorporeal membrane oxygenation and death. Institutions rapidly assembled task forces to develop treatment algorithms. At the national/international levels, collaboratives and associations assembled consensus writing groups to draft guidelines. These guidelines and algorithms were initially based on expert opinion and small case series. Some groups utilized the Delphi approach, and the resultant guidelines often mimicked those for other conditions that resembled MIS-C, like Kawasaki disease (KD). For instance, intravenous immunoglobulin (IVIG), a known effective treatment in KD, was recommended for MIS-C. Early in the pandemic many favored IVIG over steroids as first line therapy. As evidence evolved so did some guidelines which now endorse the dual use of IVIG plus steroids as first line therapy. In contrast, withholding immunotherapy became an option for some MIS-C patients with mild symptoms. Here, we review guidelines and discuss the evidence informing early recommendations, how this has evolved, the role and limitations of expert opinion and observational data, and the importance of leveraging existing research infrastructures, such as the intensive care unit collaborative (Overcoming COVID-19 surveillance registry), and the International KD Registry. Finally, we discuss strategies to rapidly develop, deploy and adapt clinical trials evaluating the treatment of such rare conditions in children, which may include alternatives to conventional clinical trial design. The emergence of MIS-C during the COVID-19 pandemic has highlighted unmet needs regarding research of a new condition.

The Future Is Now: Preparing Sport Management Graduates in Times of Disruption and Change.

COVID-19 disrupted the world, and the impacts have been experienced in many areas, including sport and higher education. Sport management academicians need to reflect on the past two years' experience, determine what worked and what did not work, and avoid the temptation of automatically returning to past practices. The authors of this manuscript applied the disruption literature and propose transformative changes in what sport management academicians teach (e.g., greater emphasis on innovation, entrepreneurship, automation, critical thinking skills to facilitate working in flexible environments and across areas), how colleagues teach (e.g., heightened integration of technology, blended learning models) and where colleagues teach (on-campus and distal delivery modes, asynchronous and synchronous delivery to students on campus and across regions/countries). Examples of start-up companies and entrepreneurial ventures are offered to help illustrate the changing sports landscape and the emerging opportunities for current and future students, graduates, and professors. Sport management professors are offered some suggestions to assist them in seizing this opportunity.