Multisystem Inflammatory Syndrome In Children Cases Research Articles

Should aortic stiffness parameters be used in MIS-C patient follow-up?

We evaluated the short- and long-term effects of multisystem inflammatory syndrome in children (MIS-C) on their cardiovascular system. The study population consisted of 38 MIS-C patients and 55 control patients. Standard echocardiographic measurements and aortic stiffness parameters were compared between the two groups at different time points. During the standard echocardiographic examination at the time of diagnosis, mitral valve insufficiency was detected in 42% of the cases, left ventricular systolic dysfunction in 36%, aortic valve insufficiency in 3%, tricuspid valve insufficiency in 13%, and coronary artery dilatation in 31%. The ejection fraction, pulse pressure of the experimental group were significantly lower than the control group (p < 0.01, p = 0.045, respectively). When aortic stiffness parameters were compared, it was seen that the parameters increased in the experimental group and the difference was significant for aortic distensibility. (p = 0.105, p = 0.029 respectively). When comparing the experimental group's results at diagnosis and at the sixth month, there was a decrease in aortic stiffness parameters at the sixth month compared to the time of diagnosis, but the difference wasn't significant (p = 0.514, p = 0.334). However, no statistically significant difference was detected when comparing the aortic distensibility results of the experimental group with the control group at the sixth month (p = 0.667). Our results showed that many pathological echocardiographic findings detected at diagnosis in MIS-C patients returned to normal within six months. Therefore, we believe that the cardiovascular follow-up period of MIS-C cases should be at least six months.

Plasma Protein Biomarkers Distinguish Multisystem Inflammatory Syndrome in Children From Other Pediatric Infectious and Inflammatory Diseases.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious hyperinflammatory complication following infection with severe acute respiratory syndrome coronavirus 2. The mechanisms underpinning the pathophysiology of MIS-C are poorly understood. Moreover, clinically distinguishing MIS-C from other childhood infectious and inflammatory conditions, such as Kawasaki disease or severe bacterial and viral infections, is challenging due to overlapping clinical and laboratory features. We aimed to determine a set of plasma protein biomarkers that could discriminate MIS-C from those other diseases. Seven candidate protein biomarkers for MIS-C were selected based on literature and from whole blood RNA sequencing data from patients with MIS-C and other diseases. Plasma concentrations of ARG1, CCL20, CD163, CORIN, CXCL9, PCSK9 and ADAMTS2 were quantified in MIS-C (n = 22), Kawasaki disease (n = 23), definite bacterial (n = 28) and viral (n = 27) disease and healthy controls (n = 8). Logistic regression models were used to determine the discriminatory ability of individual proteins and protein combinations to identify MIS-C and association with severity of illness. Plasma levels of CD163, CXCL9 and PCSK9 were significantly elevated in MIS-C with a combined area under the receiver operating characteristic curve of 85.7% (95% confidence interval: 76.6%-94.8%) for discriminating MIS-C from other childhood diseases. Lower ARG1 and CORIN plasma levels were significantly associated with severe MIS-C cases requiring inotropes, pediatric intensive care unit admission or with shock. Our findings demonstrate the feasibility of a host protein biomarker signature for MIS-C and may provide new insight into its pathophysiology.

1094. Comparison of Demographic and Clinical Characteristics in Survivors Vs. Decedents with Multisystem Inflammatory Syndrome in Children (MIS-C) During the COVID-19 Pandemic—CDC National Surveillance, February 2020-December 2022

Abstract Background Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe complication of SARS-CoV-2. Identifying clinical and demographic characteristics associated with MIS-C mortality and description of MIS-C decedents over time may help identify children at increased risk for poor outcomes and potentially inform treatment decisions. Methods This investigation included all MIS-C cases with known outcome reported to CDC MIS-C national surveillance from February 2020─December 2022. Clinical and demographic characteristics were compared between survivors and decedents. Decedents were described over time and classified by date of MIS-C illness onset into five pandemic waves corresponding to five peaks of MIS-C activity (Figure 1): (1) 2/19/2020─6/28/2020, (2) 6/29/2020─10/17/2020, (3) 10/18/2020─7/8/2021, (4) 7/9/2021─12/7/ 2021, and (5) 12/8/2021─12/31/2022. Waves 4 and 5 were periods of predominant Delta and Omicron SARS-CoV-2 variant circulation, respectively.Figure 1.Multisystem Inflammatory Syndrome in Children (MIS-C) Decedents by Pandemic MIS-C Wave, February 19, 2020-December 31, 2022, N=76 Results Seventy-six decedents and 8,691 survivors were reported (Table). A higher proportion of decedents compared with survivors were aged 16-20 years (41% vs 9%; p&amp;lt; 0.01), from the South (55% vs 41%; p=0.01) and had MIS-C illness onset in wave 1 (18% vs 7%; p&amp;lt; .01). Half (51%) of decedents had an underlying medical condition compared with 24% of survivors (p&amp;lt; 0.01). A higher proportion of decedents than survivors had severe cardiovascular (95% vs 76%), respiratory (99% vs 36%), renal (59% vs 19%), and neurologic (30% vs 4%) involvement, and fewer had mucocutaneous (33% vs 75%). Deaths in the 16-20 age group were predominant in waves 1-4 but comprised only 15% of deaths in wave 5, when 57% of decedents were aged 0-4 years (Figure 2). Race and ethnicity of decedents varied over time. Severe cardiovascular and respiratory involvement was high ( &amp;gt;85-100%) over time in decedents; other organ manifestations varied by MIS-C wave.Table.Demographic and Clinical Characteristics of Children with Multisystem Inflammatory Syndrome in Children (MIS-C)-CDC National Surveillance, February 2020-December 2022Figure 2.Demographic Characteristics and Organ Involvement of Children with Multisystem Inflammatory Syndrome in Children (MIS-C) Who Died Stratified by Pandemic MIS-C Wave, February 19, 2020-December 31, 2022, N=76 Conclusion Older age (16-20 years), residing in the South, illness early in the pandemic, underlying medical conditions, and severe organ involvement were all significantly associated with death among children with MIS-C. MIS-C decedent characteristics are dynamic and may continue to evolve with changes in underlying population immunity, SARS-CoV-2 transmission, and variant emergence. Disclosures All Authors: No reported disclosures

488. Initial laboratory markers may help distinguish between Kawasaki Disease and Multisystem Inflammatory Syndrome in Children

Abstract Background In May of 2020, the Centers for Disease Control and Prevention defined a new diagnosis, Multisystem Inflammatory Syndrome in Children (MIS-C), described as a Kawasaki-like illness and related to the SARS-CoV-2 virus. Patients with this syndrome met criteria for inflammation, along with multiple organ system involvement. Clinically distinguishing between Kawasaki Disease (KD) and MIS-C is challenging due to significant overlap between the two disease entities. Furthermore, approximately 25-50% of MIS-C cases also meet criteria for KD. Currently there is very limited data describing specific differences in laboratory markers between KD and MIS-C to guide clinicians in diagnosis and management. This study aims to assess if quantitative laboratory data markers help distinguish between KD and MIS-C. Methods We conducted a retrospective study of patients hospitalized within two network pediatric hospitals with the diagnosis of MIS-C [M35.81] or Kawasaki Disease [M30.3] between January 1, 2019 and March 31, 2021. Children with an alternate diagnosis at discharge were excluded. Demographic characteristics and laboratory data were recorded and analyzed. Results A total of 91 pediatric patients were included in the study: 40 with MIS-C and 45 with KD. Patients with MIS-C were significantly older with a median age 5.3 years, compared to 2.4 years for KD (p=0.001). Patients with KD presented with higher median white blood cell (WBC) count, absolute lymphocyte count, and platelet count compared to those with MIS-C (p&amp;lt; 0.001). A higher alanine aminotransferase (ALT) was also noted (p=0.01). Patients with MIS-C were noted to have higher median ferritin levels and C-reactive protein (CRP) (p&amp;lt; 0.001) (Table 1). Conclusion Both MIS-C and KD are autoinflammatory disease processes that have significant overlap. Identifying differences in initial laboratory values upon presentation can lead to earlier diagnosis. A normal ferritin level may indicate KD. Disclosures All Authors: No reported disclosures

Clinical Syndromes Related to SARS-CoV-2 Infection and Vaccination in Pediatric Age: A Narrative Review.

This narrative review aims to report the main clinical manifestations, therapeutic strategies, outcomes, and complications of acute SARS-CoV-2 infection in childhood and to summarize the data relating the SARS-CoV-2 vaccination efficacy and safety in pediatric age. SARS-CoV-2 infection mostly occurs asymptomatically in the pediatric population, while multisystem inflammatory syndrome in children (MIS-C) represents the most severe coronavirus disease 2019 (COVID-19)-related illness, a life-threatening event with a high morbidity rate. After the development of SARS-CoV-2 vaccines and their subsequent approval in children, the rate of infection as well as the number of its related complications have shown a drastic decrease. Fully vaccinated children are protected from the risk of developing a severe disease and a similar protective role has been observed in the reduction of complications, in particular MIS-C. However, long-lasting immunity has not been demonstrated, booster doses have been required, and reinfection has been observed. With regards to vaccine safety, adverse events were generally mild to moderate in all age groups: local adverse events were the most commonly reported. Nevertheless, a potential association between SARS-CoV-2 vaccine and the subsequent development of inflammatory manifestations has been suggested. Myocarditis has rarely been observed following vaccination; it appeared to be more frequent among adolescent males with a mild clinical course leading to a complete recovery. SARS-CoV-2 vaccine-related MIS-C cases have been described, although a univocal definition and an exact time interval with respect to vaccination has not been reported, thus not establishing a direct causal link. Current evidence about COVID-19 vaccination in children and adolescents suggest that benefits outweigh potential risks. Long-term data collection of the post-authorization safety surveillance programs will better define the real incidence of SARS-CoV-2 vaccine-related complications in the pediatric population.

COVID 19 Related Multisystem Inflammatory Syndrome in Children Admitted to PICU in Ain Shams University Hospitals

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children. A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4–6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation. Aim of the Work To evaluate the clinical profiles and risk factors for pediatric multisystem inflammatory syndrome in children with COVID-19 admitted to PICU. Patients and Methods This was a cross sectional study conducted on 45 patients admitted to pediatric intensive care unit (PICU) from June 2020 to August 2020, they were diagnosed as MIS-C cases according to CDC definition for MIS-C, using a score to assess hyperinflammatory syndrome, all patients were subjected to the following:(demographic data, clinical signs &amp; symptoms at presentation, sequential organ failure assessment (SOFA) score and laboratory investigations. Results In our study MIS-C patients presented with 100% Kawasaki disease(KD)-like symptoms and 62.2% gastrointestinal symptoms in addition to fever with shock or cardiac dysfunction. Our patients presented with the following vital data: 100% were tachycardic and hypotensive according to centiles, peripheral capillary oxygen saturation (spo2) mean 94.5(2) %, fever of mean 39(0.6) degree celsius and SOFA score mean of 9(2). KD-like features were variably seen in patients (skin rash in 55.6%, conjunctivitis in 46.7% and Cardiovascular abnormalities were seen in 100% e.g. (myocardial dysfunction, valvular regurgitation, coronary dilatation, pericardial effusion and shock). In our patients, 13 patients (28.9%) had comorbid conditions, like (hematologic e.g. ALL, Cardiac e.g. ASD&amp;VSD, Endocrinologic e.g. Diabetes mellitus), 4 of them died revealing comorbidities as a cause of higher mortality with significant p value (0.028). 39 patients (86.7%) were discharged and 6 patients (13.3%) died. Conclusion MIS-C is a hyper-infammatory syndrome affecting multiple organs and is triggered by SARS-CoV-2 infection. It is usually seen 2–4 weeks following infection. comorbidities significantly affected the short term outcome of the disease.

Variation in Early Anakinra Use and Short-Term Outcomes in Multisystem Inflammatory Syndrome in Children.

Evidence regarding effectiveness of interleukin-1 receptor antagonism in multisystem inflammatory syndrome in children (MIS-C) is lacking. We characterized variation in initial treatment with anakinra and evaluated cardiovascular outcomes associated with adding anakinra to standard initial therapy. We conducted a retrospective cohort study of MIS-C cases in a US surveillance registry from November 2020 to December 2021. Day 0 was the first calendar day of immunomodulatory treatment. Factors associated with initial anakinra use (days 0-1) were identified. We compared cases in patients ages 2-20 years receiving intravenous immunoglobulin (IVIG) and glucocorticoids versus anakinra plus IVIG and/or glucocorticoids on days 0-1, using inverse probability weighting to balance disease severity. Primary outcomes were vasopressor requirement on day 3 and impaired left ventricular ejection fraction on days 3-4. The secondary outcome was 50% reduction in C-reactive protein on day 3. Among 1,516 MIS-C cases at 44 sites, 193 (13%) patients received anakinra alone or with other immunomodulators as initial treatment (range 0-74% by site). Site accounted for 59% of residual variance in anakinra use. After balancing disease severity, initial treatment with anakinra plus IVIG and/or glucocorticoids (n=121) versus IVIG plus glucocorticoids (n=389) was not associated with significant differences in vasopressor requirement (25.6% versus 20.1%, respectively; risk ratio [RR] 1.27 [95% confidence interval (95% CI) 0.88-1.84]), ventricular dysfunction (33.7% versus 25.7%, respectively; RR 1.31 [95% CI 0.98-1.75]), or C-reactive protein reduction. We identified substantial variation in initial anakinra use in a real-world population of children with MIS-C, but no average short-term improvement in cardiovascular outcomes associated with early addition of anakinra to IVIG and/or glucocorticoids compared to IVIG and glucocorticoids alone.

COVID-19 Related Multi System Inflammatory Syndrome in Children: Scenario from a Tertiary Care Hospital in Bangladesh

Background: An association of multisystem inflammatory syndrome in children (MIS-C) with SARS-CoV-2 infection is now a well-established serious phenomenon and been increasingly reported from different countries. Objectives: The present study documents the presentation, management and immediate outcome of MIS-C patients from Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh. Study design: This was a retrospective study. Methods: This retrospective study was conducted in the department of pediatrics, BSMMU, Dhaka, Bangladesh. It included all the eligible MIS-C patients diagnosed during the study period (August 2020 to February 2022). Sixty cases fulfilled the diagnostic criteria and they had been included in the study. Data were collected using a predesigned and pre-tested questionnare from hospital records and also by interviewing the patients/parents over telephone when required. Results: Mean age of the children was 6.8year with F: M ratio of 1.2:1. All the sixty cases presented with fever associated with gastro-intestinal complications in 68% followed by other symptoms. Fifty two cases (87%) had known contacts. Laboratory evidence ofSARS-CoV-2 infection was present in 55% cases having positive serology or RT-PCR. Twelve patients (20%) had pre-existing co- morbidities. Majority of patients (48%) presented with Kawasaki Disease (KD) like illness. Mean neutrophil count, ESR, CRP, ferritin, LDH and D-dimer were higher and mean platelet and lymphocyte count were lower in this series. Interleukin-6 (IL-6) level was raised in all theseventeen (28%) patients, who were tested. Sixteen patients (27%) had chest X-ray abnormalities and ten of them had HRCT involvement. Fifteen (25%) patients had abnormalities in abdominal ultrasonogram. Coronary artery dilatation and ventricular dysfunction was present in seventeen (28%) and thirteen (22%) of MIS-C cases. IVIG and intravenous steroid was used in forty one (68%) and thirty nine (65%) children. Aspirin was given to twenty eight (47%) cases. Inotropic support was needed in 17% cases. Antibiotics were prescribed to all the patients. Fifty seven percent and 37% children were discharged without and with complications respectively. Mechanical ventilation was required in 6.6 % children who had pre-existing co-morbidities and all of them expired. Conclusion: Forty eight percent of MIS-C cases presented with KD like illness. Mortality was 6.6% and all the cases had preexisting comorbidities. MIS-C is a pediatric emergency and is of a great concern especially in children with pre-existing co-morbidities. Early diagnosis and referral to tertiary center for optimum management is essential. Bangladesh Medical Res Counc Bull 2023; 49(1): 22-31

Pediatrik Multisistem İnflamatuvar Hastalıkta (MIS-C) Gastrointestinal Sistem Tutulumu: 47 Olgunun Tek Merkez Deneyimi

Abstract&#x0D; Backgraound/Aims: Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory syndrome which was newly described during the coronavirus disease 2019 (COVID-19) pandemic in children and characterized by fever, inflammation, multiorgan dysfunction. One of the major clinical presentation is gastrointestinal system involvement. The aim of the study is to evaluate the clinical course and outcome according to the severity of gastrointestinal presentation, focusing on MIS-C cases with gastrointestinal system involvement.&#x0D; Methods: We performed a retrospective study of 47 MIS-C patients with gastrointestinal involvement in our clinic between October 2020 and March 2022. The patients were divided into two groups according to the severity of gastrointestinal involvement. The groups were compared in terms of demographic characteristics, gastrointestinal symptoms, laboratory parameters, other system involvement, length of hospital stay, treatment modalities, and clinical outcomes.&#x0D; Results: According to the severity of gastrointestinal system involvement, 44.7% (n=21) of the cases were mild to moderate, 55.3% (n=26) were severe. The most common gastrointestinal symptoms at presentation were abdominal pain (78.7%), vomiting (59.6%), and nausea (55.3%). Transaminase elevation was present in 29.8% of the cases. The most common radiological findings were ascites (36.2%) and pancreatic edema (27.7%). In cases presenting with acute pancreatitis (n=9), intensive care unit admission rates (n=6) were statistically significantly higher. Brain natriuretic peptide (p=0.020) and d-dimer (p=0.032) were statistically significantly higher in the severe group than in the mild to moderate group. &#x0D; Conclusions: In a significant part of the MIS-C cases with gastrointestinal involvement, severe findings is observed. Especially in cases presenting with pancreatitis, a more severe clinical course may be observed. Therefore, when managing patients presenting with gastrointestinal symptoms, the evaluation for pancreatitis is essential.

COVID-19 Vaccination Coverage and Demographic Characteristics of Infants and Children Aged 6 Months–4 Years — United States, June 20–December 31, 2022

Although severe COVID-19 illness and hospitalization are more common among older adults, children can also be affected (1). More than 3 million cases of COVID-19 had been reported among infants and children aged <5 years (children) as of December 2, 2022 (2). One in four children hospitalized with COVID-19 required intensive care; 21.2% of cases of COVID-19-related multisystem inflammatory syndrome in children (MIS-C) occurred among children aged 1-4 years, and 3.2% of MIS-C cases occurred among infants aged <1 year (1,3). On June 17, 2022, the Food and Drug Administration issued an Emergency Use Authorization (EUA) of the Moderna COVID-19 vaccine for children aged 6 months-5 years and the Pfizer-BioNTech COVID-19 vaccine for children aged 6 months-4 years. To assess COVID-19 vaccination coverage among children aged 6 months-4 years in the United States, coverage with ≥1 dose* and completion of the 2-dose or 3-dose primary vaccination series† were assessed using vaccine administration data for the 50 U.S. states and District of Columbia submitted from June 20 (after COVID-19 vaccine was first authorized for this age group) through December 31, 2022. As of December 31, 2022, ≥1-dose COVID-19 vaccination coverage among children aged 6 months-4 years was 10.1% and was 5.1% for series completion. Coverage with ≥1 dose varied by jurisdiction (range=2.1% [Mississippi] to 36.1% [District of Columbia]) as did coverage with a completed series (range=0.7% [Mississippi] to 21.4% [District of Columbia]), respectively. By age group, 9.7 % of children aged 6-23 months and 10.2% of children aged 2-4 years received ≥1 dose; 4.5% of children aged 6-23 months and 5.4% of children aged 2-4 years completed the vaccination series. Among children aged 6 months-4 years, ≥1-dose COVID-19 vaccination coverage was lower in rural counties (3.4%) than in urban counties (10.5%). Among children aged 6 months-4 years who received at least the first dose, only 7.0% were non-Hispanic Black or African American (Black), and 19.9% were Hispanic or Latino (Hispanic), although these demographic groups constitute 13.9% and 25.9% of the population, respectively (4). COVID-19 vaccination coverage among children aged 6 months-4 years is substantially lower than that among older children (5). Efforts are needed to improve vaccination coverage among children aged 6 months-4 years to reduce COVID-19-associated morbidity and mortality.

Evaluation of Multisystem Inflammatory Syndrome in Children (MIS-C) Cases: Clinical Features and Cardiologic Findings

Multisystem inflammatory syndrome in children (MIS-C) is a disease characterized by hyperinflammation with multiple organ involvement that develops after COVID-19 infection. In this study, we aimed to assess the clinical characteristics, cardiologic findings, and cardiac magnetic resonance imaging (MRI) results of MIS-C cases. Thirty-one patients diagnosed with MIS-C and followed up at Eskişehir Osmangazi University Faculty of Medicine between November 2020 and June 2022 were included in the study. The clinical and epidemiological characteristics and cardiological findings of the patients were evaluated retrospectively. Fifty-five percent of the thirty-one MIS-C cases were male and the mean age was 102 (2-204) months. The most common presenting symptoms were fever, rash, conjunctivitis, and abdominal pain. The most common cardiac findings were left ventricular dysfunction, myocarditis, and coronary artery dilatation. Cardiac MRI was performed in 4 of 8 patients with severe cardiac findings, and no pathologic findings were noted. Patients who had hypotension and cardiogenic shock at the time of admission, who had high ferritin, D-dimer, and IL -6 levels on laboratory tests, and who had left ventricular dysfunction and myocarditis on echocardiography had a high rate of ICU admission. The degree of cardiovascular involvement is important in following up on the disease and determining the treatment regimen. All patients should be monitored by echocardiography and cardiac MRI for possible permanent cardiac damage. Although MIS-C can lead to serious, life-threatening cardiac manifestations, early diagnosis and appropriate treatment can prevent the risk of serious cardiac morbidity and mortality in the future.

Change in Severity and Clinical Manifestation of MIS-C Over SARS-CoV-2 Variant Outbreaks in Korea.

There is difference in the incidence of multi-system inflammatory syndrome in children (MIS-C) in patients with different variants of severe acute respiratory syndrome coronavirus 2, however, little is known about the epidemiology in Asian countries. We investigated and compared the epidemiology of the MIS-C during omicron-dominant period with that of previous periods in South Korea. We obtained clinical, epidemiological and laboratory data on MIS-C cases from national MIS-C surveillance in South Korea. We defined pre-delta period as January 2020-May 2021; delta period as June 2021-December 2021; and omicron period as January 2022-April 2022. We describe the clinical characteristics and outcomes of MIS-C patients by period. A total of 91 cases were assessed to be MIS-C cases. Number of MIS-C cases have increased from six cases during pre-delta period to 66 cases during omicron period, while the incidence rate (the number of MIS-C cases per 100,000 cases of reported coronavirus disease 2019) has decreased from 38.5 cases per 100,000 (95% confidence interval [CI], 14.1-83.9) during pre-delta period to 1.6 cases per 100,000 (95% CI, 1.2-2.0) during omicron periods. During pre-delta period, 66.7% and 100% had hypotension and gastrointestinal involvement, respectively; while during omicron period, 12.1% and 6.1% had such clinical manifestations. Fifty percent of pre-delta MIS-C patients were taken intensive care unit (ICU) cares, while 10.6% of patients during omicron periods were in ICUs. Omicron period were associated with less severe clinical manifestation compared to pre-delta and delta periods. Although incidence rate of MIS-C was lower for the omicron period than pre-delta and delta periods, number of patients reported with MIS-C may pose a substantial clinical burden.

237. A Case-Control Study Investigating Household, Community, and Clinical Risk Factors Associated with Multisystem Inflammatory Syndrome in Children (MIS-C) after SARS-CoV-2 Infection

Abstract Background Risk factors for MIS-C, a rare but serious hyperinflammatory syndrome associated with SARS-CoV-2 infection, remain unclear. We evaluated household, clinical, and environmental risk factors potentially associated with MIS-C. Methods This investigation included MIS-C cases hospitalized in 14 US pediatric hospitals in 2021. Outpatient controls were frequency-matched to case-patients by age group and site and had a positive SARS-CoV-2 viral test within 3 months of the admission of their matched MIS-C case (Figure 1). We conducted telephone surveys with caregivers and evaluated potential risk factors using mixed effects multivariable logistic regression, including site as a random effect. We queried regarding exposures within the month before hospitalization for MIS-C cases or the month after a positive COVID-19 test for controls. Figure.Patient enrollment timeline. Enrollment scheme for MIS-C case-patients and SARS-CoV-2-positive outpatient controls. MIS-C case-patients were identified through hospital electronic medical records, while two outpatient controls per case were identified through registries of outpatient SARS-CoV-2 testing logs at facilities affiliated with that medical center. Caregivers of outpatient controls were interviewed at least four weeks after their positive test to ensure they did not develop MIS-C after their infection. Results We compared 275 MIS-C case-patients with 494 outpatient SARS-CoV-2-positive controls. Race, ethnicity and social vulnerability indices were similar. MIS-C was more likely among persons who resided in households with &amp;gt;1 resident per room (aOR=1.6, 95% CI: 1.1–2.2), attended a large (≥10 people) event with little to no mask-wearing (aOR=2.2, 95% CI: 1.4–3.5), used public transportation (aOR=1.6, 95% CI: 1.2–2.1), attended school &amp;gt;2 days per week with little to no mask wearing (aOR=2.1, 95% CI: 1.0–4.4), or had a household member test positive for COVID-19 (aOR=2.1, 95% CI: 1.3–3.3). MIS-C was less likely among children with comorbidities (aOR=0.5, 95% CI: 0.3–0.9) and in those who had &amp;gt;1 positive SARS-CoV-2 test at least 1 month apart (aOR=0.4, 95% CI: 0.2–0.6). MIS-C was not associated with a medical history of recurrent infections or family history of underlying rheumatologic disease. Conclusion Household crowding, limited masking at large indoor events or schools and use of public transportation were associated with increased likelihood of developing MIS-C after SARS-CoV-2 infection. In contrast, decreased likelihood of MIS-C was associated with having &amp;gt;1 SARS-CoV-2 positive test separated by at least a month. Our data suggest that additional studies are needed to determine if viral load, and/or recurrent infections in the month prior to MIS-C contribute to MIS-C risk. Medical and family history were not associated with MIS-C in our analysis. Disclosures Natasha B. Halasa, MD, Quidel: Grant/Research Support|Quidel: equipment donation|Sanofi: Grant/Research Support|Sanofi: HAI testing and vaccine donation Mark Hall, MD, Abbvie: Service on a Data Safety Monitoring Board|Kiadis: Licensing income unrelated to the current submission Mary A. Staat, MD, MPH, Centers for Disease Control and Prevention: Grant/Research Support|Cepheid: Grant/Research Support|National Institute of Health: Grant/Research Support|Uptodate: Royalties Pia S. Pannaraj, MD, MPH, AstraZeneca: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi-Pasteur: Advisor/Consultant|Seqirus: Advisor/Consultant Charlotte V. Hobbs, MD, Biofire (Biomerieux): Advisor/Consultant.

248. Change in Incidence of Multisystem Inflammatory Syndrome in Children Across the COVID-19 Pandemic in Chicago — March 2020 – March 2022

Abstract Background Peak counts of multisystem inflammatory syndrome in children (MIS-C) have followed each COVID-19 peak by 2–5 weeks. Fewer cases of MIS-C occurred after the Delta-predominant period compared to early waves of the pandemic. The Chicago Department of Public Health analyzed the ratio of MIS-C to pediatric COVID-19 hospitalization by period of variant predominance from March 2020 – mid-March 2022 to evaluate differences by variant. Methods MIS-C in Chicago residents was reported using the standard CDC MIS-C case report form. Four periods of COVID-19 infection were identified with dates defined by variant predominance (≥50%); date ranges for corresponding MIS-C periods were defined as starting 21 days after the COVID-19 period (Table 1). MIS-C cases were compared to hospitalizations as a measure of COVID-19 disease activity in children (rather than case counts which are more subject biases inherent in disease testing) among confirmed and probable COVID-19 cases in children ≤21 years reported to CDPH. Ratios of MIS-C cases per 100 corresponding pediatric hospitalizations for each variant period were calculated. Proportions of MIS-C hospitalizations with intensive care unit (ICU) admission, mechanical ventilation (MV), and receipt of vasopressors (VP) were calculated as markers of disease severity in MIS-C for each wave. Results 90 cases of MIS-C and 1,597 pediatric COVID-19 hospitalizations were reported (Table 2). The overall ratio was 5.6 MIS-C cases/100 pediatric COVID-19 hospitalizations. The first period with predominance of the original lineage had a ratio of 10.2; subsequent periods with variant predominance all had lower ratios. The Delta period had the second highest ratio which was 68% of the first period. Across waves, 74% of MIS-C patients were admitted to ICU (range, 67–82%); 11% underwent MV (range, 0–14%); and 52% received VP (range, 45–71%). Conclusion The ratio of MIS-C to pediatric COVID-19 hospitalizations varied by period of SARS-CoV-2 variant predominance. The ratio was highest in the early pandemic. There was no consistent change in MIS-C severity. Further study is needed to determine if the change in ratio is due to increased immunologic exposure (vaccination or previous infection) or if it is variant dependent. Disclosures All Authors: No reported disclosures.

1094. Multisystem Inflammatory Syndrome in Children (MIS-C) in Persons Fully Vaccinated with Two Doses of mRNA COVID-19 Vaccine Compared with Persons with Partial or No Vaccination Reported, U.S. National MIS-C Surveillance

Abstract Background CDC began collecting COVID-19 vaccination status of persons with MIS-C as part of national surveillance in May, 2021. We describe and compare MIS-C in fully vaccinated persons with MIS-C in persons with partial or no vaccination reported. Methods We identified COVID-19 vaccine age-eligible persons meeting the CDC MIS-C case definition reported by health departments as of March 28, 2022 and divided them into 3 groups for this analysis: 1) fully vaccinated (receipt of a 2-dose mRNA primary vaccine series with MIS-C onset ≥28 days after vaccine dose 2 to account for the delay between infection and MIS-C), 2) partially vaccinated (MIS-C onset after dose 1 or &amp;lt; 28 days from dose 2 or receipt of Janssen [Johnson &amp; Johnson] vaccine and 3) no vaccination reported. We compared characteristics between the groups. Results Of 7,880 MIS-C cases reported, 1,085 were vaccine eligible: 45 were fully vaccinated, 64 partially vaccinated, and 976 had no vaccine reported. Demographic characteristics were similar, although the Northeast had the lowest percentage of persons with vaccination not reported (Table). Though not statistically significant, fully vaccinated persons less frequently had severe cardiac involvement (67% vs 74%), shock (33% vs 44%), severe hematologic involvement (47% vs 54%), and mucocutaneous involvement (53% vs 63%) compared with those with no vaccine reported (Table). Forty-four percent of those fully vaccinated required ICU-level care vs 59% with no vaccine reported (p=0.053). Nineteen (2%) of those without vaccine reported died; no fully or partially vaccinated persons died. Table.Demographic and clinical characteristics of individuals with MIS-C with COVID-19 vaccine not reported compared to partially and fully vaccinated individuals Conclusion Persons who acquire SARS-CoV-2 infection after being fully vaccinated can develop MIS-C, with similar clinical characteristics to those with no vaccination reported. A lower but not statistically significant percentage of fully vaccinated persons required ICU-level care compared with those without vaccination, and there were no deaths in the fully vaccinated group. These data do not account for trends in MIS-C over time, including the influence of circulating SARS-CoV-2 variants on MIS-C clinical manifestations. We will continue to evaluate these comparisons as the sample size of reported MIS-C cases increases. Disclosures All Authors: No reported disclosures.

1865. Analysis of National Surveillance Data to Support Case Definition Revisions for Multisystem Inflammatory Syndrome in Children (MIS-C), United States, February 2020–April 2022

Abstract Background Classification of MIS-C, COVID-19, and other pediatric inflammatory conditions is challenged by phenotypic overlap and absence of diagnostic laboratory evidence. Due to public health need and based on limited data from early cases, CDC developed a necessarily broad MIS-C surveillance case definition in May 2020. Studies have since shown that some criteria do not distinguish between MIS-C and other conditions and may contribute to misclassification. To inform planned revision to the CDC definition, we evaluated the impact of narrowing these criteria on case inclusion in national MIS-C surveillance. Methods Of state and local health-department reported cases meeting the current MIS-C case definition as of 04/14/2022, we describe the proportion that met revised criteria under consideration including fever duration, C-reactive protein (CRP) elevation using a defined cutoff, and organ involvement represented by specific criteria. We also evaluated cases identified using potential combinations of revised criteria. Results Of 8,096 MIS-C cases fulfilling the original case definition, 6,332 (78%) had sufficient data for evaluation of criteria. Of these, 96% had fever for ≥2 days and 94% had a CRP ≥ 3.0 mg/dL (Table 1). Cardiac involvement defined by key features of MIS-C was present in 84% of cases (62% if BNP/proBNP elevation was excluded); 43% had shock. Dermatologic, gastrointestinal (GI) and hematologic involvement were present in 75%, 89% and 37% of cases, respectively. Neurologic (excluding headache), renal, and respiratory involvement were present in 16%, 20%, and 63% of cases, respectively. The number of cases with ≥ 2 of cardiac (without BNP/proBNP elevation), shock, dermatologic, GI, or hematologic involvement was 5,733 (91%). SARS-CoV-2 testing results are shown in Table 2. Conclusion The CDC MIS-C case definition is intentionally broad. Using national surveillance data, we evaluated case inclusion under narrower criteria, prioritizing features of MIS-C that distinguish it from similar pediatric inflammatory conditions. A surveillance case definition may not capture all cases and is not intended to replace clinical judgment. We plan to assess additional criteria combinations, describe potentially excluded cases, and incorporate findings into a revised definition. Disclosures All Authors: No reported disclosures.

Are Thyroid Functions Affected in Multisystem Inflammatory Syndrome in Children?

Multisystem inflammatory syndrome in children (MIS-C), associated with Coronavirus disease-2019, is defined as the presence of documented fever, inflammation, and at least two signs of multisystem involvement and lack of an alternative microbial diagnosis in children who have recent or current Severe acute respiratory syndrome-Coronavirus-2 infection or exposure. In this study, we evaluated thyroid function tests in pediatric cases with MIS-C in order to understand how the hypothalamus-pituitary-thyroid axis was affected and to examine the relationship between disease severity and thyroid function. This case-control study was conducted between January 2021 and September 2021. The patient group consisted of 36 MIS-C cases, the control group included 72 healthy children. Demographic features, clinical findings, inflammatory markers, thyroid function tests, and thyroid antibody levels in cases of MIS-C were recorded. Thyroid function tests were recorded in the healthy control group. When MIS-C and healthy control groups were compared, free triiodothyronine (fT3) level was lower in MIS-C cases, while free thyroxine (fT4) level was found to be lower in the healthy group (p<0.001, p=0.001, respectively). Although the fT4 level was significantly lower in controls, no significant difference was found compared with the age-appropriate reference intervals (p=0.318). When MIS-C cases were stratified by intensive care requirement, fT3 levels were also lower in those admitted to intensive care and also in those who received steroid treatment (p=0.043, p<0.001, respectively). Since the endocrine system critically coordinates and regulates important metabolic and biochemical pathways, investigation of endocrine function in MIS-C may be beneficial. These results show an association between low fT3 levels and both diagnosis of MIS-C and requirement for intensive care. Further studies are needed to predict the prognosis and develop a long-term follow-up management plan.

SARS-CoV-2 Infection and Increased Risk for Pediatric Stroke

BackgroundThere is an increased risk of stroke in adults with severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) infection, but whether there is a similar association with stroke in children is unclear. Our objective was to determine whether there is a correlation between COVID-19 infection, multisystem inflammatory syndrome in children (MIS-C), and pediatric ischemic stroke. MethodsThis was a retrospective, population-based cohort analysis between March 1, 2020, and June 30, 2021, conducted at a children's hospital. Pediatric patients with a diagnosis of ischemic stroke were identified using ICD-10 diagnoses of ischemic stroke, cerebrovascular accident, or cerebral infarction. ResultsWe identified 16 patients, seven male and nine female, with ischemic stroke. Ages were 8 months to 17 years (median 11.5 years). More Asian (6%) and black (13%) patients had strokes compared with population prevalence (2% each, respectively). No patients had active COVID-19 infection. COVID-19 antibodies were identified in five of 11 patients tested (45%), of whom three were diagnosed with MIS-C. 82% of the strokes occurred between February and May 2021. The peak incidence was in February 2021, which was two months after peak incidence of pediatric cases of COVID-19 and one month after the peak of MIS-C cases. ConclusionsOur study suggests that prior COVID-19 infection, but not acute infection, is correlated with a risk for stroke in the pediatric population. The risk for stroke appears to be distinct from the risk for MIS-C.

Clinical spectrum and short-term outcome of post-COVID multisystem inflammatory syndrome in children after the 2019 pandemic: a longitudinal cohort study

Background As a post-COVID complication in children, multisystem inflammatory syndrome in children (MIS-C) is important because of its varied and life-threatening manifestations. With this background, this study attempts to focus on MIS-C cases in an underprivileged rural setting in north-eastern India, with most patients being treated with methylprednisolone rather than intravenous immunoglobulin due to financial constraints. Methods In this prospective longitudinal cohort study at MGM Medical College, 27 MIS-C cases diagnosed following WHO criteria were included. Laboratory and radiological investigations, including echocardiography, were performed as required for diagnosis and to assess prognosis. Most patients were treated with methylprednisolone. A follow-up assessment was done six weeks after discharge for any residual impairment. Results The most frequently affected age group was 5–10 years (59.28%), while respiratory (48.14%) and cardiac (40.74%) were the most commonly involved systems. Logistic regression studies established a significant association between serum ferritin level and prolonged hospital stay (coefficient 0.0674, p=0.0041), possibly due to greater complications in cases with high ferritin levels. Organ impairment was found to increase the need for inotrope use (coefficient 3.8797, p=0.00584). Most cases were treated with methylprednisolone alone (85.18%) with a favourable response and no death occurred. Conclusion The favourable response in cases treated with methylprednisolone only affirms the effectiveness of the drug as a cheaper alternative in a resource-poor setting. The study highlights that higher ferritin levels in complicated cases leads to prolonged hospitalisation and the increased need for inotropes in cases with organ impairment.

Multi-System Inflammatory Syndrome in Neonate (MIS-N) Presenting as Bowel Obstruction: A Case Report

Background: Since the start of SARS-CoV-2 pandemic, a post-infection hyperinflammatory process in children with features similar to Kawasaki disease, termed multisystem inflammatory syndrome in children (MIS-C),1 was identified. Thousands of MIS-C cases have already been reported worldwide.2 As possible cases of MIS-C in neonates were increasingly identified, multisystem inflammatory syndrome in neonates (MIS-N) as a distinct entity was proposed as neonates may not manifest all the typical features described in older children. Case Presentation: We describe the case of a previously well term neonate with sudden signs of bowel obstruction who later had multisystem involvement (cardiac, gastrointestinal, and hematologic). The baby was born to a 23-yearold multigravida with an unremarkable prenatal history except for COVID-19 infection during her 34th week age of gestation. The mother presented with mild respiratory symptoms and resolved with supportive management. Our patient was born stable, then had sudden manifestations of feeding intolerance on the 16th day of life and upon work-up had moderate anemia, elevated inflammatory and cardiac markers, ileus, and dilatation of proximal left coronary artery. RT-PCR for SARS-CoV2 was negative. The baby was managed with intravenous immunoglobulin (IVIG) and steroids, with rapid clinical and laboratory parameters improvement thereafter. Conclusion: MIS-N is still evolving as a disease entity with no clear, directed guidance yet on diagnosis and management. Management is extrapolated from treatment of MIS-C. Additional case reports and series are warranted to increase awareness and enable better understanding of the disease pathology among clinicians for timely investigation, diagnosis, and management.