Multisystem Inflammatory Syndrome Research Articles

Neutralization of SARS-CoV-2 Omicron BQ.1, BQ.1.1 and XBB.1 variants following SARS-CoV-2 infection or vaccination in children

Emergence of highly transmissible Omicron subvariants led to increased SARS-CoV-2 infection and disease in children. However, minimal knowledge exists regarding the neutralization capacity against circulating Omicron BA.4/BA.5, BA.2.75, BQ.1, BQ.1.1 and XBB.1 subvariants following SARS-CoV-2 vaccination in children versus during acute or convalescent COVID-19, or versus multisystem inflammatory syndrome (MIS-C). Here, we evaluate virus-neutralizing capacity against SARS-CoV-2 variants in 151 age-stratified children ( <5, 5–11, 12–21 years old) hospitalized with acute severe COVID-19 or MIS-C or convalescent mild (outpatient) infection compared with 62 age-stratified vaccinated children. An age-associated effect on neutralizing antibodies is observed against SARS-CoV-2 following acute COVID-19 or vaccination. The primary series BNT162b2 mRNA vaccinated adolescents show higher vaccine-homologous WA-1 neutralizing titers compared with <12 years vaccinated children. Post-infection antibodies did not neutralize BQ.1, BQ.1.1 and XBB.1 subvariants. In contrast, monovalent mRNA vaccination induces more cross-neutralizing antibodies in young children <5 years against BQ.1, BQ.1.1 and XBB.1 variants compared with ≥5 years old children. Our study demonstrates that in children, infection and monovalent vaccination-induced neutralization activity is low against BQ.1, BQ.1.1 and XBB.1 variants. These findings suggest a need for improved SARS-CoV-2 vaccines to induce durable, more cross-reactive neutralizing antibodies to provide effective protection against emerging variants in children.

Characteristics of Multisystem Inflammatory Syndrome in Children (MIS-C) with Hyperferritinemia

Characteristics of Multisystem Inflammatory Syndrome in Children (MIS-C) with Hyperferritinemia

Cardiac Outcomes of Multisystem Inflammatory Syndrome in Children

Cardiac Outcomes of Multisystem Inflammatory Syndrome in Children

Cardiac MRI six months after the onset of multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19: A retrospective follow-up study.

In 2020, reports revealed cases called multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19 or multisystem inflammatory syndrome in children. A small proportion of patients suffer from persistent left ventricular dysfunction at discharge. The primary aim was to investigate if myocardial impairment persists during follow-up in these patients. Children fulfilling the criteria for multisystem inflammatory syndrome in children with cardiac involvement hospitalized between December 2020 and February 2022 were included in this retrospective single centre study. Cardiac MRI was performed six months after the onset of symptoms to evaluate possible persistent myocardial damage. Fifteen patients (80% male) with a median age of 8 years (interquartile range 4.5 - 13.5 years) were included. Upon admission, eight patients (53%) presented with reduced left ventricular function, with a median left ventricular ejection fraction of 54% (interquartile range 49.5%-61.5%) on transthoracic echocardiography. Elevated levels of cardiac-specific markers were found in 14 patients (93%). Cardiac MRI was performed in 12 patients at a median of 190.5 days after the onset of symptoms. Nine patients (75%) had normal left ventricular function, with a median left ventricular ejection fraction of 59.45%, while the remaining patients showed mildly to moderately reduced values. None of the patients showed signs of late gadolinium enhancement, indicating the absence of persistent myocardial scarring. During a follow-up of 6.2 months, mild to moderate cardiac impairment was revealed in 25% of patients evaluated by cardiac MRI. Although a majority of patients do not show signs of cardiac impairment, close follow-ups should be performed in a proportion of patients.

Case Series of Multisystem Inflammatory Syndrome in Neonates (MIS-N) With a Link to Coagulopathy.

Introduction Multisystem inflammatory syndrome in neonates (MIS-N) is an emerging clinical entity observed in neonates born to mothers with exposure to the SARS-CoV-2 virus before or during the antenatal period. Methods We report 18 neonates diagnosed with MIS-N from retrospectively collected data.A total of 18 neonates (13 term and five late-preterm; 10 males) admitted to the neonatal intensive care unit (NICU) of a tertiary care medical institute, between June 2021 to November 2022, were diagnosed with MIS-N. Results The median age of presentation of the 18 neonates was 1.5 days of life. All the neonates were positive for SARS-CoV-2 IgG antibodies and had elevated D-dimer levels. Respiratory system involvement was the most common (12 of 18 neonates: 66.67%). Ten out of 18 neonates (55.55%) had coagulopathy. Seven of the ten neonates with coagulopathy had central nervous system (CNS) involvement as seizures and/or intracerebral infarcts/bleeds. Cardiovascular and gastrointestinal system involvement was observed in nine (50%) and seven (38.89%) neonates, respectively. One out of 18 neonates died due to intraventricular and cerebral hemorrhage. The mortality rate was 5.55% (n=1). Ten of 18 neonates with coagulopathy required fresh frozen plasma along with repeated therapeutic doses of injection vitamin K. Eight neonates (44.44%) required human intravenous immunoglobulin (IVIG), and three neonates (16.67%) required steroids and IVIG for recovery along with supportive care. Conclusion Coagulopathy can be one of the salient features of presentation in MIS-N. In the immediate post-pandemic era, it is essential that MIS-N is considered in the differential diagnosis of neonates presenting with intracerebral bleeds/infarcts. IVIGand steroids might play an important role in the treatment of neonates with MIS-N.

Spectrum of severity of multisystem inflammatory syndrome in children: an EHR-based cohort study from the RECOVER program.

Multi-system inflammatory syndrome in children (MIS-C) is a severe post-acute sequela of SARS-CoV-2 infection in children, and there is a critical need to unfold its highly heterogeneous disease patterns. Our objective was to characterize the illness spectrum of MIS-C for improved recognition and management. We conducted a retrospective cohort study using data from March 1, 2020-September 30, 2022, in 8 pediatric medical centers from PEDSnet. We included 1139 children hospitalized with MIS-C and used their demographics, symptoms, conditions, laboratory values, and medications for analyses. We applied heterogeneity-adaptive latent class analyses and identified three latent classes. We further characterized the sociodemographic and clinical characteristics of the latent classes and evaluated their temporal patterns. Class 1 (47.9%) represented children with the most severe presentation, with more admission to the ICU, higher inflammatory markers, hypotension/shock/dehydration, cardiac involvement, acute kidney injury and respiratory involvement. Class 2 (23.3%) represented a moderate presentation, with 4-6 organ systems involved, and some overlapping features with acute COVID-19. Class 3 (28.8%) represented a mild presentation. Our results indicated that MIS-C has a spectrum of clinical severity ranging from mild to severe and the proportion of severe or critical MIS-C decreased over time.

Multisystem Inflammatory Syndrome in an Adult: A Rare Cause of ST-Segment Elevation MI

The COVID-19 pandemic is a significant worldwide health emergency. Due to the high incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, there are increasingly recognisable early and long-term outcomes of the disease. One of the uncommon complications of SARS-CoV-2 infection is multisystem inflammatory syndrome in adults (MIS-A). This is a post-sequela of SARS-CoV-2 infection associated with hyperinflammatory syndrome accompanied by extrapulmonary organ dysfunction. The prevalence of MIS-A ranges from 0.2% to 11.7% of the studied SARS-CoV-2 infection cases. The lack of awareness of this condition and unusual constellation of symptoms makes its management challenging. A 36-year-old woman who had a recent SARS-CoV-2 infection presented with chest pain and hypotension. An ECG showed ST-segment elevation in the anteroseptal wall, elevated cardiac enzymes and inflammatory markers. Transthoracic echocardiogram revealed segmental hypokinesia with a mildly reduced ejection fraction of 41%. Coronary angiogram showed normal arteries. A diagnosis of MIS-A was considered and the patient was started on steroids and IV immunoglobulin.

Incidence of Venous Thromboembolism in Pediatric Cancer Patients with COVID-19: MD Anderson Cancer Center Experience

Background: Patients with COVID-19 are at increased risk of venous thromboembolism (VTE) due to a hypercoagulable state. Multisystem inflammatory syndrome in children (MIS-C) is a unique entity in the pediatric population affected by COVID-19 which also increases the risk of VTE. This has been described in the literature and guidelines have been established across different institutions regarding anticoagulation prophylaxis. It is well known that cancer increases the risk of VTE greater than four-fold to that of the general population and, for patients receiving active chemotherapy, the risk is up to 6.5 times greater. Studies have shown that adults patients with active cancer and COVID-19 infection had increased risk of mortality due to VTE associated complications. Contrary to that, some reports have shown that incidence of VTE does not appear to be increased in adults with cancer compared to non-cancer patients. Hence, the data is yet scarce as well as conflictive. Anecdotally, we observed a decreased number of cases of VTE associated with COVID-19 infection in our pediatric cancer patients. There are limited studies that evaluate COVID-19 infection with VTE incidents and complications in this population. In this study, we report a retrospective analysis of pediatric cancer patients at our center during a span of three years to determine the incidence of COVID-19 infection with VTE and related complications. Objectives: Primary objective: Investigate the incidence of VTE in pediatric cancer patients with COVID-19 infection. Secondary objectives: Investigate COVID-19 associated complications, comorbidities in pediatric cancer patients. Methods: This is a single center retrospective cohort study. Data was extracted from COVID-19 database established at MD Anderson Cancer Center since the start of the pandemic. Patients 0 to 18 years of age affected by COVID-19 infection who were seen at MD Anderson Cancer Center from March 2020 to March 2023 were included. VTE inclusion criteria was development of thrombosis event from 14 days prior up to three months after COVID-19 infection. All cancer types were included. ICD 10 codes for diagnosis of COVID-19 infection and VTE were used to search for patients meeting the above criteria. Foundry database software was used to analyze the data and validation was done by the software checks by two independent reviewers and accordingly modified our search terms. Results: Three cohorts ( figure 1) were identified; patients with COVID-19 infection with or without VTE (Group 1), patients with VTE with or without COVID-19 infection (Group 2), and patients with both COVID-19 infection and VTE (Group 3). From group 1 (pediatric cancer with COVID infection with and without VTE), a total of 235 cancer patients ranging between 0 to 18 years of age were found affected by COVID-19 infection (Mean = 11.1 years, median = 12 years). The majority of patients were Caucasians (57.4%). Fifty percent of patients were male. From group 2 (pediatric cancer patients with VTE with or without COVID-19 infection), 272 patients were identified who had developed VTE of which 55.5% were males, and 54% were Caucasians with similar age distribution (mean = 13.1 years, median =15 years). In our study population, we identified three patients with VTE events who had COVID-19 infection (group 3, see table 1). Conclusion: The incidence of VTE in pediatric cancer patients affected by COVID-19 infection was lower compared to COVID-19 negative pediatric cancer patients. Our findings suggest that COVID-19 infection does not appear to be an additional risk factor for the development of VTE in pediatric cancer patients. Further studies are currently ongoing to investigate co-morbidities and COVID-associated complications other than VTE.

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

486. Phenotypic Clusters of Clinical Presentation and Severity Among Children with Multisystem Inflammatory Syndrome — United States, February 2020–October 2022

Abstract Background Multisystem inflammatory syndrome in children (MIS-C) is an uncommon but severe hyperinflammatory syndrome occurring weeks after SARS-CoV-2 infection. Presentation can vary and overlap with other conditions, including acute COVID-19 and Kawasaki disease. Identifying clusters of MIS-C phenotypes informs efforts to reduce misclassification, characterize pathogenesis, and tailor treatments. Here we describe clusters of presentation using the largest collection of U.S. MIS-C cases to date. Methods We analyzed 9131 MIS-C cases reported to CDC from 55 U.S. health departments; onset dates ranged from February 2020–October 2022. Thirty-one dichotomous clinical variables were selected for clustering after excluding ones with high (≥ 15%) missingness or rare (≤ 10%) or high (≥ 90%) prevalence. We excluded 595 cases with ≥ 5 missing variables and conducted multiple imputation on the remaining 8536 cases. Latent class analysis (LCA) was run using the poLCA R package; the number of clusters was selected based on decreasing information criteria and automated variable selection. Results LCA identified five clusters, two of which were characterized by distinct organ system involvement: a respiratory symptom-driven cluster primarily affecting older children (N = 483 [5.7% of cases]; median age 14.4 years), and a mucocutaneous symptom-driven cluster primarily affecting young children (N = 1956 [22.9%]; median age 5.8 years) (Fig. 1). The remaining three clusters delineated a spectrum of clinical severity, with clinically mild and moderate clusters with infrequent shock (N = 2566 [30.0%] and N = 1650 [19.3%], respectively), and a severe cluster (N = 1881 [22.0%]) with shock and ICU admission for nearly all cases (Fig. 2). The proportion of cases belonging to this clinically severe cluster decreased over time as proportions of the mild/moderate clusters increased (Fig. 3). The case fatality ratio was highest in the respiratory (5.0%) and clinically severe clusters (1.6%) compared with other MIS-C cases (0.2%; P &amp;lt; 0.001).Figure 1.Prevalence of respiratory and mucocutaneous/dermatologic symptoms for the respiratory and mucocutaneous clusters compared to all other MIS-C cases.Figure 2.Prevalence of organ system involvement, shock, and ICU admission for the three severity-defined clusters.Figure 3.Proportions of MIS-C cases by LCA-inferred cluster and month (primary y-axis); number of monthly MIS-C cases (secondary y-axis). Conclusion MIS-C cases reported to CDC national surveillance clustered into five groups with distinct symptoms and severity. Use of MIS-C phenotypic clusters in future studies may inform treatment decisions and assist with prognosis. 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

459. Characteristics and Presentations of Hospitalized Children due to three predominate COVID-19 variants within a healthcare network

Abstract Background Variants of SARS-CoV-2 caused three major waves of infections in NJ. Children and young adults were hospitalized with varying symptoms and severity of illness depending on the variant. The objectives of this study are to describe differences in the demographic and clinical characteristics, severity of illness and outcomes in pediatric patients during the different SARS-CoV-2 waves in our hospital network. Methods We conducted a retrospective study of pediatric patients admitted to one of our three network hospitals with SARS-CoV-2 infection or with post-COVID-19 inflammatory conditions such as Multisystem Inflammatory Syndrome in Children (MIS-C) during the different waves of infection. Patients who were asymptomatic but incidentally tested positive for SARS-CoV-2 and were hospitalized for unrelated indications were excluded. We defined the timelines as follows: Wave 1 occurred between March 1, 2020 and May 31, 2020; wave 2 occurred between November 1, 2020-January 31, 2021; and wave 3 occurred between December 1, 2021-February 28, 2022. Demographic characteristics, clinical features, and outcomes were recorded and compared with respect to the different variants. Results Of 351 total patients included in this study, 74 were admitted during wave 1, 94 during wave 2, and 181 during wave 3. The median age of patients decreased from wave 1 (11.5 years) to wave 3 (3 years) (p=0.0034). 87.7% of the patients were unvaccinated. The overall incidence of admissions related to COVID-19 pneumonia decreased in wave 3 compared to wave 1 and 2. COVID-19 bronchiolitis or croup admissions occurred mostly in wave 3. No significant difference in intensive care admissions was observed in any wave. Length of stay decreased across the waves (p&amp;lt; 0.0001). Treatments required did not vary between the waves except for a decrease in antibiotic use with each subsequent wave (p&amp;lt; 0.0001). Conclusion The impact of COVID-19 on the pediatric population differs from the adult population, and the overall numbers of hospitalized children has mirrored the peak in cases observed during each infection wave. Our study illustrates the changes in clinical presentation and severity observed with the different coronavirus variants. Disclosures Tara Lozy, MA in Data Science, Eli Lilly &amp; Company: Stocks/Bonds

443. Albumin is a Reliable and Accurate Biomarker for Assessing Clinical Course of Multisystem Inflammatory Syndrome in Children

Abstract Background In Spring 2020, Multisystem Inflammatory Syndrome in Children (MIS-C) emerged as a life-threatening pediatric complication to COVID-19. It is a complex and novel disease often requiring high levels of intensive care. As case definitions and guidelines are still being developed, it is imperative to identify biomarkers that can accurately assess its clinical course in hospitalized children. Methods Utilizing the electronic medical records we retrieved the charts of children who were hospitalized at the University of Minnesota Masonic children’s Hospital for treatment of MIS-C. We reviewed their clinical course including daily monitoring of various inflammatory markers and analyzed the trends of albumin and CRP. Results Between May 2020 and January 2022, thirty-six children diagnosed with MIS-C were admitted to the University of Minnesota Masonic children’s Hospital [Figure 1]. Complications included myocarditis, coronary aneurysm, coagulopathy, acute kidney injury, and shock. Seventeen children required PICU stay. All patients had elevated CRP on presentation, and values typically started to decline within 24-48 hours [Figure 2]. However, hypoalbuminemia continued to worsen for 4-5 days after admission, especially for patients requiring intensive care [Figure 3]. Both markers gradually improved for the entire cohort, reflecting the positive outcome our patients demonstrated. Conclusion Our study highlights the reliability of CRP and albumin as biomarkers for assessing MIS-C patients. While CRP values showed a wide range and high variability throughout the course of illness, albumin appeared to be more accurate, particularly in critically ill children. We recommend regular monitoring of albumin as an inflammatory marker and suggest frequent follow-up for children with systemic inflammatory disease. Disclosures All Authors: No reported disclosures

415. Misdiagnosis of multisystem inflammatory syndrome in children: A diagnostic challenge

Abstract Background As the COVID-19 pandemic continues, multisystem inflammatory syndrome in children (MIS-C) maintains its importance in the differential diagnosis of common febrile diseases. MIS-C should be promptly diagnosed because corticosteroid and/or intravenous immunoglobulin treatment can prevent severe clinical outcomes. In this study, we aimed to evaluate clinical presentation, diagnostic parameters and management of MIS-C and compare its clinical features of common febrile disease. Methods This study was conducted at a tertiary-level hospital between December 2020 and October 2022. One hundred and six children who were initially considered to have MIS-C disease were included in the study. During the follow-up period in the hospital, when the clinical and laboratory findings were re-evaluated, 38 out of 106 children were diagnosed differently. The clinical and laboratory findings of 68 children followed up with the diagnosis of MIS-C and 38 children who were initially misdiagnosed as MIS-C but with different final diagnoses were retrospectively compared. Results We identified 68 patients with MIS-C and 38 patients misdiagnosed as MIS-C during the study period. Infectious causes (71%), predominantly bacterial origin, were the most frequently confused conditions with MIS-C. Patients with MIS-C were older and had a more severe clinical course with high rates of respiratory distress, shock, and paediatric intensive care unit admission. While rash and conjunctivitis were more common among patients with MIS-C, cough, abdominal pain, diarrhoea were observed more frequently in patients misdiagnosed as MIS-C. Lower absolute lymphocyte counts, platelet counts and higher C-reactive protein and fibrinogen levels, pathological findings on echocardiography were the distinctive laboratory parameters for MIS-C. Multivariate analysis showed that older age, presence of conjunctivitis, high level of serum CRP and lower platelets were the most discriminative predictors for the diagnosis of MIS-C. Conclusion There are still no specific findings to diagnose MIS-C, which therefore can be confused with different clinical conditions. Further data are needed to assist the clinician in the differential diagnosis of MIS-C and the diagnostic criteria should be updated over time. Disclosures All Authors: No reported disclosures

Short-, mid-, and long-term complications after multisystem inflammatory syndrome in children over a 24-month follow-up period in a hospital in Lima-Peru, 2020–2022

ObjectiveTo determine the short-, mid-, and long-term complications after multisystem inflammatory syndrome in children (MIS-C) over a 24-month follow-up period in a hospital in Lima, Peru, 2020–2022, and to explore differences according to the immunomodulatory treatment received and type of SARS-CoV-2 virus circulating.MethodsAmbispective 24-month follow-up study in children &amp;lt;14 years of age diagnosed with MIS-C at the Hospital Nacional Edgardo Rebagliati Martins (HNERM).ResultsA total of 62 children were admitted with MIS-C. The most common short-term complications and serious events were intensive care unit (ICU) admission, invasive mechanical ventilation (IMV) due to respiratory failure, and shock; predominantly during the second pandemic wave (lambda predominance) and in children that received intravenous immunoglobulin (IVIG) plus a corticosteroid. Two patients died during the first wave due to MIS-C. During prospective follow-up (median of 24 months; IQR: 16.7–24), only 46.7% of patients were followed for &amp;gt;18–24 months. Of the total, seven (11.3%) patients were identified with some sequelae on discharge. Among the 43 remaining children, sequelae persisted in five (11.6%) cases (neurological, hematological, and skin problems). Six patients (13.9%) presented with new onset disease (hematologic, respiratory, neurological, and psychiatric disorders). One patient died due to acute leukemia during the follow-up period. None of them were admitted to the ICU or presented with MIS-C reactivation. Two patients presented persistence of coronary aneurysm until 8- and 24-month post-discharge.ConclusionIn our hospital, children with MIS-C frequently developed short-term complications and serious events during the acute phase, with less frequent complications in the mid- and long-term. More studies are required to confirm these findings.

Impact of anakinra use on clinical outcomes in children with moderate or severe multisystem inflammatory syndrome in children: a propensity score matched retrospective cohort study

BackgroundThe treatment of children with multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 infection involves immunomodulatory therapies such as IVIG and steroids. Anakinra, an interleukin-1 receptor inhibitor, has also been used, but its effectiveness is not established yet. As optimal regimens for MIS-C remain unknown, we aimed to assess the effect of anakinra in reducing hospital stay in patients with MIS-C.MethodsWe included children admitted from May 2020 to May 2021 diagnosed with MIS-C based on CDC criteria. The exposure of interest was anakinra use at any point during admission. The anakinra exposed group and the anakinra unexposed group were propensity score matched based on demographic and clinical severity indicators at initial presentation. Our primary outcome was length of hospital stay. Secondary outcomes were duration of vasoactive support, vasoactive inotropic score (VIS), level of respiratory support, time to fever resolution, reduction of CRP levels, and length of ICU stay. We used Wilcoxon rank sum, t-test, Chi square and Fisher’s exact tests.ResultsOf 138 children diagnosed with MIS-C, 79% had moderate or severe illness and 41% received anakinra. Of those, 31 patients who received anakinra were propensity score matched to 31 who did not. The length of stay in the hospital but not in the ICU was longer in the anakinra group. There were no differences in median duration of vasoactive support, fever resolution, CRP reduction, or VIS.ConclusionsIn patients with moderate to severe MIS-C, use of anakinra was associated with longer duration of hospital stay.

Multi-system Inflammatory Syndrome in Children in two private, urban, tertiary hospitals in Metro Manila, Philippines

Multi-system Inflammatory Syndrome in Children in two private, urban, tertiary hospitals in Metro Manila, Philippines

High Fatality Rates in Pediatric Multisystem Inflammatory Syndrome: A Multicenter Experience From the Epicenter of Brazil's Coronavirus Pandemic.

Brazil´s case fatality rate (CFR) of pediatric multisystem inflammatory syndrome in children and adolescents (MIS-C) is among the highest worldwide. Despite these concerns, limited hospital-based and comprehensive pediatric data have been published on MIS-C in Brazilian children. We performed a descriptive analysis of the MIS-C scores in 16 public and private hospitals providing secondary and tertiary care in the metropolitan area of São Paulo, Brazil. Clinical and demographic information were systematically extracted from the electronic medical records of each patient. Logistic regression analysis was performed to identify the combined effects of MIS-C phenotype, disease severity and comorbidity as dependent variables. A total of 101 patients met the MIS-C criteria and were evaluated. The median age was 67 months, 60% were male, 28.7% were black or afrodescendant and 62.3% were admitted to public hospitals. Underlying medical conditions were observed in 16.8% of patients and were associated with a longer duration of hospitalization. A Kawasaki disease-like phenotype was observed in 43.5% of patients, and they demonstrated a trend of lower median age. Children with severe MIS-C were older (median age 91 months vs. 36 months) and had a nonspecific phenotype, more cardiovascular and respiratory involvement and kidney injury; 73.3% required intensive care, 20.8% required mechanical ventilation and 35.6% required inotropic support. Four deaths occurred (CFR = 3.9%), three of which were in healthy participants. We identified a lower median age, particularly among children with Kawasaki disease-like phenotypes, those with a significant need for intensive care, and a high CFR in MIS-C. Our findings confirmed the increased severity of the disease in the selected Brazilian population.

Comparison of Myeloid-Derived Suppressor Cells (MDSC) in children with RSV vs. COVID-19

Abstract Introduction Lower respiratory tract infections (LRTI) caused by respiratory syncytial virus (RSV) result in over 100,000 deaths of infants globally. Though adults account for most COVID-19 hospitalizations, children also develop severe disease due to SARS-CoV-2. Children with severe illness due to LRTI demonstrate evidence of impaired adaptive immune function. MDSC are an immature, heterogenous cell population that expands significantly during inflammatory conditions. MDSC suppress T cell proliferation and function resulting in immunosuppression. MDSC subsets (granulocytic (G) MDSC and the monocytic (M-)MDSC) suppress T cells via distinct mechanisms. In a previous study, we observed a significant increase in G-MDSC in children with septic shock. We hypothesize that children with severe LRTI with RSV or COVID-19 will have expansion of MDSC that will be associated with differences in T cell subset composition and worse clinical outcomes. Methods Prospective, observational study in children admitted to the pediatric intensive care unit (PICU) with symptomatic RSV or COVID-19, defined by a positive polymerase chain reaction test. Children with multi-system inflammatory syndrome or positive for both RSV and COVID-19 were excluded. Pre-pandemic healthy control samples were obtained from children requiring IV placement for outpatient MRI. Peripheral blood mononuclear cells were isolated by ficoll gradient and stained for surface markers to identify MDSC (CD45+, HLA-DR-, CD33+ and CD11b+), including G- (CD15+, CD14-) and M-MDSC (CD14+, CD15-), and T cell populations. Clinical and demographic data were collected from the electronic medical record and stored in a secure database. Results We enrolled 30 children, 20 with RSV (50% male, median age 2 [1.2-5] months), 10 with COVID-19 (30 % male, median age 25 [ 3.8 – 215] months), and 30 healthy controls (64% male, median age 73.2 [57.6, 98.4] months. Children with severe LRTI due to RSV or COVID-19 have significantly increased percentage MDSC of PBMC compared to healthy controls (13% [5.6,22] vs 9.9% [5.2, 23] vs 0.95 [0.34, 2.8] respectively). Compared to children with COVID-19, children with RSV had higher percentage M-MDSC of total MDSC (90% [87,97] vs 45% (8.4, 71], p&amp;lt; 0.0001) and lower G-MDSC (1.1% [0.44, 3.0] vs 38% [17,90], p&amp;lt;0.0001). Children with RSV had a larger percentage of T regulatory cells of total CD4+ T cells (8.0% [6.1, 9.0] vs 4.3% [3.3, 5.8], p=0.01) and were more likely require non-invasive or invasive ventilatory respiratory support than those with COVID-19 (75% vs 30%, p=0.04). Conclusions Total MDSC are significantly expanded in children with severe LRTI due to RSV and COVID-19 compared to healthy controls, but with significantly different subset distributions. Children with RSV demonstrate a predominance of M-MDSC, while children with COVID-19 demonstrate significantly higher G-MDSC. Children with RSV were also more likely to have expanded Treg cell population and require higher level respiratory support. These findings suggest that MDSC composition and suppressive mechanisms may be partially driven by viral pathogen. Larger studies are needed to confirm these findings and to investigate the role of MDSC-mediated immune suppression in children with severe LRTI to identify this cell population as a potential therapeutic target.

Efficacy and Safety of mRNA COVID-19 Vaccines in Children Aged 5-11 Years: A Systematic Review and Meta-Analysis

Abstract Background Evidence of the efficacy and safety of mRNA COVID-19 vaccines in children aged 5-11 years have been emerging. Collecting these data will inform clinicians, families, and policymakers. To evaluate the efficacy and safety of mRNA COVID-19 vaccines in children aged 5-11 years, we conducted a systematic review of literatures and meta-analysis. Methods PubMed and EMBASE databases were searched on September 2022 without language restrictions. Randomized controlled trials (RCTs) and observational studies comparing vaccinated versus unvaccinated children aged 5-11 years and reporting efficacy or safety outcomes were included. Studies reporting safety outcomes in vaccinated children only (i.e., no control group) were also included. Two investigators independently extracted relevant data from each study. Odds ratios (ORs) for efficacy and safety outcomes and incidences of adverse events (AEs) following vaccination were synthesized using a random-effects model. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis and Meta-analysis of Observational Studies in Epidemiology reporting guidelines. The primary outcome was SARS-CoV-2 infections with or without symptoms. The secondary outcomes included symptomatic SARS-CoV-2 infections, hospitalizations, and multisystem inflammatory syndrome in children (MIS-C). The incidences of each AE following vaccination were also evaluated. Results Two RCTs and 15 observational studies involving 10,935,541 vaccinated (median/mean age, 8.0-9.5 years) and 2,635,251 unvaccinated (median/mean age, 7.0-9.5 years) children were included. Two-dose mRNA COVID-19 vaccination compared to no vaccination was associated with lower risks of SARS-CoV-2 infections with or without symptoms (OR, 0.47; 95% confidence interval [CI], 0.35-0.64) (Figure 1a), symptomatic SARS-CoV-2 infections (OR, 0.53; 95% CI, 0.41-0.70) (Figure 1b), hospitalizations (OR, 0.32; 95% CI, 0.15-0.68) (Figure 1c), and MIS-C (OR, 0.05; 95% CI, 0.02-0.10) (Figure 1d), while it was associated with a higher risk of any AEs compared to placebo (OR, 1.92; 95% CI, 1.26-2.91) (Figure 1e). The incidence of AEs that prevented normal daily activities was 8.8% (95% CI, 5.4-14.2%) (Figure 1f) and that of myocarditis was estimated to be 1.8/million (95% CI, 0.000-0.001%) (Figure 1g) following the second injection. Conclusions COVID-19 mRNA vaccines are safe and effective measures to prevent SARS-CoV-2 infection and severe COVID-19-related illnesses among children aged 5-11 years. Our data provided evidence for future recommendations.