Clinical Features, Laboratory Findings Outcomes in Multisystem Inflammatory Syndrome (Mis-C) Following Covid-19 Infection - a Multicenter, Observational, Ambidirectional Cohort Study in Rio De Janeiro State, Brazil

Objectives: As of March 5th, 2022, around 1.585 cases of MIS-C and 98 deaths (6,4%) were reported in Brazil. The state of Rio de Janeiro State (RJ) having 94 cases (5,9%) and 4 deaths (4,2%)1.Our aim was to evaluate clinical and laboratory features, and management of MIS-C in seven pediatric hospitals in RJ, Brazil. Method(s): Multicenter, observational, ambidirectional cohort study in seven tertiary hospitals in RJ(Brazil), assessing medical charts of pediatric inpatients (0-18 years) diagnosed with MIS-C according to WHO/CDC criteria, from August, 2020 to February, 2022. Descriptive statistics were used to analyze distributions of continuous variables, frequencies, and proportions. Result(s): A total of 112 cases of MIS-C were enrolled. The mean age was 4.2 years and thre was male predominance (59,8%). All cases had a SARS-CoV-2 contact (29.5% close contact;31.3%:positive PCR;serology:43.8%).Only 12.5% had comorbidities. Length of stay (LOS) was 7 days.Median duration of fever was 8 days. Most common symptoms were: rash(67%);gastrointestinal (67%);conjunctivitis (42%);neurological(39.6%);cardiovascular(37.5%);cervical lymphadenopathy (36.6%), and shock/hypotension(28.6%).Co-infection occurred in 3 patients. Forty-four patients fulfilled criteria for Kawasaki disease. Most patients were admitted to PICU(12;62,5%) for amedian of 2 days. Respiratory distress was seen in 18,7%;hypotension:28,6%, and shock in 23,2%. Main laboratory findings were: high C-reactive protein in 95%;D-dimer:77%, anemia:77%, thrombocytosis:63%;transaminitis:43.8%, lymphopenia:38%;hypoalbuminemia:34%;thrombocytopenia: 29%;hypertriglyceridemia:28%, and high pro-BNP in 27%. Echocardiogram was performed in 91/112 patients;abnormal in 70,3%;exhibiting myocardial dysfunction( 25%);pericardial effusion(21%);coronary dilation/aneurysms(11%) and, valvulitis (14.5%). IVIG+corticosteroids (CTC) were administered in 59.8%(67/ 112);18.6%(18/112) IVIG only;10.7%(12/112) CTC only;3.4%(4/112)biologics, and 15(13.3%) received no treatment. ASA low dose in 77.7% (87/112) and moderate/high dose in 34.8%. Oxygen support was needed in 27,7%;vasoactive amines:18,7%;dialysis:5,3%, and transfusion:18,7%.One patient died from a cytokine storm syndrome. Conclusion(s): Our study reports a higher number of MIS-C cases in RJ than the number reported to Brazilian authorities, highlighting underreporting. Our patients were younger, had fewer comorbidities, cardiovascular/gastrointestinal/renal involvement, shortest LOS in ICU, and a higher frequency of myopericarditis.

Case report: Multisystem inflammatory syndrome in children associated with COVID-19, macrophage activation syndrome, and incomplete Kawasaki disease.

Background: Multisystem inflammatory syndrome in children (MIS-C), is a severe complication of coronavirus disease 2019 (COVID-19), characterized by persistent fever, systemic inflammatory response, and organ failure. MIS-C with a history of COVID-19 may share clinical features with other well-defined syndromes such as macrophage activation syndrome, Kawasaki disease, hemophagocytic syndrome and toxic shock syndrome. Case 1: An 11-year-old male with a history of hypothyroidism and precocious puberty with positive antibody test for COVID-19 was admitted for fever, poor general condition, severe respiratory distress, refractory shock, and multiple organ failure. His laboratory examination showed elevated inflammatory parameters, and bone marrow aspirate showed hemophagocytosis. Case 2: A 13-year-old male with a history of attention deficit hyperactivity disorder and cognitive delay presented clinical manifestations of Kawasaki disease, fever, conjunctival congestion, exanthema, and hyperemia in oral mucosa, tongue, and genitals, with refractory shock and multiple organ failure. Reverse transcriptase polymerase chain reaction (RT-PCR) and antibodies for COVID-19 were negative, inflammation parameters were elevated, and bone marrow aspirate showed hemophagocytosis. Patients required intensive care with invasive mechanical ventilation, vasopressor support, intravenous gamma globulin, systemic corticosteroids, low molecular weight heparin, antibiotics, and monoclonal antibodies and, patient 2 required renal replacement therapy. Conclusions: Multisystemic inflammatory syndrome in children can have atypical manifestations, and identifying them early is very important for the timely treatment and prognosis of patients.

Clinical phenotypes of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19

The multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C) is infre-quent but potentially lethal. There are few reports of this disease and its phenotypes in Latin America. Objective: To describe the characteristics of the clinical phenotypes of MIS-C in hospitalized patients in Lima, Peru. Patients and Method: A descriptive and retrospective study in patients under 14 years old with a diagnosis of MIS-C at the Hospital Nacional Edgardo Rebagliati Martins (Lima, Peru), from April 2020 to August 2021. Clinical-demographic and microbiological variables were recorded. According to these, patients with MIS-C were classified into the shock phenotype, Kawasaki disease (KD) without shock, and the fever and inflammation phenotype, analyzing their clinical outcomes. Results: 58 patients were analyzed. 32 (55.2%) presented the shock phenotype, 15 (25.8%) Kawasaki disease (KD) phenotype without shock, and 11 (19%) fever and inflammation phenotype. In the shock phenotype, 17 had KD. The mean age was 7 +/- 3.5 years and 67.2% were males. Gastrointes-tinal and mucocutaneous manifestations predominated in all phenotypes. The mortality was 3.5%. The frequency of coronary aneurysms was 10.2%. Most patients received immunomodulatory and antiplatelet treatment. Patients with shock phenotype showed greater involvement in inflammatory markers, hematological dysfunction, and myocardial injury, with a higher frequency of respiratory failure and invasive mechanical ventilation. Conclusions: In our case series, patients with shock phenotype were the most frequent and had worse clinical outcomes. Active surveillance of clinical phenotypes is needed to make an early diagnosis and management to improve the prognosis in these patients.

Clinical phenotypes of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19

The multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C) is infre-quent but potentially lethal. There are few reports of this disease and its phenotypes in Latin America. Objective(s): To describe the characteristics of the clinical phenotypes of MIS-C in hospitalized patients in Lima, Peru. Patients and Method: A descriptive and retrospective study in patients under 14 years old with a diagnosis of MIS-C at the Hospital Nacional Edgardo Rebagliati Martins (Lima, Peru), from April 2020 to August 2021. Clinical-demographic and microbiological variables were recorded. According to these, patients with MIS-C were classified into the shock phenotype, Kawasaki disease (KD) without shock, and the fever and inflammation phenotype, analyzing their clinical outcomes. Result(s): 58 patients were analyzed. 32 (55.2%) presented the shock phenotype, 15 (25.8%) Kawasaki disease (KD) phenotype without shock, and 11 (19%) fever and inflammation phenotype. In the shock phenotype, 17 had KD. The mean age was 7 +/- 3.5 years and 67.2% were males. Gastrointes-tinal and mucocutaneous manifestations predominated in all phenotypes. The mortality was 3.5%. The frequency of coronary aneurysms was 10.2%. Most patients received immunomodulatory and antiplatelet treatment. Patients with shock phenotype showed greater involvement in inflammatory markers, hematological dysfunction, and myocardial injury, with a higher frequency of respiratory failure and invasive mechanical ventilation. Conclusion(s): In our case series, patients with shock phenotype were the most frequent and had worse clinical outcomes. Active surveillance of clinical phenotypes is needed to make an early diagnosis and management to improve the prognosis in these patients. Copyright © 2022, Sociedad Chilena de Pediatria. All rights reserved.

Amazon Experience of Severe Sarscov- 2 Infection in Children

BACKGROUND AND AIM: Some children can develop severe forms of SARS-CoV-2 infection either acutely or later. To identify the risk factors for worse outcomes in hospitalized children and adolescents with severe acute SARS-CoV-2 infection and MIS-C METHOD: This multicenter cohort study included all children and adolescents with confirmed or suspected critical SARSCoV- 2 infection admitted to the three PICU between April 2020 and September 2021. The exclusion criteria were immunocompromised status, and end-of-life decision. The main variables analyzed were epidemiological, clinical, and laboratory data, and ventilator settings at admission and after 72 h. The patients were divided into three groups (G): confirmed coronavirus disease (COVID-19) with multisystemic inflammatory syndrome in children (MIS- C) criteria (G1), confirmed COVID-19 without MIS-C criteria (G2), and MIS-C criteria without confirmed COVID-19. RESULT(S): The median age of the patients was 28 months in G1, with comorbidities in 40 patients (72.7%) (p < 0.0001). Moreover, invasive mechanical ventilation (IMV) was required in 44 patients (80%, p < 0.0001), and cardiogenic shock occurred in 26 patients (54.2%, p < 0.0001) in G1.Under nutrition (< 2 SD for weight), longer exposure time (odds ratio [OR]: 2.11;95% confidence interval [CI]: 1.37-3.25;p = 0.001), IMV time (OR: 2.6;95% CI: 1.15-5.85;p = 0.03), and length of hospital stay (OR: 10.94;95% CI: 1.93-63.1;p = 0.007) were associated with critical MIS-C in G1. CONCLUSION(S): In the Brazilian Amazon area, specifically in the Para state, we identified a cluster of more severe forms of pediatric acute or late SARS-CoV-2 infection. (Figure Presented).

Four Months Physical, Psychosocial, and Neurocognitive Follow-up of Multisystemic Inflammatory Syndrome in Children (Mis-C) after Picu Admission: A National Prospective Cohort Study

BACKGROUND AND AIM: Outcome of the novel COVID-19 related disease "Multisystemic Inflammatory Syndrome in Children (MIS-C)" is still largely unknown. We aimed to assess physical, psychosocial, and neurocognitive functioning in MIS-C survivors after PICU admission. METHOD(S): A national prospective cohort study including MIS-C children (0-17 years) admitted to one of the 7 PICUs in The Netherlands. Children were tested 3-6 months after PICU admission in a multidisciplinary follow-up program through a semi-structured interview, validated questionnaires for psychosocial outcomes, in both children and their parents, and validated neurocognitive tests in children. RESULT(S): Between March 2020 and June 2021, 49 MIS-C children attended follow-up after median 4 months (IQR 3-5) at median age 11.6 years (IQR 9.3-15.6). At follow-up, PCPC and POPC scores were normal in all children, 21 (43%) children reported impaired exercise intolerance and 20% worsening sleeping behaviour. Physical and school functioning quality of life scores were worse compared with norm data. General intelligence and verbal memory scores were comparable to norm data (N=44), whereas visual memory, sustained attention, and planning were significantly lower in a subgroup of 29 patients. Parents reported less posttraumatic stress and depressive symptoms compared with norms. CONCLUSION(S): After PICU admission, exercise intolerance, sleeping, physical and school functioning problems were reported. Overall intelligence and neurocognitive scores were normal, with subtle deviants in some neurocognitive functions indicating integration and sustained attention problems. This yields for a longer-term follow-up to assess MIS-C survivors functioning.

Deep immunophenotyping reveals biomarkers of multisystemic inflammatory syndrome in children in a Latin American cohort.

BACKGROUND: Multisystemic inflammatory syndrome in children (MIS-C) is a life-threatening disease that occurs 2-5 weeks after severe acute respiratory syndrome coronavirus 2 exposure and is characterized by severe multisystemic inflammation. Early recognition of MIS-C is key to prognosis; therefore, establishing clinical and laboratory biomarkers that predict complications is urgently needed. OBJECTIVE: We characterized the immune response and clinical features of patients with acute MIS-C and determined biomarkers of disease in a cohort of 42 Latin American patients. METHODS: Immune characterization was performed using flow cytometry from peripheral mononuclear cells and severe acute respiratory syndrome coronavirus 2-specific humoral and cellular response was performed using flow cytometry, enzyme-linked immunospot, enzyme-linked immunosorbent assay, and neutralizing antibody assays. RESULTS: MIS-C is characterized by robust T-cell activation and cytokine storm. We uncovered that while C-X-C motif chemokine ligand (CXCL) 9, IL-10, CXCL8, CXCL10, IL-6, and IL-18 are significantly elevated in patients with shock, while CCL5 was increased in milder disease. Monocyte dysregulation was specifically associated with KD-like MIS-C. Interestingly, MIS-C patients show a natural killer cell degranulation defect that is persistent after 6 months of disease presentation, suggesting it could underlie disease susceptibility. Most MIS-C had gastrointestinal involvement, and higher levels of neopterin were identified in their stools, potentially representing a biomarker of intestinal inflammation in MIS-C. Severe acute respiratory syndrome coronavirus 2-specific cellular response and neutralizing antibodies were identifiable in convalescent MIS-C patients, suggesting sustained immunity. CONCLUSION: Clinical characterization and comprehensive immunophenotyping of Chilean MIS-C cohort provide valuable insights in understanding immune dysregulation in MIS-C and identify relevant biomarkers of disease that could be used to predict severity and organ involvement.

Postcovid Multisystemic Inflammatory Syndrome in a Child with Acute Obstructive Pneumonia

Childhood inflammatory multisystemic syndrome (CIS-C) is a serious late complication of SARS-CoV-2 infection that can develop in some children and young adults. Criteria for defining SIM-C in children include fever>= 38.0degreeC, laboratory findings suggestive of an inflammatory process increased - C-reactive protein, D-dimer, VSH, ferritin, LDH, IL-6, neutrophils, procalcitonin, venous blood gas and lactate levels, brain natriuretic peptide;decreased - lymphocytes, platelets, serum albumin, serum sodium, manifestations of multisystem involvement with >2 organs/systems (cardiac, renal, respiratory, haematological, gastrointestinal, dermatological or neurological), absence of plausible alternative diagnosis, recent or currently positive COVID-19 infection, or contact with confirmed COVID-19 case within 4 weeks prior to onset of symptoms. The authors present the case of a 3-year-old girl aged 3 years and 5 months, admitted to the Pediatric Clinic of the Hospital Clinic Judetean de Urgenta Constanta in January 2022, for fever (39.5degreeC), microerythematous rash, semi-productive cough. and dyspnea. Investigations detected anticovid antibodies present, with no SARS cov2 infection diagnosed in the personal pathological history. Copyright © 2021 Badescu Anca Gabriela et al., published by Sciendo.

Cardiovascular involvement in Pediatric multisystemic inflammatory syndrome temporally associated with COVID-19 infection

In 2020, World Health Organization declared the infection with COVID-19 a pandemic. Even though the risk of infestation and mortality is lower in children than in adults, children are more prone to develop a hyperimmune state after COVID-19 infection called pediatric multi-system inflammatory syndrome or PIMS. In PIMS, cardiovascular involvement with myo-cardial injury is present in most patients. Due to the novelty of this pathology, little is known about the implication on the cardiovascular system. This review focuses on the most recent data published on the pediatric multi-system inflammatory syndrome associated with COVID-19 infection, pathophysiological mechanisms, and especially cardiovascular involvement. Furthermore, it emphasizes the role of pediatric cardiologists in its management. © 2022, Amaltea Medical Publishing House. All rights reserved.

Multisystemic Inflammatory Syndrome in Children Associated With COVID-19

Introduction: The condition of COVID-19 in children is mild or asymptomatic in most cases, but a small percentage has serious diseases that require admission to the pediatric intensive care unit, one of them is the multisystemic inflammatory syndrome in children associated with COVID-19, characterized by fever, high acute phase reactants and involvement of various organs. Objective: To report two cases with multisystemic inflammatory syndrome in children associated with COVID-19, in Huancayo City-Peru. Case report: Case 1: A 3-year-old male patient had 12-day illness period that began with upper respiratory symptoms, fever for three days, general discomfort and 4 days before admission, he showed with persistent fever, colicky abdominal pain associated with vomiting, also he had a purpuric rash on the lower limbs. As a background, his father tested positive for the PCR-RT test for COVID-19, 3 weeks before the child's admission. Case 2: A 10-year-old male patient, with a history of COVID-19 pneumonia, 15 days before admission, he had a 3-day illness period characterized by fever, fatigue and palpitations that exacerbated by physical activity. Conclusions: The multisystemic inflammatory syndrome in children associated with COVID-19 is a new disease that requires multidisciplinary management in a pediatric intensive care unit. © 2021, Editorial Ciencias Medicas. All rights reserved.

Multisystemic Inflammatory Syndrome in Children, A Disease with Too Many Faces: A Single-Center Experience.

BACKGROUND AND AIM: Multisystemic inflammatory syndrome in children (MIS-C) is a rare and severe condition associated with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection in children with onset approximately 4-6 weeks after infection. To date, the precise mechanism that causes MIS-C is not known and there are many questions related to the etiology, risk factors, and evolution of this syndrome. We aimed to describe the clinical manifestations, treatment methods, and disease evolution and analyze the main risk factors for MIS-C in children hospitalized in our clinic. MATERIAL AND METHODS: We performed a retrospective study including children with MIS-C followed-up in the 2nd Pediatric Clinic of the Emergency Clinical Hospital for Children Cluj-Napoca, Romania, for 13 months (November 2020-December 2021). RESULTS: We included in our cohort 34 children (mean age 6.8 ± 4.6 years) who met MIS-C criteria: high and prolonged fever associated with organ dysfunction (heart, lungs, kidneys, brain, skin, eyes, bone marrow or gastrointestinal organs), and autoantibodies and/or polymerase chain reaction positives for SARS-CoV-2. Nineteen patients (55.88%) had a severe form of the disease, with multiorgan failure and shock, and myocardial or respiratory failure. The number of organs affected in the severe forms was significantly higher (more than 6 in 73.70%) than in mild forms (2-3 in 60%). Cardiac dysfunction, hypoalbuminemia, hypertriglyceridemia and hyponatremia were more important in severe forms of MIS-C. These patients required respiratory support, resuscitation with fluid boluses, vasoactive drugs, or aggressive therapy. All patients with mild forms had fully recovered compared to 63.16% in severe forms. The others with severe forms developed long-term complications (dilation of the coronary arteries, premature ventricular contraction, or myocardial fibrosis). Two patients had an extremely severe evolution. One is still waiting for a heart transplant, and the other died (hemophagocytic lymphohistiocytosis syndrome with multiorgan failure). CONCLUSIONS: From mild to severe forms with multiorgan failure, shock, and many other complications, MIS-C represents a difficult challenge for pediatricians, who must be aware of the correct diagnosis and unpredictable, possibly severe evolution.

Activity of a Pediatric Emergency Department of a Tertiary Center in Bologna, Italy, during SARS-CoV-2 Pandemic.

During the SARS-CoV-2 pandemic, the pediatric emergency department (ED) of Bologna, Emilia-Romagna, Italy faced a reorganization to better deal with the new clinical needs. We herein describe the main changes in the organization and in the attendances to our pediatric ED. From the 1 March 2020 to the 31 January 2022, 796 children positive for SARS-CoV-2 presented to our pediatric ED, but only 26 required hospitalizations, of which only 9 for COVID-19 related reasons. During this period, we also registered a temporal correlation between multisystem inflammatory syndrome in children (MIS-C) admissions and the peaks of SARS-CoV-2 infection in the Italian population. Respiratory syncytial virus (RSV) remained during last year the viral infection with the highest hospitalization rate. The analysis and description of the changes in the activity of the pediatric ED during the SARS-CoV-2 pandemic may help to better understand the routinary activity and be prepared for any possible new challenge.

COVID-19: autoimmunity, multisystemic inflammation and autoimmune rheumatic patients.

Coronavirus disease 2019 (COVID-19) is associated with autoimmunity and systemic inflammation. Patients with autoimmune rheumatic and musculoskeletal disease (RMD) may be at high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this review, based on evidence from the literature, as well as international scientific recommendations, we review the relationships between COVID-19, autoimmunity and patients with autoimmune RMDs, as well as the basics of a multisystemic inflammatory syndrome associated with COVID-19. We discuss the repurposing of pharmaceutics used to treat RMDs, the principles for the treatment of patients with autoimmune RMDs during the pandemic and the main aspects of vaccination against SARS-CoV-2 in autoimmune RMD patients.

Cardiac involvement in Adult Multisystemic Inflammatory Syndrome related to COVID-19. Two case reports.

In this article we describe two cases that presented with persistent fever and a hyperinflammatory state in association with severe acute respiratory syndrome-coronavirus-2 infection with various negative reverse transcription-polymerase chain reaction results. These cases subsequently developed myocarditis with cardiogenic shock that required vasoactive drugs and had a good response to corticosteroid treatment. All cases met criteria for a definitive case of multisystemic inflammatory syndrome in adults, a recently described entity associated with coronavirus disease 2019, which has a good response to immunomodulators and a good prognosis in most cases. .

Abdominal manifestation of multisystemic inflammatory syndrome in children.

SUMMARY: Multisystemic inflammatory syndrome (MIS-C) can develop as a complication of SARS CoV-2 infection, involving the gastrointestinal system mainly by vasoconstriction, edema, glandular hyperplasia, and a procoagulant state leading to direct tissue injury. METHOD: ology: a series of cases including 8 patients with MIS-C treated in two highly complex institutions is presented. These patients, had abdominal symptoms of surgical management. RESULTS: The average age was 9.5 years and the most frequent symptoms were fever, abdominal pain, diarrhea (100%); in addition, 87.5% presented shock. The diagnosis of SARS CoV-2 was confirmed by RT-PCR test in 37.5%, antigen 12.5% and the rest of the patients showed IgM and IgG antibodies. In laboratories, the increase in acute phase reactants, Erythrocyte Sedimentation Rate (ESR), C-reactive protein, procalcitonin, as well as troponin, D dimer and proBNP, is highlighted. The surgical outcome documented 2 patients with a normal appendix, 3 patients with edematous appendicitis, and 3 patients with complicated appendicitis. CONCLUSIONS: patients with MIS-C display abdominal symptoms similar to those present in surgical emergencies and a non-negligible number of cases require surgical exploration. This condition poses a new differential diagnosis to the surgical abdomen in pediatric patients.

Multisystem Inflammatory Syndrome in Adults (MIS-A) Associated with SARS-CoV-2 Infection in a Young Adult Case from Turkey.

Weeks and even months after recovering from the SARS-CoV-2 infection, clinically more severe cases are being reported, which are suggestive of COVID-19- related multisystemic inflammatory syndromes (MIS). Firstly on March 2020, this condition was reported to be COVID-19 related to children (MIS-C). Since June 2020, a syndrome similar to multisystem inflammatory syndrome in adults (MIS-A) came to be noticed in adults as well. We reported here a case of 24-year-old young woman who had gone to a hospital with abdominal pain and later developed a severe cough, followed by development of subconjunctival bleeding, pericardial effusion, pleural effusion, and intra-abdominal fluid that we deemed them to be acute multisystemic clinical symptoms, 47 days after she had undergone a COVID-19 infection of mild clinical severity. It should be kept in mind that a multisystemic inflammatory syndrome along with a delayed immune response during COVID-19 disease can be seen not only in children but also in young adults, and seemingly severe clinical and laboratory findings can improve by controlling the inflammatory process.

Multisystemic Inflammatory Syndrome and Thrombotic Microangiopathy as Complications of COVID-19 in a Child: A Case Report.

Clinical presentations of the novel coronavirus (SARS-CoV-2) infection are quite varied, ranging from asymptomatic conditions to potentially fatal disease. The kidney is one of the affected targets of coronavirus disease (COVID-19) complications, and renal dysfunction is a significant prognostic factor for mortality. This report describes a series of clinical complications in a previously healthy child who developed nephritic syndrome with a concomitant SARS-CoV-2 infection. These complications include acute kidney injury that progressed to chronicity, multisystemic inflammatory syndrome, Kawasaki-like syndrome, and thrombotic microangiopathy.