Assessing pattern of the Pediatric Multisystem Inflammatory Syndrome (PMIS) in children during the COVID-19 pandemic: experience from the emergency department of tertiary care center of a low-middle-income country.

BACKGROUND: Pediatric Multisystem Inflammatory Syndrome (PMIS) is a hyperinflammatory condition affecting multiple organs in children, often resembling incomplete Kawasaki Disease during later phases of COVID-19 infection. Data on PMIS in low-middle-income countries, particularly in emergency department settings, is limited. OBJECTIVES: This prospective observational study at Aga Khan University Hospital, Karachi, aimed to determine the frequency, clinical presentation patterns, and laboratory parameters of children with PMIS visiting the emergency department during the COVID-19 pandemic. Secondary objectives included assessing factors associated with in-hospital mortality. METHODS: From March 2020 to September 2021, patients meeting World Health Organization PMIS criteria were enrolled. COVID-19 testing included PCR and antibody testing. Data was collected through a questionnaire and analyzed statistically. RESULTS: Among 56 PMIS patients (85.7% male, mean age 7.67 ± 4.8 years), respiratory symptoms (70%), neurological symptoms (57%), and gastrointestinal symptoms (54%) were common presentations. Signs included delayed capillary refill time (93%), low-volume pulses (89%), and hypotension (68%). COVID-19 antibodies were positive in the majority (78.6%) while PCR was positive in 18%. Risk factors for mortality included prolonged emergency department stay, and high Ferritin and Lactate Dehydrogenase levels. CONCLUSION: PMIS affects children of all ages. Respiratory and gastrointestinal symptoms are the most frequent presentations. Elevated inflammatory markers, including LDH, Ferritin, D-dimer, and Pro-BNP, correlate with higher mortality risk.

Multicentre observational study on multisystem inflammatory syndrome related to COVID-19 in Argentina.

BACKGROUND: The impact of the pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in low- and middle-income countries remains poorly understood. Our aim was to understand the characteristics and outcomes of PIMS-TS in Argentina. METHODS: This observational, prospective, and retrospective multicenter study enrolled patients younger than 18 years-old manifesting PIMS-TS, Kawasaki disease (KD) or Kawasaki shock syndrome (KSS) between March 2020 and May 2021. Patients were followed-up until hospital discharge or death (one case). The primary outcome was pediatric intensive care unit (PICU) admission. Multiple logistic regression was used to identify variables predicting PICU admission. RESULTS: Eighty-one percent, 82%, and 14% of the 176 enrolled patients fulfilled the suspect case criteria for PIMS-TS, KD, and KSS, respectively. Temporal association with SARS-CoV-2 was confirmed in 85% of the patients and 38% were admitted to the PICU. The more common clinical manifestations were fever, abdominal pain, rash, and conjunctival injection. Lymphopenia was more common among PICU-admitted patients (87% vs. 51%, p < 0.0001), who also showed a lower platelet count and higher plasmatic levels of inflammatory and cardiac markers. Mitral valve insufficiency, left ventricular wall motion alterations, pericardial effusion, and coronary artery alterations were observed in 30%, 30%, 19.8%, and 18.6% of the patients, respectively. Days to initiation of treatment, rash, lymphopenia, and low platelet count were significant independent contributions to PICU admission. CONCLUSION: Rates of severe outcomes of PIMS-TS in the present study agreed with those observed in high-income countries. Together with other published studies, this work helps clinicians to better understand this novel clinical entity.

SARS-CoV-2 infection showing signs of cerebral sinus vein thrombosis in the infantile period.

The clinical manifestations of SARS-CoV-2 infection mainly involve the respiratory system. However, there is increasing evidence that this virus can affect other organs, causing a wide range of clinical symptoms. This is the report of a 40-day-old patient who presented with sepsis and had no risk factors other than SARS-CoV-2 infection, whose radiological findings were compatible with cerebral sinus vein thrombosis.

The SARS-CoV-2 Pandemic Impacts the Management of Swiss Pediatric Intensive Care Units.

The impact of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic on pediatric intensive care units (PICUs) is difficult to quantify. We conducted an observational study in all eight Swiss PICUs between 02/24/2020 and 06/15/2020 to characterize the logistical and medical aspects of the pandemic and their impact on the management of the Swiss PICUs. The nine patients admitted to Swiss PICUs during the study period suffering from pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) and constituting 14% (9/63) of all SARS-CoV-2 positive hospitalized patients in Swiss children's hospitals caused a higher workload [total Nine Equivalents of nursing Manpower use Score (NEMS) points, p = 0.0008] and were classified to higher workload categories (p < 0.0001) than regular PICU patients (n = 4,881) admitted in 2019. The comparison of the characteristics of the eight Swiss PICUs shows that they were confronted by different organizational issues arising from temporary regulations put in place by the federal council. These general regulations had different consequences for the eight individual PICUs due to the differences between the PICUs. In addition, the temporal relationship of these different regulations influenced the available PICU resources, dependent on the characteristics of the individual PICUs. As pandemic continues, reflecting and learning from experience is essential to reduce workload, optimize bed occupancy and manage resources in each individual PICU. In a small country as Switzerland, with a relatively decentralized health care local differences between PICUs are considerable and should be taken into account when making policy decisions.

Clinical practice guidelines in multisystem inflammatory syndrome (MIS-C) related to COVID-19: a critical review and recommendations.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a serious health condition that develops from and is linked to coronavirus disease 2019. MIS-C is considered a multi-organ dysfunction involving cardiac, renal, respiratory, hematologic, gastrointestinal and neurological symptoms and groups of signs and symptoms such as rash or bilateral non-purulent conjunctivitis, hypotension or shock and acute gastrointestinal problems, which require immediate therapeutic intervention to prevent the aggravation of the patient's health condition. MIS-C is relatively new in the field of evidence-based medicine; however, there are several clinical guidelines for good clinical practice. For every disorder, the guidelines have different suggestions. Hence, based on the current status of the evidence, recommendations have been combined to form a unified guideline for therapeutic management. METHODS: This paper compares and evaluates the current MIS-C-specific clinical practice guidelines (namely, American Academy of Pediatrics, American College of Rheumatology, Helen DeVos Children's Hospital Foundation, Children's Hospital of The King's Daughters, and the Infectious Diseases Society of America). The compiled literature was then assessed by the authors separately, and an algorithm was proposed for each disorder, taking into consideration the various guidelines proposed for the management of the disorder. RESULTS: The features of MIS-C patients are unified; this is very helpful in managing its symptoms and decreasing mortality rates. In addition, recommendations for pharmacological treatment for MIS-C symptoms are formulated after cross-comparison across five different guidelines. CONCLUSIONS: This study provides a general interpretation of the results in the context of other evidence and implications for future research. It proposes a unified guideline based on the current evidence, with the best potential to maintain suitable clinical standards in the Saudi Arabian Ministry of Health.

Oral manifestations of multisystemic inflammatory syndrome in children (MIS-C) and Kawasaki disease associated to COVID-19: A systematic review.

AIMS: Multisystemic inflammatory syndrome in children (MIS-C) is a condition noted in some children asymptomatic but positive to Sars-cov-2 antibody and it presents clinical and laboratory changes similar to Kawasaki disease (KD). Oral changes have also been observed. This systematic review evaluated oral manifestations detected in children with MIS-C and KD associated to COVID-19. METHODS AND RESULTS: This work was registered at PROSPERO (#CRD42020225909), following PRISMA guidelines. A comprehensive research was conducted in MEDLINE, Web of Science, EMBASE, LILACS, Scopus, and Grey Literature through August 2021, based on original research evaluating children diagnosed with MIS-C or KD related to COVID-19. Two authors independently screened all retrieved references. Twenty five selected studies evaluated 624 children, mean age 8.78 years. The assessment of the risk of bias (ROB) showed that most of them presented low ROB. Oral manifestations were erythematous mucous membrane, oral ulcers lesions, dry, swollen and cracked lips, and strawberry tongue. CONCLUSION: MIS-C and KD share the same oral manifestations and their identification may lead to an early diagnosis.

Complejidad del diagnóstico de la enfermedad de Kawasaki en tiempos de COVID-19

Introducción: La enfermedad de Kawasaki es la principal causa de enfermedad cardiaca adquirida en la infancia, sin embargo, su diagnóstico se dificulta después de la aparición del SARS-CoV-2. Objetivo: Examinar un caso con enfermedad de Kawasaki incompleta en el contexto de la pandemia por COVID-19 y el reto diagnóstico que representa. Presentación del caso: Paciente de 5 meses de edad quien es traída por sus padres al servicio de urgencias por síntomas respiratorios superiores y múltiples episodios eméticos. Durante su hospitalización presenta fiebre de difícil control, edema en extremidades, exantema polimorfo y lengua aframbuesada, por lo que, tras descartar el síndrome inflamatorio multisistémico pediátrico temporalmente asociado al COVID 19, se diagnostica la enfermedad de Kawasaki. Se indica tratamiento con inmunoglobulina endovenosa y ácido acetilsalicílico. La paciente evolucionó de forma satisfactoria y egresó al día 10 de hospitalización. Conclusiones: La diferenciación de la enfermedad de Kawasaki con el síndrome inflamatorio multisistémico pediátrico es vital, dado que este último presenta mayor riesgo de morbilidad y mortalidad a corto plazo.

Introduction: Kawasaki disease is the main cause of heart disease acquired in childhood, however, its diagnosis is difficult after the onset of SARS-CoV-2. Objective: To examine a case with incomplete Kawasaki disease in the context of the COVID-19 pandemic and the diagnostic challenge it represents. Case presentation: A 5-month-old female patient brought by her parents to the emergency service due to upper respiratory symptoms and multiple emetic episodes. During her hospitalization, she presented fever that was difficult to control, edema in the extremities, polymorphous exanthema and a strawberry tongue, so after ruling out the pediatric multisystem inflammatory syndrome temporarily associated with COVID 19, Kawasaki disease was diagnosed. Treatment with intravenous immunoglobulin and acetylsalicylic acid is indicated. The patient progressed satisfactorily and was discharged on day 10 of hospitalization. Conclusions: The differentiation of Kawasaki disease with pediatric multisystem inflammatory syndrome is vital, given that the latter presents a higher risk of morbidity and mortality in the short term.

Rapid review of multisystem inflammatory syndrome in paediatrics: What we know one year later.

BACKGROUND: : Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) is an emerging condition that was first identified in paediatrics at the onset of the COVID-19 pandemic. The condition is also known as pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (PIMS-TS or PIMS), and multiple definitions have been established for this condition that share overlapping features with Kawasaki Disease and toxic shock syndrome. METHODS: : A review was conducted to identify literature describing the epidemiology of MIS-C, published up until March 9, 2021. A database established at the Public Health Agency of Canada with COVID-19 literature was searched for articles referencing MIS-C, PIMS or Kawasaki Disease in relation to COVID-19. RESULTS: : A total of 195 out of 988 articles were included in the review. The median age of MIS-C patients was between seven and 10 years of age, although children of all ages (and adults) can be affected. Multisystem inflammatory syndrome in children disproportionately affected males (58% patients), and Black and Hispanic children seem to be at an elevated risk for developing MIS-C. Roughly 62% of MIS-C patients required admission to an intensive care unit, with one in five patients requiring mechanical ventilation. Between 0% and 2% of MIS-C patients died, depending on the population and available interventions. CONCLUSION: : Multisystem inflammatory syndrome in children can affect children of all ages. A significant proportion of patients required intensive care unit and mechanical ventilation and 0%-2% of cases resulted in fatalities. More evidence is needed on the role of race, ethnicity and comorbidities in the development of MIS-C.

Short-term Cardiovascular Complications of Multi-system Inflammatory Syndrome in Children (MIS-C) in Adolescents and Children.

PURPOSE OF REVIEW: We provide the readers with a review of cardiac complications in children with multi-system inflammatory syndrome in children (MIS-C) and its short-term outcomes. RECENT FINDINGS: Recent reports described the acute cardiac manifestations of MIS-C in children and provided a glimpse of the short-term outcomes. SUMMARY: Children with MIS-C have been reported to acutely have variable degrees of cardiac findings including abnormal cardiac enzymes, abnormal electrocardiographs, decreased systolic function, coronary artery abnormalities from coronary dilation to giant aneurysms, mitral valve regurgitation, tricuspid valve regurgitation, aortic valve insufficiency, pericardial effusion, diastolic dysfunction, abnormal cardiac strain, and abnormal cardiac MRI. The majority of these abnormalities resolved during short-term follow-up. Further studies are needed to assess if transient or persistent cardiac complications are associated with long-term adverse cardiac events in children with MIS-C. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40124-021-00258-5.

Similarities and Differences Between COVID-19-Related Multisystem Inflammatory Syndrome in Children and Kawasaki Disease.

In December 2019, the first case of coronavirus disease (COVID-19) was first reported in Wuhan, China. As of March 2021, there were more than 120 million confirmed cases of COVID-19 and 2.7 million deaths. The COVID-19 mortality rate in adults is around 1-5%, and only a small proportion of children requires hospitalization and intensive care. Recently, an increasing number of COVID-19 cases in children have been associated with a new multisystem inflammatory syndrome. Its clinical features and laboratory characteristics are similar to those of Kawasaki disease (KD), KD shock syndrome, and toxic shock syndrome. However, this new disorder has some distinct clinical features and laboratory characteristics. This condition, also known as multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, has been observed mostly in Europe and the United States. This emerging phenomenon has raised the question of whether this disorder is KD triggered by SARS-CoV-2 or a syndrome characterized by multisystem inflammation that mimics KD. This narrative review is to discuss the differences between MIS-C and KD with the aim of increasing pediatricians' awareness of this new condition and guide them in the process of differential diagnosis.

Multisystem inflammatory syndrome in children (MIS-C) temporally associated with SARS-CoV-2: the first clinical case in Ternopil, Ukraine.

INTRODUCTION: Coronavirus disease (COVID-19) has led to a global pandemic among patients of all ages around the world. A new delayed inflammatory syndrome, with potentially severe evolution, has been described in the pediatric population, a population previously considered to be less vulnerable to the severe forms of COVID-19. CASE REPORT: We describe the first clinical case of multisystem inflammatory syndrome (MIS-C) in a 7-year-old child of the Ternopil region, Ukraine. Our clinical case fulfills the Royal College of Paediatrics and Child Health definition of MIS-C temporarily associated with COVID-19 -systemic disease with long-term fever, multiorgan dysfunction, laboratory evidence of hyperinflammation, positive SARS-CoV-2 tests, and the absence of an alternative cause that would explain the clinical picture. The patient was treated according to the treatment guidelines and subsequently was discharged with the resolution of his clinical symptoms. CONCLUSIONS: This clinical case draws the attention of general practitioners and pediatricians to the importance of timely diagnosis of a rare, but potentially severe multisystem inflammatory syndrome temporarily associated with COVID-19 in children.

Cardiovascular impact of COVID-19 with a focus on children: A systematic review.

BACKGROUND: Since the beginning of the pandemic, coronavirus disease-2019 (COVID-19) in children has shown milder cases and a better prognosis than adults. Although the respiratory tract is the primary target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), cardiovascular involvement is emerging as one of the most significant and life-threatening complications of SARS-CoV-2 infection in adults. AIM: To summarize the current knowledge about the potential cardiovascular involvement in pediatric COVID-19 in order to give a perspective on how to take care of them during the current pandemic emergency. METHODS: Multiple searches in MEDLINE, PubMed were performed using the search terms "COVID-19" or "SARS-CoV-2" were used in combination with "myocardial injury" or "arrhythmia" or "cardiovascular involvement" or "heart disease" or "congenital heart disease" or "pulmonary hypertension" or "long QT" or "cardiomyopathies" or "channelopathies" or "Multisystem inflammatory system" or "PMIS" or "MIS-C" or "Pediatric multisystem inflammatory syndrome" or "myocarditis" or "thromboembolism to identify articles published in English language from January 1st, 2020 until July 31st, 2020. The websites of World Health Organization, Centers for Disease control and Prevention, and the Johns Hopkins Coronavirus Resource Center were reviewed to provide up to date numbers and infection control recommendations. Reference lists from the articles were reviewed to identify additional pertinent articles. Retrieved manuscripts concerning the subject were reviewed by the authors, and the data were extracted using a standardized collection tool. Data were subsequently analyzed with descriptive statistics. For Pediatric multisystemic inflammatory syndrome temporally associated with COVID-19 (PMIS), multiple meta-analyses were conducted to summarize the pooled mean proportion of different cardiovascular variables in this population in pseudo-cohorts of observed patients. RESULTS: A total of 193 articles were included. Most publications used in this review were single case reports, small case series, and observational small-sized studies or literature reviews. The meta-analysis of 16 studies with size > 10 patients and with complete data about cardiovascular involvement in children with PMIS showed that PMIS affects mostly previously healthy school-aged children and adolescents presenting with Kawasaki disease-like features and multiple organ failure with a focus on the heart, accounting for most cases of pediatric COVID-19 mortality. They frequently presented cardiogenic shock (53%), ECG alterations (27%), myocardial dysfunction (52%), and coronary artery dilation (15%). Most cases required PICU admission (75%) and inotropic support (57%), with the rare need for extracorporeal membrane oxygenation (4%). Almost all of these children wholly recovered in a few days, although rare deaths have been reported (2%). Out of PMIS cases we identified 10 articles reporting sporadic cases of myocarditis, pulmonary hypertension and cardiac arrythmias in previously healthy children. We also found another 10 studies reporting patients with pre-existing heart diseases. Most cases consisted in children with severe COVID-19 infection with full recovery after intensive care support, but cases of death were also identified. The management of different cardiac conditions are provided based on current guidelines and expert panel recommendations. CONCLUSION: There is still scarce data about the role of cardiovascular involvement in COVID-19 in children. Based on our review, children (previously healthy or with pre-existing heart disease) with acute COVID-19 requiring hospital admission should undergo a cardiac workup and close cardiovascular monitoring to identify and treat timely life-threatening cardiac complications.

Severe manifestations of SARS-CoV-2 in children and adolescents: from COVID-19 pneumonia to multisystem inflammatory syndrome: a multicentre study in pediatric intensive care units in Spain.

BACKGROUND: Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) has been described as a novel and often severe presentation of SARS-CoV-2 infection in children. We aimed to describe the characteristics of children admitted to Pediatric Intensive Care Units (PICUs) presenting with MIS-C in comparison with those admitted with SARS-CoV-2 infection with other features such as COVID-19 pneumonia. METHODS: A multicentric prospective national registry including 47 PICUs was carried out. Data from children admitted with confirmed SARS-CoV-2 infection or fulfilling MIS-C criteria (with or without SARS-CoV-2 PCR confirmation) were collected. Clinical, laboratory and therapeutic features between MIS-C and non-MIS-C patients were compared. RESULTS: Seventy-four children were recruited. Sixty-one percent met MIS-C definition. MIS-C patients were older than non-MIS-C patients (p = 0.002): 9.4 years (IQR 5.5-11.8) vs 3.4 years (IQR 0.4-9.4). A higher proportion of them had no previous medical history of interest (88.2% vs 51.7%, p = 0.005). Non-MIS-C patients presented more frequently with respiratory distress (60.7% vs 13.3%, p < 0.001). MIS-C patients showed higher prevalence of fever (95.6% vs 64.3%, p < 0.001), diarrhea (66.7% vs 11.5%, p < 0.001), vomits (71.1% vs 23.1%, p = 0.001), fatigue (65.9% vs 36%, p = 0.016), shock (84.4% vs 13.8%, p < 0.001) and cardiac dysfunction (53.3% vs 10.3%, p = 0.001). MIS-C group had a lower lymphocyte count (p < 0.001) and LDH (p = 0.001) but higher neutrophil count (p = 0.045), neutrophil/lymphocyte ratio (p < 0.001), C-reactive protein (p < 0.001) and procalcitonin (p < 0.001). Patients in the MIS-C group were less likely to receive invasive ventilation (13.3% vs 41.4%, p = 0.005) but were more often treated with vasoactive drugs (66.7% vs 24.1%, p < 0.001), corticosteroids (80% vs 44.8%, p = 0.003) and immunoglobulins (51.1% vs 6.9%, p < 0.001). Most patients were discharged from PICU by the end of data collection with a median length of stay of 5 days (IQR 2.5-8 days) in the MIS-C group. Three patients died, none of them belonged to the MIS-C group. CONCLUSIONS: MIS-C seems to be the most frequent presentation among critically ill children with SARS-CoV-2 infection. MIS-C patients are older and usually healthy. They show a higher prevalence of gastrointestinal symptoms and shock and are more likely to receive vasoactive drugs and immunomodulators and less likely to need mechanical ventilation than non-MIS-C patients.

Multisystem inflammatory syndrome in children: Is there a linkage to Kawasaki disease?

Since 1967, researches have hunted for an etiology for Kawasaki Disease (KD). Meanwhile, the 2019 Coronavirus Disease (COVID-19) pandemic has produced a strange new illness termed multisystem inflammatory syndrome in children (MIS-C) and raised hopes that a cause for KD may be identified. This current review paper discusses KD and its potential connection to pediatric COVID-19 and MIS-C illness.

COVID-19 in Association With Development, Course, and Treatment of Systemic Autoimmune Rheumatic Diseases.

Autoimmune diseases and infections are often closely intertwined. Patients with autoimmune diseases are more susceptible to infections due to either active autoimmune disease or the medications used to treat them. Based on infections as environmental triggers of autoimmunity, an autoimmune response would also be expected in COVID-19. Although some studies have shown the occurance of autoantibodies and the possible development of autoimmune diseases after SARS-CoV-2 infection, current data suggest that the levels of autoantibodies following SARS-CoV-2 infection is comparable to that of some other known infections and that the autoantibodies might only be transient. The risk of SARS-CoV-2 infection in patients with a systemic autoimmune rheumatic disease (SARD) appears slightly higher compared to the general population and the course of COVID-19 disease does not seem to be very different, however, specific therapies such as glucocorticoids and anti-TNF might modulate the risk of hospitalization/death. Cytokine release syndrome is a severe complication in COVID-19. Many drugs used for the treatment of SARD are directly or indirectly targeting cytokines involved in the cytokine release syndrome, therefore it has been suggested that they could also be effective in COVID-19, but more evidence on the use of these medications for the treatment of COVID-19 is currently being collected.