COVID-19-Related Multi-systemic Inflammatory Syndrome in Children (MIS-C).

Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infections in children. This syndrome manifests about a month after the initial viral infection and is characterized by fever, multiorgan dysfunction, and systemic inflammation. This chapter will review the emergence, epidemiology, clinical characteristics, diagnosis, pathophysiology, immunomodulatory treatment, prognosis, outcomes, and prevention of MIS-C. While the pathophysiology of MIS-C remains to be defined, it is a post-infection, hyperinflammatory syndrome of childhood with elevated inflammatory cytokines.

Other Immunomodulatory Treatment for Cytokine Storm Syndromes.

Cytokine storm syndromes (CSS) include different entities such as macrophage activation syndrome, primary and secondary hemophagocytic lymphohistiocytosis (HLH), and multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. An effective management strategy is critical in CSS. While biologics have become an essential part of CSS treatment, hematopoietic stem cell transplantation (HSCT) has changed the fate of primary HLH patients. This chapter will focus on the available alternative immunomodulatory therapies in CSS, which include corticosteroids, cyclosporine A, intravenous immunoglobulin, interleukin 18 binding protein, therapeutic plasmapheresis, HSCT, and mesenchymal stromal cell-based therapies.

Use of extracorporeal hemoperfusion therapy in an adult horse with Clostridioides difficile colitis and severe systemic inflammatory response syndrome.

An 8-year-old American Quarter Horse gelding was treated with extracorporeal hemoperfusion (HP) therapy for treatment of Clostridioides difficile (C. difficile) colitis-induced systemic inflammatory response syndrome (SIRS). The gelding developed C. difficile associated peracute colitis and severe SIRS as evidenced by a positive fecal C. difficile PCR and tachypnea, tachycardia, fever, neutropenia, altered mucous membrane color, and hyperlactatemia. Concurrent acute kidney injury in the horse limited the use of routine anti-inflammatory and anti-lipopolysaccharide treatments, including flunixin meglumine and polymyxin B, because of potential for nephrosis. Extracorporeal HP therapy was performed twice within 48 hours of the onset of severe SIRS during which the horse's physical examination variables stabilized. The horse was euthanized after 4 days because of laminitis. These findings support further investigation of extracorporeal HP therapy as an adjunctive treatment for severe SIRS/sepsis in horses.

Updates on postinfectious skin rashes in pediatric dermatology.

PURPOSE OF REVIEW: This review provides updates on postinfectious skin rashes in the pediatric population from recently published literature. RECENT FINDINGS: The COVID-19 pandemic and its sequelae remain a focus of research on pediatric infectious skin rashes. Multisystem inflammatory syndrome in children (MIS-C) and reactive infectious mucocutaneous eruption (RIME) are common complications of infection with SARS-COV-2 in the pediatric population. Most cases of MIS-C show low mortality and suggest mucocutaneous symptoms do not correlate with COVID-19 disease severity. Cases of papular acrodermatitis of childhood, also known as Gianotti-Crosti, have also been reported in association with SARS-COV-2, and can present similarly in reaction to other viral infection like molluscum contagiosum, known as a Gianotti-Crosti syndrome-like reaction (GCLR). Other relevant studies on postinfectious skin rashes include updates on the management of staphylococcal scalded skin syndrome (SSSS), with newer evidence advocating for beta-lactam monotherapy without clindamycin and reduced ancillary testing. Finally, the emergence of antifungal resistance due to Trichophyton indotinae is a growing global health concern emphasizing the need for improved antifungal stewardship. SUMMARY: It is prudent for clinicians to be informed of both common and rare diagnoses that have emerged more recently in association with the COVID-19 pandemic, in addition to other diseases with newer evidence-based recommendations to guide management.

COVID-19 in Pediatric Populations.

The COVID-19 pandemic reshaped the landscape of respiratory viral illnesses, causing common viruses to fade as SARS-CoV-2 took precedence. By 2023, more than 96% of the children in the United States were estimated to have been infected with SARS-CoV-2, with certain genetic predispositions and underlying health conditions posing risk factors for severe disease in children. Children, in general though, exhibit immunity advantages, protecting against aspects of the SARS-CoV-2 infection known to drive increased severity in older adults. Post-COVID-19 complications such as multisystem inflammatory syndrome in children and long COVID have emerged, underscoring the importance of vaccination. Here, we highlight the risks of severe pediatric COVID-19, age-specific immunoprotection, comparisons of SARS-CoV-2 with other respiratory viruses, and factors contributing to post-COVID-19 complications in children.

Meta-analysis and trial sequential analysis of randomized controlled trials comparing aggressive versus non-aggressive intravenous fluid therapy in acute pancreatitis: an insight into the existence of type 2 error.

BACKGROUND AND AIM: We aimed to evaluate comparative outcomes of aggressive versus non-aggressive intravenous fluid (IVF) therapy in patients with acute pancreatitis. METHODS: A systematic search of electronic data sources and bibliographic reference lists were conducted. All randomized controlled trials (RCTs) reporting outcomes of aggressive versus non-aggressive IVF therapy in acute pancreatitis were included and their risk of bias were assessed. Effect sizes were determined for overall mortality, systemic inflammatory response syndrome (SIRS), sepsis, respiratory failure, pancreatic necrosis, severe pancreatitis, clinical improvement, AKI, and length of stay using random-effects modeling. Trial sequential analysis was conducted to determine risk of types 1 or 2 errors. RESULTS: We included 10 RCTs reporting 993 patients with acute pancreatitis who received aggressive (n = 475) or non-aggressive (n = 518) IVF therapy. Aggressive IVF therapy was associated with significantly higher rate of sepsis (OR: 2.68, P = 0.0005) and longer length of stay (MD: 0.94, P < 0.00001) compared with the non-aggressive approach. There was no statistically significant difference in mortality (RD: 0.02, P = 0.31), SIRS (OR: 0.93, P = 0.89), respiratory failure (OR: 2.81, P = 0.07), pancreatic necrosis (OR: 1.98, P = 0.06), severe pancreatitis (OR: 1.31, P = 0.38), clinical improvement (OR: 1.12, P = 0.83) or AKI (OR: 1.06, P = 0.91) between the two groups. Sub-group analysis demonstrated higher morbidity and mortality associated with the aggressive approach in more severe disease. Trial sequential analysis detected risk of type 2 error. CONCLUSIONS: Aggressive IVF therapy may be associated with higher morbidity in patients with acute pancreatitis compared with the non-aggressive approach, particularly in patients with more severe disease. It may also prolong length of hospital stay. The available evidence is subject to type 2 error indicating the need for adequately powered RCTs.

The HyperPed-COVID international registry: Impact of age of onset, disease presentation and geographical distribution on the final outcome of MIS-C.

OBJECTIVES: The aim of the study was to establish an international multicenter registry to collect data on patients with Multisystem Inflammatory Syndrome in Children (MIS-C), in order to highlight a relationship between clinical presentation, age of onset and geographical distribution on the clinical outcome. STUDY DESIGN: Multicenter retrospective study involving different international societies for rare immunological disorders.1009 patients diagnosed with MIS-C between March and September 2022, from 48 centers and 22 countries were collected. Five age groups (<1, 1-4, 5-11, 12-16, >16 years) and four geographic macro-areas, Western Europe, Central-Eastern Europe, Latin America, Asian-African resource-limited countries (LRC), were identified. RESULTS: Time to referral was significantly higher in LRC. Intensive anti-inflammatory treatment, including biologics, respiratory support and mechanic ventilation were more frequently used in older children and in European countries. The mortality rate was higher in very young children (<1 year), in older patients (>16 years of age) and in LRC. Multivariate analysis identified the residence in LRC, presence of severe cardiac involvement, renal hypertension, lymphopenia and non-use of heparin prophylaxis, as the factors most strongly associated with unfavorable outcomes. CONCLUSIONS: The stratification of patients by age and geographic macro-area provided insights into the clinical presentation, treatment and outcome of MIS-C. The mortality and sequelae rates exhibited a correlation with the age and geographical areas. Patients admitted and treated in LRC displayed more severe outcomes, possibly due to delays in hospital admission and limited access to biologic drugs and to intensive care facilities.

[Hyperinflammatory immune response syndrome PIMS-TS]. / «Nachwehen¼: Hyperinflammatorisches Immunreaktionssyndrom PIMS-TS.

INTRODUCTION: PIMS-TS is a rare hyperinflammatory immune response syndrome, usually occurring two to six weeks after SARS-CoV-2 infection, which mainly affects schoolchildren and is often associated with the need for intensive care (2). The most common clinical signs are high fever, gastrointestinal symptoms such as abdominal pain, vomiting and diarrhea, cardiovascular dysfunction (impaired LVEF, hypotension, shock) and neurological symptoms such as headache and encephalopathy (1, 2, 4). The definition criteria include various clinical and laboratory parameters, which vary slightly depending on the authors (4, 6, 7). With intensive care treatment with circulatory support and administration of methylprednisolone, mortality and long-term consequences remain low.

COVID-19, MIS-C, and long COVID in pediatric patients: an update.

COVID-19, the disease caused by SARS-CoV-2, has been disruptive worldwide. It was primarily a respiratory disease that affected many of the medically vulnerable, but the true impact of postacute sequelae of SARS-CoV-2 (PASC), which has been demonstrated to involve all organ systems, is now coming to light. In addition, a new disease entity emerged, multisystem inflammatory syndrome in children (MIS-C), which has had significant morbidity and mortality associated with it. This issue reviews the presentation, evaluation, and management of patients with COVID-19, MIS-C, and PASC. Additionally, the current literature supporting public health measures, as well as COVID-19 vaccinations and their complications are discussed.

Clinical presentation, diagnosis and management of multisystem inflammatory syndrome in children (MIS-C): a systematic review.

BACKGROUND: Knowledge about multisystem inflammatory syndrome in children (MIS-C) is evolving, and evidence-based standardised diagnostic and management protocols are lacking. Our review aims to summarise the clinical and diagnostic features, management strategies and outcomes of MIS-C and evaluate the variances in disease parameters and outcomes between high-income countries (HIC) and middle-income countries (MIC). METHODS: We searched four databases from December 2019 to March 2023. Observational studies with a sample size of 10 or more patients were included. Mean and prevalence ratios for various variables were pooled by random effects model using R. A mixed generalised linear model was employed to account for the heterogeneity, and publication bias was assessed via funnel and Doi plots. The primary outcome was pooled mean mortality among patients with MIS-C. Subgroup analysis was conducted based on the income status of the country of study. RESULTS: A total of 120 studies (20 881 cases) were included in the review. The most common clinical presentations were fever (99%; 95% CI 99.6% to 100%), gastrointestinal symptoms (76.7%; 95% CI 73.1% to 79.9%) and dermatological symptoms (63.3%; 95% CI 58.7% to 67.7%). Laboratory investigations suggested raised inflammatory, coagulation and cardiac markers. The most common management strategies were intravenous immunoglobulins (87.5%; 95% CI 82.9% to 91%) and steroids (74.7%; 95% CI 68.7% to 79.9%). Around 53.1% (95% CI 47.3% to 58.9%) required paediatric intensive care unit admissions, and overall mortality was 3.9% (95% CI 2.7% to 5.6%). Patients in MIC were younger, had a higher frequency of respiratory distress and evidence of cardiac dysfunction, with a longer hospital and intensive care unit stay and had a higher mortality rate than patients in HIC. CONCLUSION: MIS-C is a severe multisystem disease with better mortality outcomes in HIC as compared with MIC. The findings emphasise the need for standardised protocols and further research to optimise patient care and address disparities between HIC and MIC. PROSPERO REGISTRATION NUMBER: CRD42020195823.

Neonatal COVID-19 treatment: Are there new chances?

Coronavirus disease 2019 (COVID-19) is considered an infectious disease which is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neonatal COVID-19 had been occurred in many countries which would indicate the need of effective and safe treatment for these vulnerable group. In this study, we showed symptoms of corona virus in neonates, investigation of coronavirus in neonates and radiological features of neonatal COVID-19. In addition, we discussed management of neonates with COVI-19, antiviral treatment, monoclonal antibodies administration, immunomodulatory therapy, antibiotics, vitamins, and minerals in the treatment of neonatal COVID-19, and also telemedicine in neonatal COVID-19 and feeding the newborn of COVID-19 mother. We also discussed multisystem inflammatory syndrome in neonates (MIS-N), management of affected COVID-19 neonates and discussion of the complication of the neonatal COVID-19. We further discussed the methods of dealing with COVID-19 neonates and the research done on the neonatal COVID-19 treatment.

Multisystem inflammatory syndrome in children: A review.

AIM: To comprehensively review the literature on multisystem inflammatory syndrome in children (MIS-C). METHODS: Narrative review of relevant studies published between April 2020 and January 2024. RESULTS: MIS-C is a SARS-CoV-2-related hyperinflammatory syndrome developing 2-6 weeks after COVID-19 in genetically susceptible individuals. Persisting fever, mucocutaneous manifestations, GI and cardiac involvement, together with lymphopenia and elevated inflammatory and cardiac markers are the main clinical features. It is believed to recognise some pathogenetic and clinical overlap with Kawasaki disease. New case definitions have been proposed after an assessment of the diagnostic performance of existing criteria; epidemiological criterion is however progressively losing its usefulness as the pandemic turns into an endemic and in the areas with the highest rates of COVID-19 vaccination. Current guidelines recommend both intravenous immunoglobulin and glucocorticoids in the first-line immunomodulatory treatment, mainly based on comparative retrospective cohorts; the actual role of biologics remains to be adequately established. Strict follow-up is mandatory, especially for those with severe cardiac involvement, as longitudinal studies evaluate the long-term evolution of cardiac damage. CONCLUSION: In this paper, we review the epidemiological, pathogenetic, clinical and prognostic features of MIS-C, and outline the main questions which still remain unanswered after more than 3 years of research.

Delirium Associated with COVID-19 in Critically ill Children: An Observational Cohort Study.

OBJECTIVE: Delirium is an under-recognized problem in critically ill children. Although delirium is common in adults hospitalized with COVID-19, the relationship between pediatric COVID-19 and delirium has not been described. To address this gap, we characterized delirium in critically ill children with different manifestations of COVID-19 and investigated associations among demographic, disease, and treatment factors. We hypothesized that multisystem inflammatory syndrome in children (MIS-C) would be associated with a higher incidence of delirium given its underlying pathophysiology of hyperinflammation. DESIGN: Retrospective, single-center cohort study. SETTING: Quaternary-care pediatric intensive care unit (PICU). PATIENTS: Children less than 18 years of age hospitalized in the PICU between March 2020 and March 2023 with either active SARS-CoV-2 infection or serological evidence of prior infection. MEASUREMENTS AND MAIN RESULTS: The cohort included 149 PICU hospitalizations among children with evidence of COVID-19. Patients were categorized by reason for PICU admission: 75 (50%) for COVID-19 respiratory disease, 36 (24%) MIS-C, and 38 (26%) any other primary reason with positive COVID-19 testing. Delirium was diagnosed in 43 (29%) patients. Delirium incidence was highest in patients requiring invasive mechanical ventilation (IMV) (56% vs 7.5% in patients who did not require IMV, p < .001). Patients who were exposed to opioids, dexmedetomidine, paralytics or benzodiazepines more frequently experienced delirium compared to those unexposed (p < .001, p < .001, p < .001 and p = .001, respectively). After multivariable adjustment, delirium was associated with IMV (HR 3 [95% CI 1.5-5.7]), female sex (HR 2.4 [1.2-4.7]), and developmental disability (HR 3.4 [95% CI 1-11.1]). There was no association between delirium and reason for PICU hospitalization. CONCLUSIONS: Delirium was common among children hospitalized with COVID-19. The overall incidence was much less than has been reported in adults with COVID-19. Delirium reduction efforts should focus on children with developmental disability and minimizing ongoing risks during IMV.

Management of Systemic Inflammatory Response Syndrome After Cardiovascular Interventions. Diagnostic, Prognostic, and Therapeutic Implications.

A substantial number of patients may experience systemic inflammatory response syndrome (SIRS) and related adverse events after transcatheter aortic valve implantation and endovascular aortic aneurysm repair. Although a clear etiology has not been established, endothelial disruption and tissue-ischemic response secondary to the foreign material may represent the trigger events. A latency period (0 to 48 hours) may occur between the initial injury and onset of symptoms mirroring an initial local response followed by a systemic response. Clinical presentation can be mild or severe depending on external triggers and characteristics of the patient. Diagnosis is challenging because it simulates an infection, but lack of response to antibiotics, negative cultures are supportive of SIRS. Increased in-hospital stay, readmissions, major cardiovascular events, and reduced durability of the device used are the main complications. Treatment includes non-steroidal anti-inflammatory drugs or corticosteroids. In conclusion, further studies are warranted to fully explore pathophysiologic mechanisms underpinning SIRS and the possibility of enhancing device material immune compatibility to reduce the inflammatory reaction of the host tissue.

COVID-19 admissions: Trying to define the real impact of infection in hospitalized patients.

INTRODUCTION AND OBJECTIVE: Several studies have suggested that the hospitalization rate for COVID-19 in children and adolescents may reflect the prevalence of the infection rather than the severity of the disease. The aim of this study was to describe the clinical features of hospitalised paediatric patients with SARS-CoV-2 infection in order to understand if the infection was the reason for admission. METHODS: Retrospective cohort study including patients aged 0-18 years with SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) admitted to a tertiary care children's hospital in Spain between 01/01/2020 and 12/31/2021. RESULTS: 228 patients were included, corresponding to 150 cases of COVID-related admission (SARS-CoV-2 infection as main cause of hospitalization) and 78 of non-COVID-related admission (SARS-CoV-2 infection unrelated to the hospitalization). In the group of COVID-related admissions, 58 patients had comorbidities. Forty-nine patients had acute respiratory disease (pneumonia, bronchospasm or bronchiolitis). Multisystem inflammatory syndrome in children was diagnosed in 27 and was significantly more frequent in the first year of the pandemic (wild type virus). Eighty percent of patients with acute respiratory disease needed respiratory support, mostly low-flow oxygen therapy. The severity of the disease was similar in all virus variants. Two patients (both with severe comorbidities) died from COVID-related conditions. CONCLUSIONS: In our study, one third of the patients were admitted with SARS-CoV-2 infection but not because of it. Acute respiratory disease was less frequent and had a better prognosis compared to the adult population, while MIS-C was a major cause of morbidity and hospitalization. The fatality rate was extremely low.

Lower-dose intravenous immunoglobulin therapy for geriatric inflammatory bowel disease accompanied by COVID-19 multisystem inflammatory syndrome: A case report.

RATIONALE: This article presents a complex case of refractory severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related inflammatory bowel disease (IBD) and outlines its diagnostic and therapeutic challenges. Considering inadequate responses to conventional and steroid treatments, the potential efficacy of intravenous immunoglobulin is explored. PATIENT CONCERNS: The patient, an elderly individual, experienced short-term fever and sore throat after encountering the coronavirus disease 2019 pandemic. Despite receiving a 3-dose inactivated SARS-CoV-2 vaccine, the patient tested positive for the viral antigen and developed worsening symptoms, including diarrhea and recurrent fever. Initial antibiotic treatment for bacterial enteritis proved ineffective. DIAGNOSES: Further evaluation, including endoscopy and pathology, confirmed the diagnosis of IBD with concurrent multisystem inflammatory syndrome (MIS) in adults, as evidenced by tachycardia and elevated inflammatory markers. INTERVENTIONS: Following unsuccessful treatment with mesalazine, probiotics, corticosteroids, and supportive care, the patient underwent lower-dose intravenous immunoglobulin therapy. OUTCOMES: The patient experienced symptom improvement, with resolution of fever, diarrhea, and inflammation. At the 30-day follow-up, the patient remained afebrile, without diarrhea, and exhibited favorable mental status. LESSONS: Elderly individuals infected with SARS-CoV-2 may develop severe systemic inflammatory responses. The patients in this report predominantly presented with IBD following SARS-CoV-2 infection, accompanied by MIS. Favorable clinical outcomes were achieved following lower-dose intravenous immunoglobulin immunotherapy, which demonstrated superior efficacy compared to glucocorticoids in managing such conditions. Future research should prioritize investigating immunotherapy application strategies in IBD and MIS. Notably, the significant clinical improvement observed with lower-dose intravenous immunoglobulin administration could optimize the utilization of this limited medical resource.

Clinical presentation and management of multisystem inflammatory syndrome in children associated with covid-19: a retrospective observational descriptive study in a pediatric hospital in Syria.

OBJECTIVE: Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 is a rare and serious medical condition. This study aims to review the clinical presentation, laboratory parameters, outcomes, and management of MIS-C cases in a pediatric hospital in Syria. METHODS: This retrospective observational study aimed to investigate MIS-C between May 2020 and October 2021. Data collection involved extracting information from medical records, and patients were identified based on the case definition established by the World Health Organization (WHO). Various laboratory investigations, diagnostic evaluations, clinical presentations, and treatments were performed to assess patients. Descriptive statistical analysis was conducted using Microsoft Excel. RESULTS: A total of 232 COVID-19 cases were reported with COVID-19 Infection. Among these cases, 25 (10.77%) were identified as MIS-C. The median age of the patients was 5.5 years, with the majority being male patients (72%). Patients experienced fever (100%), bilateral conjunctivitis (88%), rash (84%), gastrointestinal symptoms (76%), and cardiac dysfunction (72%). Other notable findings included oral cavity changes (64%), edema (36%), cervical lymphadenopathy (36%), and neurological manifestations (28%). Respiratory symptoms were uncommon (16%). All patients recovered, with no recorded deaths. CONCLUSION: The predominant presence of positive SARS-CoV-2 IgG in the majority of patients in this study supports the post-infectious nature of MIS-C. Respiratory symptoms were less prevalent in both pediatric COVID-19 and MIS-C patients. Early supportive care is crucial in management, although additional research is needed to establish definitive guidelines. Larger studies are necessary to overcome the limitations of this study and to enhance our understanding of MIS-C in pediatric COVID-19 patients.

Multisystem inflammatory syndrome in children: an Umbrella review.

We conducted an Umbrella review of eligible studies to evaluate what patient features have been investigated in the multisystem inflammatory syndrome in children (MIS-C) population, in order to guide future investigations. We comprehensively searched MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from December 1, 2019 to the May 6, 2022. The time period was limited to cover the coronavirus disease-2019 (COVID-19) pandemic period. The protocol was registered in the PROSPERO registry (CRD42022340228). Eligible studies included (1) a study population of pediatric patients ≤21 years of age diagnosed with MIS-C; (2) an original Systematic review or Mata-analysis; (3) published 2020 afterward; and (4) was published in English. A total of 41 studies met inclusion criteria and underwent qualitative analysis. 28 studies reported outcome data of MIS-C. 22 studies selected clinical features of MIS-C, and 6 studies chose demographic data as a main topic. The mortality rate for children with MIS-C was 1.9% (interquartile range (IQR) 0.48), the ICU admission rate was 72.6% (IQR 8.3), and the extracorporeal membrane oxygenation rate was 4.7% (IQR 2.0). A meta-analysis of eligible studies found that cerebral natriuretic peptide in children with MIS-C was higher than that in children with COVID-19, and that the use of intravenous immunoglobulin (IVIG) in combination with glucocorticoids to treat MIS-C compared to IVIG alone was associated with lower treatment failure. In the future, for patients with MIS-C, studies focused on safety of surgery requiring general anesthesia, risk factors, treatment, and long-term outcomes are warranted.