Bilateral keratouveitis associated with COVID-19 multisystem inflammatory syndrome in children.

We report the case of a 16-year-old girl admitted to hospital with multisystem inflammatory syndrome in children (MIS-C) secondary to COVID-19. Conjunctivitis-like symptoms prompted ocular examination, which demonstrated peripheral confluent corneal opacities and anterior uveitis. Uveitis laboratory investigations were negative, and with topical steroid treatment her signs and symptoms resolved completely. These features may be overlooked in the setting of MIS-C, where patients are systemically unwell and are typically examined at the bedside.

A unilateral whiteout lung in child with multisystem inflammatory syndrome associated with COVID-19 due to SARS-CoV-2: one case report of a boy.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a relatively new and rare complication of COVID-19. This complication seems to develop after the infection rather than during the acute phase of COVID-19. This report aims to describe a case of MIS-C in an 8-year-old Thai boy who presented with unilateral lung consolidation. Unilateral whiteout lung is not a common pediatric chest radiograph finding in MIS-C, but this is attributed to severe acute respiratory failure. CASE PRESENTATION: An 8-year-old boy presented with persistent fever for seven days, right cervical lymphadenopathy, and dyspnea for 12 h. The clinical and biochemical findings were compatible with MIS-C. Radiographic features included total opacity of the right lung and CT chest found consolidation and ground-glass opacities of the right lung. He was treated with intravenous immunoglobulin and methylprednisolone, and he dramatically responded to the treatment. He was discharged home in good condition after 8 days of treatment. CONCLUSION: Unilateral whiteout lung is not a common pediatric chest radiographic finding in MIS-C, but when it is encountered, a timely and accurate diagnosis is required to avoid delays and incorrect treatment. We describe a pediatric patient with unilateral lung consolidation from the inflammatory process.

Clinical and immunological features in children with multisystem inflammatory syndrome associated with SARS-CoV-2.

BACKGROUND AND AIM: MIS-C is characterized by intense immune activation and increased production of cytokines. The aim of our study was to analyse the changes of cellular and humoral immune responses in children with MIS-C, depending on the severity of the disease. METHODS: To conduct the study, the results of clinical, hematological and immunological parameters in children with severe and extremely severe MIS-C were compared. A total of 50 patients participated in the study, which were divided into 3 groups, of which: 20 children with extremely severe MIS-C treated in the ICU (MIS-C ICU "+"); 15 children with severe MIS-C, but without the need for hospitalization in the ICU (MIS-C ICU "-"); 15 children who had COVID-19 and absence MIS-C (MIS-C "-") made up the control group. RESULTS: In patients with MIS-C hospitalized in the ICU, heart and liver damage, hematological changes, and the development of severe complications such as edematous syndrome, polyserositis, DIC, and cardiogenic shock were statistically more common. Both groups of children with MIS-C had CD3+ T-cell lymphopenia and a decrease in CD95 expression. In the group of children with MIS-C hospitalized in the ICU, a significant increase in the relative number of B-lymphocytes, CD3-HLA-DR+ and CD25 and decrease of NK-cells was observed. CONCLUSIONS: The risk of hospitalization in the ICU in children with MIS-C is associated with more profound immune dysregulation, as evidenced by our data. (www.actabiomedica.it).

Acute cerebellar ataxia during acute COVID-19: A case series and review of the literature.

Acute coronavirus disease 2019 (COVID-19)-associated cerebellar ataxia without multisystem inflammatory syndrome in children (MIS-C) or encephalopathy in children has been rarely reported. We reviewed medical records of hospitalized children who had developed cerebellar ataxia during the acute phase of COVID-19 infection, without MIS-C or encephalopathy, in our center. We also conducted a literature review and summarized the clinical characteristics, treatment, and outcomes. We found three cases in our center and additional three cases in the literature. All patients were male and five were preschool children. The cerebellar symptoms started between day 2 and day 10 during the acute phase of the COVID-19 infection. Two cases were complicated by mutism. One patient received therapy for acute cerebellar ataxia with corticosteroids, and others did not receive any specific therapy for acute cerebellar ataxia. The symptoms improved completely in all patients, with the recovery interval ranging from one week to two months. Further studies are warranted to elucidate the pathogenesis of acute cerebellar ataxia during acute COVID-19 in children.

Incidence and Clinical Phenotype of Multisystem Inflammatory Syndrome in Children After Two SARS-CoV-2 Pandemic Waves: A Croatian Prospective Nationwide Study.

This prospective nationwide study in Croatia (March 1, 2020-December 31, 2021) embraced 121 children with multisystem inflammatory syndrome. Incidence rates, disease course and outcomes were similar to those reported from other European countries. The severe acute respiratory syndrome coronavirus 2 virus Alpha strain appeared associated with a higher propensity to result in multisystem inflammatory syndrome in children than the Delta strain but did not appear related to disease severity.

Differentiating abdominal pain due to COVID-19 associated multisystem inflammatory syndrome from children with acute appendicitis: a score system.

PURPOSE: Differentiating abdominal pain due to coronavirus disease (COVID-19)-associated multisystem inflammatory syndrome (MIS-C) in children with acute appendicitis (AA) can cause diagnostic dilemmas. This study aimed to evaluate the efficacy of a previously described scoring system and improve its diagnostic ability in differentiating between these diseases. METHODS: This study was conducted between March 2020 and January 2022. Patients who had MIS-C with gastrointestinal system (GIS) involvement and patients who underwent surgery for appendicitis were included. First, all patients were evaluated using the new scoring system (NSS). The groups were compared by adding new MISC-specific parameters to NSS. The scoring system was evaluated using propensity score matching (PSM). RESULTS: A total of 35 patients with abdominal pain due to GIS involvement in MIS-C (group A) and 37 patients with AA who had ALT, PRC, and D-dimer results at their first admission (group B) were included in the study. The mean age of patients in group A was lower than that of patients in group B (p < 0.001). False NSS positivity was found in 45.7% of the patients with MIS-C. Lymphocyte (p = 0.021) and platelet counts (p = 0.036) were significantly lower in the blood count and serum D-dimer (p = 0.034), C-reactive protein (CRP) (p < 0.001), and procalcitonin (p < 0.001) were significantly higher in the MIS-C group. We created a scoring system called the Appendicitis-MISC Score (AMS) using the NSS and new parameters. The sensitivity and specificity of AMS diagnostic scores were 91.9% and 80%, respectively. CONCLUSION: MIS-C with GIS involvement may present as acute abdomen. It is difficult to differentiate this condition from acute appendicitis. AMS has been shown to be useful for this differentiation.

Giant coronary aneurysms in an infant: Dilemma of MIS-C.

COVID-19 related multisystem inflammatory syndrome in children (MIS-C) can present with cardiovascular complications like shock, arrhythmias, pericardial effusion, and coronary artery dilatation. The majority of MIS-C associated coronary artery abnormalities are dilation or small aneurysms which are transient and resolve in a few weeks. We present here a case of a 3-month-old child who was noted to have giant aneurysms of her coronary arteries (LAD and RCA) 26 days after testing positive for COVID-19. She was treated with IVIG, infliximab, and glucocorticoids along with aspirin, clopidogrel, and enoxaparin. She did not show any signs of coronary ischemia or cardiac dysfunction but continued to have persistent giant coronary artery aneurysms involving the LAD (z-score ∼35) and RCA (z-score ∼30). This study emphasizes the importance of early detection and aggressive management of MIS-C to prevent potentially life-threatening consequences.

A comparison of pediatric inflammatory multisystem syndrome temporarily-associated with SARS-CoV-2 and Kawasaki disease.

The connection between Pediatric Inflammatory Multisystem Syndrome (PIMS) and Kawasaki Disease (KD) is not yet fully understood. Using the same national registry, clinical features and outcome of children hospitalized in Germany, and Innsbruck (Austria) were compared. Reported to the registry were 395 PIMS and 69 KD hospitalized patients. Patient age in PIMS cases was higher than in KD cases (median 7 [IQR 4-11] vs. 3 [IQR 1-4] years). A majority of both PIMS and KD patients were male and without comorbidities. PIMS patients more frequently presented with organ dysfunction, with the gastrointestinal (80%), cardiovascular (74%), and respiratory (52%) systems being most commonly affected. By contrast, KD patients more often displayed dermatological (99% vs. 68%) and mucosal changes (94% vs. 64%), plus cervical lymph node swelling (51% vs. 34%). Intensive care admission (48% vs. 19%), pulmonary support (32% vs. 10%), and use of inotropes/vasodilators (28% vs. 3%) were higher among PIMS cases. No patients died. Upon patient discharge, potentially irreversible sequelae-mainly cardiovascular-were reported (7% PIMS vs. 12% KD). Despite differences in age distribution and disease severity, PIMS and KD cases shared many common clinical and prognostic characteristics. This supports the hypothesis that the two entities represent a syndrome continuum.

Multisystem Inflammatory Syndrome in Adults Accompanied with Kikuchi-Fujimoto Disease.

We herein report a case of multisystem inflammatory syndrome in adults (MIS-A) complicated with Kikuchi-Fujimoto disease (KFD). A previously healthy 41-year-old man presented with painful swelling of the cervical lymph nodes, fever, diarrhea, conjunctivitis, edema, and hypotension one month after the onset of asymptomatic coronavirus disease 2019. Laboratory investigations revealed an elevation of CRP, and echocardiography indicated diastolic dysfunction. We diagnosed the patient to have MIS-A. Histopathology of the lymph nodes showed necrotizing lymphadenitis. After the initiation of hydrocortisone and diuretics, his symptoms resolved immediately. This case suggested that post-viral immune dysregulation in MIS-A could play a role in the etiology of KFD.

Multisystem Inflammatory Syndrome in Children (MIS-C).

PURPOSE OF REVIEW: The novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has developed into a pandemic. A unique challenge of this pandemic has been the emergence of multisystem inflammatory syndrome in children (MIS-C), a rare post-infectious hyperinflammatory disorder associated with SARS-CoV-2. This syndrome is characterized by overwhelming systemic inflammation, fever, hypotension, and cardiac dysfunction. This disorder may also have features overlapping with Kawasaki disease (KD), macrophage activation syndrome (MAS), and toxic shock syndrome (TSS). The goal of this review is to outline the presenting features, presumed immunopathogenesis, management, and outcomes of patients with MIS-C. RECENT FINDINGS: Patients with MIS-C present with characteristics that fall within a wide clinical spectrum. Main features include fever, gastrointestinal symptoms such as abdominal pain and diarrhea, and cardiac complications such as myocarditis and coronary artery aneurysms, although various other features have been reported. Younger children may present with features of Kawasaki-like disease, and older children are often admitted to the intensive care unit with cardiogenic shock. Current treatment guidelines recommend intravenous immunoglobulins (IVIG) and glucocorticoids, with utilization of biologics in refractory cases. Fortunately, the majority of patients recover, with resolution of the systemic inflammation and cardiac abnormalities. Mortality from MIS-C is rare. This review provides an overview of the presenting features, proposed pathogenesis, suggested therapies, and outcomes of MIS-C. Clinicians must have a high clinical suspicion for this disorder in children who have had recent COVID-19 infection or exposure and present with a significant inflammatory response. Understanding of this disorder continues to evolve, and prompt diagnosis and treatment allow for the best possible outcome for patients with MIS-C.

Aseptic meningitis in multisystem inflammatory syndrome in children associated with coronavirus disease 2019: a case report.

BACKGROUND: As the coronavirus disease 2019 infections are still ongoing, there is an increasing number of case reports and case series with various manifestations of life-threatening multisystem inflammatory syndrome in children . Our case aims to remind all providers to scrutinize for clinical manifestations, including neurological symptoms, which may mimic aseptic meningitis. CASE PRESENTATION: A 5-year-old Albanian male child with obesity was admitted to the pediatric intensive care unit due to persistent fever, headache, vomiting, abdominal pain, mucocutaneous manifestations, and fatigue. Initial laboratory results revealed high level of inflammatory markers, including C-reactive protein of 156.8 mg/l, erythrocyte sedimentation rate of 100 mm/hour, procalcitonin of 13.84, leukocytosis with neutrophilia, and lymphopenia. Liver and renal functions, and capillary blood electrolytes (Na, K, Ca), were also altered. Cerebrospinal fluid was slightly turbid, with a white blood cell count of 128/mm3 (80% mononuclear cells and 20% polymorphonuclear), consistent with aseptic meningitis. The clinical presentation with prolonged fever, multiorgan dysfunction, and elevated inflammatory markers, with no plausible alternative diagnosis, matches the case definition of multisystem inflammatory syndrome in children. Combining corticosteroid methylprednisolone with intravenous immunoglobulin was effective. CONCLUSIONS: Apart from the most common presentation of multisystem organ dysfunction, neurological manifestations of multisystem inflammatory syndrome in children such as aseptic meningitis, may be present as an immune response post-viral to coronavirus disease 2019. Given the rapid deterioration of children with multisystem inflammatory syndrome, early treatment with immunoglobulins and corticosteroids should be considered.

Severe diabetic foot infections without systemic inflammatory response syndrome: Prospective validation of a new category.

We aimed to validate the prognostic value of subclassifying moderate diabetic foot infections into two categories: moderate and moderate/severe. We conducted a prospective study of a cohort of 200 patients with moderate and severe infections. Moderate infections were subclassified after applying a previously published score. Variables associated with prognosis were: need for any amputation, major amputation, need for hospitalisation, length of hospitalisation, length of antibiotic therapy, reinfection rate and infection-related mortality. Infections were moderate in 111 cases (55.5%) and severe in 89 (44.5%). Osteomyelitis (OM) was diagnosed in 114 cases (57%), 73 moderate (36.5%) and 41 severe (20.5%). Patients with severe OM had a higher rate of amputations, major amputations, hospitalisations and need for antibiotic therapy, and a longer duration of antibiotics when compared with moderate OM. After applying the score, moderate infections were subclassified into 73 moderate cases (65.7%) and 38 moderate/severe cases (34.3%). Moderate/severe had a higher rate of amputations, major amputations, hospitalisations and need for antibiotics than moderate ones. No differences regarding prognosis were found between moderate/severe and severe infections with systemic inflammatory response syndrome. Moderate/severe diabetic foot infections, which could also be known as severe infections without systemic inflammatory response syndrome, should be recognised as a new subgroup. We propose to merge severe diabetic foot infections with and without systemic inflammatory response syndrome into a unique category due to its prognostic value. Furthermore, OM should be added to both moderate and severe new categories of diabetic foot infections.

Circulating Endothelial Cells: A New Possible Marker of Endothelial Damage in Kawasaki Disease, Multisystem Inflammatory Syndrome in Children and Acute SARS-CoV-2 Infection.

BACKGROUND: Kawasaki Disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) are pediatric diseases characterized by systemic inflammation and vascular injury, potentially leading to coronary artery lesions (CALs). Data on vascular injury occurring during acute COVID-19 (AC19) in children are still lacking. The aim of our study was to investigate endothelial injury in KD-, MIS-C- and AC19-dosing circulating endothelial cells (CECs). METHODS: We conducted a multicenter prospective study. CECs were enumerated by CellSearch technology through the immunomagnetic capture of CD146-positive cells from whole blood. RESULTS: We enrolled 9 KD, 20 MIS-C and 10 AC19. During the acute stage, the AC19 and KD patients had higher CECs levels than the MIS-C patients. From the acute to subacute phase, a significant CEC increase was observed in the KD patients, while a mild decrease was detected in the MIS-C patients. Cellular clusters/syncytia were more common in the KD patients. No correlation between CECs and CALs were found in the MIS-C patients. The incidence of CALs in the KD group was too low to investigate this correlation. CONCLUSIONS: Our study suggests a possible role of CECs as biomarkers of systemic inflammation and endothelial dysfunction in KD and MIS-C and different mechanisms of vascular injury in these diseases. Further larger studies are needed.

Multisystem inflammatory syndrome in children: clinical presentation, management, and short- and long-term outcomes.

OBJECTIVE: In this study, it was aimed to evaluate the demographic, clinical and laboratory characteristics of MIS-C patients in our hospital, to share our treatment approach, and to assess the outcomes of short- and long-term follow-up. METHODS: MIS-C patients who were admitted and treated in our hospital between July 2020 and July 2021 were evaluated. Demographic, clinical, laboratory, and follow-up data were collected from patient records retrospectively. RESULTS: A total of 123 patients with MIS-C (median age, 9.6 years) were included the study. Nineteen (15.4%) were mild, 56 (45.6%) were moderate, and 48 (39%) were severe MIS-C. High CRP, ferritin, pro-BNP, troponin, IL-6, and D-dimer values were found in proportion to the severity of the disease (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p = 0.005, p < 0.001), respectively. Two (1.6%) patients died. The mean follow-up period was 7.8 months. Valve failure, left ventricular dysfunction/hypertrophy, coronary involvement, and pericardial effusion were the most common cardiac pathologies in the short- and long-term follow-up of the patients. In the long-term follow-up, the most common reasons for admission to the hospital were recurrent abdominal pain (14.2%), cardiac findings (14.2%), pulmonary symptoms (8%), fever (7.1%), neuropsychiatric findings (6.2%) and hypertension (3.5%). Neuropsychiatric abnormalities were observed significantly more common in severe MIS-C patients at follow-up (p = 0.016). In the follow-up, 6.2% of the patients required recurrent hospitalization. CONCLUSION: MIS-C is a serious and life-threatening disease, according to short-term outcomes. In addition to the cardiac findings of patients with MIS-C, long-term outcomes such as neuropsychiatric findings, persistent gastrointestinal symptoms, fever and pulmonary symptoms should be monitored. Key Points • In MIS-C patients, attention should be paid not only to cardiac findings, but also to symptoms related to other systems. • Patients should be followed up in terms of neuropsychiatric findings, persistent gastrointestinal symptoms, fever and pulmonary symptoms that may occur during follow-up.

Guillain-Barré Syndrome in a Child With Multisystem Inflammatory Syndrome Related to COVID-19.

Guillain-Barré syndrome has been associated with acute severe acute respiratory syndrome coronavirus 2 infection in children. Here, we report a 4-year-old boy who developed Guillain-Barré syndrome in the course of multisystem inflammatory syndrome related to COVID-19.

Medium-Term Cardiac Outcomes in Young People with Multi-system Inflammatory Syndrome: The Era of COVID-19.

Multi-system inflammatory syndrome in children (MIS-C) causes widespread inflammation including a pancarditis in the weeks following a COVID infection. As we prepare for further coronavirus surges, understanding the medium-term cardiac impacts of this condition is important for allocating healthcare resources. A retrospective single-center study of 67 consecutive patients with MIS-C was performed evaluating echocardiographic and electrocardiographic (ECG) findings to determine the point of worst cardiac dysfunction during the admission, then at intervals of 6-8 weeks and 6-8 months. Worst cardiac function occurred 6.8 ± 2.4 days after the onset of fever with mean 3D left ventricle (LV) ejection fraction (EF) 50.5 ± 9.8%. A pancarditis was typically present: 46.3% had cardiac impairment; 31.3% had pericardial effusion; 26.8% demonstrated moderate (or worse) valvar regurgitation; and 26.8% had coronary dilatation. Cardiac function normalized in all patients by 6-8 weeks (mean 3D LV EF 61.3 ± 4.4%, p < 0.001 compared to presentation). Coronary dilatation resolved in all but one patient who initially developed large aneurysms at presentation, which persisted 6 months later. ECG changes predominantly featured T-wave changes resolving at follow-up. Adverse events included need for ECMO (n = 2), death as an ECMO-related complication (n = 1), LV thrombus formation (n = 1), and subendocardial infarction (n = 1). MIS-C causes a pancarditis. In the majority, discharge from long-term follow-up can be considered as full cardiac recovery is expected by 8 weeks. The exception includes patients with medium sized aneurysms or greater as these may persist and require on-going surveillance.

Severe myopathy complicating multisystem inflammatory syndrome in adults (MIS-A) in a young man.

We report the case of a man in his early 30s who presented with high fever, cervical lymphadenopathy, maculopapular rash and considerably elevated inflammatory markers. Further evaluations revealed cardiomyopathy and renal failure. During hospitalisation he developed profound generalised muscle weakness caused by diffuse myopathy without elevated creatine kinase. He was eventually diagnosed with multisystem inflammatory syndrome in adults (MIS-A) after it was established that he had been suffering from COVID-19 5 weeks prior to presentation. He was started on intravenous immunoglobulins and high-dose corticosteroids, after which symptoms resolved rapidly. MIS-A is a rare but severe complication of COVID-19, whose pathogenesis is insufficiently understood. This case provides further insight into this new disease entity by describing a previously unreported disease progression with severe inflammatory myopathy without elevated creatine kinase.