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1.
Canadian Journal of Cardiology ; 2023.
Article in English | ScienceDirect | ID: covidwho-2165167

ABSTRACT

Multisystem inflammatory syndrome in children (MIS-C) has emerged as a rare, delayed hyperinflammatory response to SARS-CoV-2 infection, and causes severe morbidity in the pediatric age group. While MIS-C shares many clinical similarities to Kawasaki disease (KD), important differences in epidemiologic, clinical, immunologic and potentially genetic factors exist and suggest potential differences in pathophysiology and points to be explored and explained. Epidemiologic features include male predominance, peak age of 6-12 years, and specific racial and/or ethnicity predilections. MIS-C is characterized by fever, prominent gastrointestinal symptoms, mucocutaneous manifestations, respiratory symptoms, and neurological complaints, and patients often present with shock. Cardiac complications are frequent and include ventricular dysfunction, valvular regurgitation, pericardial effusion, coronary artery dilation and aneurysms, conduction abnormalities, and arrhythmias. Emerging evidence regarding potential immunologic mechanisms suggest that an exaggerated T-cell response to a superantigen on the SARS-CoV-2 spike glycoprotein, as well as the formation of autoantibodies against cardiovascular, gastrointestinal, and endothelial antigens, are major contributors to the inflammatory milieu of MIS-C. Further studies are needed to determine both shared and distinct immunologic pathway(s) that underlie the pathogenesis of MIS-C versus both acute SARS-CoV-2 infcction and KD. There is evidence to suggest that the rare risk of more benign mRNA vaccine –associated myopericarditis is outweighed by a reduced risk of more severe MIS-C. In the current review, we synthesize the published literature to describe associated factors and potential mechanisms regarding an increased risk of MIS-C and cardiac complications, provide insights into the underlying immunologic pathophysiology, and define similarities and differences with KD.

2.
Frontiers in pediatrics ; 10, 2022.
Article in English | EuropePMC | ID: covidwho-2147242

ABSTRACT

Background Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition that can potentially develop after SARS-CoV-2 infection in children. Gastrointestinal manifestation in MIS-C can mimic acute abdomen, potentially leading to unnecessary surgical treatment. Immune-mediated mechanisms seem to be a determining factor in its pathogenesis, and histological studies can help to shed light on this aspect. We describe three cases of children diagnosed with MIS-C that underwent appendectomy. Methods We retrospectively collected the clinical features and histological findings of three previously healthy children who underwent appendectomy for clinical suspicion of acute appendicitis but were later diagnosed with MIS-C. Findings The three children presented with prominent abdominal manifestations and fever leading to the suspicion of acute abdomen. Histological findings showed transmural and perivascular inflammation. Notably, CD68+ macrophages were predominant in the child with milder abdominal symptoms without cardiac injury, while CD3+ lymphocytes in the patient presented with more severe abdominal pain and cardiovascular involvement at admission. Interpretation Gastrointestinal symptoms of children with MIS-C improve after proper immunomodulatory therapy, conversely showing inadequate response to surgical appendectomy. Histological findings revealed different inflammatory cell infiltration that primarily involved perivisceral fat and vessels, and subsequently mucosal tissue, in contrast to other forms of acute appendicitis. Our findings suggest that this kind of peri-appendicitis in MIS-C could represent a focal sign of systemic inflammation, with different histological patterns compared to other forms of acute appendicitis.

3.
Int J Mol Sci ; 23(17)2022 Sep 03.
Article in English | MEDLINE | ID: covidwho-2010114

ABSTRACT

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.


Subject(s)
COVID-19 , Mucocutaneous Lymph Node Syndrome , Vascular System Injuries , Biomarkers , COVID-19/complications , Child , Endothelial Cells/pathology , Humans , Mucocutaneous Lymph Node Syndrome/complications , Mucocutaneous Lymph Node Syndrome/diagnosis , Prospective Studies , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/diagnosis
4.
Viruses ; 13(10)2021 10 07.
Article in English | MEDLINE | ID: covidwho-1463839

ABSTRACT

SARS-CoV-2 infection in children can trigger cardiovascular manifestations potentially requiring an intensive treatment and defining a new entity named Multisystem Inflammatory Syndrome in Children (MIS-C), whose features partially overlap with Kawasaki Disease (KD). A cross-sectional study including all diagnoses of MIS-C and KD from April 2020 to May 2021 in our metropolitan area was conducted evaluating clinical, laboratory (including immunological response, cytokines, and markers of myocardial damage), and cardiac (coronary and non-coronary) features at onset of the diseases. Evolution of ventricular dysfunction, valve regurgitations, and coronary lesions was documented. The severity of the disease was also considered based on the need for inotropic support and ICU admission. Twenty-four MIS-C were diagnosed (14 boys, median age 82 months): 13/24 cases (54.17%) presented left ventricular dysfunction, 12/24 (50%) required inotropic support, and 10/24 (41.67%) developed coronary anomalies (CALs). All patients received steroids and IVIG at a median time of 5 days (IQR1:4, IQR3:6.5) from onset of fever and heart function normalized 6 days (IQR1: 5, IQR3: 7) after therapy, while CALs persisted in one. One patient (12.5%) required infliximab because of refractory disease and still presented CALs 18 days after therapy. During the same study period, 15 KD were diagnosed: none had ventricular dysfunction, while 7/15 (46.67%) developed CALs. Three out of 15 patients (20%) still presented CALs 46 days from onset. Compared to KD, MIS-C pts have significantly higher IL8 and similar lymphocytes subpopulations. Despite a more severe presentation and initial cardiac findings compared to KD, the myocardial injury in MIS-C has a rapid response to immunomodulatory treatment (median time 6 days), in terms of ventricular function, valve regurgitations, and troponin. Incidence of CALs is similar at onset, but it tends to regress in most of the cases of MIS-C differently than in KD where CALs persist in up to 40% in the subacute stage after treatment.


Subject(s)
COVID-19/complications , COVID-19/pathology , Mucocutaneous Lymph Node Syndrome/pathology , Myocardium/pathology , Systemic Inflammatory Response Syndrome/pathology , Ventricular Dysfunction, Left/pathology , Adolescent , COVID-19/diagnosis , COVID-19/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Infant, Newborn , Interleukin-10/blood , Interleukin-8/blood , Italy/epidemiology , Male , Mucocutaneous Lymph Node Syndrome/diagnosis , Prospective Studies , SARS-CoV-2/metabolism , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/epidemiology , Ventricular Dysfunction, Left/virology
5.
Pediatr Pulmonol ; 57(1): 66-74, 2022 01.
Article in English | MEDLINE | ID: covidwho-1449941

ABSTRACT

BACKGROUND: Lockdown measures during the SARS-CoV-2 pandemic determined radical changes to behavioral and social habits, that were reflected by a reduction in the transmission of respiratory pathogens and in anthropogenic atmospheric emissions. OBJECTIVE: This ecological study aims to provide a descriptive evaluation on how restrictive measures during the SARS-CoV-2 pandemic impacted Pediatric Emergency Department (PED) referrals for asthma exacerbations, and their potentially associated environmental triggers in Bologna, a densely populated urban area in Northern Italy. METHODS: Files of children evaluated for acute asthma during 2015 to 2020 at the PED of Sant'Orsola University Hospital of Bologna were retrospectively reviewed. Historical daily concentration records of particulate (PM2.5 , PM10 ) and gaseous (NO2 , C6 H6 ) air pollutants, and pollen were concurrently evaluated, including specific PM chemical tracers for traffic-related air pollution (TRAP). RESULTS: In 2020, asthma-related PED referrals decreased compared to referral rates of the previous 5 years (p < 0.01). This effect was particularly marked during the first lockdown period (March to May), when the drastic drop in PED referrals was associated with a reduction of high-priority cases up to 85% and by 54%, on average. A concomitant reduction in the concentrations of traffic-related air pollutants was observed in the range of 40%-60% (p < 0.01). CONCLUSIONS: The lower rate of asthma exacerbations in childhood was in this study paralleled with reduced TRAP levels during the pandemic. Synergic interactions of the multiple consequences of lockdowns likely contributed to the reduced exacerbations, including decreased exposure to ambient pollutants and fewer respiratory infections, identified as the most important factor in the literature.


Subject(s)
Air Pollutants , Air Pollution , Asthma , COVID-19 , Air Pollutants/analysis , Air Pollutants/toxicity , Air Pollution/analysis , Air Pollution/statistics & numerical data , Asthma/epidemiology , Communicable Disease Control , Emergency Service, Hospital , Environmental Monitoring , Humans , Pandemics , Particulate Matter/analysis , Referral and Consultation , Retrospective Studies , SARS-CoV-2
7.
J Pediatric Infect Dis Soc ; 10(6): 714-721, 2021 Aug 14.
Article in English | MEDLINE | ID: covidwho-1358467

ABSTRACT

BACKGROUND: Children with coronavirus disease-2019 (COVID-19) have a milder clinical course than adults. We describe the spectrum of cardiovascular manifestations during a COVID-19 outbreak in Emilia-Romagna, Italy. METHODS: A cross-sectional multicenter study was performed, including all patients diagnosed with Kawasaki disease (KD), myocarditis, and multisystem inflammatory syndrome in children (MIS-C) from February to April 2020. KD patients were compared with those diagnosed before the epidemic. RESULTS: KD: 8 patients (6/8 boys, all negative for severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2]): complete presentation in 5/8, 7/8 immunoglobulin (IVIG) responders, and 3/8 showed transient coronary lesions (CALs). Myocarditis: one 5-year-old girl negative for SARS-CoV-2 and positive for parvovirus B19. She responded to IVIG. MIS-C: 4 SARS-CoV-2-positive boys (3 patients with positive swab and serology and 1 patient with negative swab and positive serology): 3 presented myocardial dysfunction and pericardial effusion, and 1 developed multicoronary aneurysms and hyperinflammation; all responded to treatment. The fourth boy had mitral and aortic regurgitation that rapidly regressed after steroids. CONCLUSIONS: KD, myocarditis, and MIS-C were distinguishable cardiovascular manifestations. KD did not show a more aggressive form compared with previous years: coronary involvement was frequent but always transient. MIS-C and myocarditis rapidly responded to treatment without cardiac sequelae despite high markers of myocardial injury at the onset, suggesting a myocardial depression due to systemic inflammation rather than focal necrosis. Evidence of actual or previous SARS-CoV-2 infection was documented only in patients with MIS-C.


Subject(s)
COVID-19 , Cardiovascular Diseases , Adolescent , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Child , Cross-Sectional Studies , Female , Humans , Male , SARS-CoV-2 , Systemic Inflammatory Response Syndrome
9.
Pediatr Rheumatol Online J ; 19(1): 29, 2021 Mar 16.
Article in English | MEDLINE | ID: covidwho-1136233

ABSTRACT

BACKGROUND: There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. METHODS: The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group - KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients' outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. RESULTS: One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p < 0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p < 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data. CONCLUSION: Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths.


Subject(s)
COVID-19/physiopathology , Coronary Artery Disease/physiopathology , Hypotension/physiopathology , Lymphopenia/physiopathology , Mucocutaneous Lymph Node Syndrome/physiopathology , Myocarditis/physiopathology , Systemic Inflammatory Response Syndrome/physiopathology , Age Distribution , Antirheumatic Agents/therapeutic use , Aspirin/therapeutic use , C-Reactive Protein/metabolism , COVID-19/epidemiology , COVID-19/metabolism , COVID-19/therapy , Child , Child, Preschool , Cough/physiopathology , Diarrhea/physiopathology , Dyspnea/physiopathology , Female , Glucocorticoids/therapeutic use , Heart Failure/physiopathology , Humans , Hyperferritinemia/metabolism , Hyperferritinemia/physiopathology , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Infant , Intensive Care Units, Pediatric , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Italy/epidemiology , Male , Mucocutaneous Lymph Node Syndrome/epidemiology , Mucocutaneous Lymph Node Syndrome/metabolism , Mucocutaneous Lymph Node Syndrome/therapy , Platelet Aggregation Inhibitors/therapeutic use , SARS-CoV-2 , Shock/physiopathology , Systemic Inflammatory Response Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/metabolism , Systemic Inflammatory Response Syndrome/therapy , Tachypnea/physiopathology , Troponin T/metabolism , Vomiting/physiopathology
10.
ESC Heart Fail ; 8(1): 761-765, 2021 02.
Article in English | MEDLINE | ID: covidwho-1064346

ABSTRACT

A 6-year-old African boy with multi-viral infection including parvovirus B19 and severe acute respiratory syndrome coronavirus 2 was admitted for persistent fever associated with respiratory distress and myocarditis complicated by cardiogenic shock needing ventilatory and inotropic support. Coronary aneurysms were also documented in the acute phase. Blood tests were suggestive of macrophage activation syndrome. He was treated with intravenous immunoglobulins, aspirin, diuretics, dexamethasone, hydroxychloroquine, and prophylactic low molecular weight heparin. Normalization of cardiac performance and coronary diameters was noticed within the first days. Cardiac magnetic resonance imaging, performed 20 days after the hospitalization, evidenced mild myocardial interstitial oedema with no focal necrosis, suggesting a mechanism of cardiac stunning related to cytokines storm rather than direct viral injury of cardiomyocytes.


Subject(s)
COVID-19/complications , Coronary Aneurysm/etiology , Myocarditis/etiology , Acute Disease , COVID-19/pathology , Child , Coronary Aneurysm/diagnostic imaging , Coronary Aneurysm/pathology , Echocardiography , Humans , Magnetic Resonance Imaging , Male , Myocarditis/diagnostic imaging , Myocarditis/pathology , Tomography, X-Ray Computed
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