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1.
Cardiology in the Young ; 32(Supplement 2):S239, 2022.
Article in English | EMBASE | ID: covidwho-2062096

ABSTRACT

Background and Aim: Cardiac involvement in multisystem inflam-matory syndrome in children (MIS-C) associated with Coronavirus 2019 disease (COVID-19) is often observed with high risk of hearth failure. Early diagnosis and treatment are man-datory for a good outcome. The aim is to describe cardiovascular involvement, management and early outcome for patients with MIS-C and to analyze the differences in cardiovascular manifesta-tions between two groups: younger and older than 6 years old. Method(s): This retrospective observational study describes cardio-vascular clinical manifestations, laboratory findings, cardiac imag-ing, according to different age groups, and treatment in patients with diagnosis of MIS-C admitted to the Pediatric Istitute Giannina Gaslini between March 2020 and September 2021. Result(s): We collected 25 patients. Median age at onset of symptoms was 5 years old (interquartile range IQR, 3-12 y), 12 boys (56%). Immunoglobulin G antibodies were positive in 70% cases, Polymerase chain reaction (PCR) nasal/throat swab test for COVID-19 was positive in 15% cases, at the admission. The remaining cases had close contacts of COVID-19 positive cases. Predominant coronary artery abnormalities were observed in age group up to 6 years old (n.13) with development of small and medium aneurysms in half of cases and low rate of mild ventricular dysfunction. While children between 7-18 years of age present myopericardial involvement with ventricular dysfunction in 67% cases, from mild to moderate. Only two cases of transient coronary dilatation. Frequent electrocardiogram abnormalities: ventricular repolarization anomalies and reversibile QTc prolon-gation interval. Laboratory findings showed rised inflammatory markers and only mild elevation of cardiac enzymes compared to an early and significant NT-pro-BNP increase. All patients were treated with intravenous immunoglobulin and corticosteroids. Some cases needed anakinra. Aspirin and heparin was adminis-trated. No inotropes requied but only cardioprotective therapy. No need of Intensive Care Unit. Conclusion(s): This case-series shows the frequent cardiovascular involvement in MIS-C with a peculiar distribution, according to differents age's group: coronary artery anomalies in young ones, myopericardial disease in old ones. Prompt multi target anti-inflammatory therapy could have an effect to favorable outcome.

2.
Pediatric Rheumatology ; 20(SUPPL 1), 2022.
Article in English | EMBASE | ID: covidwho-1677513

ABSTRACT

Introduction: COVID-19 severe pneumonia has been associated to systemic inflammation and elevation of blood parameters and reminiscent of cytokine storm syndrome. Stimulation of PBMC from patients with severe COVID-19 have shown a high secretion of IL-1β, a pivotal cytokine driving inflammatory phenotypes, which maturation and secretion is regulated by NLRP3 inflammasome. Steroidal anti-inflammatory therapies have shown efficacy in reducing mortality in critically ill patients, however the mechanisms by which SARS-CoV2 virus triggers such an extensive inflammation remain unexplained. Objectives: The overall objective of this study was to investigate if SARS-CoV2 drives inflammation in COVID-19 patients through NLRP3 inflammasome activation and IL-1β secretion. Methods: Samples from SARS-CoV2 infected patients, were collected at day 0 and at 3 and 7 following treatment with anakinra. Fresh monocytes, purified through adherence, were cultured for 3, 6, 18 h in the presence or absence of LPS (100 ng/ml) and MCC950 (10μM). Release of IL-1β, IL-1Ra, IL-6, TNF-α, IL-18 was quantified by ELISA kit. Relative gene expression analysis of ORF3a gene was performed by RT-qPCR. THP-1 cells were transfected with a plasmid containing ORF3a sequence by nucleofection. NLRP3 inflammasome and ASC speck formation were detected by confocal microscopy and/or by FACS analysis. Results: In the present study we show that circulating monocytes from COVID-19 patients display ASC specks, index of NLRP3 activation, and spontaneously secrete IL-1β in vitro. This spontaneous activation reverts following patient's treatment with the IL-1 receptor antagonist anakinra. Transfection of a monocytic cell line with cDNA coding for the ORF3a SARS-CoV2 protein, resulted in NLRP3- dependent ASC speck formation. The involvement of ORF3a in inflammasome activation was further supported by the detection by RT-PCR of ORF3a in monocytes from COVID-19 patients. Conclusion: In summary, these results provide a mechanistic explanation for the strong inflammatory manifestations associated to COVID-19 and further evidence that NLRP3 and IL-1β targeting could represent an effective strategy in this disease.

3.
Pediatric Rheumatology ; 18(SUPPL 3), 2020.
Article in English | EMBASE | ID: covidwho-1094038

ABSTRACT

Introduction: Italy was affected by the SARS-CoV-2 epidemic after its outbreak in China. With a 4-weeks delay after the peak in adults, we observed an abnormal number of patients with characteristics of a multi-inflammatory disease and similarities with Kawasaki Disease (KD). Others reported similar cases, defined PIMS-TS or MIS-C.1,2 Objectives: To better characterize clinical features and treatment response of PIMS-TS and to explore its relationship with KD. Methods: We conducted an observational, retrospective, multicenter study. On April 24th-2020 the Rheumatology Study Group of the Italian Pediatric Society launched a national online survey, to enroll patients diagnosed with KD or with a multisystem inflammatory disease between February 1st 2020 and May 31st. The population was then divided into two different groups: 1) Classical and incomplete KD, named Kawasaki Disease Group (KDG);2) KD-like multi-inflammatory syndrome, named KawaCOVID (KCG). An expert panel of pediatric rheumatologists re-analyzed every single patient to ensure appropriate classification. Data were collected with an online database. Results: 149 cases were studied, 96 with KDG and 53 with KCG. The two population significantly differed for clinical characteristics (see table 1). Lymphopenia, higher CRP levels, elevated Ferritin and Troponin-T characterized KCG such as lower WBC and platelets (all p values<0,05). 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 on KCG showed minor complications while on KDG a majority of patients had persistence of CAA. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data between the two groups Conclusion: Our study would suggest that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD, possibly triggered by SARS-CoV-2, and PIMS-TS. Older age at onset and clinical peculiarities, like the occurrence of myocarditis, characterize this multiinflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths.

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