MULTISYSTEM INFLAMMATORY SYNDROME IN CHILDREN ACROSS 16 LATIN AMERICAN COUNTRIES: A MULTICENTER STUDY FROM THE REKAMLATINA NETWORK

BackgroundMultisystem Inflammatory Syndrome in Children (MIS-C) is one of the most feared complications following SARS-CoV2 infection in children and adolescents. Few multinational multicenter studies from Latin America have been published.ObjectivesTo describe the clinical presentation, management, and outcomes of MIS-C in Latin America.MethodsObservational, prospective and retrospective, multicenter study to gather information from 84 participating centers across 16 Latin American countries, between August January 1, 2020 and June 30, 2022.ResultsOf the 1,239 reported cases of MIS-C, 84.2% were previously healthy. The most frequent clinical manifestation in our studied population was abdominal pain (N=804, 64.9%), followed by conjunctival injection (N=784, 63.3%). The median days of fever at the time of hospital admission was 5 and a significant number of subjects required admission to an intensive care unit (N=589, 47.8%). A total of 538 (47.2%) patients had an abnormal initial echocardiogram. Most of the subjects (N= 1,096, 88.7%) were treated with intravenous immunoglobulin (IVIG), while 76.7% (N= 947) were treated with steroids, of which 10.6% (N= 100) did not receive IVIG. The death rate attributed to MIS-C was 4.88%, with a rate of 3.39% for those initially diagnosed with MIS-C and 8.85% for those whose admission diagnosis was not MIS-C (P= 0.00001).ConclusionOne of the most significant findings from our study was the death rate, especially in those not initially diagnosed with MIS-C, in whom it was higher. This highlights the importance of increasing awareness and making an earlier diagnosis of MIS-C in Latin America.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Kawasaki disease in the time of COVID-19-the international kawasaki disease registry

Background and Aim: The considerable overlap in case definition and clinical features between patients with COVID-19 associated Multisystem Inflammatory Syndrome in Children (MIS-C) and Kawasaki disease (KD) suggests shared pathogenesis. We sought to compare demographic, clinical presentation, management and outcomes of patients by COVID-19 status. Method(s): The International KD Registry (IKDR) began enrolling patients with clinical features of either acute MIS-C or KD or fever with hyperinflammation beginning in January 2020. The IKDR is unique regarding broad patient selection and includes sites from North, Central and South America, Europe, Asia and the Middle East. Patient groups stratified by COVID-19 status were compared. Result(s): As of October 6, 2021, 1330 patients were registered from 31 sites. COVID status was POSITIVE for 59% (confirmed household COVID-19 contact and/or positive SARS-CoV-2 PCR or serology), POSSIBLE for 4% (suggestive clinical features but some negative tests or absent exposure), NEGATIVE for 23%, and UNKNOWN (no known exposure and testing not com-pleted) for 14% (TABLE). Most of the UNKNOWN patients were from early in the COVID-19 pandemic before MIS-C was defined and before COVID-19 serologic testing was widely used. POSITIVE and POSSIBLE patients were older, had fewer KD clinical criteria, greater gastrointestinal symptoms, were more likely to present with shock and require ICU admission and inotropic support. POSSIBLE patients had greater days from symptom onset to first immune modulation treatment, with no differences between groups regarding days from admission to first treatment. Most patients in each group received intravenous immune globu-lin, with POSITIVE and POSSIBLE patients more likely to have received steroids and anakinra. NEGATIVE and UNKNOWN patients had higher maximal coronary artery Z scores, with a trend to having higher categories of aneurysm involvement. Conclusion(s): While there was considerable overlap in presentation, management and outcomes between COVID-19 POSITIVE/POSSIBLE (presumed MIS-C) and COVID NEGATIVE/UNKNOWN patients (presumed KD), COVID-19 POSITIVE/POSSIBLE patients had more severe presentations and required more intensive management, although coronary artery outcomes trended to be less severe. Patient recruitment con-tinues, and in-depth comparison of laboratory features and appli-cation of machine learning approaches to patient differentiation and prediction of optimal management pathways are forthcoming.

Early signs of myocardial remodeling in children with multisystem inflammatory syndrome associated with COVID-19 and cardiac involvement

Background and Aim: Multisystem Inflammatory Syndrome in Children (MIS-C) associate with Coronavirus disease-19 is a life-threatening clinical condition in which cardiovascular system is frequently affected. Shock, cardiac arrhythmias, myocarditis, reduced left ventricular ejection fraction (LVEF), pericardial effu-sion, and coronary artery dilatation are amongst the most common cardiac complications. In this study, we aim to assess myocardial status in patient with cardiac involvement in MIS-C. Method(s): Over a 14-month period, we retrospectively collected clinical, biological, echocardiographic data in children who were admitted to our hospital with a diagnosis of MIS-C and cardiac involvement. WHO criteria for clinical case definition of MIS-C were adopted. Elevation in brain-natriuretic-peptide and troponin-I, electrocardiographic abnormalities, echocardio-graphic evidence of pericarditis, myocarditis, reduced LVEF, valvular disease, and coronary artery dilatation were including cri-teria. LV indexed end-diastolic (EDVi), end-systolic (ESVi), stroke volumes were measured with Cardiac Magnetic Resonance (CMR). T2 mapping, Cine-RM and late gadolinium enhance-ment studies were performed. Result(s): 14 children were identified and included in the study, 71% of which were male. Median age at disease onset was 7 years old (IQR 5 to 9 years). All patients underwent cardiological evaluation in the first 48 hours of hospital staying. LVEF was lt;45% in 28.6% and lt;35% in 14.3% of patients. Myocarditis was detected in 78.6%, pericarditis in 28.6%, valvular damage in 35.7%, coronary abnormalities in 42.9%. All patients underwent CMR after on average 4 months (median: 3.87, IQR 2 to 4) from disease onset, after full clinical and biological recovery. ESVi and stroke volumes resulted within normal range in 100%. CMR abnormalities were observed in 21%. Particularly, left ventricular EDVi resulted elevated in 7%, delayed washout in T2 was described in 7%, and increased T2 mapping in 7%. Conclusion(s): Despite complete clinical and biological resolution, increased EDVi, delayed washout in T2 and increased T2 mapping at follow-up CMR in patient with cardiac involvement due to MIS-C may be signs of myocardial remodeling.

Long-term cardiac outcome in patients with multisystem inflammatory syndrome in children (MIS-C)

Introduction: Multisystem Inflammatory Syndrome in children (MISC) was initially described during the first phase of COVID-19 pandemic as a severe clinical condition with systemic inflammation and multi-organ involvement. Many patients show features of Kawasaki Disease. Cardiac involvement, from myocarditis to coronary abnormalities, is a key feature of the syndrome, but there are still little data concerning the long-term outcome in these patients. Objectives: The aim of our study was to evaluate long-term cardiac outcome in patients diagnosed with MIS-C during the first phase of COVID-19 pandemic in Italy. Methods: We previously published the results of the Italian multicenter survey of MIS-C, launched by the Rheumatology Study Group of Italian Pediatric Society during the first wave of COVID-19 pandemic. For each patient who received MIS-C diagnosis, we collected demographic, clinical, laboratory data, imaging findings, and treatment information in an online anonymized database (RedCAP). Data collection included all the admission period and all follow/up visits. For the purpose of this study, we analyzed all patients with at least 3months of follow/up mainly focusing on heart involvement. Results: Fifty-three patients who received MIS-C diagnosis between February 1st and May 31st 2020 were included in our study. The median age at diagnosis was 7 years (IQR 4,5-11). Forty-one patients showed cardiac involvement during the course of the disease. Treatment with IVIG was reported in 66% of patients at diagnosis and glucocorticoids in 56,6%. Four patients received treatment with IL-1 receptor antagonist (anakinra) and one with hydroxychloroquine. Use of vasoactive agents was reported in 20,8% of patients. No case of death was reported in our population. Data on cardiac outcome were available for 33 patients after a median time of follow-up of 6 months (IQR 7.2- 4.08). Twenty-eight out of 33 patients presented a cardiac involvement during hospitalization for MIS-C: 17 had myocarditis, 5 had pericarditis, 3 coronary artery abnormalities, 8 heart failure, 9 valvular insufficiency, 11 shock or hypotension. For each patient cardiac outcome was assessed by heart ultrasonography. At the end of our follow-up period only four patients still had heart abnormalities: all of them presented mild valvular insufficiency and 2 patients still had ultrasonographic signs of hypokinesia. None of them was on medication. Conclusion: MIS-C is an emerging inflammatory condition that spreads among the pediatric population in parallel to SARS-CoV2 pandemic. The disease is frequently complicated by cardiological involvement but, differently to Kawasaki disease, myocarditis and shock are the most common complications. As we reported in our previous study, short-term outcome is usually good in children with MIS- C and heart involvement. With this study we also provide a long-term cardiac follow-up and we showed that only a minority of patients with previous cardiac involvement presented minor heart abnormalities. Furthermore, no patients developed new heart disease during follow-up.

Challenges during Metis-Solar Orbiter commissioning phase

Metis is the visible light and UV light imaging coronagraph on board the ESA-NASA mission Solar Orbiter that has been launched February 10th, 2020, from Cape Canaveral. Scope of the mission is to study the Sun up close, taking high-resolution images of the Sun’s poles for the first time, and understanding the Sun-Earth connection. Metis coronagraph will image the solar corona in the linearly polarized broadband visible radiation and in the UV HI Ly-α line from 1.6 to 3 solar radii when at Solar Orbiter perihelion, providing a diagnostics, with unprecedented temporal coverage and spatial resolution, of the structures and dynamics of the full corona. Solar Orbiter commissioning phase big challenge was Covid-19 social distancing phase that affected the way commissioning of a spacecraft and its payload is typically done. Metis coronagraph on-board Solar Orbiter had its additional challenges: to wake up and check the performance of the optical, electrical and thermal subsystems, most of them unchecked since Metis delivery to spacecraft prime, Airbus, in May 2017. The roadmap to the fully commissioned coronagraph is here described throughout the steps from the software functional test, the switch on of the detectors of the two channels, UV and visible, to the optimization of the occulting system and the characterization of the instrumental stray light, one of the most challenging features in a coronagraph. © 2021 ESA and CNES

Pediatric systemic multi-inflammatory diseases in Italy during SARS-COV-2 epidemic: From Kawasaki disease to Kawacovid

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.