Multisystem inflammatory syndrome in children: results of a multicenter Italian survey during SARS-COV2 pandemic

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. We previously published the results of the Italian multicenter survey of MIS-C, launched by the Rheumatology Study Group of Italian Pediatric Society We suggested that SARS-Cov- 2 might determine two types of inflammatory diseases in children: the classic KD, that could be triggered by the coronavirus, and the multisystem inflammatory syndrome, which has some specific clinical peculiarities. Objectives: The aim of our study was to analyze clinical features, laboratory findings and treatment strategies in patients diagnosed with MIS-C in Italy during SARS-CoV2 pandemic and evaluate if different outcomes may be related to different disease phenotype in order to establish specific prognostic criteria. Methods: This is an observational, retrospective, multicenter study. We enrolled the children hospitalized between September 1st 2020 and April 30th, 2021 with clinical diagnosis of multi-inflammatory syndrome (MIS-C). For each patient who received MISC diagnosis, we collected demographic, clinical, laboratory data, imaging findings, and treatment information in an online anonymized database (REDCap). We focused on the following main outcomes: the presence of heart abnormalities at dischargement, ICU admission, need of respiratory support or vasoactive agents and number of IVIG cycle administered analyzing a possible relationship with different disease phenotype. Results: 186 children were included in the study. The median age at presentation was 8 years (4-11), 103 (55%) patients were male and 83 (45%) female. 23 (12%) patients had pre-existing comorbidities. 130 (70%) patients presented a positive IgG serology for SARS-CoV-2 and 51% of patients reported a close contact. Markers of systemic inflammation at onset was elevated in all patients: CRP 143,2 mg/dl (111,0- 156,3), ESR 51,5 mm/h (51,0 -54,5), neutrophils 8200/mmc (6490-9011), D-dimer 2175 ng/ml (1076 - 2814). 16 (8%) children needed oxygen supplementation at baseline. 129 patients showed cardiac involvement characterized by myocarditis (23%), valve dysfunction (20%), hypotension (19%) and heart failure (15%). MAS was a complication in 11(6%) patients. ICU admission was required in 40 patients (22%). In our study, a majority of patients were treated with glucocorticoids (77%) and intravenous immunoglobulin (91%), of which 9% receveid two doses of IGEV. At dischargement heart ultrasonography showed valvular insufficiency (19%) and coronary abnormalities (8%). Conclusion: MIS-C has an extensive clinical spectrum that led to serious and life-threating illness. Systemic inflammation and specific organ involvement of cardiac and gastrointestinal involvement are the hallmarks. Good outcomes depends on prompt recognition and timely treatment, based on the combined use of glucocorticoids, high-dose immunoglobulins and anti-cytokine therapy.

Children with Kawasaki disease or Kawasaki-like syndrome (MIS-C/PIMS) at the time of COVID-19: are they all the same? Case series and literature review.

Since the coronavirus disease 2019 (COVID-19) outbreak started, children have been considered marginally involved compared to adults, with a quite significant percentage of asymptomatic carriers. Very recently, an overwhelming inflammatory activation, which shares clinical similarities with Kawasaki disease (KD), has been described in children exposed to COVID-19. We report three KD-like cases that occurred during the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a highly affected area of Northern Italy. The clinical presentation was characterized by the presence of unremitting fever, diarrhea and elevated inflammatory markers. Case #1 and Case #2 occurred one week apart and shared other clinical features: laboratory tests confirmed COVID-19 exposure and high inflammatory activation with myocardial involvement. Case #3 followed a more typical pattern for KD. Interestingly, this patient showed lower levels of procalcitonin, C-reactive protein, D-dimers, and ferritin compared to the other two cases, whereas platelet count was higher. We hypothesize that SARS-CoV-2 might act in children as a trigger, either inducing a classical KD phenotype or causing a systemic inflammatory response leading to a severe KD-like phenotype, eventually characterized by myocardial impairment. We think that bringing these cases and their differences to the attention of the rheumatology community during the COVID-19 pandemic will be beneficial in order to highlight the importance of early diagnosis and to increase awareness of this new phenomenon.

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.