Paediatric inflammatory multisystem syndrome in Canada: population-based surveillance and role of SARS-CoV-2 linkage.

BACKGROUND: Paediatric inflammatory multisystem syndrome (PIMS) is a rare condition temporally associated with SARS-CoV-2 infection. Using national surveillance data, we compare presenting features and outcomes among children hospitalized with PIMS by SARS-CoV-2 linkage, and identify risk factors for intensive care (ICU). METHODS: Cases were reported to the Canadian Paediatric Surveillance Program by a network of >2800 pediatricians between March 2020 and May 2021. Patients with positive versus negative SARS-CoV-2 linkages were compared, with positive linkage defined as any positive molecular or serologic test or close contact with confirmed COVID-19. ICU risk factors were identified with multivariable modified Poisson regression. RESULTS: We identified 406 children hospitalized with PIMS, including 49.8% with positive SARS-CoV-2 linkages, 26.1% with negative linkages, and 24.1% with unknown linkages. The median age was 5.4 years (IQR 2.5-9.8), 60% were male, and 83% had no comorbidities. Compared to cases with negative linkages, children with positive linkages experienced more cardiac involvement (58.8% vs. 37.4%; p < 0.001), gastrointestinal symptoms (88.6% vs. 63.2%; p < 0.001), and shock (60.9% vs. 16.0%; p < 0.001). Children aged ≥6 years and those with positive linkages were more likely to require ICU. CONCLUSIONS: Although rare, 30% of PIMS hospitalizations required ICU or respiratory/hemodynamic support, particularly those with positive SARS-CoV-2 linkages. IMPACT: We describe 406 children hospitalized with paediatric inflammatory multisystem syndrome (PIMS) using nationwide surveillance data, the largest study of PIMS in Canada to date. Our surveillance case definition of PIMS did not require a history of SARS-CoV-2 exposure, and we therefore describe associations of SARS-CoV-2 linkages on clinical features and outcomes of children with PIMS. Children with positive SARS-CoV-2 linkages were older, had more gastrointestinal and cardiac involvement, and hyperinflammatory laboratory picture. Although PIMS is rare, one-third required admission to intensive care, with the greatest risk amongst those aged ≥6 years and those with a SARS-CoV-2 linkage.

Distinct phenotypes of multisystem inflammatory syndrome in children: a cohort study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a severe disease with an unpredictable course and a substantial risk of cardiogenic shock. Our objectives were to (a) compare MIS-C phenotypes across the COVID-19 pandemic, (b) identify features associated with intensive care need and treatment with biologic agents. METHODS: Youth aged 0-18 years, fulfilling the World Health Organization case definition of MIS-C, and admitted to the Alberta Children's Hospital during the first four waves of the COVID-19 pandemic (May 2020-December 2021) were included in this cohort study. Demographic, clinical, biochemical, imaging, and treatment data were captured. RESULTS: Fifty-seven MIS-C patients (median age 6 years, range 0-17) were included. Thirty patients (53%) required intensive care. Patients in the third or fourth wave (indicated as phase 2 of the pandemic) presented with higher peak ferritin (µg/l, median (IQR) = 1134 (409-1806) vs. 370 (249-629), P = 0.001), NT-proBNP (ng/l, median (IQR) = 12,217 (3013-27,161) vs. 3213 (1216-8483), P = 0.02) and D-dimer (mg/l, median (IQR) = 4.81 (2.24-5.37) vs. 2.01 (1.27-3.34), P = 0.004) levels, and higher prevalence of liver enzyme abnormalities (n(%) = 17 (68) vs. 11 (34), P = 0.02), hypoalbuminemia (n(%) = 24 (100) vs. 25 (81), P = 0.03) and thrombocytopenia (n(%) 18 (72) vs. 11 (34), P = 0.007) compared to patients in the first two waves (phase 1). These patients had a higher need of non-invasive/mechanical ventilation (n(%) 4 (16) vs. 0 (0), P = 0.03). Unsupervised clustering analyses classified 47% of the patients in the correct wave and 74% in the correct phase of the pandemic. NT-proBNP was the only significant contributor to the need for intensive care in all applied multivariate regression models. Treatment with biologic agents was significantly associated with peak CRP (mg/l (median, IQR = 240.9 (132.9-319.4) vs. 155.8 (101.0-200.7), P = 0.02) and ferritin levels (µg/l, median (IQR) = 1380 (509-1753) vs. 473 (280-296)). CONCLUSIONS: MIS-C patients in a later stage of the pandemic displayed a more severe phenotype, reflecting the impact of distinct SARS-CoV-2 variants. NT-proBNP emerged as the most crucial feature associated with intensive care need, underscoring the importance of monitoring.

Central nervous system manifestations of monogenic autoinflammatory disorders and the neurotropic features of SARS-CoV-2: Drawing the parallels.

Central nervous system (CNS) involvement in monogenic autoinflammatory disorders (AID) is increasingly recognized and can be life threatening. Therefore, a low threshold to consider CNS disease should be maintained in patients with systemic inflammation. Hyperinflammation is also a key feature of severe acute COVID-19 and post COVID-19 entities such as multisystem inflammatory syndrome in children. Like AID, COVID-19 patients can present with severe CNS involvement. The impact of COVID-19 on AID and CNS involvement in particular is still obscure, nevertheless dreaded. In the current review, we synthesize the spectrum of CNS manifestations in monogenic AID. We explore common pathophysiological and clinical features of AID and COVID-19. Moreover, we assess the impact of immune dysregulation associated with SARS-CoV-2 infections and post COVID-19 hyperinflammation in AID. The striking commonalities found between both disease entities warrant caution in the management of AID patients during the current pandemic.