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.

Management of Pediatric Kidney Transplant Patients During the COVID-19 Pandemic: Guidance From the Canadian Society of Transplantation Pediatric Group.

PURPOSE OF THE PROGRAM: To provide guidance on the management of pediatric kidney transplant patients during the COVID-19 pandemic. SOURCES OF INFORMATION: Program-specific documents, preexisting, and related to COVID-19; documents from provincial, national, and international kidney transplant societies/agencies and organ procurement agencies; national and international webinars, including webinars that we hosted for input and feedback; with additional information from formal and informal review of published academic literature. METHODS: Challenges in the care of pediatric kidney transplant patients during the COVID-19 pandemic were highlighted within the Canadian Society of Transplantation (CST) Pediatric Group. It identified pediatric kidney transplant nephrologists (including a pediatric nephrologist ethicist) across the country and formed a workgroup. The initial guidance document was drafted and members of the workgroup reviewed and discussed all suggestions in detail via e-mail and virtual meetings. Disagreements were resolved by consensus. The document was reviewed by the CST Kidney Transplant Working Group, by the Canadian Society of Nephrology (CSN) COVID-19 Rapid Response Team (RRT), and an infectious disease expert. The suggestions were presented at an interactive webinar sponsored by CSN in collaboration with the CST and Canadian Association of Pediatric Nephrologists (CAPN), and attended by pediatric kidney health care professionals for further peer input. Final revisions were made based on feedback received. CJKHD editors reviewed the parallel process peer review and edited the manuscript for clarity. KEY FINDINGS: We identified 8 key areas of pediatric kidney transplant care that may be affected by the COVID-19 pandemic: (1) transplant activity, (2) outpatient clinic activity, (3) monitoring, (4) multidisciplinary care, (5) medications (immunosuppression and others), (6) patient/family education/support, (7) school and employment, and (8) management of pediatric kidney transplant patients who are COVID-19 positive. We make specific suggestions for each of these areas. LIMITATIONS: A full systematic review of available literature was not undertaken for the sake of expediency in development of this guideline. There is a paucity of literature to support evidence-based recommendations at this time. Instead, these guidelines were formulated based on expert opinion derived from available knowledge/experience and are subject to the biases associated with this level of evidence. The parallel review process that was created to expedite the publication of this work may not be as robust as standard arms' length peer review processes. IMPLICATIONS: These recommendations are meant to serve as a guide to pediatric kidney transplant directors, clinicians, and administrators for providing the best patient care in the context of limited resources while protecting patients and health care providers wherever possible by limiting exposure to COVID-19. We recognize that recommendations may not be applicable to all provincial/local health authority practices and that they may not be delivered to all patients given the time and resource constraints affecting the individual provincial/local health jurisdiction.