Cardiac assessment and inflammatory markers in children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV2 (PIMS-TS) treated with methylprednisolone versus intravenous immunoglobulins: 6-month follow-up outcomes of the randomised controlled Swissped RECOVERY trial.

Background

Previous findings from the Swissped RECOVERY trial showed that patients with Pediatric Inflammatory Multisystem Syndrome-Temporally Associated with SARS-CoV-2 (PIMS-TS) who were randomly assigned to intravenous immunoglobulins or methylprednisolone have a comparable length of hospital stay. Here, we report the 6-month follow-up outcomes of cardiac pathologies and normalisation of clinical or laboratory signs of inflammation from this study population.

Methods

This pre-planned follow-up of patients with PIMS-TS included the Swissped RECOVERY Trial reports on the 6-month outcomes of the cohort after randomisation, with a focus on cardiac, haematological, and biochemical findings. The trial was an investigator-initiated randomised multicentre open-label two-arm trial in children and adolescents hospitalised with PIMS-TS at ten hospitals in Switzerland. Cardiological assessments and laboratory analyses were prospectively collected in the intention-to-treat analysis on pre-defined intervals after hospital discharge. Differences between randomised arms were investigated using Chi-square test for categorical and Wilcoxon test for continuous variables. The trial is registered with the Swiss National Clinical Trials Portal (SNCTP000004720) and ClinicalTrials.gov (NCT04826588).

Findings

Between May 21, 2021 and April 15, 2022, 75 patients with a median age of 9.1 years (IQR 6.2-12.2) were included in the intention-to-treat population (37 in the methylprednisolone group and 38 in the intravenous immunoglobulin group). During follow-up, the incidence of abnormal left ventricular systolic function, coronary artery aneurysms (CAA), and other signs of inflammation were comparable in both groups. However, we detected cardiac abnormalities with low incidence and a mild degree grade of pathology. CAAs were observed in 2/38 children (5.3%) in the IVIG group and 1/37 children (2.7%) in the methylprednisolone group at 6-month follow-up (difference proportion 0.75; 95% confidence interval (CI) -0.05 to 1.0; p = 0.39).

Interpretation

Methylprednisolone alone may be an acceptable first-line treatment as left ventricular systolic dysfunction and clinical/laboratory evidence for inflammation quickly resolved in all children. However, our findings need further confirmation through larger studies as our sample size is likely to be of insufficient power to address rare clinically relevant adverse outcomes.

Funding

NOMIS, Vontobel, and Gaydoul Foundation.

Informations de copyright

© 2023 The Author(s).

Déclaration de conflit d'intérêts

LJS was supported by grants from the NOMIS Foundation, the Vontobel Foundation, and the Gaydoul Foundation for this study. Swiss PedNet (https://www.swisspednet.ch/) provided infrastructure support for study coordination and monitoring. JB received grant support paid to the institution from the European and Developing Countries Clinical Trials Partnership (PediCaP, RIA2017MC-2023), Horizon 2020 (NeoIPC, grant 965328), the Swiss National Science Foundation (KIDS-STEP, grant 173532), National Institute for Health Research (CAP-IT, project 13/88/11), Innosuisse (SPEARHEAD flagship grant), the Swiss Personalised Health Network (Secretariat for Education Research and Innovation) (SwissPedHealth, award NDS-2021-911), in the past 36 months; consulting fees paid to the institution from Shionogi, Sandoz, Basilea, and GSK; payments to the institution for presentations, lectures, speakers bureaus, manuscript writing or educational events in the past 36 months from Pfizer, Sandoz, and Bayer; participated at independent data monitoring committee boards of Avenir trial (member, expenses), Lakana trial (member, unfunded), CURLY trial (Chair, unfunded) in the past 36 months; is the vice president of the SwissPedNet (unpaid) and leadership of Severe Bacterial Infection and Antimicrobial Resistance working group of the Penta Foundation (unpaid). TW gave presentations for Novartis (payment to the institution) in the past 36 months. All other authors declare no competing interests.