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

Abstract

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.

Keywords: Children; Coronary artery aneurysm; Immunoglobulins; Methylprednisolone; PIMS-TS; RCT.

Fig. 1

Study flow chart. Figure shows the Swissped RECOVERY study cohort until discharge/death or censored at 28 days and during the follow-up (described in this publication). ITT: intention-to-treat; MPS: methylprednisolone; IVIG: intravenous immunoglobulins.

Fig. 2

Early, intermediate, and late cardiac Follow-up examinations: Left ventricular (LV) systolic function and coronary artery (CA) involvement. (A) Echocardiographic findings during Follow-up (FU) in children with PIMS-TS treated with intravenous immunoglobulins (IVIG) or methylprednisolone (MPS) as per protocol. Stacked bar charts depicting the percentage of examinations with varying degrees of LV systolic dysfunction, abnormal coronary arteries, normal function, or “unspecified” abnormalities at the indicated time points. (B) Stacked bar charts depicting the percentage of children with varying degrees of coronary artery enlargement (large/giant, medium or small aneurysms, "dilation only"), with other cardiac abnormalities (“unspecified” or decreased myocardial contractility) or without any cardiac abnormalities at the indicated time points. Note that “unspecified” in this context refers to abnormalities other than “decreased myocardial contractility”, “abnormal coronary arteries” or “pericardial effusion”. Number of children with echocardiograms is indicated in the headings of the Figures. (C) Z Score counts in all echocardiograms during FU with documented abnormal coronary artery size. Categorisation into coronary artery "dilatation only", "mild", "medium" or "large" CAA, respectively, was done using the AHA classification.