P2.007: Short-, mid-, and long-term cardiovascular outcomes after multisystem inflammatory syndrome in children (MIS-C): a systematic review.

Background: Multisystem inflammatory syndrome in children (MIS-C) may lead to persistent cardiovascular events, and neurological or psychological sequelae. However, few studies have published mid- and long-term follow-up data, and their findings differ, involving small sample sizes and reflecting disparities in income levels. Therefore, our objective is to estimate the frequency of short-, mid-, and long-term cardiovascular outcomes after MIS-C over the four years since the onset of the SARS-CoV-2 pandemic.

Methods: Systematic review, protocol registration number: CRD42022336784 (PROSPERO). We searched in Pubmed/Medline, Scopus, Embase, SciELO, LILACS, Cochrane Library, and Web of Science from January 2020 to May 2024. We performed a random-effects models meta-analysis, assessed heterogeneity and the risk of bias.

Results: Eighty-four studies (n=4,778) were included, 50% were prospective cohort studies. Most were conducted in the United States (29.76%), India (15.48%), with 61.9% originating from high-income countries. Eight studies (9.5%) included a comparator group (acute COVID-19, healthy children, and classic myocarditis). The majority (45.24%) used the CDC criteria for MIS-C; most participants were of school age (65.48%) and male (60.25% ± 11.46%). Comorbidities were not predominant (median 14.29%, interquartile range: 8.94–26.42%). Only one study reported SARS-CoV-2 vaccination, with fewer than 10% of patients vaccinated. There were no studies with a low risk of bias.
Likewise, the majority of studies (40.48%) conducted 6-month follow-up assessments. Only ten, two, and four studies reported follow-up at 12, 18, and 24 months, respectively. The frequency of cardiovascular outcomes progressively decreased over time (Figure 1), reaching zero in most reports. Most of these outcomes resolved within 6 to 9 months. Two studies reported persistent coronary abnormalities at 24-month follow-up, with one patient affected in each. Other studies described the presence of myocardial edema and/or fibrosis on cardiac MRI up to 12 months, although with considerable variability (13.4%; 95% CI: 0.0–60.0) (Table 1).
Considering studies with a comparator group, one study comparing MIS-C (n=183) and acute COVID-19 (n=372) found that, at 5 months of follow-up, cardiovascular-related sequelae were more frequent in the MIS-C group (49.7% vs. 22.6%). Another study reported that all 10 patients with MIS-C had recovered ventricular function by 3 months after discharge, whereas 3 of 11 patients (27%) with classic myocarditis had persistent ventricular dysfunction. The remaining studies had follow-up durations of no more than six months and were mostly limited by small sample sizes. Some used advanced cardiac imaging techniques, such as strain echocardiography or cardiac MRI, and did not find significant differences in cardiovascular outcomes; however, differences were observed when compared to healthy controls.

Conclusion: We found that the occurrence of cardiovascular events decreased over time; however, some were still reported up to 12 and 24 months after MIS-C. Long-term cohort studies are necessary to confirm our findings.