Persistent left ventricular systolic dysfunction at ≥6 months after SARS-CoV-2–associated MIS-C: a systematic review and rare-event meta-analysis
8 affiliations
- 1Faculty of Medicine, Semmelweis University
- 2Department of Pediatrics, Ministry of National Guard Health Affairs
- 3King Abdullah International Medical Research Center
- 4King Saud bin Abdulaziz University for Health Sciences
- 5Department of Pediatrics, Faculty of Medicine, King Abdulaziz University
- 6Department of Pediatrics, King Abdulaziz University Hospital
- 7Saveetha College of Nursing, Saveetha Institute of Medical and Technical Sciences
- 8University of Johannesburg
Abstract
Background: Multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 frequently involves acute myocardial dysfunction. However, the prevalence of persistent left ventricular (LV) systolic dysfunction at longer-term follow-up remains uncertain. We therefore performed a systematic review and meta-analysis to estimate the prevalence of persistent LV systolic dysfunction at ≥6 months after MIS-C.
Methods: We included observational cohort studies reporting longitudinal echocardiographic follow-up in children and adolescents aged <21 years with SARS-CoV-2–associated MIS-C. The prespecified primary outcome was persistent LV systolic dysfunction, defined as left ventricular ejection fraction (LVEF) < 55% at ≥6 months. Study-level events and denominators were extracted and harmonized using the number of children who underwent ≥6-month echocardiography as the endpoint-specific denominator. Pooled prevalence was estimated using an intercept-only binomial logistic-normal generalized linear mixed model (GLMM) fitted directly to study-level event counts and denominators without continuity correction. The originally prespecified random-effects logit model with restricted maximum likelihood estimation and Hartung–Knapp–Sidik–Jonkman confidence intervals, together with alternative continuity corrections and transformation-based approaches, was retained as sensitivity analysis under sparse-event conditions.
Results: Ten cohorts met the inclusion criteria and contributed to quantitative synthesis, comprising 432 children with echocardiography at ≥6 months. Persistent LV systolic dysfunction occurred in 3 children, corresponding to a crude observed proportion of 0.69% (3/432). In the revised primary continuity-correction-free binomial logistic-normal GLMM, the pooled prevalence was 0.69% (95% CI, 0.22%–2.13%). Given that only three events were observed, this model-based estimate should not be interpreted as a precise estimate of the underlying population prevalence. Continuity-corrected sensitivity models yielded pooled estimates from 1.62% to 2.23%, further demonstrating numerical sensitivity to the treatment of zero-event cohorts.
Conclusion: Persistent LV systolic dysfunction was infrequently observed among children with MIS-C reassessed by echocardiography at ≥6 months. However, only three events were identified, so the available evidence is insufficient to determine the exact population prevalence with precision. Inference is further limited by heterogeneous follow-up and potential selection bias from nonuniform late imaging. Larger prospective cohorts with standardized long-term surveillance are needed.
Related
- Graves’ Disease and the Heart: Severe Reversible Left Ventricular Systolic Dysfunction With Apical Thrombus in a Young Woman With Relapsed Thyrotoxicosis
- Nebivolol for the Prevention of Left Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy: the NEBIDYS trial
- Development and Population-Based Prognostic Utility Assessment of an ICD-10-CM-Based Prediction Model to Identify Left Ventricular Systolic Dysfunction: Discrimination Performance and Population-Based Evaluation in 83,357 Patients with Acute Coronary Syndrome
- External validation of artificial intelligence-guided electrocardiogram (AI-ECG) in detecting asymptomatic left ventricular dysfunction: A systematic review and meta-analysis
- Longitudinal Transcriptomic Analysis Identifies Persistent Immune-Related Signature Associated With Restrictive Left Ventricular Filling Patterns After Heart Transplantation
BibTeX
@article{shafeen2026persistent,
title = {{Persistent left ventricular systolic dysfunction at ≥6 months after SARS-CoV-2–associated MIS-C: a systematic review and rare-event meta-analysis}},
author = {Khaled Shafeen and Mohammed Al Qahtani and Abeer Alnajjar and Musub Alam and Karthiga Gurumurthy and Clara Glynis Masala and Wojood Al Othman and Nujud Abdullah Al Essa and Mutab Almutiri and Amr Esmail and Maryam Al Qannas and Mohammed Shahab Uddin},
journal = {Frontiers in Cardiovascular Medicine},
year = {2026},
month = nov,
doi = {10.3389/fcvm.2026.1931919},
url = {https://www.frontiersin.org/articles/10.3389/fcvm.2026.1931919/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Persistent left ventricular systolic dysfunction at ≥6 months after SARS-CoV-2–associated MIS-C: a systematic review and rare-event meta-analysis
AU - Khaled Shafeen
AU - Mohammed Al Qahtani
AU - Abeer Alnajjar
AU - Musub Alam
AU - Karthiga Gurumurthy
AU - Clara Glynis Masala
AU - Wojood Al Othman
AU - Nujud Abdullah Al Essa
AU - Mutab Almutiri
AU - Amr Esmail
AU - Maryam Al Qannas
AU - Mohammed Shahab Uddin
PY - 2026
DA - 2026/11/04
JO - Frontiers in Cardiovascular Medicine
DO - 10.3389/fcvm.2026.1931919
UR - https://www.frontiersin.org/articles/10.3389/fcvm.2026.1931919/full
AB - Background: Multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 frequently involves acute myocardial dysfunction. However, the prevalence of persistent left ventricular (LV) systolic dysfunction at longer-term follow-up remains uncertain. We therefore performed a systematic review and meta-analysis to estimate the prevalence of persistent LV systolic dysfunction at ≥6 months after MIS-C. Methods: We included observational cohort studies reporting longitudinal echocardiographic follow-up in children and adolescents aged <21 years with SARS-CoV-2–associated MIS-C. The prespecified primary outcome was persistent LV systolic dysfunction, defined as left ventricular ejection fraction (LVEF) < 55% at ≥6 months. Study-level events and denominators were extracted and harmonized using the number of children who underwent ≥6-month echocardiography as the endpoint-specific denominator. Pooled prevalence was estimated using an intercept-only binomial logistic-normal generalized linear mixed model (GLMM) fitted directly to study-level event counts and denominators without continuity correction. The originally prespecified random-effects logit model with restricted maximum likelihood estimation and Hartung–Knapp–Sidik–Jonkman confidence intervals, together with alternative continuity corrections and transformation-based approaches, was retained as sensitivity analysis under sparse-event conditions. Results: Ten cohorts met the inclusion criteria and contributed to quantitative synthesis, comprising 432 children with echocardiography at ≥6 months. Persistent LV systolic dysfunction occurred in 3 children, corresponding to a crude observed proportion of 0.69% (3/432). In the revised primary continuity-correction-free binomial logistic-normal GLMM, the pooled prevalence was 0.69% (95% CI, 0.22%–2.13%). Given that only three events were observed, this model-based estimate should not be interpreted as a precise estimate of the underlying population prevalence. Continuity-corrected sensitivity models yielded pooled estimates from 1.62% to 2.23%, further demonstrating numerical sensitivity to the treatment of zero-event cohorts. Conclusion: Persistent LV systolic dysfunction was infrequently observed among children with MIS-C reassessed by echocardiography at ≥6 months. However, only three events were identified, so the available evidence is insufficient to determine the exact population prevalence with precision. Inference is further limited by heterogeneous follow-up and potential selection bias from nonuniform late imaging. Larger prospective cohorts with standardized long-term surveillance are needed.
SN - 2297-055X
ER -