Multisystem Inflammatory Syndrome in Children (MIS-C) Has Long-Term Effects on Microcirculation

Background: The precise underlying mechanisms of multisystem inflammatory syndrome in children (MIS-C) as a postinfectious reaction to COVID-19 remain unclear. While it is known that microvascular and endothelial dysfunction contribute to its acute clinical manifestation, there is limited knowledge about its lasting effects. In this longitudinal study, we conducted microcirculatory and endothelial assessments in MIS-C patients both during the acute phase and three to six months thereafter.

Methods: This prospective case-control study included patients diagnosed with MIS-C according to the WHO criteria at the Children's University Hospital of the LMU Munich, Germany. We employed sublingual Sidestream Dark Field (SDF) imaging to visualize the microcirculation and analyzed parameters such as the microvascular flow index (MFI), total vessel density (TVD), the proportion of perfused vessels (PPV), and vessel diameter distribution. Furthermore, we used peripheral arterial tonometry (EndoPAT) to measure the reactive hyperemia index (RHI), which assesses endothelial function, and the augmentation index (AIx@75), reflecting arterial stiffness.

Results: Our study included 17 MIS-C patients and 17 matched controls. During the acute phase (N = 7, 5 males), we observed significant microcirculatory changes associated with MIS-C, including marked reductions in MFI, TVD, and PPV, as well as alterations in vessel distribution leading to capillary rarefaction. Interestingly, all these abnormalities persisted during follow-up examinations, even in the absence of any signs of inflammation (N = 16, 10 males). These findings remained consistent after adjusting for age, sex, and BMI (MIS-C vs. Controls: MFI: 2.30 (0.51) vs. 2.79 (0.29); p = 0.010; TVD: 15.96 (3.35) mm/mm² vs. 19.65 (1.51) mm/mm²; p < 0.001; PPV: 12.14 (3.01) % vs. 17.85 (3.19) %; p < 0.001). Furthermore, we observed a significant increase in arterial stiffness.

Conclusion: Our findings collectively suggest that MIS-C patients experience significant acute and persistent microvascular dysfunction. These observations may reflect disease-specific pathological aspects and have implications for long-term cardiovascular health.

Publication History

Article published online:
13 February 2024