Impairment of Microcirculation and Endothelial Function in Children with Multisystem Inflammatory Syndrome (MIS-C)/Pediatric Inflammatory Multisystem Syndrome (PIMS): A Long-Term Study

ABSTRACT

Background: Multisystem inflammatory syndrome in children (MIS-C)/pediatric inflammatory multisystem syndrome(PIMS) is a rare but severe hyper inflammation following exposure to SARS-CoV-2. The exact pathogenesis is unknown, butSARS-CoV-2 is linked to vascular-endothelial pathology. We therefore longitudinally analyzed endothelial function and microcirculation in children with MIS-C/PIMS. Method(s) Overall 17 pediatric patients with MIS-C/PIMS (mean age 9.4 +/- 4.5 years;30% female) were included in our study. They were examined during the acute phase and in follow-up visits after 3 and 6 months. We assessed the reactive hyperemia index (RHI) as a surrogate for the endothelial function using the Endo PAT device. The microcirculation was visualized using sublingual sidestream dark field (SDF) imaging, which permits analyzing the microvascular flow index (MFI)(0 = no flow, 1 = intermittent, 2 = sluggish, 3 = continuous). Result(s) During the acute phase of MIS-C/PIMS both, macrovascular and microvascular markers were distinctively restricted. Mean RHI was 1.11 +/- 0.25 indicating limited endothelial function in comparison to a group of healthy controls(mean RHI = 1.36 +/- 0.22;n = 14;mean age 12.8 +/- 2.2 years;50% female). After 3 months, mean RHI improved to 1.42+/-0.45 and even increased to 1.75 +/- 0.66 after 6 months. SDF imaging revealed an impaired microcirculatory flow during the acute phase (mean MFI 2.45 +/- 0.28), which surprisingly did not improve after three months (mean MFI 2.45 +/- 0.33).Six months after the acute phase, the microvascular flow ameliorated toward a more continuous flow (mean MFI 2.66 +/- 0.29). Conclusion(s) Our preliminary results indicate an impaired microcirculation and endothelial function in children with MIS-C/PIMS. The process of full vascular recovery seems to take several months. More research in this field is necessary to better understand the patho physiology and the time course of this rare new SARS-CoV-2-related syndrome.