Presumptive Neonatal Multisystem Inflammatory Syndrome in Children Associated with Coronavirus Disease 2019.

OBJECTIVE: The study aimed to alert the neonatal community to the possibility of multisystem inflammatory syndrome in children (MIS-C) like disease in critically ill neonates born to mothers with coronavirus disease 2019 (COVID-19). STUDY DESIGN: Diagnosis of MIS-C like disease was pursued after echocardiography showed severely depressed ventricular function and pathological coronary artery dilation in the setting of medically refractory multisystem organ failure and maternal COVID-19 infection. The neonate did not respond to standard medical therapy, and there was no alternative disease that could explain the clinical course. High index of clinical suspicion coupled with low risk of intravenous immunoglobulin (IVIG) prompted us to pursue IVIG administration even though the neonate did not meet classic criteria for MIS-C. RESULT: Following treatment with IVIG, there was rapid clinical improvement. Ventricular function improved within 15 hours and coronary artery dilation resolved in 8 days. There was no recurrence of disease during follow-up. CONCLUSION: COVID-19 associated MIS-C like disease has not been well described in neonates. As typical features may be conspicuously absent, a high index of suspicion is warranted in critically ill neonates born to mothers with COVID-19. Echocardiography may provide critical diagnostic information and narrow the differential diagnosis. KEY POINTS: · COVID-19 associated MIS-C can present in neonates.. · Echocardiography is helpful in raising suspicion for MIS-C in neonates.. · Consider MIS-C in the differential diagnosis of ill neonates born to mothers with COVID-19..

Chloroquine differentially modulates coronary vasodilation in control and diabetic mice.

BACKGROUND AND PURPOSE: Chloroquine is a traditional medicine to treat malaria. There is increasing evidence that chloroquine not only induces phagocytosis but regulates vascular tone. Few reports investigating the effect of chloroquine on vascular responsiveness of coronary arteries have been made. In this study, we examined how chloroquine affected endothelium-dependent relaxation in coronary arteries under normal and diabetic conditions. EXPERIMENTAL APPROACH: We isolated coronary arteries from mice and examined endothelium-dependent relaxation (EDR). Human coronary endothelial cells and mouse coronary endothelial cells isolated from control and diabetic mouse (TALLYHO/Jng [TH] mice, a spontaneous type 2 diabetic mouse model) were used for the molecular biological or cytosolic NO and Ca2+ measurements. KEY RESULTS: Chloroquine inhibited endothelium-derived NO-dependent relaxation but had negligible effect on endothelium-derived hyperpolarization (EDH)-dependent relaxation in coronary arteries of control mice. Chloroquine significantly decreased NO production in control human coronary endothelial cells partly by phosphorylating eNOSThr495 (an inhibitory phosphorylation site of eNOS) and attenuating the rise of cytosolic Ca2+ concentration after stimulation. EDR was significantly inhibited in diabetic mice in comparison to control mice. Interestingly, chloroquine enhanced EDR in diabetic coronary arteries by, specifically, increasing EDH-dependent relaxation due partly to its augmenting effect on gap junction activity in diabetic mouse coronary endothelial cells. CONCLUSIONS AND IMPLICATIONS: These data indicate that chloroquine affects vascular relaxation differently under normal and diabetic conditions. Therefore, the patients' health condition such as coronary macrovascular or microvascular disease, with or without diabetes, must be taken account into the consideration when selecting chloroquine for the treatment of malaria.