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Background and objectiveCOVID-19 infection in pregnancy significantly increases risks of adverse pregnancy outcomes. However, little is known how the innate immunity at the placental maternal-fetal interface responds to COVID-19 infection. Type I IFN cytokines are recognized as a key component of the innate immune response against viral infection. In this study, we specifically evaluated expression of IFN antiviral signaling molecules in placentas from women infected with COVID-19 during pregnancy.MethodsExpression of IFN activation signaling pathway molecules, including cyclic GMP–AMP synthase (cGAS), stimulator of interferon genes (STING), interferon regulatory factor 3 (IRF3), Toll-like receptor 7 (TLR7), mitochondrial antiviral-signaling protein (MAVS), and IFNβ were determined in formalin-fixed paraffin embedded (FFPE) placental tissue sections (villous and fetal membrane) by immunostaining. A total of 20 placentas were examined, 12 from COVID-19 patients and 8 from non-COVID-19 controls. Patient demographics, clinical data, and placental pathology report were acquired via EPIC medical record review.ResultsExcept BMI and placental weight, there was no statistical difference between COVID and non-COVID groups in maternal age, gestational age at delivery, gravity/parity, delivery mode, and newborn gender and weight. In COVID-exposed group, the main pathological characteristics in the placental disc are maternal and fetal vascular malperfusion and chronic inflammation. Compared to non-COVID controls, expression of IFN activation pathway molecules were all upregulated with distinct cell-type specific distribution in COVID-exposed placentas: STING in villous and decidual stromal cells; IRF3 in cytotrophoblasts (CTs) and extra-villous trophoblasts (EVTs); and TLR7 and MAVS in syncytiotrophoblasts (STs), CTs, and EVTs. Upregulation of STING, MAVS and TLR7 was also seen in fetal endothelial cells.ConclusionsSTING, IRF3, TLR7, and MAVS are key viral sensing molecules that regulate type I IFN production. Type I IFNs are potent antiviral cytokines to impair and eradicate viral replication in infected cells. The finding of cell-type specific distribution and activation of these innate antiviral molecules at the placental maternal-fetal interface provide plausible evidence that type I IFN pathway molecules may play critical roles against SARS-CoV-2 infection in the placenta. Our findings also suggest that placental maternal-fetal interface has a well-defined antiviral defense system to protect the developing fetus from SARS-CoV-2 infection.

A migraine is a clinical diagnosis with a presentation of one or more severe unilateral or bilateral headache(s) often preceded by an aura and typically accompanied by nausea, vomiting, photophobia, and/or phonophobia. This neurological disease is often debilitating and greatly affects the quality of life of those it inflicts. In fact, a recent study conducted by the Global Burden of Disease and published in The Lancet Neurology revealed that migraines ranked second to only back pain as the most disabling disease. Triggers for migraines have ranged from female sex, low socioeconomic status, and diet to loud noises, sleep hygiene, and stress. Along with its clinical presentation, laboratory tests and imaging help rule out other potential causes of the headache and lead to a diagnosis of migraine. Migraines are typically divided into three phases: prodromal, headache, and postdrome. The pathophysiology of each phase remains under investigation, with differing theories regarding their pathways. Existing therapies are abortive therapies for acute migraines or preventative therapies. Abortive therapy consists of NSAIDs and triptans. Preventative therapies include tricyclic antidepressants, calcium channel blockers, beta-blockers, and anticonvulsants. In this review, we focus on the role of NSAIDs and the COX-2 inhibitor, celecoxib oral solution, for the abortive treatment of acute migraines.