962 Miami mother-baby COVID collaborative: a prospective study linking circulating factors, placental findings and pregnancy complications

Abstract

A hallmark of SARS-CoV2 (SV) infection is systemic proinflammation. We hypothesize that in pregnancy, the maternal response to viral infection leads to a local proinflammatory, antiangiogenic, prothrombotic milieu at the maternal fetal interphase, contributing to placental lesions and leading to placenta mediated complications (PMC). We developed and measured a customized array of cytokine, chemokine, anti-angiogenic, vascular, oxidative stress and apoptotic markers from patients enrolled in the Miami Mother Baby Covid Collaborative (MMBCC), a prospective perinatal sample collection study, offered to all women delivering at a large urban hospital in Miami, FL between 04/20/20 & 07/31/20. Maternal serum concentrations from randomly selected SV+ patients (Group [G] 1), healthy SV- (G2) & G1’s umbilical cord plasma (G3) were analyzed by LuminexTM multiplex assay system. An expert perinatal pathologist graded placentas (Amsterdam Placental Workshop Group criteria). Mean serum concentrations of proinflammatory markers were higher in G1 vs G2: IL-1(P=.02), IL-6 (P=.03), IL-8 (P=.001), IL-12 (P=.03), IL-17 (P=.01), IFNγ (P=.01), IP-10 (P=.001), MIP-1α (P=.03), MIP-1β (P=.001), but not TNFα (P=.10). See Table 1. Interestingly, all G1 patients with elevated serum IL-6 concentrations (cutoff 4.455 pg/ml, AUC 0.7955) exhibited placental fetal vascular malperfusion (FVM). FVM was identified in al G3 samples with an elevated MCP-1 (cutoff: 45.22 pg/ml, AUC: 0.6591). Maternal age, BMI, & ethnicity were similar, while delivery gestational age, birthweight & preeclampsia were borderline different between G1 & G2 (P=.08). See Table 2. For the first time, we report that elevated antepartum maternal concentrations of IL-6 predict FVM. FVM is also highly correlated with cord blood levels of MCP-1. Trends in cytokine/chemokine patterns in the setting of SV+ infection appear to be distinct in the maternal versus fetal circulation, and both are linked to specific placental defects, especially FVM, which has been linked to fetal growth restriction and fetal central nervous system injury.View Large Image Figure ViewerDownload Hi-res image Download (PPT)