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Maternal immune profiles of abnormal prenatal ultrasonographic findings following SARS-CoV-2 infection

      Objective

      Changes in maternal immunity following infections may lead to adverse maternal and neonatal outcomes, but data on the immunological consequences following SARS-CoV-2 infection in pregnancy is limited. This study evaluates the correlation of COVID19-induced alteration of maternal immunity with prenatal ultrasonographic abnormalities.

      Study Design

      A prospective observational cohort study conducted at a single tertiary care center of pregnant women diagnosed with SARS-CoV-2 by reverse-transcription polymerase chain reaction between March 2020 and February 2021. Maternal serum specimens were collected at initial diagnosis, and patients underwent serial prenatal ultrasonography following diagnosis of infection. Isolated sera were subjected to high-throughput Next Generation Sequencing-based proteomics multiplexing to detect over 1400 cytokines and serum proteins. The sera proteome profiles of SARS-CoV-2 positive pregnancies with abnormal ultrasounds were compared to those of gestational age-matched healthy controls.

      Results

      Of 72 SARS-CoV-2 positive mother-infant dyads, 28 (38.9%) had a prenatal ultrasonographic abnormality. The most common findings were placentomegaly (PM, n=17) and fetal growth restriction (FGR, n=8). When compared to healthy pregnant controls (n=17), SARS-CoV-2 positive pregnancies with abnormal ultrasound findings had distinct highly inflammatory immune profiles. 182 and 41 cytokines were significantly altered (p < 0.05, -2 < fold change > 2) in COVID19-affected pregnancies with PM and FGR, respectively. Four common serum proteins (ERBB4, TGFBR3, NCAM1, PLA2G7) were altered for both ultrasonographic abnormalities but demonstrated inverse responses with a downregulation in PM and an upregulation in FGR.

      Conclusion

      SARS-CoV-2 infected pregnancies that develop PM or FGR have distinct immune profiles consistent with a pronounced inflammatory response, providing insight into the pathogenesis of COVID19 and changes in maternal immunity following infection. The altered cytokines may serve as potential biomarkers to predict perinatal complications after SARS-CoV-2 infection in pregnancy.
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