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Placental findings in SARS-CoV-2 maternal infection by severity and timing of maternal disease

      Objective

      To determine if maternal SARS-CoV-2 infection is associated with patterns of placental injury and whether these findings differ by gestational age (GA) at time of infection or disease severity.

      Study Design

      A retrospective cohort study was performed at UC San Diego between 03/2020 to 02/2021. Placentas from pregnancies with a positive SARS-CoV-2 test were matched to two SARS-CoV-2 negative controls, based on delivery date. Control placentas were sent to pathology for routine clinical indications. Placental pathologic lesions were defined based on standard criteria and included maternal and fetal malperfusion, chronic villitis (CV), chorioamnionitis, fibrin deposition, villous edema and chorangiosis. CV was deemed severe when associated with avascular villi or perivillous fibrin. Bivariate analysis was performed with independent Student’s T test and Pearson’s chi-square. Logistic regression was used to control for relevant covariates.

      Results

      We included 133 SARS-CoV-2 positive cases and 266 controls. Maternal age was greater (31.2 vs 29.7 years, p=0.01) and GA at delivery was lower (37.3 vs 38.7 weeks, < 0.001) in the control group. There was higher rate of preterm delivery and hypertensive complications in the control group (Table 1). CV, severe CV, patchy villous edema and chorangiosis were more common in the SARS-CoV-2 group (Table 2) CV and severe CV remained significant after controlling for GA at delivery (aOR = 1.99, p = 0.006; aOR= 2.98, p< 0.001). When compared by disease severity, chorangiosis was more common in moderate-severe SARS-CoV-2 infections than mild/asymptomatic infections (52.9% vs 26.1%, p=0.04); other histopathologic findings did not differ by GA at time of infection or disease severity.

      Conclusion

      CV, patchy villous edema, and chorangiosis were more common in patients with infected with SARS-CoV-2 during pregnancy. The latter two findings are associated with abnormal fetal blood flow, while CV is consistent with maternal T cell-based immune response, suggesting potential mechanisms of placental (and thus neonatal) injury, even in the absence of vertical transmission.
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