Adverse Fetal Outcomes and Histopathology of Placentas Affected by COVID-19: A Report of Four Cases.

Coronavirus disease 2019 (COVID-19) has had significant impacts on mothers and neonates. In this report, we present four unique cases of COVID-19 infections in pregnancy and its effects on the mother, fetus, and placenta. Four mothers presented to the hospital during their pregnancy. Each had tested COVID-19-positive 1-29 days prior to admission. Gestational age ranged from 16 weeks six days to 36 weeks six days. Three of the four cases resulted in fetal demise or infant expiration. The common finding among all four cases was pathologic changes in the placenta. Most of the placentas were small for gestational age and had extensive villous infarction. There was also histiocytic intervillositis with villous necrosis and perivillous fibrin deposition. The placentas demonstrated positive staining of syncytiotrophoblasts for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike S1 subunit protein. SARS-CoV-2 RNA was detected in tissue samples of two of the fetuses demonstrating vertical transmission. A higher incidence of severe COVID-19 disease course has been observed in pregnant women. Prior to the SARS-CoV-2 pandemic, chorionic histiocytic intervillositis of the placenta was rarely seen, and mostly of unknown etiology. The increase in placental fibrin levels results in decreased maternal placenta blood flow ensuing hypoxic stress in the fetus. Intrauterine hypoxia has been associated with alterations in brain structure and function resulting in defects in motor skills, cerebral palsy, decreased brain weight, schizophrenia, and other forms of cognitive impairment.