Intrauterine SARS-CoV-2 infection – a case confirming transplacental transmission followed by divergence of the viral genome

Abstract

Pregnant women and their newborns may be at particular risk for poor outcomes due to the coronavirus (COVID-19) pandemic. Intrauterine SARS-CoV-2 transmission has been suggested but most reports have not ruled out postpartum infection. We demonstrate a confirmed case of transplacental transmission of SARS-CoV-2 in a neonate born to a mother infected in the third trimester. Comprehensive virological, pathological and genetic investigations establish that intrauterine SARS-CoV-2 transmission occurred via the following chain of events; I) maternal viremia in a seemingly mildly symptomatic patient, II) high viral load in the placenta with massive perivillous fibrin deposition, acute intervillositis in areas with strong positivity for SARS-CoV-2 and chorangiosis in the areas less affected by infection and inflammation, III) intrauterine fetal distress with pathological cardiotocography and acidemia in validated umbilical cord blood gases and IV) mild neonatal COVID-19. Whole genome sequencing of isolates from the mother and placenta revealed a single variant of the virus. Interestingly, the neonate displayed a mixed SARS-CoV-2 population, harboring both an identical strain to the mother as well as a population with one single-nucleotide polymorphism difference, indicating intrapatient genetic drift.