COVID-19 vaccination protects infected pregnant women from developing SARS-CoV-2 placentitis and decreases the risk for stillbirth

Introduction: The impact of COVID-19 infection in pregnant women remained unclear for a long time. Previous research showed that SARS-CoV-2 virus is able to infect the placenta, potentially causing significant lesions leading to placental insufficiency. The impact of maternal vaccination status on the prevalence of SARS-CoV-2 placentitis remains unclear. We characterized placental lesions in SARS-CoV-2 infected pregnant women and studied the impact of vaccination on placental involvement. Methods: We retrospectively studied 180 placentas sent to the Department of Pathology in UZ Leuven or AZ Turnhout between January 2020 and August 2022, from non-vaccinated and vaccinated mothers suffering a SARS-CoV-2 proven infection during pregnancy. All reports and hematoxylin-eosin stained sections were revised by two pathologists to determine the presence of histopathological lesions that have been described in SARSCoV-2 infection. SARS-CoV-2 immunostainings were available for a subgroup of 109 placentas. We gathered clinical data: date of delivery, date of positive serologic test result, vaccination status, SARS-CoV-2 variant and outcome of the pregnancy. Results: Of the 180 placentas, 37,2% showed histopathological lesions and in 12,8% an immunohistochemically proven SARS-CoV-2 placentitis was present. SARS-CoV-2 immunohistochemical positivity was only seen in nonvaccinated mothers. The risk of fetal demise was more than 5 times higher for non-vaccinated mothers and their placentas showed significantly more syncytiotrophoblast necrosis and chronic histiocytic intervillositis compared to vaccinated mothers (both p < 0,001). Discussion: Maternal vaccination was associated with a reduced risk of SARS-CoV-2 placentitis and stillbirth. This study provides new evidence of the protective effect of vaccination on the placenta.