Placental localization of SARS-CoV-2 in low-risk paucisymptomatic woman affected by COVID-19

INTRODUCTION We report a case of stillbirth in a 33-years-old Caucasian woman at 36+1 weeks of gestation (WG), with a positive nasopharyngeal swab (NFS) for COVID-19 and preterm labor in the absence of vertical transmission. METHODS Histologic examination of the placenta was performed after fixation in 10% buffered formalin. The fetal and placental samples underwent routine processing with paraffin embedding, and staining with hematoxylin and eosin for microscopic morphological evaluation. Additional maternal surface samples were later additionally fixed in 2.5% glutaraldehyde in 1X PBS pH 7.4, and processed for examination by transmission electron microscopy Paraffin embedded placental tissue sections were used for immunohistochemical staining with anti-platelets CD61 antibody and anti SARS-CoV Spike Antibody Viral infection of the placenta was assessed by the presence of SARS-CoV-2 RNA by real time RT-PCR assay. Swabs were obtained from fetal right and left main bronchus, small intestine and rectum to detect SARS-CoV-2 RNA by RT-PCR assay. RESULTS Sectioning and examination of the cut placental surface showed a diffuse marbled appearance and a focal hemorrhagic area. At light microscope, the placental tissue showed multiple areas of hemorrhagic/ischemic necrosis and thrombosis of several maternal and fetal vessels with mural/ luminal fibrin and platelet deposition defining a clear picture of fetal vascular malperfusion.SARS-CoV-2 RNA in placental tissue was revealed by real time rRT-PCR assay. Virus particles were uniquely identified by Electron Microscopy mainly within the cytoplasm of endothelial cells, in the cytosol and in cytoplasmic vacuoles, or adjacent to damaged endothelial cells. CONCLUSIONS In our case, fetal vascular malperfusion was likely casually associated with the infection;indeed, our unique Electron Microscopy images clearly showed that the marked SARS-CoV-2 endotheliotropism involved the intravillous fetal capillaries likely leading to cell dysfunction and procoagulant activity. Since placental infection does not always correlate with infection of the fetus, it is possible that a time interval may ensue between these two processes;a stillbirth that occurs in this time frame can be mechanistically explained by an overriding process of severe endothelial dysfunction occurring within intravillous capillaries or massive hypoperfusion of the intervillous space. The consequences of placentotropic COVID-19 include the possible occurrences of vertical transmission or fetal death resulting from maternal and/or fetal placental hypoperfusion the prevailing mechanism being dependent by unknown determinants. The diffuse thrombosis and subsequent ischemia of fetal capillaries induced by COVID-19 cannot be predicted by standard clinical surveillance nor prevented by anticoagulants and represent a severe burden of Sars-Cov-2 infection.