Placental lesions and SARS-Cov-2 infection: Diffuse placenta damage associated to poor fetal outcome

Abstract

Introduction: Pregnant women with covid-19 are more likely to experience preterm birth. The virus seems to be associated with a wide range of placental lesions, none of them specific.

Method: We collected cases of Covid-19 maternal infection during pregnancy associated with poor pregnancy outcomes, for which we received the placenta. We studied clinical data and described pathological findings of placenta and post-mortem examination of fetuses. We performed an immunohistochemical study and RT-PCR of SARS-Cov-2 on placenta samples.

Results: We report 5 cases of poor fetal outcome, 3 fetal deaths and 2 extreme premature neonates, one with growth restriction, without clinical and biological sign of SARS-Cov-2 infection. All placenta presented massive perivillous fibrin deposition and large intervillous thrombi associated with strong SARS-Cov-2 expression in trophoblast and SARS-CoV-2 PCR positivity in amniotic fluid or on placenta samples. Chronic histiocytic intervillositis was present in 4/5 cases. Placental ultrasound was abnormal and the sFLT1-PIGF ratio was increased in one case. Timing between mothers' infection and the poor fetal outcome was ≤10 days in 4 cases. The massive placental damage are directly induced by the virus whose receptors are expressed on trophoblast, leading to trophoblast necrosis and massive inflammation in villous chamber, in a similar way it occurs in diffuse alveolar damage in adults infected by SARS-Cov-2.

Discussion: SARS-Cov-2 can be associated to a rare set of placental lesions which can lead to fetal demise, preterm birth, or growth restriction. Stronger surveillance of mothers infected by SARS-Cov-2 is required.

Keywords: COVID-19; Fetal demise; Histopathology; Placenta; Prenatal ultrasounds; SARS-Cov-2; sFLT1/PIGF.

Fig. 1

Prenatal ultrasounds and gross features of placenta (case 5): A: prenatal ultrasounds at 26 GW: hypoechoic lacunae (red arrows) B: prenatal ultrasounds at 26 GW: coexistence of hyperechoic lesion (green arrows) and hypoechoic lesion (red arrows) suggestive of calcification and infarction respectively. Blue circle: Fetus C: gross features on cut sections after formalin fixation: whitish mottled net-like appearance involving at least 80% of parenchyma suggestive of massive fibrin deposition D: gross features on cut sections after formalin fixation: same anomalies on higher magnification.

Fig. 2

Microscopic features of the placenta on HES (Hematoxylin Eosin Saffron) A & B: x 5: 2 different cut sections showing large intervillous thrombi (black arrows) C: x 200: MPFD with trophoblast necrosis (black arrow), fibrin deposits (green arrow) along with CHI (blue arrow).

Fig. 3

Immunohistochemical study A: CD68 antibody x 80: numerous histiocytes in the intervillous chamber B: CD3 antibody x 80: numerous lymphocytes inside or adjacent to the trophoblast.

Fig. 4

Immunohistochemical study of Sars-Cov2 on placenta A: case 2 (34+5 GW) x 25: diffuse and strong expression on trophoblast B: negative control x 25: placenta from annon-infected mother at 34 GW: no expression on trophoblast C: case 4 × 200 (22 +4 GW): diffuse and strong expression on trophoblast D: negative control x 200: placenta from a non-infected mother at 22 GW: no expression on trophoblast.