Placental Pathology Findings during and after SARS-CoV-2 Infection: Features of Villitis and Malperfusion

Abstract

Since the outbreak of coronavirus disease 2019 (COVID-19), there has been a debate whether pregnant women are at a specific risk for COVID-19 and whether it might be vertically transmittable through the placenta. We present a series of five placentas of SARS coronavirus 2 (SARS-CoV-2)-positive women who had been diagnosed with mild symptoms of COVID-19 or had been asymptomatic before birth. We provide a detailed histopathologic description of morphological changes accompanied by an analysis of presence of SARS-CoV-2 in the placental tissue. All placentas were term deliveries (40th and 41st gestational weeks). One SARS-CoV-2-positive patient presented with cough and dyspnoea. This placenta showed prominent lymphohistiocytic villitis and intervillositis and signs of maternal and foetal malperfusion. Viral RNA was present in both placenta tissue and the umbilical cord and could be visualized by in situ hybridization in the decidua. SARS-CoV-2 tests were negative at the time of delivery of 3/5 women, and their placentas did not show increased inflammatory infiltrates. Signs of maternal and/or foetal malperfusion were present in 100% and 40% of cases, respectively. There was no transplacental transmission to the infants. In our cohort, we can document different time points regarding SARS-CoV-2 infection. In acute COVID-19, prominent lymphohistiocytic villitis may occur and might potentially be attributable to SARS-CoV-2 infection of the placenta. Furthermore, there are histopathological signs of maternal and foetal malperfusion, which might have a relationship to an altered coagulative or microangiopathic state induced by SARS-CoV-2, yet this cannot be proven considering a plethora of confounding factors.

Keywords: COVID-19; Chronic villitis; Malperfusion; Placenta.

Fig. 1

Findings of the placenta with manifest COVID-19. a Macroscopic image showing inhomogeneous and unusually condensed placental parenchyma and an area of infarction (arrow). b Chronic villitis and intervillositis (haematoxylin and eosin [H&E], 40×). c, d Characterisation of the inflammatory infiltrate consisting primarily of cytotoxic T-cells expressing CD8 (c) and fewer macrophages expressing CD68 (d) (immunohistochemistry, 200×). e, f Lymphohistiocytic villitis resulting in chorionic vasculitis and subsequent fresh (e) and already organizing thrombosis (f) (H&E, 100×). g Intervillous increase of fibrin as result of maternal malperfusion (H&E, 100×). h Presence of SARS-CoV-2 in decidual cells (red) (in situ hybridization for SARS-CoV-2, 200×).

Fig. 2

Findings of placentas with no presence of SARS-CoV-2 at the time of delivery and expression of ACE2. a Features of subtle chronic villitis in patient 5 showing acute chorioamnionitis as major finding. The lymphohistiocytic infiltrate was sparse in contrast to patient 2 (H&E, 100×). b Decidual arteriopathy in patient 1: decidual artery showing complete necrosis of the arterial wall and intraluminal fibrosis. The patient did not show evidence of preeclampsia or gestation-related hypertension. c Foetal vessel in patient 1 showing a small thrombus. In contrast to patient 2, the thrombus was not wall-adherent and there were no signs of vasculitis (H&E, 200×). c, d Immunohistochemistry for ACE2 showing weak expression in the extravillous invasive trophoblast (immunohistochemistry, 40×).