SARS-COV2 placentitis and pregnancy outcome: A multicentre experience during the Alpha and early Delta waves of coronavirus pandemic in England

Abstract

Background: Pregnant women with SARS-CoV-2 infection experience higher rates of stillbirth and preterm birth. A unique pattern of chronic histiocytic intervillositis (CHI) and/or massive perivillous fibrin deposition (MPFD) has emerged, coined as SARS-CoV-2 placentitis.

Methods: The aim of this study was to describe a cohort of placentas diagnosed with SARS-CoV-2 placentitis during October 2020-March 2021. Cases with a histological diagnosis of SARS-CoV-2 placentitis and confirmatory immunohistochemistry were reported. Maternal demographic data, pregnancy outcomes and placental findings were collected.

Findings: 59 mothers delivered 61 infants with SARS-CoV-2 placentitis. The gestational age ranged from 19 to 41 weeks with most cases (78.6%) being third trimester. 30 infants (49.1%) were stillborn or late miscarriages. Obese mothers had higher rates of pregnancy loss when compared with those with a BMI <30 [67% (10/15) versus 41% (14/34)]. 47/59 (79^.7%) mothers had a positive SARS-CoV-2 PCR test either at the time of labour or in the months before, of which 12 (25^.5%) were reported to be asymptomatic. Ten reported only CHI, two cases showed MPFD only and in 48 placentas both CHI and MPFD was described.

Interpretation: SARS-CoV2 placentitis is a distinct entity associated with increased risk of pregnancy loss, particularly in the third trimester. Women can be completely asymptomatic and still experience severe placentitis. Unlike 'classical' MPFD, placentas with SARS-CoV-2 are generally normal in size with adequate fetoplacental weight ratios. Further work should establish the significance of the timing of maternal SARS-CoV-2 infection and placentitis, the significance of SARS-CoV2 variants, and rates of vertical transmission associated with this pattern of placental inflammation.

Funding: There was not funding associated with this study.

Keywords: COVID-19; Chronic histiocytic intervillositis; Massive perivillous fibrin deposition; Placentitis; SARS-CoV2; Stillbirth.

Figure 1

Macroscopic image of term placenta, serially sectioned, showing extensive fibrin deposition throughout the parcenchyma.

Figure 2

Haematoxylin and eosin stained section at x 200 magnification showing a placenta affected by an inflammatory cell infiltrates within the intervillous space with necrosis of the trophoblast and perivillous fibrin deposition.

Figure 3

Haematoxylin and eosin stained section at x 400 magnification showing trophoblast necrosis characterised by ‘smudging’ of the nuclei and karyorrhectic debris within the intervillous space.

Figure 4

Immunohistochemical staining of placental parenchyma with SARS-CoV2 immunohistochemical stain (x200 magnification) with expression in the syncytiotrophoblast.

Figure 5

High magnification electron microscopy image of formalin fixed paraffin processed trophoblast cytoplasm showing possible Covid19 virion budding into endoplasmic reticulum (at 3 o'clock) and a couple of vacuoles containing 3 and 2 possible complete virus particles (at 7 o'clock and 11 o'clock). The spherical virus particles contain black dots, which are cross-sections through the viral nucleocapsid (as shown within rectangles).

Figure 6

High magnification electron microscopy image of formalin fixed paraffin processed possible multiple Covid19 virions in apex of cytotrophoblast cell within vacuoles (as shown within rectangle).

Figure 7

High magnification electron microscopy image of formalin fixed paraffin processed possible multiple Covid19 virions in perivillous fibrin lying free and within a vacuole (at 10 o'clock) (as shown within rectangle).