Pandemic stress and SARS-CoV-2 infection are associated with pathological changes at the maternal-fetal interface

Abstract

Introduction: The reported effects of SARS-CoV-2 on pregnancy outcomes are conflicting; studies frequently overlook the placenta, which is critical for the health of the mother and infant(s). This study aimed to determine the effect of pandemic stress ± SARS CoV-2 infection on placental histopathology.

Methods: Women were recruited in Canada (n = 69); France (n = 21) or in the UK (n = 25), between March and October 2020. Historic controls (N = 20) were also included. Placenta and fetal membrane samples were collected rapidly after delivery and were fixed and stained for histopathological analysis. Maternal demographical data and obstetric outcomes were recorded.

Results: Over 80% of the placentas from SARS-CoV-2+ pregnancies had histopathological abnormalities: predominantly structural (71-86%) or inflammatory (9-22%), depending on geographical location. Excessive fibrin was seen in all sites, whereas deciduitis (Canada), calcifications (UK), agglutinations and chorangiosis (France) predominated in different locations. The frequency of abnormalities was significantly higher than in SARS-CoV-2 negative women (50%, p < 0.05). Demographic and obstetric data were similar in the SARS-CoV-2+ women across all sites - characterised by predominantly Black/Middle Eastern women, and women with elevated body mass index.

Discussion: Overall, the frequency of placental abnormalities is increased in SARS-CoV-2+ women, but the incidence of placental abnormalities is also higher in SARS-CoV-2- women that gave birth during the pandemic, which highlights the importance of appropriate control groups to ascertain the roles of pandemic stress and SARS-CoV-2 infection on the placenta and pregnancy outcomes.

Keywords: Coronavirus disease 2019 (COVID-19); Infection; Pandemic stress; Placenta; Pregnancy; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Fig. 1

Example of placental abnormalities observed in placentas from SARS-CoV-2+ pregnancies. Representative images of normal histopathology (A, D, G). The predominant abnormalities observed in the Canada cohort were accelerated villous maturation (B) and deciduitis (C); in the UK cohort, calcifications (E) and excess fibrin (F); whilst in the France cohort excess syncytial knots (H) and chorangiosis (I) were observed. Hematoxylin-eosine staining. Scale bar in A, B, D, E, F are 500 μm and higher magnification 100 μm. Scale bar in C: 200 μm and higher magnification 100 μm.

Fig. 2

Placental lesions distribution across all sites. Graphical representation of the lesion distribution in Canada (A), UK (B) and France (C) showing the overlapping presentation of structural and inflammatory defects and the percentage of each subtype of structural defect. Cong: congestive; Calc: calcification; Chor: chorangiosis; FVM: fetal vascular malperfusion; MVM: maternal vascular malperfusion.