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. 2022 Aug 3;19(15):9517.
doi: 10.3390/ijerph19159517.

SARS-CoV-2 Infection in Pregnancy: Placental Histomorphological Patterns, Disease Severity and Perinatal Outcomes

Yin Ping Wong  1 , Geok Chin Tan  1 , Siti Zarqah Omar  2 , Muaatamarulain Mustangin  1 , Yogesh Singh  3   4 , Madhuri S Salker  4 , Nor Haslinda Abd Aziz  5 , Mohamad Nasir Shafiee  5
Affiliations

SARS-CoV-2 Infection in Pregnancy: Placental Histomorphological Patterns, Disease Severity and Perinatal Outcomes

Yin Ping Wong et al. Int J Environ Res Public Health. .

Abstract

The association between maternal COVID-19 infection, placental histomorphology and perinatal outcomes is uncertain. The published studies on how placental structure is affected after SARS-CoV-2 virus in COVID-19-infected pregnant women are lacking. We investigated the effects of maternal SARS-CoV-2 infection on placental histomorphology and pregnancy outcomes. A retrospective cohort study on 47 pregnant women with confirmed SARS-CoV-2 infection, matched with non-infected controls, was conducted. Relevant clinicopathological data and primary birth outcomes were recorded. Histomorphology and SARS-CoV-2 immunohistochemistry analyses of placental tissues were performed. Only 1 of 47 cases showed SARS-CoV-2 immunoreactivity in the syncytiotrophoblasts. Histologically, decidual vasculopathy (n = 22/47, p = 0.004), maternal vascular thrombosis (n = 9/47, p = 0.015) and chronic histiocytic intervillositis (n = 10/47, p = 0.027) were significantly higher in the COVID-19-infected placentas when compared to the control group. Maternal vascular thrombosis was a significant feature in the active COVID-19 group. A significant lower gestational age (p < 0.001)) at delivery and a higher caesarean section rate (p = 0.007) were observed in the active SARS-CoV-2-infected cases, resulting in a significant lower fetal-placental weight ratio (p = 0.022) and poorer Apgar score (p < 0.001). Notably, active (p = 0.027), symptomatic (p = 0.039), severe-critical (p = 0.002) maternal COVID-19 infection and placental inflammation (p = 0.011) were associated with an increased risk of preterm delivery. Altered placental villous maturation and severe-critical maternal COVID-19 infection were associated with an elevated risk of poor Apgar scores at birth (p = 0.018) and maternal mortality (p = 0.023), respectively.

Keywords: COVID-19; SARS-CoV-2; histomorphology; maternal death; neonatal outcomes; placenta; pregnancy.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Histological characteristics of SARS-CoV-2-infected placentas (n = 47).
Figure 2
Figure 2
Histopathological features of placentas in SARS-CoV-2 infected patients. (A) Maternal arteriole with atherosis (H&E ×100). (B) Tenney Parker changes: increase in syncytial knotting in a 32-week placenta (H&E ×200). (C) Chronic villitis/villitis of unknown aetiology (H&E ×200). (D) Chronic histiocytic intervillositis (H&E ×200) with (E) immunohistochemistry with CD68 highlighting the presence of histiocytes within the intervillous space (CD68, ×200) and (F) immunohistochemistry with SARS-CoV-2 spike protein demonstrating the presence of viral protein within cytoplasms of syncytiotrophoblasts (SARS-CoV-2, ×400).
Figure 3
Figure 3
Forest plot showing adjusted logistic regression model to assess the association between maternal COVID-19 status and histopathological features with adverse maternal and neonatal outcomes, i.e., maternal death, poor Apgar scores and preterm delivery. Odds ratio (OR) and 95% confidence intervals (CI) are depicted. * statistically significant; ** adjusted for maternal age and comorbid.
See this image and copyright information in PMC

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