# Maternal infection with SARS‐CoV‐2 during early pregnancy induces hypoxia at the maternal–fetal interface

## TL;DR

Early pregnancy SARS-CoV-2 infection causes hypoxia and metabolic changes at the maternal-fetal interface, which may affect fetal development.

## Contribution

This study reveals how SARS-CoV-2 infection in early pregnancy induces hypoxia and alters cell metabolism at the maternal-fetal interface.

## Key findings

- SARS-CoV-2 infection in the first trimester increases hypoxia inducible factor (HIF) levels at the maternal-fetal interface.
- Immune cells show low HIF expression, possibly linked to immune activation.
- Metabolic and transcriptome changes decrease as pregnancy progresses beyond 12–16 weeks.

## Abstract

The coronavirus disease 2019 (COVID‐19) pandemic increases the risk of adverse fetal outcomes during pregnancy. Maternal infection during pregnancy, particularly with cytomegalovirus (CMV), hepatitis B and C virus, and human immunodeficiency virus can have detrimental effects on both mother and fetus, potentially leading to adverse outcomes such as spontaneous abortion or neonatal infection. However, the impact of severe acute respiratory syndrome coronavirus (SARS‐CoV‐2) infection on the maternal–fetal interface remains poorly understood. In this study, we initially utilised immunofluorescence and immunohistochemical to investigate placental samples from pregnant women who were infected with SARS‐CoV‐2 during the first trimester. Our data indicate that infection in the first trimester induces an upregulation of hypoxia inducible factor (HIF) levels at the maternal–fetal interface. Subsequently, single‐cell RNA sequencing and metabolomics sequencing analyses reveal alterations in maternal–fetal interface. Remarkably, immune cells exhibited low expression levels of HIF possibly associated with immune activation. Furthermore, our findings demonstrate a gradual reduction in transcriptome and metabolic changes as gestation progressed beyond 12–16 weeks compared to samples obtained at 6–8 weeks gestation. Overall, our study suggests that early‐stage SARS‐CoV‐2 infection during the first trimester leads to severe hypoxia and aberrant cell metabolism at the maternal–fetal interface which gradually resolves as pregnancy progresses. Nevertheless, these abnormal changes may have long‐term implications for maternal–fetal interface development.

Severe acute respiratory syndrome coronavirus (SARS‐CoV‐2) infection can cause hypoxia at the maternal–fetal interface in the first trimester, resulting in differential gene expression in different cells and metabolic abnormalities, which are weakened but persist in the second trimester.