Abstract

Background
Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent physiological and immunological abnormalities following acute coronavirus disease 2019. Although systemic effects of long COVID are increasingly recognized, its potential impact on placental biology and the maternal–fetal interface remains insufficiently understood. Given the placenta’s central role in immune regulation, vascular homeostasis, and fetal development, sustained post-viral disturbances may have important implications for pregnancy outcomes.

Methods
A narrative synthesis of the literature was conducted using PubMed/MEDLINE, Scopus, EMBASE, and Web of Science. Publications from January 2020 to June 2025 were screened using combinations of keywords including “long COVID,” “post-acute sequelae of SARS-CoV-2,” “placenta,” “maternal–fetal interface,” “epigenetics,” and “immune dysregulation.” Relevant experimental, translational, and clinical studies examining molecular mechanisms linking SARS-CoV-2 infection with placental dysfunction were included.

Results
Emerging evidence indicates that long COVID may affect placental physiology through several interacting mechanisms. These include persistence of viral components within tissues, chronic immune activation with sustained cytokine signaling, endothelial dysfunction affecting placental perfusion, and metabolic alterations linked to mitochondrial stress. In parallel, maternal infection may induce epigenetic modifications such as altered DNA methylation, histone remodeling, and dysregulation of non-coding RNAs. These molecular disturbances may compromise trophoblast function and placental vascular integrity, potentially contributing to complications including preeclampsia, fetal growth restriction, and preterm birth.

Conclusions
Long COVID may exert sustained molecular effects on the placenta, with potential consequences for maternal and fetal health. Further longitudinal and mechanistic studies are required to clarify causality, persistence of these alterations, and their clinical significance.