COVID-19 and pregnancy: clinical outcomes; mechanisms, and vaccine efficacy

Abstract

As the COVID-19 pandemic continues into its third year, emerging data indicates increased risks associated with SARS-CoV-2 infection during pregnancy, including pre-eclampsia, intrauterine growth restriction, preterm birth, stillbirth, and risk of developmental defects in neonates. Here, we review clinical reports to date that address different COVID-19 pregnancy complications. We also document placental pathologies induced by SARS-CoV-2 infection, entry mechanisms in placental cells, and immune responses at the maternal-fetal interface. Since new variants of SARS-CoV-2 are emerging with characteristics of higher transmissibility and more effective immune escape strategies, we also briefly highlight the genomic and proteomic features of SARS-CoV-2 investigated to date. Vector and mRNA-based COVID-19 vaccines continue to be rolled out globally. However, because pregnant individuals were not included in the vaccine clinical trials, some pregnant individuals have safety concerns and are hesitant to take these vaccines. We describe the recent studies that have addressed the effectiveness and safety of the current vaccines during pregnancy. This review also sheds light on important areas that need to be carefully or more fully considered with respect to understanding SARS-CoV-2 disease mechanisms of concern during pregnancy.

Fig 1

Schematic organization of SARS-CoV-2 genome and proteome. SARS-CoV-2 possesses a positive-sense single-stranded RNA (ssRNA) genome of nearly 30kb in size. The ssRNA is translated into a polypeptide which is further cleaved by viral proteases into individual proteins. ORF1a and ORF1b encode nonstructural proteins (nsp1-nsp16), the other ORFs encode structural proteins spike (S), membrane (M), envelope (E), and nucleocapsid (N). Accessory proteins are also encoded in the genome such as: ORF3, ORF6, ORF7, ORF8, and ORF10. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig 2

Schematic representation of different compartments of the placenta colonized with SARS-CoV-2. The placenta comprises different types of cells that form a strong physiological and immune barrier around the fetus. The outer trophoblast layer is a physical barrier divided into 2 layers: the inner cytotrophoblasts (purple) lining the basement membrane and outer multi nucleated (blue color lined with black solid line) syncytiotrophoblasts (STBs). The decidua is the maternal part containing blood vessels and different types of cells such as mesenchymal stem cells and decidual natural killer cells (dNKs). The intervillous space is filled with maternal blood. Based upon multiple studies, SARS-CoV-2 was shown to colonize mainly in STBs, extravillous trophoblasts (EVTs), cytotrophoblasts maternal decidua and fetal macrophages (Hofbauer cells). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)