Potential molecular and cellular mechanisms for adverse placental outcomes in pregnancies complicated by SARS-CoV-2 infection—A scoping review

BACKGROUND: Emerging evidence suggests that SARS-CoV-2 infection during pregnancy can result in placental damage and poor placental outcomes. However, the mechanisms by which SARS-CoV-2 infection leads to placental damage are not well understood. With a rapid expansion of literature on this topic, it is critical to assess the quality and synthesize the current state of literature. The objective of this scoping review is to highlight underlying mechanisms of SARS-CoV-2 mediated placental pathology in pregnant individuals and identify literature gaps regarding molecular and cellular mechanisms of poor placental outcomes. METHODS: The review was conducted and reported following the recommendations of the PRISMA extension for Scoping Reviews. The study protocol was registered with Open Science Framework (https://osf.io/p563s/). Five databases (MEDLINE, EMBASE, Scopus, CINAHL, PubMed) were searched for studies published between September 2019 until April 2022. Studies assessing placental outcomes with respect to SARS-CoV-2 infection in pregnancy were eligible for inclusion. Outcomes of interest included histopathology, and molecular or cellular analysis. All records were uploaded into Covidence and extracted using the Joanna Briggs Institute method. Studies were assessed for risk of bias using the Newcastle Ottawa scale and a narrative synthesis of results was generated. RESULTS: Twenty-seven studies reporting on molecular and/or cellular mechanisms of SARS-CoV-2 mediated placental outcomes were included in this review. SARS-CoV-2 infection was associated with perturbations in the ACE2 pathway, inflammatory mediators and immune cell populations and mitochondrial function in placentas. CONCLUSIONS: Our findings suggest that changes in the ACE2 pathway, mitochondrial dysfunction, and/or inflammatory processes may lead to placental damage observed in SARS-CoV-2 infection during pregnancy. More research is needed to understand the role of these pathways further, in addition to data collection related to trimester, severity, and strain.