A new study by researchers from Elson S. Floyd College of Medicine, Washington State University-USA, the Department of Obstetrics and Gynecology, University of Washington-USA and the Department of Women and Newborn Research, Intermountain Health Care-Utah-USA has found that SARS-CoV-2 infections impairs the antiviral innate immune gene expression in the human placenta.
The study findings were published in the peer reviewed American Journal of Obstetrics & Gynecology.
https://www.ajog.org/article/S0002-9378(22)00747-5/fulltext
Pregnant women who become infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more susceptible to hospitalization, critical illness, and numerous adverse perinatal complications (e.g., stillbirth, preeclampsia, preterm birth) and are associated with a higher likelihood of requiring ICU admission and mechanical ventilation as well as higher mortality rates.1-10
Expression of these canonical receptors is increased, however, in syncytiotrophoblast cells from third trimester placentas of pregnant women with severe COVID-19 disease.16, 19-22 Numerous case series indicate that vertical transmission of SARS-CoV-2 to the fetus is low.9, 20, 23 How the placenta responds to a SARS-CoV-2 infection in pregnancy is unclear; an antiviral immune response has significant implications for both placental and fetal health.
Antiviral innate immunity primarily relies upon the synthesis and secretion of type I interferons (IFN), such as IFN-α and IFN-β, which further stimulate the production of hundreds to thousands of IFN stimulated genes, cytokines, and chemokines.24 SARS- CoV-2 is known to evade antiviral innate immunity through impairing placental innate immunity and gene expression during an acute infection.
Viral non-structural protein 1 (Nsp1) and open reading frame 6 (ORF6) inhibit phosphorylation of signal transducer and activator-of-transcription (STAT) 25 proteins and impede mRNA production or processing while promoting host mRNA destruction.25-27
Impaired STAT protein phosphorylation by SARS-CoV-2 suppresses IFN expression and signaling, broadly evading innate immune responses.27, 28 To what extent a placental infection by SARS-CoV-2 modulates the placental antiviral innate immune response is unclear.29-34
A robust or dysregulated innate immune response may increase risk for inflammatory tissue injury or placental compromise and contribute to deleterious fetal outcomes including stillbirth.11, 35-40
A spectrum of placental pathology has been linked to a maternal SARS-CoV-2 infection including chronic histiocytic intervillositis, fibrin deposition, trophoblast necrosis and, in some cases, chronic villitis or acute chorioamnionitis; notably, stillbirth cases have been closely associated with the triad of chronic histiocytic intervillositis, fibrin deposition and trophoblast necrosis.9, 19, 41-48
Prior reports of placental pathology associated with COVID-19 have attributed these changes to maternal hypoxia from underlying respiratory impairment; whether an interferon and/or cytokine response to SARS-CoV-2 infection may contribute to a placental pathologic profile is unclear.
Moreover, whether maternal disease status impacts the relationship between a SARS-CoV-2 infection, placental innate immune response, and placental histopathology is unknown.
The study objective was to evaluate the profile of the placental antiviral innate immune response following maternal COVID-19 disease in a large placental biobank that allowed for analysis of factors that are typically not explored due to smaller sample sizes (i.e., labor status, placental pathology, time interval between infection and delivery, and COVID-19 disease severity).
We hypothesized that the placental antiviral response might be upregulated by a recent SARS-CoV-2 infection in pregnancy; however, a SARS-CoV-2 infection may also harm cytotrophoblast and syncytiotrophoblast cells later in the disease course to impair the placental antiviral immune response.
Thus, the placental antiviral innate immune response may clear SARS-CoV-2 at the expense of placental cellular health and immune defense.
