Diminished antiviral innate immune gene expression in the placenta following a maternal SARS-CoV-2 infection

• Published in: American journal of obstetrics and gynecology 2023-04, Vol.228 (4), p.463.e1-463.e20
• Main Authors: Coler, Brahm, Wu, Tsung-Yen, Carlson, Lindsey, Burd, Nicole, Munson, Jeff, Dacanay, Matthew, Cervantes, Orlando, Esplin, Sean, Kapur, Raj P., Feltovich, Helen, Adams Waldorf, Kristina M.
• Format: Article
• Language: English
• Subjects: Antiviral Agents - metabolism; Case-Control Studies; chorioamniotic membrane; chorionic villous; COVID-19; COVID-19 - pathology; COVID-19 Testing; Female; fetus; Gene Expression; Humans; immune response; Immunity, Innate; Infant, Newborn; Infectious Disease Transmission, Vertical; Original Research: Obstetrics; placenta; Placenta - metabolism; Pregnancy; Pregnancy Complications, Infectious - diagnosis; Premature Birth - metabolism; RNA, Viral - metabolism; SARS-CoV-2
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2022.09.023

COVID-19 is caused by the SARS-CoV-2 virus and is associated with critical illness requiring hospitalization, maternal mortality, stillbirth, and preterm birth. SARS-CoV-2 has been shown to induce placental pathology. However, substantial gaps exist in our understanding of the pathophysiology of COVID-19 disease in pregnancy and the long-term impact of SARS-CoV-2 on the placenta and fetus. To what extent a SARS-CoV-2 infection of the placenta alters the placental antiviral innate immune response is not well understood. A dysregulated innate immune response in the setting of maternal COVID-19 disease may increase the risk of inflammatory tissue injury or placental compromise and may contribute to deleterious pregnancy outcomes. We sought to determine the impact of a maternal SARS-CoV-2 infection on placental immune response by evaluating gene expression of a panel of 6 antiviral innate immune mediators that act as biomarkers of the antiviral and interferon cytokine response. Our hypothesis was that a SARS-CoV-2 infection during pregnancy would result in an up-regulated placental antiviral innate immune response. We performed a case–control study on placental tissues (chorionic villous tissues and chorioamniotic membrane) collected from pregnant patients with (N=140) and without (N=24) COVID-19 disease. We performed real-time quantitative polymerase chain reaction and immunohistochemistry, and the placental histopathology was evaluated. Clinical data were abstracted. Fisher exact test, Pearson correlations, and linear regression models were used to examine proportions and continuous data between patients with active (10 days since diagnosis) at the time of delivery. Secondary regression models adjusted for labor status as a covariate and evaluated potential correlation between placental innate immune gene expression and other variables. SARS-CoV-2 viral RNA was detected in placental tissues from 5 women with COVID-19 and from no controls (0/24, 0%). Only 1 of 5 cases with detectable SARS-CoV-2 viral RNA in placental tissues was confirmed to express SARS-CoV-2 nucleocapsid and spike proteins in syncytiotrophoblast cells. We detected a considerably lower gene expression of 5 critical innate immune mediators (IFNB, IFIT1, MXA, IL6, IL1B) in the chorionic villi and chorioamniotic membranes from women with active or recovered COVID-19 than controls, which remained significant after adjustment for labor status. The