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

BACKGROUND: 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. OBJECTIVE: 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. STUDY DESIGN: 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) vs recovered COVID-19 (>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. RESULTS: 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. There were minimal correlations between placental gene expression and other studied variables including gestational age at diagnosis, time interval between COVID-19 diagnosis and delivery, prepregnancy body mass index, COVID-19 disease severity, or placental pathology. CONCLUSION: A maternal SARS-CoV-2 infection was associated with an impaired placental innate immune response in chorionic villous tissues and chorioamniotic membranes that was not correlated with gestational age at COVID-19 diagnosis, time interval from COVID-19 diagnosis to delivery, maternal obesity, disease severity, or placental pathology.

Virulence, phenotype and genotype characteristics of invasive group B Streptococcus isolates obtained from Swedish pregnant women and neonates.

Group B streptococci (GBS) are bacteria that can cause preterm birth and invasive neonatal disease. Heterogeneous expression of virulence factors enables GBS to exist as both commensal bacteria and to become highly invasive. A molecular epidemiological study comparing GBS bacterial traits, genotype and host characteristics may indicate whether it is possible to predict the risk of perinatal invasive GBS disease and more accurately target intrapartum antibiotic prophylaxis. A total of 229 invasive GBS isolates from Swedish pregnant women or neonates were assessed for virulence and phenotypic traits: hemolysis zone, hemolytic pigment (Granada agar), Streptococcus B Carrot Broth (SBCB) assay, CAMP factor, and hyaluronidase activity. Genes regulating hemolytic pigment synthesis (covR/covS, abx1, stk1, stp1) were sequenced. Of the virulence factors and phenotypes assessed, a Granada pigment or SBCB score ≥ 2 captured more than 90% of EOD isolates with excellent inter-rater reliability. High enzyme activity of hyaluronidase was observed in 16% (36/229) of the invasive GBS isolates and notably, in one case of stillbirth. Hyaluronidase activity was also significantly higher in GBS isolates obtained from pregnant/postpartum individuals versus the stillbirth or neonatal invasive isolates (p < 0.001). Sequencing analysis found that abx1 (g.T106I), stk1 (g.T211N), stp1 (g.K469R) and covS (g.V343M) variants were present significantly more often in the higher (Granada pigment score ≥ 2) versus lower pigmented isolates (p < 0.001, each variant). Among the 203 higher Granada pigment scoring isolates, 22 (10.8%) isolates had 3 of the four sequence variants and 10 (4.9%) had 2 of the four sequence variants. Although heterogeneity in GBS virulence factor expression was observed, the vast majority were more highly pigmented and contained several common sequence variants in genes regulating pigment synthesis. High activity of hyaluronidase may increase risk for stillbirth and invasive disease in pregnant or postpartum individuals. Our findings suggest that testing for GBS pigmentation and hyaluronidase may, albeit imperfectly, identify pregnant people at risk for invasive disease and represent a step towards a personalized medical approach for the administration of intrapartum antibiotic prophylaxis.