Histopathological and molecular effects on the placenta after SARS-CoV-2 infection during pregnancy

Recent studies posted on medRxiv* The preprint server evaluated the molecular and histopathological effects on the placenta after infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) during pregnancy.

Background

The 2019 Coronavirus Disease (COVID-19) pandemic has caused more than 435 million infections worldwide to date. COVID-19 infection causes many clinical manifestations, from asymptomatic diseases to complex multiple organ failure and death in severe cases.

The immune system of pregnant women undergoes dynamic changes that promote fetal tolerance. Pregnant women with severe COVID-19 are at higher risk of intensive care unit (ICU) admission, extracorporeal membrane oxygenation, and ventilator than non-pregnant individuals, according to some studies. Become. Another study reports that active COVID-19 infection during labor is associated with neonatal and obstetric complications.

SARS-CoV-2 is a host angiotensin converting enzyme 2 (ACE2) receptor and a transmembrane protease serine 2 (TMPRSS2) Enter the host cell. During pregnancy, placental syncytiotrophoblasts and cytotrophoblast cells express ACE2 and TMPRSS2. However, SARS-CoV-2 is rarely transmitted vertically to the fetus, and there are few reports of SARS-CoV-2 in the placenta and neonatal fetal compartments.

the study

In this study, researchers evaluated changes in placental histopathology and gene expression delivered from SARS-CoV-2 IgG-positive individuals and compared them to IgG-negative pregnant individuals.

Study participants were recruited as part of the Generation C study, a prospective pregnancy cohort study investigating the effects of COVID-19 during pregnancy. Maternal blood samples were taken at various times, their electronic medical records were reviewed, and IgG serological tests were used to confirm the history of COVID-19. An enzyme-linked immunosorbent assay (ELISA) test detected anti-spiked (anti-S) IgG for serological testing. Placental samples were collected after delivery and histopathological examination was performed according to standard protocols.

Ribonucleic acid (RNA) was isolated from formaldehyde-fixed paraffin-embedded (FFPE) tissue block and its concentration was measured using Nanodrop. Gene expression is a NanoString code with 50 probes containing stress response genes, immune or inflammatory response genes, SARS-CoV-2 response host genes, SARS-CoV-2 nucleocapsid (N), and envelope (E) genes. It was analyzed in the set panel. Above all.

result

Approximately 45 participants from the Generation C study were included, 15 of whom were IgG positive and 30 were IgG negative. Two IgG-positive subjects were SARS-CoV-2 positive at birth and admission. The median gestational age of IgG serology was 35 weeks. All births were births, with 37 at maturity and 8 at preterm birth. No difference in gestational age was observed between the study groups, with a median gestational age of newborns at birth of approximately 39 weeks. In the negative IgG cohort, 66.7% of newborns were male, compared with 33.3% in the positive IgG cohort.

For gene expression profiling, 44 samples (29 from the IgG-negative group and 15 from the IgG-positive participants) were analyzed for 48 genes. Nine genes were excluded from differential gene expression analysis because they were below background levels in both cohorts. These were host cell invading genes such as TMPRSS2 and ACE2, and stress and immune response genes such as IL17A, IFNL3, IL23A, IFNA1, ORPM1 and SARS-CoV-2 N and E genes. When SARS-CoV-2 IgG status was adjusted for covariates, three genes were associated with IgG serological status.

The authors noted that the trophoblast marker genes CGB3 and PSG3 were downregulated and CXCL10 was overexpressed compared to IgG-negative participants. When gene expression analysis was adjusted for cell-type proxies and covariates, IgG-positive status correlated with increased CXCL10, DDX58, and TLR3 genes.

Conclusion

The current study assesses the effects of COVID-19 infection during pregnancy by assessing molecular and histopathological changes in the placenta, and trophoblast-specific and immune responses among IgG-positive and IgG-negative subjects. I found a genetic difference. Placental expression of CGB3 and PSG3 was lower in IgG-positive subjects compared to IgG-negative participants.

PSG3, which is secreted into the mother’s circulatory system during pregnancy, is involved in angiogenesis and immunomodulatory function. CGB3, which encodes the beta3 subunit of the human chorionic gonadotropin (hCG) hormone, was involved in maternal immune tolerance and angiogenesis. CXCL10, an pro-inflammatory chemokine, was higher in IgG-positive subjects. In addition, the TLR3 and DDX58 genes were overexpressed in the placenta from IgG-positive participants.

Although the study participants were demographically diverse, the sample size was limited and the number of placentas from IgG-positive subjects was relatively small. In addition, there are no data on the timing, clinical severity, and neonatal serological status of COVID-19 infection. Therefore, more research is needed to investigate changes throughout the placental transcriptome.

*Important Notices

medRxiv publishes unpeer-reviewed preliminary scientific reports and should not be considered definitive, guide clinical / health-related behaviors, or be treated as established information.