American Study Discovers That SARS-CoV-2 Infections Impairs Antiviral Innate Immune Gene Expression In The Placenta!

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! This places pregnant women who contract the virus even in asymptomatic or mild symptomatic settings still susceptible to developing varying health conditions and also possibly affecting the unborn child.


 
The COVID-19 disease caused by the SARS-CoV-2 virus has been 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 risk for inflammatory tissue injury or placental compromise and contribute to deleterious pregnancy outcomes.
 
The study team sought to determine the impact of a maternal SARS-CoV-2 infection on placental immune response by evaluating gene expression of a panel of six antiviral innate immune mediators that act as biomarkers of the antiviral and interferon cytokine response.
 
Their hypothesis was that a SARS-CoV-2 infection during pregnancy would result in an upregulated placental antiviral innate immune response.
 
The study team performed a case control study on placental tissues [chorionic villous (CV) tissues and chorioamniotic membrane (CAM)] collected from pregnant patients with (N=140) and without (N=24) COVID-19 disease.
 
The researchers also performed real-time quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Placental histopathology was evaluated. Clinical data was abstracted. Fisher’s exact test, Pearson correlations, and linear regression models were used to examine proportions and continuous data between patients with active (<10 days since diagnosis) versus recovered COVID-19 (>10 days since diagnosis) at 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 vRNA 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 vRNA in placental tissues was confirmed to express SARS-CoV-2 nucleocapsid and spike proteins in syncytiotrophoblast cells.
 
The study findings showed a significantly lower gene expression of five critical innate immune mediators (IFNB, IFIT1, MXA, IL6, IL1B) in CV and CAM from women with active or recovered COVID-19 compared to 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 from COVID-19 diagnosis and delivery, pre-pregnancy body mass index, COVID-19 disease severity or placental pathology.
 
The study findings showed that a maternal SARS-CoV-2 infection was associate d 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, timer interval from COVID-19 diagnosis to delivery, maternal obesity, disease severity or placental pathology.
 
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
 
Senior author, Dr Kristina Adams Waldorf, a professor of obstetrics and gynecology at the University of Washington School of Medicine told Thailand Medical News, "This is the largest study to date of placentas from women who had COVID-19 during their pregnancies. We were surprised to find that women who had COVID-19 during their pregnancies had placentas with an impaired immune response to new infection."
 
Dr Adams Waldorf added, "This study findings was the tip of the ‘iceberg’ in how COVID-19 might affect fetal or placental development.”
 
Earlier in the pandemic, there was a fallacy that COVID-19 did not appear to harm the developing fetus because there were so few babies born with COVID-19 infection.
 
Dr Adams Waldorf commented, “Alarmingly, what we're seeing now is that the placenta is vulnerable to COVID-19, and the infection changes the way the placenta works, and that in turn is likely to impact the development of the fetus."
 
Co-author Dr Helen Feltovich, a professor and associate medical director for maternal fetal medicine imaging at Intermountain Healthcare in Utah added, "To date, the studies about how COVID-19 might affect fetal or child development are very limited as the children are still very young.”
 
She warned, “Our study suggests that babies born to mothers infected with COVID-19 at any point during their pregnancy will need to be monitored as they grow up.”
 
Typically, the placenta provides nourishment, oxygen, and immune protection for the fetus until the time of birth.
 
Research studies led by Dr Adams Waldorf have shown that women who contract COVID-19 have a significantly higher mortality rate than do women who do not contract COVID-19. Numerous other studies have also found that pregnant women are more likely to risk hospitalizations or preterm birth, according to the U.S. Center for Disease Control and Prevention.
 
The study team also noted that it's unknown how different SARS-CoV-2 variants may affect the mother or fetus.
 
Dr Adams Waldorf said, "Studying each of the variants in real time is really challenging because they just keep coming so fast, we can't keep up. We do know that the COVID-19 Delta variant was worse for pregnant individuals, because there was a spike in stillbirths, maternal deaths and hospitalizations at that time."
 
Adams Waldorf stressed that regardless of the variant, it's important that women not catch COVID-19.
 
She also advised that women who are pregnant should continue to mask and stay within a strict bubble. She acknowledges that may mean isolating for the duration of the pregnancy.
 
She added, "The disease may be mild, or it may be severe, but we're still seeing these abnormal effects on the placenta. It seems that after contracting COVID-19 in pregnancy, the placenta is exhausted by the infection, and can't recover its immune function."
 
For the current research, a total of 164 pregnant individuals were studied, consisting of 24 uninfected healthy patients as a control group and 140 individuals who contracted COVID-19. Both groups delivered at about the same time, 37 to 38 weeks. Preterm birth occurred at almost 3 times the rate with the patients with COVID-19 when compared with those without. About 75% of the patients with COVID-19 were either asymptomatic or had mild symptoms, according to the study.
 
All placental tissues were obtained with patient approval through either the Intermountain Healthcare Research Institutional Review Board, in Salt Lake City, Utah, or the University of Washington Human Subjects Division. Placental tissues were collected by medical providers at the time of delivery.
 
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