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Research finds COVID19 may cause foetal inflammation even without placental infection

Pregnant women with SARS-CoV-2 had a reduction in an immune cell type called T-cells, which helps drive antiviral responses

Detroit: According to a new study, SARS-CoV-2, the virus that causes COVID-19, may cause fetal inflammation even in the absence of placental infection.

The study has been published in the 'Nature Communications Journal'.

Pregnant women have a higher risk of severe illness if infected with COVID-19. Infection increases the risk of preterm birth, stillbirth, and pre-eclampsia.

The study reported that COVID-19 infection during pregnancy may cause inflammatory immune responses in the foetus, even if the virus does not infect the placenta.

The study, conducted by Nardhy Gomez-Lopez, PhD, associate professor of the WSU Department of Obstetrics and Gynecology, and section head of the Maternal-Fetal Immunobiology Unit, and Roberto Romero, MD, D.Med.Sci., chief of the NIH's Perinatology Research Branch, based at the Wayne State University School of Medicine, and professor of Molecular Obstetrics and Genetics at the WSU School of Medicine, details changes in antibodies, immune cell types and inflammatory markers in maternal blood, umbilical cord blood and placental tissues.

"We found that in pregnant mothers who contract the virus, SARS-CoV-2 induces a foetal immune response even in the absence of placental infection or symptoms in the newborn. The potential long-term effects of this inflammatory process on infants require further study," Dr Gomez-Lopez said.

The researchers evaluated 23 pregnant women. Twelve tested positive for SARS-CoV-2, and of those, eight were asymptomatic, one had mild symptoms and three had severe COVID-19. After delivery, the researchers compared immune responses between mothers and their newborns by comparing maternal blood and umbilical cord blood.

Inflammatory immune responses triggered by the virus were observed in women, their newborns, and placental tissues regardless of whether the mothers displayed symptoms.

The study team described the following observations:

1. Pregnant women with SARS-CoV-2 had a reduction in an immune cell type called T-cells, which helps drive antiviral responses.

2. Infected mothers developed antibodies against the virus whether or not they had symptoms, and some of these antibodies were found in the umbilical cord blood.

3. Infected mothers had a higher level of immune activity markers (i.e., cytokines) in blood regardless of symptoms. The elevated cytokines are interleukin-8, interleukin-15 and interleukin-10.

4. Infants born to infected mothers, even if the mother had no symptoms, had an inflammatory response reflected by higher levels of interleukin-8. This elevation was observed even though the foetus presumably did not have COVID-19.

While the virus was absent in placentas, the placentas from infected mothers had altered ratios of immune cell types. The researchers also found altered immune activity (measured by changes in RNA transcripts) in the placenta and cord blood of infants born to infected mothers. These findings indicated that the neonatal immune system is affected by maternal infection by SARS-CoV-2 even if the virus is not detected in the placenta.

"This study provides insight into the maternal-foetal immune responses triggered by SARSCoV-2 and emphasizes the rarity of placental infection. Most pregnant women with SARS-CoV-2 infection are asymptomatic or only experience mild symptoms. Regardless, in the first six months of the COVID-19 pandemic, it was documented that infected pregnant women are at an increased risk for hospitalization, mechanical ventilation, intensive care unit admission, and preterm birth, but rates of maternal mortality were reported to be similar between pregnant and non-pregnant women," Dr Romero said.

"More recently, it has been clearly shown that pregnant women are at high risk for severe disease and death, as well as preterm birth. Investigating host immune responses in pregnant women who are infected, even if they are asymptomatic, is timely," Dr Romero added.

These latest findings will help researchers better understand COVID-19 during pregnancy. The authors noted that the potential long-term effects of this inflammatory process on infants require further study.

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