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Covid-19 during pregnancy: Study shows evidence of fetal inflammation without placental infection

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Dr Veena Aggarwal, Consultant Womens’ Health, CMD and Editor-in-Chief, IJCP Group & Medtalks Trustee, Dr KK’s Heart Care Foundation of India    20 January 2022

A new study from the National Institutes of Health (NIH) has demonstrated immune responses in the fetus following SARS-CoV-2 infection of the mother during pregnancy,  even though the virus did not infect the placenta. The study is published in the journal Nature Communications.1  

Twenty-three pregnant women constituted the study group. Out of these, 12 tested positive for SARS-CoV-2 on RT PCR. Eight of the Covid-positive women did not have symptoms, one had mild symptoms, while three participants had severe disease. The umbilical cord blood and maternal blood were compared for immune responses. All SARS-CoV2-positive women had term deliveries except one, who delivered preterm by emergency cesarean section.

All Covid-positive women developed anti-SARS-CoV-2 antibodies regardless of their symptom status, which were also detected in the umbilical cord blood. A decrease in T cells was noticed in women who tested positive for the infection, but not in their newborns. Compared to the control group, women infected with SARS-CoV-2 showed a proinflammatory cytokine response evident by increased levels of interleukin (IL)-8 (5.9-fold change), IL-10 (2.3-FC) and IL-15 (1.5-FC). Whereas, infants born to the infected mothers, even the asymptomatic ones, showed higher levels of IL-8 (2-FC).

IgM and IgG levels in the peripheral circulation were raised in pregnant women with SARS-CoV-2 infection. However, only IgG was detected in the cord blood indicating passive placental transfer of this antibody. No IgM levels were detected in the fetus suggesting that the fetus did not develop acute SARS-CoV-2 infection. Presence of IgM in the fetus suggests fetal infection with SARS-CoV-2, because IgM cannot cross the placenta because of its large molecular weight. Also, SARS-CoV-2 RNA and proteins were not detected in the placental samples of women with Covid using RT-qPCR technique and histology of chorioamniotic membranes, basal plate and placental villi.

Pregnant women are at risk of developing severe Covid-19, even though they are not at higher risk of contracting the infection. But once infected, they are more likely to develop both maternal and fetal complications if they become infected.

A notable finding was evidence of mild immune response in the fetus following maternal infection even though the fetus did not develop Covid-19 and SARS-CoV-2 was not detected in the placenta. The sterility of the placenta was also not disturbed by the virus. The authors speculate that the fetal inflammation may result in long-term morbidities. This study describing the maternal, fetal and placental humoral and cellular immune responses in Covid-positive pregnant women has added to the growing evidence on the impact of Covid-19 during pregnancy. However, these findings need corroboration by further studies.

Reference

  1. Garcia-Flores V, et al. Maternal-fetal immune responses in pregnant women infected with SARS-CoV-2. Nat Commun. 2022; 13: 320. https://doi.org/10.1038/s41467-021-27745-z.

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