Emerging Reports of Transplacental Transmission of Covid-19 From Mother to Fetus Conflicts With Previous Findings that Transmission is Unlikely

Emerging Reports of Transplacental Transmission of Covid-19 From Mother to Fetus Conflicts With Previous Findings that Transmission is Unlikely

In the ever-evolving pandemic of SARS-CoV-2 (commonly referred to as Covid-19), there appears to be an ongoing shift in the medical community with respect to the question of whether Covid-19 can be transmitted in utero from mother to fetus. While early studies showed that transmission was unlikely, recent reports of apparent transmission have emerged creating conflicting findings.

In our previous blog post entitled “Covid-19 Not Transmitted from Mother to Fetus According to Case Study in Wuhan, China”, we discussed a report about four women who were all Covid-positive and actively symptomatic in their third trimester of pregnancy. Three of the four babies tested negative for Covid-19 (the parents did not consent to testing for the fourth baby) and none of the babies displayed any symptoms consistent with Covid-19. Therefore, the authors felt that it did not appear that the virus was being transmitted vertically from mother to fetus.

A recent National Institutes of Health study, however, found that the placenta lacks two major protein molecules used by Covid-19 to cause infection, indicating that it is unlikely for the virus to be transmitted from mother to fetus.1 The study explained that Covid-19 requires two protein molecules for cell entry and infection: the angiotensin-converting enzyme 2 (“ACE2”) receptor and the transmembrane serine protease 2 (“TMPRSS2”). These two proteins are normally found in cells and tissue of vital organs and vessels that are the targeted infection areas of Covid-19, such as the nose, airways, lungs, and gastrointestinal tract. The study investigated the detection of ACE2 and TMPRSS2 in the placenta throughout pregnancy, as well as third trimester chorioamniotic membranes—the membranes that make up the amniotic sac that surrounds and protects the fetus. The study estimated a very small percentage (less than 1/10,000 cells) showed detection ACE2 and TMPRSS2 in the placenta in any of the three trimesters, as well as in the chorioamniotic membranes in the third trimester. Due to the insignificant amounts of ACE2 and TMPRSS2 in the placenta, the authors of the study concluded that Covid-19 is unlikely transferrable from mother to fetus. By contrast, highly transferrable diseases from mother to fetus, such as Zika Virus and Cytomegalovirus, spread infection through cell receptors that are highly detected in placental cells.

The National Institutes of Health study noted that despite the small amounts of ACE2 and TMPRSS2 in the placenta, it is still possible for Covid-19 to transfer from mother to fetus in certain individuals with pregnancy complications. There have been reports of a small fraction of infants born to Covid-19 positive mothers who also tested positive for the disease at one to four days of life. However, these infants tested negative on day six or seven of life. Additionally, two case reports detected some transference of COVID-19. One case involved a COVID-19 positive woman who was severely affected and died from COVID-19. The premature infant tested negative after delivery, but 24 hours later tested positive. In the second case, the virus was detected in the placenta and umbilical cord from a woman with severe pre-eclampsia, placental abruption, and other complications—yet none of the fetal tissues tested positive, leaving no clear indication of transmission from mother to fetus.

Another publication raised concern that mother to fetus Covid-19 transmission may be possible. One report showed possible vertical transmission of Covid-19 from mother to newborn where blood work was drawn at two hours of life from the neonate that had an elevated IgM antibody level.2 While the authors could not rule out exposure at birth and noted that no testing was done of the amniotic fluid or placenta, they appeared to still suspect in utero transmission based on noting that IgM antibodies do not usually appear until three to seven days after infection.

At the same time that the National Institutes of Health study was published, a report from France asserted that they had the first confirmed case of transplacental transmission of Covid-19 during the last weeks of pregnancy.3 The mother presented at 35 2/7 weeks gestation with the E and S genes of Covid-19 detected in her blood and in her nasopharyngeal and vaginal swabs. Three days after admission, the baby had to be delivered by C-section due to a Category III fetal heart tracing. The amniotic membrane was intact, so amniotic fluid was collected prior to rupture of membranes. The fluid tested positive for both the E and S genes. Blood and bronchoscopic bronchoalveolar lavage fluid were collected and also tested positive for the E and S genes. Nasopharyngeal and rectal swabs were collected at one hour of life—again positive for both Covid-19 genes. Testing of the placenta was positive for both genes, and the placenta showed higher viral loads than seen in the amniotic fluid or in the maternal and neonatal blood. Based on the positive results for the E and S genes of Covid-19 in the amniotic fluid, placenta and the neonates blood work done at approximately one and a half hours of life, the authors concluded that there was transplacental transmission of Covid-19 from the mother to fetus during the third trimester.

While Covid-19 is widespread and provides new complications that the medical field is continuously learning, there appears to be no clear answer at this time as to whether or not the virus can be transmitted from mother to fetus.

1. Roger Pigqu-Regi, Roberto Romero, et al., Does the human placenta express the canonical cell entry mediators for SARS-CoV-2?, eLife Sciences (July 14, 2020), https://elifesciences.org/articles/58716.
2. Dong, L. et al., Possible vertical transmission of SARS-CoV-2 from an infected mother to her newborn, JAMA 323, 1848-1849 (2020)
3. Vivant, A. et al., Transplacental transmission of SARS-CoV-2 infection, Nature Communication (2020) 11:3572.