The effect of SARS-CoV-2 infection on pregnant mothers, the placenta, and infants

The rapid outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19) pandemic. This RNA virus, belonging to the family Coronaviridae, has claimed more than 5.7 million lives worldwide. Scientists have conducted various types of experimental and survey-based studies to understand better the pathogenesis of the SARS-CoV-2 virus, its transmission pattern, and how it impacts various age groups with or without comorbidities. Although many studies have been conducted, the effect of SARS-CoV-2 infection on pregnant mothers, placentas, and infants is not well characterized.

Study: The clinical impact of maternal COVID-19 on mothers, their infants, and placentas with an analysis of vertical transfer of maternal SARS-CoV-2-specific IgG antibodies. Image Credit: FamVeld/Shutterstock

Background

Previous studies have not reported any specific histological findings in the placenta of pregnant women infected by SARS-CoV-2. Additionally, all the available studies have suggested that the occurrence of trans-placental viral transmission is a rare event. However, in the rare occasions where a SARS-CoV-2 infection of the placenta was found, no specific viral changes were found. 

A small study has published contradicting findings, which revealed the presence of chronic histiocytic intervillositis, perivillous fibrin deposition, and trophoblastic necrosis in the placentas of SARS-CoV-2 positive women. This study used the RNA in situ hybridization (ISH) technique. Interestingly, the same study also reported that infants tested negative although the placentas were infected, implying that SARS-CoV-2 infected placenta did not pass on the virus to the infant. Another study speculated the occurrence of moderate to severe maternal hypoxia, which may cause changes in the maternal vascular malperfusion (MVM). 

Scientists have indicated the need for more research on SARS-CoV-2 infected mothers, to determine the common and rare effects of SARS-CoV-2 on the placenta. A group of scientists focussed on assessing if SARS-CoV-2 infection causes any particular histologic change in the placenta. They also analyzed if a pregnant mother with COVID-19 infection could pass on the virus to infants and if so, the survival rate of both mother and infant. This study has been published on the medRxiv* preprint server. 

A new study

The authors conducted a retrospective, observational cohort study in Chapel Hill, USA, that included 115 mothers infected with SARS-CoV-2 and singleton pregnancies from December 1, 2019, to May 31, 2021. They documented the detailed data of the infants, i.e., weight, length, head circumference, survival rate, congenital abnormalities, and hearing loss. Additionally, scientists recorded maternal complications and placental pathology, which was classified as per Amsterdam criteria. As around 90% of the mothers in the study cohort did not receive any specific therapy for SARS-CoV-2 and none were vaccinated, researchers could characterize the natural course of SARS-CoV-2 infection on the placenta, mother, and infant. 

Main findings

The current study reported that the maternal transmission of SARS-CoV-2 was very low, i.e., 0.87% and the transmission was not via the placenta. As only one infant in the original cohort was infected with SARS-CoV-2, the authors constructed a second small cohort to determine if mothers with COVID-19 developed SARS-CoV-2-specific IgG antibodies and whether these IgG antibodies were passed on to their newborns. In this part of the study, researchers found that all mothers, except one immunosuppressed participant, developed SARS-CoV-2-specific IgG antibodies and transferred all or a majority of these antibodies to their infants.

The finding of this study is in line with previous research that exhibited mothers with COVID-19 generate SARS-CoV-2-specific IgG antibodies and transfers them to their infants. The current study further added to these data by demonstrating that one of the six SARS-CoV-2-specific IgG antibodies tested were transferred and retained by the infant, regardless of the trimester of the maternal SARS-CoV-2 infection. Consistent with previous studies, most placentas investigated in the current study revealed no significant gross or microscopic abnormalities.

Scientists found that the majority of the mothers with SARS-CoV-2 infections delivered at term and their newborns were healthy, i.e., medically insignificant to zero complications were observed. No deaths (mothers or infants) were reported in this study cohort. However, researchers found that 13% of the mothers in the study cohort suffered moderate to severe COVID-19 infection, were at significant risk of the incidence of premature births, maternal respiratory failure, delivery complications, delivery by C-section, maternal supplemental oxygen requirement, preeclampsia, and admission of their infants to the NICU. The current study also revealed that pre-existing Type 1 or Type 2 diabetes mellitus is one of the most significant contributing factors for developing moderate to severe SARS-CoV-2 infection.

Strengths and limitations

The main strength of this study is the large size of the cohort and the duration of the study. The authors assessed first and second trimester maternal SARS-CoV-2 infections and followed maternal and infant outcomes. A limitation of the study includes the lack of truly normal control placentas. Additionally, the analysis was based on the mothers’ chart, which might present a risk of bias.

However, even if a biased report existed, it had not affected the placental examination. In the future, more studies are needed to determine if there are specific circumstances along with the time of the maternal COVID-19 infection and if they are correlated with the development of MVM and a significant reduction in placental weight.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.