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Review
. 2020 Dec;40(13):1655-1670.
doi: 10.1002/pd.5765. Epub 2020 Oct 4.

Mechanisms and evidence of vertical transmission of infections in pregnancy including SARS-CoV-2s

Aniza P Mahyuddin  1   2 , Abhiram Kanneganti  1 , Jeslyn J L Wong  1 , Pooja S Dimri  1 , Lin L Su  1   2 , Arijit Biswas  1   2 , Sebastian E Illanes  3 , Citra N Z Mattar  1   2 , Ruby Y-J Huang  2   4 , Mahesh Choolani  1   2
Affiliations
Review

Mechanisms and evidence of vertical transmission of infections in pregnancy including SARS-CoV-2s

Aniza P Mahyuddin et al. Prenat Diagn. 2020 Dec.

Abstract

There remain unanswered questions concerning mother-to-child-transmission of SARS-CoV-2. Despite reports of neonatal COVID-19, SARS-CoV-2 has not been consistently isolated in perinatal samples, thus definitive proof of transplacental infection is still lacking. To address these questions, we assessed investigative tools used to confirm maternal-fetal infection and known protective mechanisms of the placental barrier that prevent transplacental pathogen migration. Forty studies of COVID-19 pregnancies reviewed suggest a lack of consensus on diagnostic strategy for congenital infection. Although real-time polymerase chain reaction of neonatal swabs was universally performed, a wide range of clinical samples was screened including vaginal secretions (22.5%), amniotic fluid (35%), breast milk (22.5%) and umbilical cord blood. Neonatal COVID-19 was reported in eight studies, two of which were based on the detection of SARS-CoV-2 IgM in neonatal blood. Histological examination demonstrated sparse viral particles, vascular malperfusion and inflammation in the placenta from pregnant women with COVID-19. The paucity of placental co-expression of ACE-2 and TMPRSS2, two receptors involved in cytoplasmic entry of SARS-CoV-2, may explain its relative insensitivity to transplacental infection. Viral interactions may utilise membrane receptors other than ACE-2 thus, tissue susceptibility may be broader than currently known. Further spatial-temporal studies are needed to determine the true potential for transplacental migration.

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Conflict of interest statement

The authors declare no potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The placenta is a physical and immunological barrier. The main (middle) panel shows the cellular constituents and architecture of the maternal‐fetal interface. These comprise a microscopic section of the gross placenta, which is shown, for orientation, together with the fetus inside the uterine cavity (right panel). The possible routes of pathogen migration from mother to fetus, and across the placental barrier, are described in the coloured boxes (1‐5). The left panel is an expanded view of the cell membrane from a chorionic villus cell depicting the presence of ACE‐2 receptor, and the absence of TMPRSS2 in this cell type (the putative location is boxed in and crossed‐out). Co‐expression of both ACE‐2 and TMPRSS2 is required for SARS‐CoV‐2 virion entry into the cell cytoplasm [Colour figure can be viewed at wileyonlinelibrary.com]
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