Discussion
Vertical transmission is the passage of infectious agents from an infected mother to her offspring. This may occur across the placenta, through breastmilk, or from direct contact during or after birth [8]. Concerning transplacental vertical transmission, disease-causing organisms overcome the protective barrier to infect the offspring during the antenatal, perinatal, or postnatal periods of gestation [8]. The result often increases fetal morbidity and mortality from complications like organ injury, morphological abnormalities, intrauterine growth restriction, and intrauterine fetal demise [9]. As a result, trimester-specific pregnancy screenings are done for infections with known vertical transmission. These include Parvovirus, Human immunodeficiency virus, Zika, Varicella-zoster, Rubella, Cytomegalovirus, and Toxoplasmosis [8,9]. Due to the novelty of SARS-CoV-2, there is insufficient evidence on transplacental transmission of this virus. Nonetheless, there are proposed mechanisms by which it may take place.
Understanding the structure and function of the placenta is essential when considering mechanisms of transplacental transmission. The placenta is the interface between the maternal and fetal circulatory systems and is composed of fetal-derived progenitor cells which differentiate into cytotrophoblasts and syncytiotrophoblasts [8]. It is needed for fetal nourishment and protection against pathogens that may be present in the maternal circulation. It is believed that the syncytiotropho-blast layer confers a broad non-specific resistance to microbial infections [8]. However, some pathogens are able to overcome this barrier through unique mechanisms. For instance, the Zika virus, which causes congenital microcephaly, may be able to penetrate the placenta due to its ability to infect different cells of the placenta as well as cells of the maternal immune system [8].
With regards to transplacental transmission of SARS-CoV-2, it is essential to understand how the virus infects cells of the body. SARS-CoV-2 infects host cells by binding to angiotensin-converting enzyme 2 (ACE2), a membrane-bound aminopeptidase [10,11]. This leads to receptor-mediated endocytosis of the virus, which is necessary for replication [11]. While ACE2 is predominantly expressed in the heart, lungs, kidneys, and gastrointestinal tract, recent studies uncovered ACE2 expression in various placental tissues and fetal organs [10–12]. While this expression is low in early gestational ages, it increases significantly in later stages of pregnancy [11], thereby increasing the risk of fetal infection. Although similar viruses like severe acute respiratory syndrome coronavirus 1 have not demonstrated the ability to cause fetal infection, SARS-CoV-2 is able to bind ACE2 with much higher affinity [11], thus increasing the probability of transplacental transmission.
While the presence of ACE2 in the placenta provides a plausible mechanism for transplacental transmission, only 3 studies have found evidence in support of its occurrence. Dong et al. described a case of a newborn that tested positive for anti-SARS-CoV-2 immunoglobulin M (IgM) 2 h after birth [13]. This class of antibody dominates the early phase of infection and is unable to cross the placenta. Although this neonate tested negative for SARS-CoV-2, the positive IgM antibodies suggest an immune response of fetal origin. Furthermore, intrapartum exposure was unlikely to be the cause since IgM may take up to 3 to 7 days to be detectable [13]. Additionally, other studies detected SARS-CoV-2 in placental tissue using electron microscopy and PCR [14,15]. This provides evidence that SARS-CoV-2 is able to infect the placenta and possibly cause fetal infection.
However, in a recent study, researchers were unable to detect viral particles in products of conception from infected mothers [16]. Furthermore, all babies born to these mothers tested negative for SARS-CoV-2. These findings suggest that, in most cases, the placenta is able to protect the fetus from SARS-CoV-2 infection. This also explains the paucity of reported cases suspicious for transplacental transmission of SARSCoV-2. At this time, the literature identifies 3 other cases of neonates testing positive for SARS-CoV-2 as early as 16 h after birth from infected mothers [17]. Similar to our case, a strict infection control protocol was followed and the babies were delivered via cesarean section. Although no products of conception in these cases were tested for viral particles, the positive PCR results within the first 24 h and strict infection control protocol make transplacental transmission more likely than peripartum transmission.