COVID-19 in 28-Week Triplets Caused by Intrauterine Transmission of SARS-CoV-2—Case Report

Abstract

Since the beginning of the COVID-19 pandemic, in-utero transmission of SARS-CoV-2 remains a rarity and only very few cases have been proven across the world. Here we depict the clinical, laboratory and radiologic findings of preterm triplets born at 28 6/7 weeks to a mother who contracted COVID-19 just 1 week before delivery. The triplets showed SARS-CoV-2 positivity right after birth, developed significant leukopenia and early-onset pulmonary interstitial emphysema. The most severely affected triplet I required 10 days of high-frequency oscillatory ventilation due to failure of conventional invasive ventilation, and circulatory support for 4 days. Despite a severe clinical course in two triplets (triplet I and II), clinical management without experimental, targeted antiviral drugs was successful. At discharge home, the triplets showed no signs of neurologic or pulmonary sequelae. Placental immunohistology with SARS-CoV-2 N-protein localized strongly to syncytiotrophoblast cells and, to a lesser extent, to fetal Hofbauer cells, proving intrauterine virus transmission. We discuss the role of maternal viremia as a potential risk factor for vertical transmission. To the best of our knowledge, our report presents the earliest unequivocally confirmed prenatal virus transmission in long-term surviving children, i.e., at the beginning of the third trimester.

ACE2 Receptors Finding in Placenta with Intrauterine Fetal COVID-19 Infection: A Meta-Analysis

“…Six research articles [11][12][13][14][15][16] reported between 76 babies that were born from mothers infected with COVID-19, 10 babies among them were found infected with COVID-19 (10.5%), the diagnosis of COVID-19 in pregnant women and infants was based on RT-PCR, which proves that even though the placenta has ACE2 receptors does not cause the baby to be directly infected, this may be related to the function of the placenta which has physical and immunological defense functions as a barrier, and the presence of decidual macrophages for antimicrobial function, as well as placental T cells for regulation of maternal-fetal tolerance and virus-specific CD8+T cells. The decidua protects the fetus from infection, while the syncytiotrophoblast and cytotrophoblast in the placenta act as an additional barrier to the passage of infection and exhibit varying resistance to pathogens.…”

“…Expression of ACE2 receptors in 72 placenta samples combined from six research articles [11][12][13][14][15][16] by pregnant women infected with COVID-19 was found in the syncytiotrophoblast (100%), cytotrophoblast (56.9%), extravillous trophoblast (33.3%), decidual cells (2.7%), villous stromal cells (1.3%), and stromal cells (1.3%) from the placenta, this is in line with the evidence of the presence of ACE2 receptors in the placenta at the maternal-fetal interface including parts of the syncytiotrophoblast, cytotrophoblast, decidual perivascular cells, and stromal cells. 20 In Colson et al 11 study, ACE2 receptor expression was found to be quite high in syncytiotrophoblasts at <30 weeks' gestation and decreased >30 weeks' by histological score (H-score), it was also found in Zhao et al 16 Study that ACE2 receptor expression was high in early pregnancy, the different findings on ACE2 receptor expression because ACE2 receptors tend to be found to be high in early gestation, but relatively low ACE2 receptors in pregnant women with COVID-19 are associated with premature placentas and severe infections, thus, the placenta not only expresses ACE2 receptors as a portal of entry for the virus, but is also responsive to infection and results in downregulation which is an indication of infection.…”

“…In 72 pregnant women infected with COVID-19 alongside 76 neonates from pregnant women based on six selected articles (Table 2), it was found that 8/76 (10.5%) neonates were infected with COVID-19 with RT-PCR confirmation. There are five studies that report the days and gestational age of pregnant women when infected with SARS-CoV-2 before giving birth, 4 of the 5 studies reported the gestational age of pregnant women when infected with SARS-CoV-2 are during 23 weeks + 1 day to 40 weeks [11][12][15][16] and 4 days -17 antepartum. 13 Five of the six studies reported the severity of COVID-19…”

“…Figure 1 PRISMA Flowchart symptoms in pregnant women infected with SARS-CoV-2, one study had a higher proportion of patients with asymptomatic disease 13 , whereas the other four studies had a higher proportion of patients with symptomatic disease. [11][12][14][15][16] These six studies [11][12][13][14][15][16] (Table 2) showed that there are expression of ACE2 receptors in 72 placental samples from 72 pregnant women infected with COVID-19 using the immunohistochemical analysis method, the results of the analysis is ACE2 receptors can be found on syncytiotrophoblasts from 72/72 (100%), cytotrophoblasts 41/72 (56.9%), extravillous trophoblast 24/72 (33.3%), decidual cells 2/72 (2.7%), stromal cells and villous stroma cell 1/72 (1.3%).…”

“…Six studies [11][12][13][14][15][16] (table 3) reported on analyzing the findings of ACE2 receptors in the placenta. The combined proportions showed that the proportion of ACE2 receptors found in placental syncytiotrophoblast was 98.3 (95% CI 94.3-99.9), cytotrophoblast 40.3 (95% CI 2.3-88.9), and extravillous trophoblast 35.2 (95% CI 0.2-88.5) of 72 samples placenta.…”