Abstract
Until September 2021, the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2; COVID-19) pandemic caused over 217 million infections and over 4.5 million deaths. In pregnant women, the risk factors for the need of intensive care treatment are generally the same as in the overall population. Of note, COVID-19-positive women deliver earlier than COVID-19-negative women, and the risk for severe neonatal and perinatal morbidity and mortality is significantly higher. The probability and pathways of vertical transmission of the virus from the pregnant woman to the fetus are highly controversial. Recent data have shown that 54 (13%) of 416 neonates born to COVID-19-positive women were infected. Here, we investigated term placentas collected before the SARS-CoV-2 pandemic and studied the main COVID-19 receptors angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine subtype 2 (TMPRSS2), as well as neuropilin 1 (NRP1). We performed real-time PCR and immunofluorescence on cryosections in combination with markers for syncytiotrophoblast, endothelial cells, macrophages and stromal cells. The PCR studies showed expression of both the truncated delta form of ACE2, which does not bind the COVID-19 spike protein, and the long form. The ACE2 antibody used does not distinguish between the two forms. We did not observe expression of the canonical SARS-CoV-2 entry machinery on syncytio- and cytotrophoblast. ACE2 and TMPRSS2 are co-expressed in a subpopulation of stromal cells, which in part are CD68-positive macrophages. NRP1 is localized to endothelial cells. In sum, the term placenta is not an organ that directly favors vertical transmission of COVID-19; however, microtraumas and placentitis may weaken its barrier function.
Highlights
As of August 31, 2021, the World Health Organization has confirmed over 217 million infections and over 4.5 million deaths caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2; COVID-19) [https://www.arcgis.com/apps/dashboards/bda7594740fd40299423467b48e9ecf6]
We investigated term placentas collected before the SARS-CoV-2 pandemic and studied the main COVID-19 receptors Angiotensin-converting enzyme 2 (ACE2), Transmembrane protease serine subtype 2 (TMPRSS2), as well as Neuropilin 1 (NRP1)
Our IF studies of ACE2 in term placenta were performed with an antibody raised against aa 19 to aa 740 of ACE2, and not distinguishing between the short and the long splice variant
Summary
As of August 31, 2021, the World Health Organization has confirmed over 217 million infections and over 4.5 million deaths caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2; COVID-19) [https://www.arcgis.com/apps/dashboards/bda7594740fd40299423467b48e9ecf6]. Villar et al studied vertical transmission of COVID-19 and compared 706 pregnant women with COVID-19 to 1424 pregnant women without COVID-19. The risk for severe neonatal and perinatal morbidity and mortality was significantly higher in the group of COVID-19+ women. 416 neonates born to COVID-19+ women were tested for the virus, and of these, 54 (13%) were COVID-19+. Thereby, cesarian delivery may have increased the risk for neonates to test positively (RR, 2.15; 95% CI, 1.18-3.91), and Villar et al emphasize that contamination during cesarian resection has to be taken into consideration. In a previous review on 324 pregnant women with COVID-19, only 3 of 155 neonates tested were COVID-19+ [Juan et al, 2020]. More recent studies confirmed increased risks of preterm delivery and maternal mortality caused by COVID-19 infection [Mullins et al, 2021]. Transfer of anti-COVID-19 IgG from mother to fetus is very likely, but IgM antibodies, which are unlikely to pass the placental barrier, have been detected in some newborns [Zeng et al, 2020; Dong et al, 2020]
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