Single-cell expression profiles of ACE2 and TMPRSS2 reveals potential vertical transmission and fetus infection of SARS-CoV-2

Abstract

Morbidity and mortality of coronavirus disease 2019 (COVID-19) is age-dependent. It remains unclear whether vertical severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurs during pregnancy and how such infection will affect fetal development. Here, we performed single-cell transcriptomic analysis of placenta and other tissues from fetuses in comparison with those from adults using public-available datasets. Our analysis revealed that a very small proportion of trophoblast cells expressed the Angiotensin I Converting Enzyme 2 (ACE2) gene, suggesting a low possibility of vertical transmission of SARS-CoV-2 from mother to fetus during pregnancy. We found that the fetal adrenal gland, heart, kidney and stomach were susceptible to SARS-CoV-2 infection, because these organs contained cell clusters that expressed high levels of the ACE2 gene. In particular, a higher proportion of ACE2-expressing cell clusters in the adrenal gland and kidney also expressed the Transmembrane Serine Protease 2 (TMPRSS2) gene compared with other organs. Surprisingly, ACE2-expressing type II alveolar (AT2) equivalent cells were absent in fetal lungs. This is in sharp contrast to adult lungs. As ACE2 expression is regulated by various conditions, including oxygen concentration, inflammation and smoking, caution is warranted to avoid triggering potential ACE2 expression in fetal and placental tissue.

Keywords: COVID-19; SARS-CoV-2; fetus; pathogenesis; placenta.

Figure 1

Single-cell analysis of lungs and placenta. (A) t-distributed stochastic neighbor embedding (TSNE) plot showing sub-clusters of placenta cells, and (B) ACE2 expression in placenta. (C) TSNE plot showing sub-clusters of lung cells, (D) ACE2 and (E) TMPRSS2 expression in lungs from the adult and fetal groups.

Figure 2

Profiling of ACE2- and TMPRSS2-positive cells in different tissues. (A) t-distributed stochastic neighbor embedding (TSNE) plot of ACE2-positive cells. Cells from the merged adult, fetal and placenta groups are indicated by different dot shapes. (B) Violin plot of ACE2 expression in different tissues from the adult and fetal groups. (C) TSNE plot of TMPRSS2-positive cells. Cells from the merged adult, fetal and placenta groups are indicated by different dot shapes. (D) Violin plot of TMPRSS2 expression in different tissues from the adult and fetal groups. (E) Bar plot showing the percentage of cells expressing ACE2 and TMPRSS2 in the adult and fetal groups.

Figure 3

Single-cell analysis of liver, pancreas and stomach. (A) t-distributed stochastic neighbor embedding (TSNE) plot showing sub-clusters of liver cells, (B) ACE2 and (C) TMPRSS2 expression in liver from the adult and fetal groups. (D) TSNE plot showing sub-clusters of stomach cells, (E) ACE2 and (F) TMPRSS2 expression in stomach from the adult and fetal groups. (G) TSNE plot showing sub-clusters of pancreas cells, (H) ACE2 and (I) TMPRSS2 expression in pancreas from the adult and fetal groups.

Figure 4

Single-cell analysis of heart and muscle. (A) t-distributed stochastic neighbor embedding (TSNE) plot showing sub-clusters of myocardial cells and (B) ACE2 expression in myocardial cells from the adult and fetal groups. (C) TSNE plot showing sub-clusters of muscle cells and (D) ACE2 expression in muscle from the adult and fetal groups.

Figure 5

Single-cell analysis of adrenal gland and kidney. (A) t-distributed stochastic neighbor embedding (TSNE) plot showing sub-clusters of kidney cells, (B) ACE2 and (C) TMPRSS2 expression in kidney from the adult and fetal groups. (D) TSNE plot showing sub-clusters of adrenal gland cells, (E) ACE2 and (F) TMPRSS2 expression in adrenal gland from the adult, neonatal and fetal groups.

Figure 6

Expression of double positive (ACE2- and TMPRSS2- positive) and single positive (ACE2- or TMPRSS2- positive) cells. (A) t-distributed stochastic neighbor embedding (TSNE) plot displaying TMPRSS2 expression in ACE2-positive cells. (B) TSNE plot showing ACE2 expression in TMPRSS2-positive cells. (C) Percentage of double positive cells in each single positive population for the different tissues.