Single-cell analysis of human lung epithelia reveals concomitant expression of the SARS-CoV-2 receptor ACE2 with multiple virus receptors and scavengers in alveolar type II cells

Guangchun Han; Ansam Sinjab; Warapen Treekitkarnmongkol; Patrick Brennan; Kieko Hara; Kyle Chang; Elena Bogatenkova; Beatriz Sanchez-Espiridion; Carmen Behrens; Boning Gao; Luc Girard; Jianjun Zhang; Boris Sepesi; Tina Cascone; Lauren Byers; Don L. Gibbons; Jichao Chen; Seyed Javad Moghaddam; Edwin J. Ostrin; Junya Fujimoto; Jerry Shay; John V. Heymach; John D. Minna; Steven Dubinett; Paul A. Scheet; Ignacio I. Wistuba; Edward Hill; Shannon Telesco; Christopher Stevenson; Avrum E. Spira; Linghua Wang; Humam Kadara

While ACE2 was expressed in a low fraction of lung epithelial cells (roughly 1.7%), its levels among all lung cell subsets were highest in AT2 cells. ACE2-expressing AT2 cells co-expressed genes with crucial roles in lung pathological conditions such as COPD, pneumonia and pathogen infection including the viral binding scavenger DMBT1 and which overall were higher in cells derived from smokers relative to non/light smokers. We also found that DMBT1 positively correlated with AT2 cell fractions and with ACE2 itself within the AT2 compartment. Our findings suggest that ACE2- The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.16.045617 doi: bioRxiv preprint COVID-19 in lung cancer and clinical studies are warranted to explore this conjecture. Our analysis also revealed significantly elevated ACE2 levels, among ACE2-positive AT2 and malignant cells, in patients who were on hypertension treatment with losartan compared to those without antihypertensive therapy. While our finding is in line with previous reports suggesting that antihypertensive agents may augment ACE2 expression 28, 29, 50 , it needs to be interpreted with caution. Our patient cohort is very limited in size and our study was designed with a focus on singlecell analysis of lung epithelial cells. We thus cannot construe the implications of this finding on COVID-19 management 50, 51 and further studies are warranted to better (e.g., larger cohort) explore the association between treatment with antihypertensive drugs and ACE2 expression in human cells.