Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

Christoph Muus; Malte D Luecken; Gokcen Eraslan; Avinash Waghray; Graham Heimberg; Lisa Sikkema; Yoshihiko Kobayashi; Eeshit Dhaval Vaishnav; Ayshwarya Subramanian; Christopher Smillie; Karthik Jagadeesh; Elizabeth Thu Duong; Evgenij Fiskin; Elena Torlai Triglia; Christophe Becavin; Meshal Ansari; Peiwen Cai; Brian Lin; Justin Buchanan; Sijia Chen; Jian Shu; Adam L Haber; Hattie Chung; Daniel T Montoro; Taylor Adams; Hananeh Aliee; Samuel J Allon; Zaneta Andrusivova; Ilias Angelidis; Orr Ashenberg; Kevin Bassler; Christophe Becavin; Inbal Benhar; Joseph Bergenstrahle; Ludvig Bergenstrahle; Liam Bolt; Emelie Braun; Linh T Bui; Mark Chaffin; Evgeny Chichelnitskiy; Joshua Chiou; Thomas M Conlon; Michael S Cuoco; Marie Deprez; David S Fischer; Astrid Gillich; Joshua Gould; Minzhe Guo; Austin J Gutierrez; Arun C Habermann; Tyler Harvey; Peng He; Xiaomeng Hou; Lijuan Hu; Alok Jaiswal; Peiyong Jiang; Theodoros Kapellos; Christin S Kuo; Ludvig Larsson; Michael A Leney-Greene; Kyungtae Lim; Monika Litvinukova; Ji Lu; Leif S Ludwig; Wendy Luo; Henrike Maatz; Elo Maddissoon; Lira Mamanova; Kasidet Manakongtreecheep; Charles-Hugo Marquette; Ian Mbano; Alexi M McAdams; Ross J Metzger; Ahmad N Nabhan; Sarah K Nyquist; Jose Ordovas-Montanes; Lolita Penland; Olivier B Poirion; Segio Poli; CanCan Qi; Daniel Reichart; Ivan Rosas; Jonas Schupp; Rahul Sinha; Rene V Sit; Kamil Slowikowski; Michal Slyper; Neal Smith; Alex Sountoulidis; Maximilian Strunz; Dawei Sun; Carlos Talavera-Lopez; Peng Tan; Jessica Tantivit; Kyle J Travaglini; Nathan R Tucker; Katherine Vernon; Marc H Wadsworth; Julia Waldman; Xiuting Wang; Wenjun Yan; Ali Onder Yildirim; William Zhao; Carly G K Ziegler; Aviv Regev

The presence of dual-positive cells in the lung, heart, and kidney may reflect that cells in these organs may be direct targets of viral infection and pathology 5, 55 . Dual-positive cells in the sustentacular and basal cells of the olfactory epithelium (Fig. 1c) may be associated with a loss of the sense of smell 56 . Dual-positive cells in the corneal and conjunctival epithelium, may contribute to viral transmission 4, 57 . Dual positive cardiomyocytes may be related to "direct" cardiomyocyte damage (see Tucker et al. companion manuscript 58 ), whereas heart pericytes may indicate a vascular component to the cardiac dysfunction, and could contribute to increased troponin leak in patients without coronary artery disease. Notably, ACE2-expressing heart pericytes in another dataset (Tucker et al) is even higher (30%) than any other tissue dataset analyzed here (max. 21 .7% in kidney, Extended Data Fig. 4) . Despite the lymphopenia observed with COVID-19 2,4,59,60 , we did not typically observe ACE2 mRNA expression in scRNA-seq profiles in the bone marrow or cord blood (Fig. 1a,b) , although there was ACE2 expression in some tissue macrophages, including alveolar and heart macrophages (Extended Data Fig. 4) . Further studies of ACE2 RNA and protein expression in COVID-19 disease tissue will help elucidate its expression in immune cells 61 .