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

Tissue programs (Fig. 4a, Extended Data Fig. 10a 10a for visualization of selected genes, and Supplementary Tables 6 for the full list). These include phagosome structure, antigen processing and presentation, and apoptosis. Among the tissue program genes we highlight: CEACAM5 (lung, nasal, gut programs) and CEACAM6 79 (lung), surface attachment factors for coronavirus spike protein; SLPI (lung, nasal), a secreted protease inhibitor that is associated with virus resistance 80 ; PIGR (lung, gut), the polymeric immunoglobulin receptor that may promote antibody-dependent enhancement via IgA 81 ; and, CXCL17 (lung, nasal), a mucosal chemokine that attracts dendritic cells and monocytes to the lungs 82 . In addition, the tissue programs yielded multiple genes that are associated with cholesterol and lipid metabolic pathways and endocytosis (DHCR24, LCN2, FASN); high expression of both MHC I (B2M, HLA-B) and MHC II (HLA-DRA, DRB1, CTSS, CD74) pathways, expanding on prior evidence that AT2 cells can serve as antigen presenting cells in infection 83 ; genes indicating preparation against cellular injury through ROS inhibition, preventing proteases, or through antiviral responses (interferons, extracellular RNAse, etc: PLAC8, TXNIP); complement genes (C3, C4BPA); genes involved in immune modulation (BTG1); and, tight junction genes (DST, CLDN3, CLDN4).