Multimodal single-cell omics analysis identifies epithelium-immune cell interactions and immune vulnerability associated with sex differences in COVID-19

作     者：Yuan Hou Yadi Zhou Michaela U.Gack Justin D.Lathia Asha Kallianpur Reena Mehra Timothy A.Chan Jae U.Jung Lara Jehi Charis Eng Feixiong Cheng Yuan Hou;Yadi Zhou;Michaela U.Gack;Justin D.Lathia;Asha Kallianpur;Reena Mehra;Timothy A.Chan;Jae U.Jung;Lara Jehi;Charis Eng;Feixiong Cheng

作者机构：Genomic Medicine InstituteLerner Research InstituteCleveland ClinicClevelandOHUSA Florida Research and Innovation CenterCleveland ClinicPort Saint LucieFLUSA Department of Cardiovascular and Metabolic ScienceLerner Research InstituteCleveland ClinicClevelandOHUSA Department of Molecular MedicineCleveland Clinic Lerner College of MedicineCase Western Reserve UniversityClevelandOHUSA Department of Population and Quantitative Health SciencesCase Western Reserve UniversityClevelandOHUSA Neurological InstituteCleveland ClinicClevelandOHUSA Center for Immunotherapy and Precision Immuno-OncologyCleveland ClinicClevelandOHUSA Department of Cancer BiologyLerner Research InstituteCleveland ClinicClevelandOHUSA Department of Genetics and Genome SciencesCase Western Reserve University School of MedicineClevelandOHUSA Case Comprehensive Cancer CenterCase Western Reserve University School of MedicineClevelandOHUSA 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2021年第6卷第8期

页      面：2586-2599页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 100102[医学-免疫学] 10[医学] 

基　　金：This work was supported by the National Institute of Aging(R01AG066707 and 3R01AG066707-01S1) the National Heart,Lung,and Blood Institute(R00HL138272)to F.C This work has been also supported in part by the VeloSano Pilot Program(Cleveland Clinic Taussig Cancer Institute)to F.C.and J.D.L This work was partly supported by NIH P01 CA245705 and NIH R01 NS109742 to J.D.L 

主　　题：elevated epithelium analysis 

摘      要：Sex differences in the susceptibility of SARS-CoV-2 infection and severity have been controversial,and the underlying mechanisms of COVID-19 in a sex-specific manner remain *** we inspected sex differences in SARS-CoV-2 infection,hospitalization,admission to the intensive care unit(ICU),sera inflammatory biomarker profiling,and single-cell RNA-sequencing(scRNA-seq)profiles across nasal,bronchoalveolar lavage fluid(BALF),and peripheral blood mononuclear cells(PBMCs)from COVID-19 patients with varying degrees of disease *** propensity score-matching observations revealed that male individuals have a 29%elevated likelihood of SARS-CoV-2 positivity,with a hazard ratio(HR)1.32(95%confidence interval[Cl]1.18-1.48)for hospitalization and HR 1.51(95%Cl 1.24-1.84)for admission to *** from male patients at hospital admission had elevated neutrophil-lymphocyte ratio and elevated expression of inflammatory markers(C-reactive protein and procalcitonin).We found that SARS-CoV-2 entry factors,including ACE2,TMPRSS2,FURIN,and NRP1,have elevated expression in nasal squamous cells from male individuals with moderate and severe *** observed male-biased transcriptional activation in SARS-CoV-2-infected macrophages from BALF and sputum samples,which offers potential molecular mechanism for sex-biased susceptibility to viral ***-cell interaction network analysis reveals potential epithelium-immune cell interactions and immune vulnerability underlying male-elevated disease severity and mortality in ***,monocyte-elevated expression of Toll-like receptor 7{TLR7)and Bruton tyrosine kinase{BTK)is associated with severe outcomes in males with *** summary,these findings provide basis to decipher immune responses underlying sex differences and designing sex-specific targeted interventions and patient care for COVID-19.