{"doi":"10.1101/2020.12.01.407007","title":"Multimodal Single-Cell Omics Analysis of COVID-19 Sex Differences in Human Immune Systems","abstract":"Abstract Sex differences in the risk of SARS-CoV-2 infection have been controversial and the underlying mechanisms of COVID-19 sexual dimorphism remain understudied. Here we inspected sex differences in SARS-CoV-2 positivity, hospitalization, admission to the intensive care unit (ICU), sera immune profiling, and two single-cell RNA-sequencing (snRNA-seq) profiles from nasal tissues and peripheral blood mononuclear cells (PBMCs) of COVID-19 patients with varying degrees of disease severity. Our propensity score-matching observations revealed that male individuals have a 29% increased likelihood of SARS-CoV-2 positivity, with a hazard ration (HR) 1.32 (95% confidence interval [CI] 1.18-1.48) for hospitalization and HR 1.51 (95% CI 1.24-1.84) for admission to ICU. Sera from male patients at hospital admission had decreased lymphocyte count and elevated inflammatory markers (C-reactive protein, procalcitonin, and neutrophils). We found that SARS-CoV-2 entry factors, including ACE2, TMPRSS2, FURIN and NRP1, have elevated expression in nasal squamous cells from males with moderate and severe COVID-19. Cell-cell network proximity analysis suggests possible epithelium-immune cell interactions and immune vulnerability underlying a higher mortality in males with COVID-19. Monocyte-elevated expression of Toll like receptor 7 (TLR7) and Bruton tyrosine kinase (BTK) is associated with severe outcomes in males with COVID-19. These findings provide basis for understanding immune responses underlying sex differences, and designing sex-specific targeted treatments and patient care for COVID-19.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":127763,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8763,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":105381,"name":"Yadi Zhou","orcid":"0000-0002-6049-0545","position":1,"is_corresponding":false},{"id":105617,"name":"Michaela U. Gack","orcid":"0000-0002-2163-2598","position":2,"is_corresponding":false},{"id":240691,"name":"Justin D. Lathia","orcid":"0000-0003-3168-7290","position":3,"is_corresponding":false},{"id":228047,"name":"Asha Kallianpur","orcid":"0000-0002-6483-523X","position":4,"is_corresponding":false},{"id":249755,"name":"Reena Mehra","orcid":"0000-0002-6222-2675","position":5,"is_corresponding":false},{"id":69956,"name":"Timothy A. Chan","orcid":"0000-0002-9265-0283","position":6,"is_corresponding":false},{"id":107313,"name":"Jae U. Jung","orcid":"0000-0003-4559-8774","position":7,"is_corresponding":false},{"id":228048,"name":"Lara Jehi","orcid":"0000-0002-8041-6377","position":8,"is_corresponding":false},{"id":228051,"name":"Charis Eng","orcid":"0000-0002-3693-5145","position":9,"is_corresponding":false},{"id":69831,"name":"Feixiong Cheng","orcid":"0000-0002-1736-2847","position":10,"is_corresponding":false},{"id":105382,"name":"Yuan Hou","orcid":null,"position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-18T23:15:34.966380Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}