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suck abstract from ncbi


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pmid34330889      Signal+Transduct+Target+Ther 2021 ; 6 (1): 292
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  • Multimodal single-cell omics analysis identifies epithelium-immune cell interactions and immune vulnerability associated with sex differences in COVID-19 #MMPMID34330889
  • Hou Y; Zhou Y; Gack MU; Lathia JD; Kallianpur A; Mehra R; Chan TA; Jung JU; Jehi L; Eng C; Cheng F
  • Signal Transduct Target Ther 2021[Jul]; 6 (1): 292 PMID34330889show ga
  • 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 understudied. Here 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 severities. Our 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 [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 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 COVID-19. We 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 infection. Cell-cell interaction network analysis reveals potential epithelium-immune cell interactions and immune vulnerability underlying male-elevated disease severity and mortality in COVID-19. Mechanistically, monocyte-elevated expression of Toll-like receptor 7 (TLR7) and Bruton tyrosine kinase (BTK) is associated with severe outcomes in males with COVID-19. In summary, these findings provide basis to decipher immune responses underlying sex differences and designing sex-specific targeted interventions and patient care for COVID-19.
  • |*Sex Characteristics[MESH]
  • |Adult[MESH]
  • |Aged[MESH]
  • |COVID-19/*immunology/pathology[MESH]
  • |Cell Communication/*immunology[MESH]
  • |Female[MESH]
  • |Humans[MESH]
  • |Leukocytes, Mononuclear/*immunology/pathology[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Nasal Mucosa/*immunology/pathology[MESH]
  • |SARS-CoV-2/*immunology[MESH]


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