Sex difference and smoking predisposition in patients with COVID-19

Cai, Hua

doi:10.1016/s2213-2600(20)30117-x

Cited by 568 publications

(587 citation statements)

References 4 publications

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“…We next sought to understand how the expression of each of these three key genes --ACE2, TMPRSS2, and CTSL --in specific cell subsets may relate to three key covariates that have been associated with disease severity: age (older individuals are more severely affected), sex (males are more severely affected), and smoking (smokers are more severely affected) 62 . We integrated samples across many studies, as no single dataset generated to date is sufficiently large to address this question.…”

Section: Ace2 and Tmprss2 Expression In Airway Epithelial And At2 Celmentioning

confidence: 99%

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

Muus

Luecken

Eraslan

et al. 2020

Preprint

251

326

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The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) and associated proteases, transmembrane protease serine 2 (TMPRSS2) and Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess the cell type-specific RNA expression of ACE2, TMPRSS2, and CTSL through an integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs. Joint expression of ACE2 and the accessory proteases identifies specific subsets of respiratory epithelial cells as putative targets of viral infection in the nasal passages, airways, and alveoli. Cells that co-express ACE2 and proteases are also identified in cells from other organs, some of which have been associated with COVID-19 transmission or pathology, including gut enterocytes, corneal epithelial cells, cardiomyocytes, heart pericytes, olfactory sustentacular cells, and renal epithelial cells. Performing the first meta-analyses of scRNA-seq studies, we analyzed 1,176,683 cells from 282 nasal, airway, and lung parenchyma samples from 164 donors spanning fetal, childhood, adult, and elderly age groups, associate increased levels of ACE2, TMPRSS2, and CTSL in specific cell types with increasing age, male gender, and smoking, all of which are epidemiologically linked to COVID-19 susceptibility and outcomes. Notably, there was a particularly low expression of ACE2 in the few young pediatric samples in the analysis. Further analysis reveals a gene expression program shared by ACE2 + TMPRSS2 + cells in nasal, lung and gut tissues, including genes that may mediate viral entry, subtend key immune functions, and mediate epithelial-macrophage cross-talk. Amongst these are IL6, its receptor and co-receptor, IL1R, TNF response pathways, and complement genes. Cell type specificity in the lung and airways and smoking effects were conserved in mice. Our analyses suggest that differences in the cell type-specific expression of mediators of SARS-CoV-2 viral entry may be responsible for aspects of COVID-19 epidemiology and clinical course, and point to putative molecular pathways involved in disease susceptibility and pathogenesis.

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Section: Ace2 and Tmprss2 Expression In Airway Epithelial And At2 Celmentioning

confidence: 99%

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

Muus

Luecken

Eraslan

et al. 2020

Preprint

251

326

View full text Add to dashboard Cite

show abstract

“…The smoking rate in China is much higher in men than in women (288 million men vs 12.6 million women; 2018 data). 10 Likewise, in Italy, men are more likely to smoke than women at any age (1.12x to 1.7x, depending on age cohort; 2018 data). 11 Similar gender-specific trends are also present in the US, where 17.6% of smokers are men as compared to 13.6% of women.…”

Section: How Does This Improve Population Health?mentioning

confidence: 99%

Sex- and Gender-specific Observations and Implications for COVID-19

Walter

McGregor

2020

WestJEM

124

100

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“…The major alleged cause of this phenomenon, is a general poorer male health condition, related mostly to a higher cigarette consumption and more common heart disease (2). In spite of these reports, there have been other published opinions, raising the possibility of an intrinsic protective immunomodulation mediated by estrogen receptor pathway.…”

Section: Introductionmentioning

confidence: 99%

May patients receiving 5-alpha-reductase inhibitors be in higher risk of COVID-19 complications?

2020

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COVID-19 pandemic is a major challenge for global and national healthcare providers.Number of new cases is continuously increasing with an emerging trend showing worse prognosis in males in comparison to females. Based on this observation, our proposed hypothesis is that 5-alpha-reductase inhibitors, that are commonly used for BPH treatment, may be one of the factors contributing to poorer prognosis in males.3

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Sex difference and smoking predisposition in patients with COVID-19

Cited by 568 publications

References 4 publications

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

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

Sex- and Gender-specific Observations and Implications for COVID-19

May patients receiving 5-alpha-reductase inhibitors be in higher risk of COVID-19 complications?

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