Smoking modulates different secretory subpopulations expressing SARS-CoV-2 entry genes in the nasal and bronchial airways.

SARS-CoV-2 infection and disease severity are influenced by viral entry (VE) gene expression patterns in the airway epithelium. The similarities and differences of VE gene expression (ACE2, TMPRSS2, and CTSL) across nasal and bronchial compartments have not been fully characterized using matched samples from large cohorts. Gene expression data from 793 nasal and 1673 bronchial brushes obtained from individuals participating in lung cancer screening or diagnostic workup revealed that smoking status (current versus former) was the only clinical factor significantly and reproducibly associated with VE gene expression. The expression of ACE2 and TMPRSS2 was higher in smokers in the bronchus but not in the nose. scRNA-seq of nasal brushings indicated that ACE2 co-expressed genes were highly expressed in club and C15orf48+ secretory cells while TMPRSS2 co-expressed genes were highly expressed in keratinizing epithelial cells. In contrast, these ACE2 and TMPRSS2 modules were highly expressed in goblet cells in scRNA-seq from bronchial brushings. Cell-type deconvolution of the gene expression data confirmed that smoking increased the abundance of several secretory cell populations in the bronchus, but only goblet cells in the nose. The association of ACE2 and TMPRSS2 with smoking in the bronchus is due to their high expression in goblet cells which increase in abundance in current smoker airways. In contrast, in the nose, these genes are not predominantly expressed in cell populations modulated by smoking. In individuals with elevated lung cancer risk, smoking-induced VE gene expression changes in the nose likely have minimal impact on SARS-CoV-2 infection, but in the bronchus, smoking may lead to higher viral loads and more severe disease.

Medication selection for clinical treatment of COVID-19

The 2019 coronavirus disease(COVID-19), like most viral infections, has no specific medications and no targeted treatment besides vaccines. In clinic, medicinal treatment is mainly aimed at the harm that the immune system is activated to the limit or out of control after the patients are infected with the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2). This study systematically reviewed clinical treatment of COVID-19 since its outbreak by combining the diagnosis and treatment plan for COVID-19 from First to Seventh Edition issued by the National Health Protection Commission of China. The strategy of selecting medication for treating COVID-19 is proposed and the efficacy and risk of various Western medications currently used in clinical practice were evaluated. The purpose of this study is to provide theoretical basis and clinical cases for clinicians in madication selection for Corona virus disease 2019(Covid-19) and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).