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Int J Mol Sci ; 21(10)2020 May 21.
Article in English | MEDLINE | ID: covidwho-327277


The COVID-19 pandemic is marked by a wide range of clinical disease courses, ranging from asymptomatic to deadly. There have been many studies seeking to explore the correlations between COVID-19 clinical outcomes and various clinical variables, including age, sex, race, underlying medical problems, and social habits. In particular, the relationship between smoking and COVID-19 outcome is controversial, with multiple conflicting reports in the current literature. In this study, we aim to analyze how smoking may affect the SARS-CoV-2 infection rate. We analyzed sequencing data from lung and oral epithelial samples obtained from The Cancer Genome Atlas (TCGA). We found that the receptor and transmembrane protease necessary for SARS-CoV-2 entry into host cells, ACE2 and TMPRSS2, respectively, were upregulated in smoking samples from both lung and oral epithelial tissue. We then explored the mechanistic hypothesis that smoking may upregulate ACE2 expression through the upregulation of the androgen pathway. ACE2 and TMPRSS2 upregulation were both correlated to androgen pathway enrichment and the specific upregulation of central pathway regulatory genes. These data provide a potential model for the increased susceptibility of smoking patients to COVID-19 and encourage further exploration into the androgen and tobacco upregulation of ACE2 to understand the potential clinical ramifications.

Androgens/metabolism , Coronavirus Infections/metabolism , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/metabolism , Serine Endopeptidases/genetics , Smoking/metabolism , Up-Regulation , Alveolar Epithelial Cells/metabolism , Coronavirus Infections/epidemiology , Coronavirus Infections/genetics , Humans , Mouth Mucosa/metabolism , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/epidemiology , Pneumonia, Viral/genetics , Receptors, Androgen/genetics , Receptors, Androgen/metabolism , Serine Endopeptidases/metabolism , Smoking/epidemiology , Smoking/genetics
Am J Respir Crit Care Med ; 202(2): 219-229, 2020 07 15.
Article in English | MEDLINE | ID: covidwho-324576


Rationale: Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease (COVID-19), a predominantly respiratory illness. The first step in SARS-CoV-2 infection is binding of the virus to ACE2 (angiotensin-converting enzyme 2) on the airway epithelium.Objectives: The objective was to gain insight into the expression of ACE2 in the human airway epithelium.Methods: Airway epithelia sampled by fiberoptic bronchoscopy of trachea, large airway epithelia (LAE), and small airway epithelia (SAE) of nonsmokers and smokers were analyzed for expression of ACE2 and other coronavirus infection-related genes using microarray, RNA sequencing, and 10x single-cell transcriptome analysis, with associated examination of ACE2-related microRNA.Measurements and Main Results: 1) ACE2 is expressed similarly in the trachea and LAE, with lower expression in the SAE; 2) in the SAE, ACE2 is expressed in basal, intermediate, club, mucus, and ciliated cells; 3) ACE2 is upregulated in the SAE by smoking, significantly in men; 4) levels of miR-1246 expression could play a role in ACE2 upregulation in the SAE of smokers; and 5) ACE2 is expressed in airway epithelium differentiated in vitro on air-liquid interface cultures from primary airway basal stem/progenitor cells; this can be replicated using LAE and SAE immortalized basal cell lines derived from healthy nonsmokers.Conclusions: ACE2, the gene encoding the receptor for SARS-CoV-2, is expressed in the human airway epithelium, with variations in expression relevant to the biology of initial steps in SARS-CoV-2 infection.

Betacoronavirus , Coronavirus Infections/metabolism , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/metabolism , Respiratory Mucosa/metabolism , Case-Control Studies , Female , Humans , Lung/metabolism , Male , Pandemics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sex Factors , Smoking/metabolism , Trachea/metabolism
ACS Chem Neurosci ; 11(9): 1206-1209, 2020 05 06.
Article in English | MEDLINE | ID: covidwho-101631


The novel coronavirus SARS-CoV-2, which was identified after a recent outbreak in Wuhan, China, in December 2019, has kept the whole world in tenterhooks due to its severe life-threatening nature of the infection. The virus is unlike its previous counterparts, SARS-CoV and MERS-CoV, or anything the world has encountered before both in terms of virulence and severity of the infection. If scientific reports relevant to the SARS-CoV-2 virus are noted, it can be seen that the virus owes much of its killer properties to its unique structure that has a stronger binding affinity with the human angiotensin-converting enzyme 2 (hACE2) protein, which the viruses utilize as an entry point to gain accesses to its hosts. Recent reports suggest that it is not just the lung that the virus may be targeting; the human brain may soon emerge as the new abode of the virus. Already instances of patients with COVID-19 have been reported with mild (anosmia and ageusia) to severe (encephalopathy) neurological manifestations, and if that is so, then it gives us more reasons to be frightened of this killer virus. Keeping in mind that the situation does not worsen from here, immediate awareness and more thorough research regarding the neuroinvasive nature of the virus is the immediate need of the hour. Scientists globally also need to up their game to design more specific therapeutic strategies with the available information to counteract the pandemic. In this Viewpoint, we provide a brief outline of the currently known neurological manifestations of COVID-19 and discuss some probable ways to design therapeutic strategies to overcome the present global crisis.

Betacoronavirus/pathogenicity , Brain/virology , Coronavirus Infections/physiopathology , Pneumonia, Viral/physiopathology , Aged , Ageusia/virology , Autopsy , BCG Vaccine/administration & dosage , BCG Vaccine/immunology , Betacoronavirus/chemistry , Betacoronavirus/metabolism , Brain/pathology , Brain/physiopathology , Brain Diseases/immunology , Brain Diseases/pathology , Brain Diseases/virology , Coronavirus Infections/diagnosis , Coronavirus Infections/transmission , Coronavirus Infections/virology , Cytokines/immunology , Humans , Inflammation/immunology , Inflammation/pathology , Inflammation/virology , MicroRNAs/genetics , Olfaction Disorders/virology , Olfactory Mucosa/pathology , Olfactory Mucosa/physiopathology , Olfactory Mucosa/virology , Pandemics , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/diagnosis , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , RNA Interference , Receptors, Nicotinic/metabolism , Serine Endopeptidases/metabolism , Smoking/metabolism , Smoking/pathology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism