The epicenter of the original outbreak in China has high male smoking rates of around 50%, and early reported death rates have an emphasis on older males, therefore the likelihood of smokers being overrepresented in fatalities is high. In Iran, China, Italy, and South Korea, female smoking rates are much lower than males. Fewer females have contracted the virus. If this analysis is correct, then Indonesia would be expected to begin experiencing high rates of Covid-19 because its male smoking rate is over 60% (Tobacco Atlas). Smokers are vulnerable to respiratory viruses.Smoking can upregulate angiotensin-converting enzyme-2 (ACE2) receptor, the known receptor for both the severe acute respiratory syndrome (SARS)-coronavirus (SARS-CoV) and the human respiratory coronavirus NL638. This could also be true for new electronic smoking devices such as electronic cigarettes and "heat-not-burn" IQOS devices. ACE2 could be a novel adhesion molecule for SARS-CoV-2 causing Covid-19 and a potential therapeutic target for the prevention of fatal microbial infections, and therefore it should be fast tracked and prioritized for research and investigation. Data on smoking status should be collected on all identified cases of Covid-19.Little attention has been given to the role of smoking in either the transmission of the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, actual virus) or mortality rate of Covid-19 (name of the disease caused). Smokers contract more respiratory ailments, including colds (commonly rhinoviruses, but also coronaviruses) than non-smokers. Smokers also show double the influenza rate and increased rates of bacterial pneumonia and tuberculosis [1][2][3][4][5]. The damage caused to the lungs by smoking makes patients more susceptible to pulmonary infections, both bacterial and viral [6]. Smokers are 34% more likely than non-smokers to contract the flu [6]. Han and colleagues conclude that literature evidence showed that smoking was consistently associated with a higher risk of hospital admissions after influenza infection [7]. Smoking is the primary etiological factor behind chronic obstructive pulmonary disease (COPD) in the developed world, but environmental pollution and degrading air quality are also responsible in developing countries. It is now the fourth leading cause of death in the world [8]. Vaccination against influenza is strongly recommended for patients with COPD, as the frequency and progression of exacerbations are strongly linked to respiratory viruses

ACE2 is the primary receptor for SARS‐CoV‐2. We demonstrate that lower airway expression of ACE2 is increased in older adults and males. Lower ACE2 expression in epithelial cells also occurs in people with asthma and is associated with reduced furin and increased ADAM‐17 expression. This may partly explain the relative sparing of people with asthma from severe COVID‐19.

Two interesting publications in the European Respiratory Journal recently by RUSSO et al. [1] and LEUNG et al. [2] discuss the possible role of nicotine in this pandemic and the "furious pursuit for better therapeutics".Not surprisingly, the angiotensin-converting enzyme 2 (ACE-2) is known to be the likely host receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Further, at a basic level, cellular mechanisms of nicotinic receptor activity promote SARS-CoV-2 entry and proliferation in epithelial cells through co-expression of ACE-2. Hence, this is the theory postulated by OLDS and KABBANI [3] for how nicotine consumption represents a special risk factor in coronavirus disease 2019 (COVID-19).On the other hand, and very surprisingly, Changeux et al. [4] hypothesise that the nicotinic receptor also plays a key role in the pathophysiology and might represent a target for the prevention and control of COVID-19 infection. Again, on a basic level, the hypothesis is that the SARS-CoV-2 virus is a nicotinic agent which competes with nicotine for the receptor. The backbone of this hypothesis proposes that under controlled settings, nicotinic agents (such as nicotine patches) could provide an efficient treatment for an acute infection such as COVID-19.So, tenuously, is the argument centred around the need for data about alternative nicotine delivery systems and their risk/benefit ratio in relation to ? Possibly, but are there perhaps other ways…? Soluble ACE-2 might impact viral spread, since binding to soluble receptor has been shown to block SARS-CoV-2 entry. BATLLE et al. [6] argue that, if given in its soluble form as an appropriate recombinant ACE-2 protein, this may represent a new tool to combat the spread of COVID-19.Similarly, GUO et al. [7] opined that exogenous supplement of recombinant human (rh)ACE-2 might be a brilliant idea in the treatment of COVID-19. Here the soluble ACE-2 may act as the bait to neutralise the spike protein on the surface of the SARS-CoV-2, thus inhibiting entry. Further, GUO et al. [7] referenced a recent study that demonstrated fusion protein of rhACE-2 (with an Fc fragment) showing high affinity binding to the receptor-binding domain of SARS-CoV-2. This, again, provides a basis for further drug development as fusion protein technology has been very successfully deployed in various therapeutic areas, such as rheumatology and haemophilia.

No abstract

The RE1-silencing transcription factor (REST)/ neuron-restrictive silencer factor (NRSF) can repress transcription of a battery of neuronal differentiation genes in non-neuronal cells by binding to a specific consensus DNA sequence present in their regulatory regions. However, REST/NRSF -/-mice suggest that the absence of REST/NRSF-dependent repression alone is not sufficient for the expression of these neuronal differentiation genes and that the presence of other promoter/enhancer-specific activators is required. Here we describe the construction of a recombinant transcription factor, REST-VP16, by replacing repressor domains of REST/NRSF with the activation domain of a viral activator VP16. In transient transfection experiments, REST-VP16 was found to operate through RE1 binding site/neuronrestrictive enhancer element (RE1/NRSE), activate plasmid-encoded neuronal promoters in various mammalian cell types and activate cellular REST/ NRSF target genes, even in the absence of factors that are otherwise required to activate such genes. Efficient expression of REST-VP16 through adenoviral vectors in NT2 cells, which resemble human committed neuronal progenitor cells, was found to cause activation of multiple neuronal genes that are characteristic markers for neuronal differentiation. Thus, REST-VP16 could be used as a unique tool to study neuronal differentiation pathways and neuronal diseases that arise due to the deregulation of this process.