Smoking, ACE-2 and COVID-19: ongoing controversies

Abstract

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 COVID-19 [5]? 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.

Addictions in the COVID-19 era: Current evidence, future perspectives a comprehensive review

“…There are few data concerning the sole effect of nicotine (substitute treatments) and its interaction with the ACE. Studies on the effects of e-cigarettes' electronic nicotine delivery systems (e-cigarettes, vaping) on RAS are inconclusive and also lead to controversies ( Leung and Sin, 2020 ; Majmundar et al, 2020 ; Pino et al, 2020 ). Health providers in the US question whether the vaping epidemic might have contributed to the large amount of hospitalizations for COVID-19 among young individuals ( Pino et al, 2020 ).…”

COVID-19 and addiction

“…Contradictory evidences of non-association (sometimes even negative association) of smoking and COVID-19 severity among have also come up, albeit these studies are limited by small, heterogenous study population, underreporting of smoking status and statistical fallacies [20e23]. Future research must be directed to delineate more stringent association between smoking status (both current and past), associated comorbidities and COVID-19, possibility of transmission of SARS-CoV2 via secondhand smoking, hazards of e-cigarettes and vaping [24]. Based on some perplexing data revealing a negative association between smoking and COVID-19 and the fact that nicotine might possess a immunomodulatory effect to blunt the cytokine storm, there is a newly generated interest in using nicotine as a therapeutic against SARS-CoV2 [22,25e27].…”

Smoking increases the risk of infectious diseases: A narrative review

“…The current COVD-19 pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 370000 deaths 85 . The relationship between smoking and COVID-19 is controversial 86 . Many studies show that smoking increases the incidence and severity of COVID-19.…”