A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications

Abstract

SARS-CoV-2 epidemics raises a considerable issue of public health at the planetary scale. T here is a pressing urgency to find treatments based upon currently available scientific knowledge. T herefore, we tentatively propose a hypothesis which hopefully might ultimately help saving lives. Based on the current scientific literature and on new epidemiological data which reveal that current smoking status appears to be a protective factor against the infection by SARS-CoV-2 [1], we hypothesize that the nicotinic acetylcholine receptor (nAChR) plays a key role in the pathophysiology of Covid-19 infection and might represent a target for the prevention and control of Covid-19 infection. Symptomatic Covid-19 disease (as caused by SARS-CoV-2 virus) is observed in 2.5 percent of infected individuals [2] indicating an individual variability in the clinical presentation. Among the epidemiological and clinical features of Covid-19, the following features are of special interest for understanding the patho-physiolology, namely: (1) in outpatients with favorable outcome : neurological/psychiatric disorders, especially loss of sense of smell which is specific of the disease and (2) in hospitalized older patients with a poor prognosis : systemic hyperinflammatory syndrome with increased levels of circulating cytokines and atypical acute respiratory distress syndrome with loss of neurological control of lung perfusion regulation and hypoxic vasoconstriction [3]. T his raises the issue of the basis of inter-individual variability for the susceptibility to infection.T he nAChR appears as a hypothetical clue for the main clinical manifestations of Covid-19. It is accepted that the angiotensin converting enzyme 2 (ACE2), represents the principal receptor molecule for SARS- . ACE2 is expressed at the transcriptomic level in the lung, the small intestine and colon, in the kidney, in the testis, in the heart muscle and in the brain, yet the protein is not detected in the lung [7]. In the brain, ACE2 is expressed in both neurons and glia and particularly present in the brain

A Systematic Review and Meta-Analysis of Hospitalised Current Smokers and COVID-19

“…Most of them have been systematic reviews and meta-analyses focusing on the association between smoking, disease progression and severity of the outcomes for COVID-19 patients (largely showing a positive relation between these factors) [ 8 , 12 , 14 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. However, to the best of our knowledge, just a few works have focused on studying the low prevalence of current smokers within hospitalised COVID-19 patients—mainly found in clinical data from China outbreak reports or early USA data—and more importantly, proposing potential pathophysiological explanations for these findings [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. In this sense, nicotine or nicotinic receptor agonists were early proposed as plausible anti-inflammatory mediators acting on the immune system to counteract the “cytokine storm” found in severe SARS-CoV-2 infected patients [ 43 ].…”

Could the smoking gun in the fight against COVID-19 be the (rh)ACE-2?

“…On the other hand, and very surprisingly, Changeux et al 4 hypothesize 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 SARS-CoV-2 virus is a nicotinic agent which competes with nicotine for the receptor.…”

COVID‐19 breakthroughs: separating fact from fiction

“…In early May, the WHO released a statement that urged scientists and the media to be cautious about publishing unproven claims that tobacco or nicotine could reduce the risks of infection with SARS‐CoV‐2 [38]. This statement was prompted by the release of a controversial preprint article from researchers in France who hypothesised that nicotine could have a protective effect against SARS‐CoV‐2 infection, based on unpublished observations that relatively few smokers were found amongst hospitalised COVID‐19 patients in Paris [48]. As a result, the media ran stories with salacious headlines, leading the public to believe that smoking can reduce the risk of contracting COVID‐19.…”