The recent emergence of COVID‐19 has resulted in a worldwide crisis, with large populations locked down and transportation links severed. While approximately 80% of infected individuals have minimal symptoms, around 15–20% need to be hospitalized, greatly stressing global healthcare systems. As of March 10, the death rate appears to be about 3.4%, although this number is highly stratified among different populations. Here, we focus on those individuals who have been exposed to nicotine prior to their exposure to the virus. We predict that these individuals are ‘primed’ to be at higher risk because nicotine can directly impact the putative receptor for the virus (ACE2) and lead to deleterious signaling in lung epithelial cells.
In the absence of long‐term immunization or effective therapies for COVID‐19, public health management must rely on rapid responses for the identification, treatment, and management of the infection and extra care for vulnerable (high‐risk) populations. Emergent evidence supports the involvement of smoking as a key predisposing factor for COVID‐19‐related illness severity and mortality based on a recent study of 1,590 patients from 575 hospitals in 31 province/autonomous regions/provincial municipalities across China . Age‐ and sex‐matched comparisons indicate that mortality and symptom severity are higher in smokers and former smokers. These findings may begin to shed light on mechanisms that account for responses of infected individuals such as the old vs. young and males vs. females in China and now elsewhere. In a recent report based on 1099 patients with COVID‐19 from 552 hospitals in 30 provinces in China, 58% of the patients were men, indicating that there might be a sex predisposition to COVID‐19, with men more prone to being affected. However, it is more likely that this sex predisposition reflects the higher smoking rate in men than in women in China (288 million men and 12.6 million women were smokers in 2018) .
Smoking has long been known to be a key causative agent of cardiovascular and pulmonary illnesses through its direct actions on various types of nicotinic receptors expressed in cardiac tissue, lungs, and blood vessels . Smoking is also significantly associated with high mortality rates in infections of various respiratory viruses including those that underlie annual (seasonal) influenza . Interaction between nicotine exposure, nicotinic receptor signaling, and modulation of the RAS has been recognized, yet remains understudied. In this case, however, smoking appears to participate in a direct cellular process that effects COVID‐19 infection and possible outcome, in a mechanism involving the ability of the nicotinic receptor to regulate ACE2 protein expression in cells. Smoking is also known to cause lung damage through the activation of inflammatory cytokines and programmed cell death in the pulmonary tissue and direct actions on circulating immune cells such as T cell. Of particular interest, lung AT2 cells exposed to nicotine show altered expression of the ACE2 protein that may underlie enhanced exposure of the putative receptor to COVID‐19 spike protein, and recent analysis of a large dataset from RNA‐seq and DNA microarray supports the finding that smoking is associated with increased ACE2 expression in the lung . Prolonged nicotine exposure systemically—through various kinds of smoking habits—may thus provide a cellular mechanism for viral susceptibility and illness severity during the course of the infection in the lungs as well as other organ systems.
Tobacco formulations are not just nicotine and often contain a varied mixture of >5000 chemicals, with potential carcinogenic, cardiovascular, and respiratory properties. In addition to nicotine, cigarettes contain toxins such as carbon monoxide and polycyclic aromatic hydrocarbons, which also perturb the function of the cardiovascular, pulmonary, and immune systems, and at this point, such toxins may also contribute to COVID‐19 disease outcome. Chronic nicotine use, systemically through cigarette and other tobacco products or indirectly possibly through secondhand smoke, now presents an important factor in COVID‐19 vulnerability in various populations. Alarming increases in nicotine consumption and mortalities throughout Asia and rises in the distribution of electronic cigarette (e‐cig) formulations worldwide point to augmenting vulnerability to respiratory infecting viruses such as COVID‐19 . With more data rapidly emerging in various countries and locations, it will be important to critically consider evidence between virus‐related infection and illness as well as resilience in relation to nicotine consumption. These findings aim to prioritize public health efforts of identifying populations at risk and aid in venues for critical intervention.