The question of how nicotine impacts the risk and severity of COVID-19 arose early in the pandemic, driven by a puzzling observation. Initial hospitalization data suggested that the proportion of active smokers among patients was lower than expected based on general population smoking rates. This statistical anomaly led researchers to question whether nicotine, the psychoactive component of tobacco, might offer some form of biological protection against the SARS-CoV-2 virus. The scientific community investigated this idea, exploring the mechanisms by which the virus enters human cells and how nicotine might interfere. The resulting inquiry examined the biological theory, the practical risks of nicotine delivery methods, and the final clinical evidence.
The ACE2 Receptor Hypothesis
The scientific speculation centered on the primary mechanism the SARS-CoV-2 virus uses to infect human cells. The virus utilizes a spike protein on its surface to bind to the Angiotensin-Converting Enzyme 2 (ACE2) receptor, which is abundant on lung and airway cells. The initial hypothesis was that nicotine might modulate this receptor or a related cellular pathway, thereby disrupting the viral entry process.
One line of reasoning suggested nicotine could act as a therapeutic agent by binding to nicotinic acetylcholine receptors (nAChRs) in the lungs and nervous system. Researchers proposed this binding might interfere with the virus’s ability to attach to the ACE2 receptor, or that the nicotine could trigger an anti-inflammatory response. This protective theory inspired small-scale trials of nicotine patches.
Conversely, laboratory-based studies pointed to nicotine having the opposite effect. In vitro experiments indicated that exposure to nicotine could increase the expression of ACE2 receptors on the cell surface. A higher density of ACE2 receptors creates more entry points for the virus, potentially making the host more susceptible to infection and increasing the viral load. This suggested that nicotine was a factor that could worsen the outcome of the infection.
Respiratory Risk Factors Associated with Nicotine Delivery Systems
Regardless of the theoretical action of the nicotine molecule itself, the real-world delivery systems—combustible cigarettes and electronic nicotine delivery systems (ENDS)—introduce a separate layer of risk. Smoking and vaping severely compromise the respiratory system, creating a pre-damaged environment vulnerable to a severe viral infection like COVID-19. Inhaling smoke or vapor introduces toxic chemicals and fine particles that damage the delicate structure of the lung epithelium.
This damage includes the impairment of mucociliary clearance, a crucial self-cleaning mechanism in the airways. Smoke and vapor paralyze or destroy the cilia that line the respiratory tract, preventing them from sweeping mucus, pathogens, and debris out of the lungs. The resulting buildup of mucus and inability to clear foreign invaders make the lungs a more hospitable environment for the SARS-CoV-2 virus to replicate.
Both smoking and vaping trigger chronic inflammation throughout the respiratory system. Exposure to these aerosols increases inflammatory immune cells and cytokines, which are signaling molecules that govern the immune response. This pre-existing inflammatory state can prime the immune system for an exaggerated and harmful reaction, contributing to the “cytokine storm” that causes severe lung damage. Non-nicotine components in tobacco smoke have been shown to upregulate key cellular components, including the ACE2 receptor, aiding the virus’s ability to enter cells.
Clinical Findings on Nicotine Use and COVID-19 Outcomes
The early, confusing data that suggested a protective effect was largely superseded by comprehensive epidemiological studies providing a clearer clinical reality. Large-scale analyses confirmed that current and former users of nicotine delivery products faced substantially higher risks of poor outcomes. These studies consistently demonstrated that smoking was a significant risk factor for COVID-19 disease progression.
Smokers were found to be more likely to develop severe forms of the disease, requiring admission to an intensive care unit, and facing a greater need for mechanical ventilation. Data showed that individuals who smoked were approximately 45% more likely to die and 39% more likely to receive mechanical ventilation compared to non-smokers. These findings cemented the consensus that the overwhelming damage and inflammatory effects of smoking and vaping far outweighed any hypothetical protective effect from nicotine.
Some clinical trials were launched to test the anti-inflammatory or prophylactic potential of therapeutic nicotine, such as patches, in a controlled setting. However, these trials largely failed to provide conclusive evidence of a protective effect in the acute phase of the disease. While one observational study suggested that receiving nicotine replacement therapy was associated with a reduced mortality rate, researchers cautioned this did not prove a causal link. The final clinical verdict is unequivocal: using a nicotine delivery system significantly increases the risk of severe illness, hospitalization, and death from COVID-19.