Do Viruses Target Nicotine Receptors to Make Us Sick?
Viruses like SARS-CoV-2 do not primarily target nicotinic acetylcholine receptors (nAChRs) to cause infection, but they may secondarily disrupt cholinergic signaling pathways, potentially contributing to disease severity through loss of anti-inflammatory control. 1
Primary Viral Entry Mechanism
The evidence is clear that SARS-CoV-2 enters cells through ACE2 receptors, not nAChRs. 1 The first stage of infection involves binding of the viral spike protein to angiotensin-converting enzyme 2 (ACE2) in the lung or nasopharynx, followed by proteolytic cleavage by transmembrane protease serine 2 (TMPRSS2). 2 This is the established mechanism of viral entry—nAChRs are not the primary gateway for infection. 1
Secondary Disruption of Cholinergic Pathways
While viruses don't "target" nAChRs for entry, there is theoretical evidence that SARS-CoV-2 may interact with these receptors as part of its pathophysiology:
The α7 nAChRs normally mediate the cholinergic anti-inflammatory reflex, where acetylcholine acts on immune cells to suppress nuclear factor-κB-dependent transcription, thereby downregulating proinflammatory cytokine production. 1
When this system is disrupted by viral infection, the loss of anti-inflammatory control may contribute to the hyperinflammatory "cytokine storm" seen in severe COVID-19. 1
Nicotine can stimulate the cholinergic anti-inflammatory response by activating α7 nAChRs, which suppresses nuclear factor-κB-dependent transcriptional events and leads to downregulation of cytokine production. 2
The Critical Distinction: Theory vs. Clinical Reality
This interaction is theorized rather than proven—the evidence for nAChRs as viral co-receptors remains speculative and based primarily on molecular similarity analyses, not clinical validation. 1, 3
Animal Model Evidence (Not Applicable to Humans)
In animal models, nicotine by itself appears to exert anti-inflammatory effects, decreasing lung vascular permeability and leukocyte infiltration. 2
However, insufficient epidemiological or experimental evidence exists to support the assertion that nicotine might decrease the hyperinflammatory response in people with COVID-19. 2
The Smoking Paradox: Why This Doesn't Matter Clinically
Despite any theoretical receptor interactions, cigarette smoking unequivocally increases the risk of poor COVID-19 outcomes, including hospital admission, disease progression, and mortality. 1
Mechanisms of Harm That Override Any Theoretical Benefits:
Smokers have higher baseline inflammation and oxidative stress, decreased phagocytic clearance by macrophages, increased airway permeability, and risk of acute respiratory distress syndrome (ARDS). 1
Tobacco smoke contains polyaromatic hydrocarbons causing immune suppression, acrolein suppressing cytokine production and innate immunity, and carbon monoxide diminishing oxygen-carrying capacity—all worsening viral infections. 1
Smoking increases the risk of chronic lung disease, cardiovascular disease, and diabetes, which are associated with poorer outcomes in SARS-CoV-2-infected individuals. 2
Combustion products induce oxidative stress, promote inflammation and vascular injury, and establish a prothrombotic state that could promote SARS-CoV-2 infection and contribute to increased severity. 2
Clinical Recommendations
Smoking cessation should be strongly encouraged, as any theoretical anti-inflammatory effects of nicotine are vastly outweighed by the documented harms of tobacco use. 2, 1
Important Caveats:
Nicotine has severe adverse cardiopulmonary effects and is highly addictive, so recreational use of nicotine products should be strongly discouraged. 1
Nicotine is associated with coronary artery disease, atherosclerosis, aortic aneurysms, peptic ulcers, gastrointestinal cancer, and may promote tumor angiogenesis. 1
Any potential anti-inflammatory benefits observed in animal models are significantly outweighed by nicotine's harmful effects, particularly its high addiction potential. 1
The effects of nicotine are dose-dependent and context-dependent, with different doses stimulating different (sometimes opposite) effects. 1
Bottom Line
Viruses do not "target" nicotine receptors to make us sick—they use ACE2 receptors for entry. 1 Any secondary interaction with nAChRs is theoretical and does not change clinical management. The overwhelming evidence shows that smoking worsens viral infections through multiple mechanisms of immune suppression, inflammation, and tissue damage. 2, 1