Smoking and COVID: Effects on Lungs and Immunity

Smoking worsens nearly every stage of a COVID-19 infection, from the moment the virus latches onto airway cells to the lingering symptoms that can persist for months afterward. Cigarette smoke increases the number of molecular “docking sites” the virus uses to enter the lungs, weakens the immune defenses meant to fight it off, and amplifies the inflammatory damage that drives people into intensive care. The relationship is not as straightforward as early pandemic headlines suggested, though, and a few puzzling findings about current smokers muddied the picture for years before larger, better-designed studies clarified what was really going on.

How Smoking Rolls Out the Welcome Mat for the Virus

SARS-CoV-2 enters human cells by binding to a protein on the cell surface called ACE2. Think of ACE2 as a doorknob the virus grabs to pull itself inside. A second protein, TMPRSS2, acts like a key that helps the virus finish the job. Smoking increases the amount of both proteins sitting on the surface of airway cells, effectively adding more doorknobs and more keys for the virus to exploit.

Mouse studies showed that animals exposed to the highest dose of cigarette smoke had roughly 80 percent more ACE2 in their lungs compared to unexposed animals, and human bronchoscopy samples from smokers showed about 30 to 55 percent more ACE2 than samples from nonsmokers, depending on where in the airway researchers looked.¹ Cell-culture experiments confirmed that cigarette smoke extract significantly boosts ACE2 at both the gene-expression and protein level in human bronchial cells.² The upregulation isn’t limited to ACE2 alone: smokers and people with COPD also showed significantly elevated levels of both TMPRSS2 and furin, another enzyme the virus can use to enter cells, in their small airways and deeper lung tissue.³

Researchers have traced much of this effect to benzo[a]pyrene, one of the most studied carcinogens in cigarette smoke. Benzo[a]pyrene activates a specific nuclear receptor that binds to the promoter regions of the ACE2 and TMPRSS2 genes and cranks up their production.⁴ Beyond direct gene activation, there is also an epigenetic layer: smokers tend to show reduced methylation of the ACE2 gene, which essentially leaves the gene in a more “readable” state so cells produce more of the protein.⁵ The result is that a smoker’s airways are primed to let the virus in more efficiently across multiple biological pathways at once.

Damaged Defenses Before the Virus Even Arrives

Even before any viral exposure, smoking has already degraded the lungs’ first lines of defense. The airways are lined with tiny hair-like structures called cilia that sweep mucus, trapped particles, and pathogens up and out of the respiratory tract. Chronic cigarette smoke exposure is ciliotoxic: it slows ciliary beating, thickens mucus, depletes the thin liquid layer that cilia need to function, and ramps up oxidative stress, all of which lengthen the time it takes to clear inhaled threats.⁶ When SARS-CoV-2 lands in these sluggish, inflamed airways, it has more time and more cellular targets to establish infection.

Smoking also warps the immune system’s inflammatory response in ways that set the stage for the kind of runaway inflammation that makes COVID-19 deadly. Long-term tobacco smoke exposure keeps airway tissues in a state of chronic, low-grade inflammation, with elevated levels of inflammatory cells and cytokines, including interleukin-6 (IL-6). That same cytokine is a central driver of the “cytokine storm” seen in severe COVID-19 cases, where the immune system’s overreaction causes widespread organ damage.⁷ A smoker’s immune system, in other words, is already primed toward the type of exaggerated inflammatory response that COVID exploits.

What the Severity and Mortality Data Actually Show

Early in the pandemic, some hospital case series seemed to show that smokers were underrepresented among COVID-19 patients, sparking a brief and ultimately misguided narrative that smoking might be protective. Careful analysis later identified multiple biases in those early reports: smokers who stayed home with mild symptoms were undercounted, smoking status was inconsistently recorded in medical charts, and hospitalized patients were not representative of the broader infected population.⁸

Once larger studies and meta-analyses arrived, the picture shifted firmly against smoking. A meta-analysis pooling data from multiple studies found that current smokers had about 26 percent higher odds of dying from COVID-19 compared to nonsmokers, while former smokers had roughly 76 percent higher odds of death.⁹ Another meta-analysis found that any smoking history was tied to significantly higher odds of ICU admission and mortality, with the pooled odds of death roughly 58 percent higher for smokers.¹⁰

An interesting pattern shows up across several large studies: former smokers often appear to fare worse than current smokers. A population-based study in the Netherlands found that former smokers had about 30 percent higher risk of COVID-19 death after full adjustment, while current smokers had a slightly elevated but statistically non-significant risk.¹¹ A study of U.S. veterans similarly found that former smokers had higher 30-day mortality than both current smokers and nonsmokers.¹² The likely explanation is not that quitting makes you worse off; rather, many former smokers quit because they had already developed serious lung or heart disease, and that accumulated damage is what drives their higher risk. Current smokers who have not yet developed those conditions may look artificially healthier by comparison.

Lung Tissue Damage During and After Infection

Beyond helping the virus get in and weakening the immune response, smoking compounds the physical destruction that COVID-19 inflicts on lung tissue. Laboratory studies have shown that prior cigarette smoke exposure worsens SARS-CoV-2-induced damage to the airway lining through loss of the junctions that hold cells together, further ciliary dysfunction, excessive mucus production, and the development of lung fibrosis, where normal tissue is replaced by stiff scar tissue.¹³

COVID-19 is also known for causing blood clots, particularly in the lungs. The virus damages the endothelium, the thin cell layer lining blood vessels, and triggers abnormal clotting. Smoking history, along with older age, male sex, and conditions like diabetes and obesity, is recognized as a contributor to endothelial dysfunction and venous blood clots in COVID-19 patients.¹⁴ A smoker’s blood vessels are already chronically stressed; layering a viral infection that independently attacks the vascular system on top of that creates a compounding problem.

Weaker Vaccine Protection for Smokers

Vaccination was the main tool for reducing severe COVID-19, but the protection it provides is not uniform across all populations. A systematic review of 23 studies found that current smokers showed substantially lower antibody levels or faster decline in vaccine-induced antibodies compared to nonsmokers in 17 of those studies.¹⁵ A study of Japanese healthcare workers quantified the gap: exclusive cigarette smokers had antibody titers about 19 percent lower than never-smokers after receiving the Pfizer vaccine, and users of heated tobacco products were not far behind with about 11 percent lower titers.¹⁶ Another study found that smoking was significantly associated with lower antibody titers three months after vaccination.¹⁷

Lower antibody levels do not necessarily mean zero protection, and the clinical significance of these differences is still debated. Cell-mediated immunity, which antibody tests do not capture, also plays a role in fighting off the virus. Still, if you are a smoker, the evidence suggests your body may extract less benefit from each vaccine dose, which matters when immunity already wanes over time for everyone.

Smoking and Long COVID

The damage from the intersection of smoking and COVID-19 does not always end when the acute infection resolves. A literature review examining post-acute COVID symptoms found compelling evidence linking smoking to a higher risk of developing long COVID, particularly symptoms like shortness of breath, cardiovascular problems (including rapid heart rate and elevated blood pressure), and cognitive or mental-health difficulties.¹⁸ A French community-based survey found that smokers had roughly double the odds of developing tachycardia or high blood pressure persisting beyond 60 days after infection, and more than double the odds of lingering skin symptoms.¹⁹

This makes biological sense given what we know about the underlying mechanisms. Smoking causes chronic vascular inflammation and impairs the lungs’ ability to repair themselves. COVID-19 independently causes endothelial damage and can leave behind fibrotic tissue. When both insults overlap, recovery is slower and more incomplete. The connection between smoking and upper-airway long COVID symptoms like persistent loss of smell appears less certain, but the cardiovascular and respiratory links look fairly strong.

Quitting Helps, but the Timeline Matters

A large Chinese survey of more than 22,000 people who had tested positive for COVID-19 offers one of the clearest pictures of how cessation timing affects outcomes. Current smokers had more than three times the odds of developing COVID-related pneumonia compared to never-smokers, and people who had quit within the previous ten years had similarly elevated odds. But former smokers who had quit more than ten years earlier showed no statistically significant increase in pneumonia risk at all.²⁰ The same pattern held for hospitalization and severe disease.

Ten years is a long time, and this does not mean quitting yesterday is pointless. Many of the acute immune-system effects of smoking, like suppressed antibody production and impaired mucociliary clearance, begin to improve within weeks to months of quitting. But the deeper structural damage to lung tissue and blood vessels takes much longer to heal, and some of it may never fully reverse. The takeaway is that quitting at any point confers some benefit, but the earlier someone quits, the more their COVID-19 risk profile comes to resemble that of a never-smoker.

Secondhand Smoke Is Not a Bystander

You do not have to be the one lighting up to experience smoking-related COVID-19 risk. A multicenter case-control study found that people exposed to secondhand smoke at home had about three times the odds of developing severe COVID-19 compared to those without exposure. Secondhand smoke at the workplace was associated with roughly double the odds of severe disease.²¹ A study focused on Latinx families in the San Francisco Bay Area found that any secondhand smoke exposure was associated with increased odds of COVID-19 infection itself, not just severity.²²

These findings are worth considering in households where nonsmoking members include older adults, immunocompromised individuals, or young children. Secondhand smoke causes many of the same airway changes that direct smoking does, including mucociliary impairment and chronic inflammation, just at somewhat lower intensity. During waves of a respiratory pandemic, that baseline degradation of airway defenses can translate into meaningfully worse outcomes.

Vaping and E-Cigarettes

The question of whether vaping carries similar COVID-19 risks is harder to answer because the research base is thinner and the products vary widely. A mouse study found that animals exposed to vaporized e-liquid and then infected with a coronavirus experienced more severe lung inflammation and higher mortality than control mice.²³ A systematic review and meta-analysis of respiratory effects in human vapers found moderate evidence that current vapers who had never smoked cigarettes had higher rates of respiratory symptoms, lung inflammation, and lung damage compared to non-users, but findings on COVID-19 and other respiratory infections were inconsistent.²⁴

A cross-sectional analysis found that people who used vaporizers for either tobacco or cannabis had about 89 percent higher odds of reporting shortness of breath during COVID-19 compared to non-users, and people who both smoked and vaped had double the odds.²⁵ The evidence is not as deep or consistent as what exists for cigarette smoking, but the direction of the findings is clearly not reassuring for vapers. Anyone who switched from cigarettes to e-cigarettes with the belief that their lungs would be completely protected during a respiratory pandemic should understand that the aerosol still irritates airways and may still impair local immune defenses.

Cannabis Smoking and COVID-19

Cannabis smoke contains many of the same combustion byproducts as tobacco smoke, so it is reasonable to wonder whether it carries similar risks. The evidence here is genuinely mixed. A longitudinal cohort study found that dried cannabis users self-reported higher rates of multiple COVID-19 infections compared to non-users, even after accounting for vaccination status, while tobacco use alone did not show the same association in that study.²⁶ On the other hand, a genetically informed analysis using Mendelian randomization found no causal association between genetically predicted cannabis use and any COVID-19 outcome.²⁷

The discrepancy may reflect confounding: people who use cannabis might differ from non-users in social behaviors, exposure patterns, or willingness to report infections, in ways that observational surveys cannot fully untangle. Cannabis smoke does irritate airways and could plausibly impair mucociliary clearance, but the immunological picture is complicated by the fact that cannabinoids also have some anti-inflammatory properties. The cross-sectional analysis mentioned earlier found that exclusive cannabis use was independently associated with higher odds of reporting shortness of breath during COVID-19, with about 56 percent higher odds than non-users.²⁵ The safest interpretation right now is that inhaling any combustion product is unlikely to do your airways any favors during a respiratory infection, even if cannabis and tobacco may affect the immune system through different pathways.