Nicotine and COVID-19: The Research

Early hospital data in 2020 showed fewer smokers than expected among COVID-19 patients, which led to a hypothesis that nicotinic receptors are involved in the infection and to randomised trials of nicotine patches. This page collects the published research on nicotine and COVID-19 as the papers report it, each summarised in plain language with its PubMed record.

This collection is research only: papers found on PubMed, each described as its own abstract reports it. Cell and animal results are labelled as such, and harms are listed beside benefits. It is not medical advice.

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The Papers (17)

Newest first. Study types on this page — Human trial: 1 · Human observational study: 3 · Review: 4 · Cell study: 3 · Other: 6. Each summary is written from the paper’s own abstract; follow the PubMed link for the full record.

Very low nicotine content cigarettes for smoking cessation: Examining a facilitated extinction approach and dosing schedule

Human trial, 2026. This randomized trial tested very low nicotine content cigarettes as a step toward quitting in 127 adults who smoked and wanted to quit (58% female). For 5 weeks before their quit date, people either switched to the very low nicotine cigarettes all at once or cut nicotine content gradually, and got either standard quit-smoking counseling or a 'facilitated extinction' approach, in which they kept smoking at their usual rate in many different settings. Overall, 80% finished treatment, more often in the gradual groups (88% versus 72%). Craving for the study cigarettes, satisfaction from smoking and cigarettes smoked per day all fell. Two months after treatment, lab-confirmed abstinence was 29% and 31%, with no differences between the groups. The authors say this approach may help people quit and is practical enough to test in larger trials.

Drobes DJ, Sutton SK, Conn MR et al. (2026). Very low nicotine content cigarettes for smoking cessation: Examining a facilitated extinction approach and dosing schedule. Drug Alcohol Depend. — PubMed PMID: 41314054 · doi:10.1016/j.drugalcdep.2025.112971

Long-term WBE monitoring of alcohol, nicotine, and caffeine in two Spanish cities: COVID-19 impacts and beyond

Human observational study, 2025. Researchers tested 192 samples of untreated sewage, each collected over 24 hours from nine wastewater treatment plants in Madrid and Guadalajara, Spain, between 2021 and 2025, to estimate how much alcohol, nicotine and caffeine the whole population was using. From 2021 to 2024, nicotine and alcohol use went down in both cities. Nicotine fell by about 800 mg/day per 1000 people in Madrid and about 500 mg/day per 1000 people in Guadalajara, while caffeine use stayed about the same or rose slightly. Nicotine and alcohol were highest over the 2022-2023 New Year, the first holiday without COVID-19 restrictions, and were lower over the next New Year holidays.

Melones-Peña N, Pérez T, Pardo MC et al. (2025). Long-term WBE monitoring of alcohol, nicotine, and caffeine in two Spanish cities: COVID-19 impacts and beyond. Environ Sci Pollut Res Int. — PubMed PMID: 41266906 · doi:10.1007/s11356-025-37060-5

COVID-19 Disease and Chronic Health Outcomes Associated with Nicotine Use in a Great Plains Tribal Community: A Community-Based Study

Human observational study, 2025. Researchers surveyed 562 adults from 289 households on the Cheyenne River Sioux reservation and compared self-reported health among people who used only e-cigarettes, only cigarettes, both, or neither. Over half of the participants (53%) used nicotine, and the median number of puffs per day was 15 for e-cigarette users, 100 for cigarette smokers and 20 for people who used both. Compared with non-users, nicotine users had lower odds of reporting COVID-19, high blood pressure and high cholesterol, and lower odds of severe COVID-19 infection, but higher odds of a longer COVID-19 recovery time. All health outcomes were self-reported in a survey, and the study looked at associations at one point in time rather than testing nicotine directly.

Tillery A, O'Leary R, Aherrera A et al. (2025). COVID-19 Disease and Chronic Health Outcomes Associated with Nicotine Use in a Great Plains Tribal Community: A Community-Based Study. J Racial Ethn Health Disparities. — PubMed PMID: 39256325 · doi:10.1007/s40615-024-02145-3

Determination of soluble angiotensin-converting enzyme 2 in saliva samples and its association with nicotine

Human observational study, 2023. Researchers measured nicotine and a soluble form of the ACE2 protein in people's saliva. ACE2 is the main doorway the COVID-19 virus uses to enter cells. They pooled data from two studies of 634 and 302 people and found that people with the highest saliva nicotine levels had slightly higher soluble ACE2 than those with the lowest levels, and cotinine, a breakdown product of nicotine, showed a similar pattern. The links were weak, and the authors concluded that saliva nicotine is only loosely associated with soluble ACE2 levels.

Bru S, González-Marrón A, Lidón-Moyano C et al. (2023). Determination of soluble angiotensin-converting enzyme 2 in saliva samples and its association with nicotine. Environ Res. — PubMed PMID: 36195157 · doi:10.1016/j.envres.2022.114443

Nicotine in Combination with SARS-CoV-2 Affects Cells Viability, Inflammatory Response and Ultrastructural Integrity

Cell study, 2022. Researchers treated human lung cells grown in the lab with nicotine. They then exposed the cells to substances that mimic bacterial or viral infection, or infected them with SARS-CoV-2, the virus that causes COVID-19. With the infection-mimicking substances, nicotine lowered two inflammatory signals (IL6 and TNFα). With the real virus, nicotine made things worse: it increased the virus's damage to the cells, raised inflammatory signals, and caused severe cell injury that looked like two kinds of inflammatory cell death. These results come from cells only, but the authors concluded that nicotine has no protective role in COVID-19.

Sansone L, de Iure A, Cristina M et al. (2022). Nicotine in Combination with SARS-CoV-2 Affects Cells Viability, Inflammatory Response and Ultrastructural Integrity. Int J Mol Sci. — PubMed PMID: 36012747 · doi:10.3390/ijms23169488

The smoker's paradox during the COVID-19 pandemic? The influence of smoking and vaping on the incidence and course of SARS-CoV-2 virus infection as well as possibility of using nicotine in the treatment of COVID-19 - Review of the literature

Review, 2021. This review looked at studies published up to November 2020 on how smoking, vaping and nicotine might affect catching COVID-19 and how severe it gets, and whether nicotine could be used to treat it. The studies disagreed: some reported that smoking and nicotine lower the number of ACE2 receptors, which the coronavirus uses to get into cells, while others reported more of these receptors in smokers. Some studies also found fewer current smokers in hospital with COVID-19 than expected, and the authors suggest nicotine might help restore the body's nicotinic cholinergic system and possibly calm the cytokine storm. The authors concluded there is no clear answer yet, did not recommend smoking as a way to fight the pandemic, and said both the link between smoking and COVID-19 and nicotine as a possible treatment need more study.

Korzeniowska A, Ręka G, Bilska M et al. (2021). The smoker's paradox during the COVID-19 pandemic? The influence of smoking and vaping on the incidence and course of SARS-CoV-2 virus infection as well as possibility of using nicotine in the treatment of COVID-19 - Review of the literature. Przegl Epidemiol. — PubMed PMID: 34328284 · doi:10.32394/pe.75.03

From nicotine to the cholinergic anti-inflammatory reflex - Can nicotine alleviate the dysregulated inflammation in COVID-19?

Review, 2021. This review article looks at whether nicotine might calm the runaway inflammation, called a cytokine storm, that can happen in severe COVID-19. The authors explain that nicotine and a related experimental compound, GTS-21, switch on a nerve-based anti-inflammatory pathway through the α7 nicotinic receptor. Earlier research found that this lowers HMGB1, an inflammation signal that is high in patients with severe COVID-19 and is linked to worse outcomes. No new experiments were done: the authors only propose that compounds which switch on this pathway, such as nicotine or GTS-21, could be a possible treatment approach worth studying in severe COVID-19.

Gauthier AG, Lin M, Wu J et al. (2021). From nicotine to the cholinergic anti-inflammatory reflex - Can nicotine alleviate the dysregulated inflammation in COVID-19?. J Immunotoxicol. — PubMed PMID: 33860730 · doi:10.1080/1547691X.2021.1875085

Nicotinic cholinergic system and COVID-19: In silico identification of interactions between α7 nicotinic acetylcholine receptor and the cryptic epitopes of SARS-Co-V and SARS-CoV-2 Spike glycoproteins

Other, 2021. This was a computer modeling study only; no people, animals or cells were tested. The researchers used computer models to see how the spike proteins of SARS-CoV and SARS-CoV-2, the virus that causes COVID-19, might fit against the human α7 nicotinic acetylcholine receptor, a receptor that nicotine acts on. In every model, the contact area included a large part of the spike's 'toxin-like' section, which resembles part of a snake venom toxin, and the spot on the receptor where such toxins bind. The authors say this supports the idea that nicotine and similar substances that activate the same receptors might be protective, and that antibodies against this part of the spike protein should be studied further.

Lagoumintzis G, Chasapis CT, Alexandris N et al. (2021). Nicotinic cholinergic system and COVID-19: In silico identification of interactions between α7 nicotinic acetylcholine receptor and the cryptic epitopes of SARS-Co-V and SARS-CoV-2 Spike glycoproteins. Food Chem Toxicol. — PubMed PMID: 33503469 · doi:10.1016/j.fct.2021.112009

Nicotine Changes Airway Epithelial Phenotype and May Increase the SARS-COV-2 Infection Severity

Cell study, 2020. Researchers exposed human airway lining cells grown in the lab to nicotine at a concentration meant to match what a person takes in from one cigarette, for 1 hour, 48 hours or continuously. Acting through a nicotinic receptor called alpha-7, nicotine made the cells survive and multiply more, delayed their normal aging, lowered the protective protein p53, raised growth signals such as VEGF and EGFR, cut the cells' energy (ATP) production, and made them move more and grow without anchoring, changes linked to a more tumor-like state. These results come only from lab-grown cells, and the experiments did not use the virus. The authors still concluded, from these findings and earlier evidence, that nicotine is likely involved in how severe SARS-CoV-2 infection becomes.

Lupacchini L, Maggi F, Tomino C et al. (2020). Nicotine Changes Airway Epithelial Phenotype and May Increase the SARS-COV-2 Infection Severity. Molecules. — PubMed PMID: 33379366 · doi:10.3390/molecules26010101

Nicotine and the nicotinic cholinergic system in COVID-19

Review, 2020. This review looks at how nicotine and the body's nicotinic receptor system might affect COVID-19. The authors agree that smoking does harm and support quitting smoking to lower COVID-19 risk. They also argue that nicotine itself, or drugs that act on nicotinic receptors, could have a possible treatment role, because these may affect mood and inflammation and might interfere with how the virus enters or copies itself in cells. The authors present this as a possibility and a hypothesis. The paper reports no new experiments in people, animals or cells.

Tizabi Y, Getachew B, Copeland RL et al. (2020). Nicotine and the nicotinic cholinergic system in COVID-19. FEBS J. — PubMed PMID: 32790936 · doi:10.1111/febs.15521

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

Other, 2020. This short article puts forward an idea, a hypothesis, about Covid-19 and does not report a new experiment. The authors cite early population data suggesting that people who currently smoked appeared less likely to be infected by the virus that causes Covid-19. From this they propose that the nicotinic acetylcholine receptor, the receptor that nicotine acts on, plays a key role in how the infection develops. They suggest the receptor could be a target for preventing and controlling Covid-19, but the article did not test this in people, animals or cells.

Changeux JP, Amoura Z, Rey FA et al. (2020). A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications. C R Biol. — PubMed PMID: 32720486 · doi:10.5802/crbiol.8

Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm

Other, 2020. This paper puts forward a hypothesis; it is not a study. Severe COVID-19 can set off a 'cytokine storm', in which the immune system releases too many inflammatory signals. The authors suggest nicotine might calm that storm, because it switches on a type of nicotinic receptor (α7) that is part of the body's own anti-inflammation pathway, and they note nicotine is already used in ulcerative colitis to reduce inflammation. They point to early clinical reports from China suggesting smokers were statistically less likely to be hospitalized, and they propose nicotine as a possible treatment for severely ill patients, but they did not test it in patients, animals or cells.

Gonzalez-Rubio J, Navarro-Lopez C, Lopez-Najera E et al. (2020). Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm. Front Immunol. — PubMed PMID: 32595653 · doi:10.3389/fimmu.2020.01359

How nicotine can inhibit cytokine storm in the lungs and prevent or lessen the severity of COVID-19 infection?

Other, 2020. This is a short letter that puts forward an idea; it is not a new experiment. It starts from survey reports suggesting that people who smoke were less likely to catch COVID-19, or had milder breathing symptoms, than non-smokers. The authors suggest nicotine may calm the inflammatory response in the lungs. Because immune cells in the lungs called macrophages largely shape how the body responds to and clears the virus, the letter reviews recent findings that could explain how nicotine might change the way these cells respond during COVID-19.

Kloc M, Ghobrial RM, Kubiak JZ (2020). How nicotine can inhibit cytokine storm in the lungs and prevent or lessen the severity of COVID-19 infection?. Immunol Lett. — PubMed PMID: 32522666 · doi:10.1016/j.imlet.2020.06.002

COVID-19 and the nicotinic cholinergic system

Other, 2020. This short letter discusses COVID-19 and the body's nicotinic cholinergic system, the network of receptors that nicotine acts on. The authors note that smoking appears to be uncommon among people hospitalised with COVID-19. They propose that some COVID-19 symptoms could be linked to a breakdown of the cholinergic anti-inflammatory pathway, a nerve-based system that helps calm inflammation. They suggest that substances that activate nicotinic receptors should be studied as possible treatments; the letter reports no new experiments or patient data.

Farsalinos K, Angelopoulou A, Alexandris N et al. (2020). COVID-19 and the nicotinic cholinergic system. Eur Respir J. — PubMed PMID: 32444400 · doi:10.1183/13993003.01589-2020

COVID-19 and nicotine as a mediator of ACE-2

Other, 2020. This is a short letter to a lung medicine journal, written early in the COVID-19 pandemic, about how nicotine might be connected to ACE-2. ACE-2 is the protein on the surface of cells that the COVID-19 virus uses to get in. The letter suggests that the alpha-7 nicotinic receptor, which nicotine acts on, may increase the amount of ACE-2 on cells. This is an idea put forward for discussion. The abstract reports no experiment, no participants and no measured results.

Leung JM, Yang CX, Sin DD (2020). COVID-19 and nicotine as a mediator of ACE-2. Eur Respir J. — PubMed PMID: 32350104 · doi:10.1183/13993003.01261-2020

COVID-19 and smoking: is nicotine the hidden link?

Cell study, 2020. This short letter asks whether nicotine itself could help explain a possible link between smoking and COVID-19. The authors report that, in human airway lining cells grown in the laboratory, nicotine acting through one type of nicotinic receptor (the alpha7 receptor) increased the amount of ACE-2, the protein the COVID-19 virus uses to enter cells. This result comes only from cells in a dish and was not tested in people.

Russo P, Bonassi S, Giacconi R et al. (2020). COVID-19 and smoking: is nicotine the hidden link?. Eur Respir J. — PubMed PMID: 32341101 · doi:10.1183/13993003.01116-2020

Is nicotine exposure linked to cardiopulmonary vulnerability to COVID-19 in the general population?

Review, 2020. This review, written early in the COVID-19 pandemic, looks at people who were exposed to nicotine before they caught the virus. The authors propose that these people may be 'primed' for a higher risk of serious illness, because nicotine can act directly on ACE2, the likely entry point the virus uses to get into cells, and can trigger harmful signalling in the cells that line the lungs. This is a prediction based on known biology. The review reports no new study in people that tests it.

Olds JL, Kabbani N (2020). Is nicotine exposure linked to cardiopulmonary vulnerability to COVID-19 in the general population?. FEBS J. — PubMed PMID: 32189428 · doi:10.1111/febs.15303

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