Long COVID can feel like being adrift at sea, tiringly kicking those legs to stay above water. Social media provides lifebuoys but many turn out to be tricks of the light.
What about nicotine? On Facebook, you will find sober recommendations to try nicotine patches to save you from drowning in the fatigue of long COVID, as well as more conspiratorial takes on the problematic substance. I have seen听听declaring nicotine to be 鈥渢he slandered savior鈥濃�攁ccompanied by the hashtag 鈥�#BigPharmaLies,鈥� no less鈥攁nd the听听that the World Health Organization (WHO) is trying to ban tobacco, which contains nicotine, knowing full well that it is a cure and a way to stop the WHO鈥檚 鈥渄epopulation agenda.鈥� On the platform, end users knock elbows with enthusiastic chiropractors and more moderate physicians, all trying to make sense of the nicotine-long-COVID connection.
This idea that nicotine can treat long COVID originates from an early observation which led to a hypothesis. But what happens when the evidence for this hypothesis doesn鈥檛 completely add up?
Long COVID is real but incredibly complex
While the WHO declared the end of COVID-19 as a global health emergency in the summer of 2023, most seem to forget an important part of听: 鈥渋t does not mean the disease is no longer a global threat.鈥� As we go about our lives ignoring the virus, it continues to infect, debilitate, and kill every week.
The organization COVID-19 Resources Canada, led by infectious disease researcher Tara Moriarty, estimates that, as of this writing,听听颈蝉听肠耻谤谤别苍迟濒测听infected with the coronavirus. This estimate comes from limited wastewater surveillance, test positivity rates, and excess mortality, because we no longer have straightforward numbers to rely on: the Government of Canada only reports on the percentage of COVID-19 tests that are positive, a statistic of limited use as few people continue to test themselves鈥攅arlier this month, the statistic only included听听for the entire country that week.
As with other infections, COVID-19 can linger, and those long-term symptoms are referred to as long COVID. We still do not have a clear picture of how many people infected by the coronavirus will go on to develop long COVID. I have seen sources that put the percentage at 1% and others at more than 10%. What counts as long COVID is not easy to judge. If I catch the virus and a week later start feeling pain in my joints, is it due to the illness or was I 鈥渟cheduled鈥� to develop arthritis at this point in my life? The symptoms of long COVID are also numerous, and they involve every organ system in the body. Defining long COVID remains the subject of debates.
Research into the condition has unearthed听听that make it hard to decide if long COVID is a single entity or more an umbrella term for various independent complications from the initial infection. In some long COVID patients, we see alterations in cells of the immune system; higher levels of antibodies directed at the body鈥檚 own cells; dormant viruses, like the Epstein-Barr virus, being awakened; an insufficient production of antibodies against the coronavirus; indications that the coronavirus remains in the body in hidden reservoirs; and many more telltale signs of dysregulation and dysfunction. Not every long COVID patient checks all of these boxes, which leads to contradictions and attempts at separating long COVID into discrete entities. Yet, far from being a peculiar condition, long COVID often resembles myalgic encephalomyelitis/chronic fatigue syndrome or ME/CFS: indeed, it is estimated that about听听of all long COVID patients meet the criteria for ME/CFS, itself a poorly understood, draining condition.
Treating long COVID has proven difficult; yet some claim it is as simple as applying a nicotine patch on the arm.
A pack of Gauloises a day keeps the doctor away?
The nicotinic hypothesis was formulated quickly: a month after our own university moved to working from home, a group in Paris proposed their theory in a听听promptly published in听Comptes Rendus Biologies.听At the time, it looked as if smokers were protected from the infection. In听, smokers were听耻苍诲别谤谤别辫谤别蝉别苍迟别诲听in patients hospitalized with the new disease. Doctors were seeing fewer of them than they would expect based on the percentage of the population that smokes鈥攁nd on the fact that smoking generally predisposes you to a number of respiratory infections, including听,听, and听. The Parisian medical researchers wondered what could explain this.
We knew at the time that the coronavirus binds to the ACE2 receptors expressed on the outside of cells in our airways, like a key fitting into a lock. But because COVID was often accompanied by an inflammatory component, it was hypothesized that the virus could听also听bind to another type of receptor: nicotinic acetylcholine receptors or nAChRs for short. These receptors usually interact with the neurotransmitter acetylcholine, but molecules in some snake venoms and strains of the rabies virus can also bind to them because of a short sequence of amino acids. And this sequence was shared, the Parisian team found, by the spike protein that the coronavirus displayed at its surface like a crown of thorns. The new virus could thus,听in theory, displace acetylcholine from nAChRs and cause damage.
The hypothesis went on that, because nicotine binds to these same receptors very, very strongly, smokers were protected from the more severe effects of the coronavirus. The spike protein wanted to access this lock, but nicotine keys were already jammed in there and they were in no hurry to leave. Hence the otherwise unsound proposal, in the team鈥檚 April 2020 paper, that 鈥渘icotine may be suggested as a potential preventative agent against COVID-19 infection.鈥� French doctors were not telling their countrymen to pick up a pack of Gauloises; they highlighted that nicotine is a 鈥渄rug of abuse鈥� and that smoking is bad, but they wondered about 鈥渘icotinic agents鈥� in controlled settings. Perhaps nicotine patches.
The scientific evidence for this hypothesis is, at this point, artificial and far from conclusive. A team has shown that, when听听to predict what will happen, the coronavirus鈥� spike protein听听to these nicotinic receptors. Researchers have also forced cells in the lab (namely human kidney cells and frog egg cells) to express certain types of nicotinic receptors and put them in a solution containing a fragment of the spike protein created in the lab, and the听听听. On either side of the debate, fans can pick the papers that support their position, but what the data reveals is that if this hypothesis is indeed true, it comes with a number of caveats.
Speaking of caveats, those early reports that smokers were underrepresented in COVID hospital wards were听, using data sets where the smoking status of a significant portion of hospitalized patients was missing or where people who had recently stopped smoking were categorized not as smokers but as 鈥渇ormer smokers.鈥�
Oh, and the French team that proposed the nicotinic hypothesis and suggested that maybe nicotine could prevent COVID-19? Its star scientist, Jean-Pierre Changeux, received听听to fund his research in the mid-90s, according to newspaper听Le Monde.
The safety of nicotine
Online, people with long COVID are experimenting with nicotine patches and reporting on their experience. The听听(formerly 鈥淭he Nicotine Test鈥� or TNT) is a Facebook group that gives desperate long COVID patients a treatment strategy: start with tiny doses, ramp it up, stay at that dose, then taper down to find the minimally effective dose. Nicotine gums, sprays, and lozenges are not recommended because they deliver spikes of nicotine, which come with a risk of addiction; transdermal patches have a slow, continuous release, thus lowering that risk. (The Nicotine Patch Test鈥檚听听states that nicotine replacement therapy is not recommended for patients with cardiovascular issues, presumably because the stimulating properties of nicotine can raise blood pressure and increase the risk of irregular heart rhythms.)
Nicotine patches have typically been tested in smokers who want to quit; their safety in non-smokers is far less certain. On the one hand, the stimulant is stripped of the toxic substances that make up a cigarette, and a听听of clinical trials using nicotine replacement therapy to quit smoking (which includes not just patches, but gum, sprays, and oral preparations as well) published by the Cochrane Collaboration failed to find serious complications from its use in over 64,000 participants. Nicotine patches have been tested in non-smokers, to see if they might benefit people with cognitive issues or Parkinson鈥檚 disease, for example, and a look at听听showed that, aside from nausea and skin itching, they were well tolerated. But these studies did not formally evaluate if their participants became addicted to them. Nicotine patches are thus听thought听to be safer and听thought听to be not nearly as addictive as cigarettes in nonsmokers. We unfortunately don鈥檛 have a clearer answer than that.
Some people with long COVID report that nicotine patches听, while others say their symptoms worsened. These anecdotes are not conclusive; rather, they can be hypothesis generating. In the absence of good, validated treatments for long COVID, I can understand the desire to try just about anything, especially when debilitating symptoms can last for months, years, perhaps the rest of someone鈥檚 life.
In these waters, however, wade bearers of hope who seem ready to do away with good science. One big proponent of nicotine for long COVID is a chiropractor and acupuncturist whose听听is to 鈥減ut [their] faith in God鈥檚 healing power.鈥� A听, in part penned by researchers that are either administrators or moderators of The Nicotine Test Facebook group, mentions that ivermectin is known to alleviate the symptoms of an acute COVID infection, even though they should know by now that ivermectin has been听听as a treatment for the disease and that slight improvement in symptom resolution comes from self-reports听in people who knew they were taking a drug and not a placebo. I have also seen functional medicine practitioners get involved. Functional medicine is not a specialty of medicine, but a siren song听for doctors to practice alternative medicine听by overtesting their patients and recommending an expensive collection of dietary supplements in the hope of fixing things.
Long COVID is a mess layered on top of a web of suffering people. One of the valid 鈥渢reatments鈥� for it is pacing yourself, which is a guideline for surviving through the brain fog and fatigue but not a resolution of either of them. A long list of options is being tested鈥攁s听n-of-1 experiments at home, as pilot studies, or as the few funded formal studies on long COVID鈥攁nd they include antivirals, probiotics, and even tirzepatide (Zepbound), a new weight-loss medication.
Nicotine patches听might听help some people with long COVID, even though our current understanding of how it would do so remains patchy. It is unlikely to be a game-changer and its long-term safety is unclear to me. As funds to study the condition dry up, experimentation will move away from the clinic and into the hands of individuals, where variables can be harder to control.
As for how to avoid long COVID, the answer has not changed since we鈥檝e understood how the virus spreads: masking, air filtration, and vaccination remain key, even as we choose to ignore them in our embrace of normalcy.
Take-home message:
-The idea behind using nicotine patches to treat long COVID comes from the observation that smokers appeared to be less likely to be hospitalized with COVID-19 early during the pandemic
-A French group of scientists hypothesized that nicotine, which is found in cigarettes, binds a type of receptor inside the body, thus preventing the coronavirus itself from binding to it
-There are problems with this hypothesis: the underrepresentation of smokers in COVID wards was due to incomplete data, and experiments in the lab trying to validate if the coronavirus does bind to the same receptor as nicotine have resulted in contradictory results
-While nicotine patches are relatively safe in smokers trying to quit, the risk of developing a nicotine addiction in nonsmokers who use them has not been properly evaluated. Nicotine patches, as opposed to cigarettes and other types of nicotine replacement therapy, are thought to not lead to addiction because the dose of nicotine is low and continuous
