Can a regimen of nicotine patches alleviate Long COVID symptoms? Research shows a clear "maybe".

From our community: Do nicotine patches help with Long COVID symptoms?

New blog series: From our community
In the blog category &ldquo;From our community&rdquo;, we address treatments that are being discussed controversially by people affected by Long COVID and health care professionals. In the Altea <a href="https://altea-community.com/">forum</a>, in <a href="https://altea-network.com/en/stories">stories</a>, and in discussions with those affected, we have seen a number of treatment suggestions that are not officially recommended (yet). To help judge the safety and effectiveness of these treatments, we are exploring the science behind them. We are aiming to provide an overview of the available evidence, evaluate whether or not the available data is reliable, and summarize which risks might be associated with these treatments. Today, we want to assess nicotine patches.
&nbsp;
The nicotinic hypothesis
In the beginning of the pandemic, it was observed that smokers were <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276022/">less often</a> infected by SARS-CoV-2 then non-smokers. This observation led to what is called the nicotinic hypothesis.
After a scientific <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337760/">brief report</a> showed that COVID-19 cases where higher in countries with fewer smokers, a series of papers examined the phenomenon. In the excitement of the early pandemic, a scientific debate about smoking and COVID-19 ensued in which authors disputed each other&rsquo;s findings, re-analyzed each other&rsquo;s data, and stated opposing conclusions.
<ul>
<li>In 2020, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118593/">a letter to the editor </a>of the European Journal of Internal Medicine claimed that their data shows that smoking has no relationship with COVID-19 symptoms.</li>
<li>A subsequent <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254011/">letter</a> emphasized that just because the first letters data did not show evidence, does not mean there is none. The authors of the second letter performed a different statistical analysis on the data of the first group and showed that active smoking does increase the severity of COVID-19 infection.</li>
<li>A follow up <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202479/">letter</a> of a third researcher performed an updated meta-analysis on the first letter and found that their conclusion may be based on an inaccurate analysis.</li>
<li>While multiple theories concerning the topic of smokers being potentially protected against SARS-CoV-2 evolved, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910565/">more</a> <a href="https://pubmed.ncbi.nlm.nih.gov/32788164/">articles</a> discussed the flaws in already published analyse</li>
<li>A recent <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10306417/#:~:text=The%20study%20found%20that%20while,CI%3A%200.69%E2%80%931.10).">mini-review</a> comparing the likelihood of infection and severeness of later disease found that between January 2020 and April 2022, 31 articles stated that smoking increases the risk of infection, while 13 articles stated the opposite.</li>
</ul>
The effects of non-cigarette products like hookah and e-cigarettes are even more unclear. What remains to be evaluated is the effect of nicotine replacement without the side effects of smoking.
&nbsp;
The science behind the hypothesis
Although not without <a href="https://www.pnas.org/doi/10.1073/pnas.2204242119">controversy</a>, it was <a href="https://pubmed.ncbi.nlm.nih.gov/36650574/">shown</a> that a protein of SARS-CoV-2 binds to a receptor called nAChR (nicotinic acetylcholine receptor). This bond could compromise interneural communication, meaning communication between cells of the nervous system (neurons). A disturbance in interneural communication can lead to cognitive and neuromuscular symptoms that align with Long COVID symptoms. nAChRs are named after their affinity to nicotine. This gave researchers the idea to saturate the receptors with nicotine from patches developed for smokers to inhibit binding of SARS-CoV-2.
A recent <a href="https://pubmed.ncbi.nlm.nih.gov/36650574/">case study</a> tested nicotine patches in four patients with Long COVID. The study included one woman and three men between the ages of 19 and 52 who suffered from numerous Long COVID symptoms after a PCR-confirmed SARS-CoV-2 infection with a mild course. The patients were instructed to apply one nicotine patch with the lowest dose (7.5 mg) every morning. One patient purchased the wrong patches and applied a patch with a higher dose (15 mg). All four patients improved noticeably and quickly on the regimen.
A clinical case study is not a controlled clinical trial but instead documents singular clinical observations in interesting cases. It has no control group or blinded results but serves as a good indicator of what could be an interesting topic for an upcoming large, well-organized and thus expensive randomized controlled trial (see <a href="https://altea-network.com/en/blog/111-understanding-clinical-studies">Altea: understanding clinical studies</a>).
To date, the above-mentioned case study is the only published clinical study on nicotine patches we are aware of. We are hoping for more data and randomized controlled trials in the future.
&nbsp;
<img src="https://adm.altea-network.com/assets/bc4144e6-37c2-4a0e-8c70-88fa3397f99d?width=1573&amp;height=1443" alt="Altea Blog Nicotine Study Design V3.png" />
Case study: the effect of nicotine patches on Long COVID symptoms was tested in four patients.
&nbsp;
Why nicotine patches? Can&rsquo;t I just start smoking?
Store-bought cigarettes contain about <a href="https://www.sciencedirect.com/science/article/abs/pii/S036012850600013X">4800</a> substances of which 69 have been <a href="https://pubs.acs.org/doi/epdf/10.1021/tx000260u">proven</a> to be cancerous. According to the <a href="https://www.who.int/news-room/fact-sheets/detail/tobacco">World Health Organization</a>, smoking kills more than 8 million people each year. 1.3 million of those deaths are non-smokers who are exposed to second-hand smoke. Skin patches rely on the active ingredient nicotine without many of the harmful substances in cigarettes and without smoke harming the lungs. Nicotine itself <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041956/">might stimulate tumor growth</a> but is not established as a cancerous substance. It is however addictive and linked to cardiovascular risk.
<blockquote>
Nicotine replacement therapies are well researched and less harmful than smoking.
</blockquote>
As a means to stop smoking, nicotine replacement therapies such as patches, gums, lozenges and nasal sprays have been <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491776/">thoroughly researched</a> over the years. They are deemed generally safe and universally recommended due to having less of a negative impact than smoking cigarettes.
However, nicotine replacement can increase the risk of <a href="chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https:/d1wqtxts1xzle7.cloudfront.net/63449782/IJOHD-5-2-69-7520200527-26670-1kusbiz-libre.pdf?1590647355=&amp;response-content-disposition=inline%3B+filename%3DNicotine_replacement_therapy_A_smoking_c.pdf&amp;Expires=1700668782&amp;Signature=LD3~Aox0p6dVQ7pjyINrGXonb5LK0fTDZiuChxJOFtGNrDaGI8dHQYbZqHWdpqp0j0aw0IEwCgqtb0-tbPDwggcZHNq-n--O-4N4I3t9QiDD8HbNevnyOC7vcWXMQYPNTC7zMczsOUSuZMvUkUizU660QFnGdEX9mdlNT0XuRfsVS~bjDO~9ukFvBRi8X0uGxPXVUOIrCHUv9FNxj8kfoIs6iLO44~OlbYEv7vY0m4Ts1D6YTlrG-iKHKimfVg-gQFO3bu1fBmF3DAI~gnU9bp15EfZD4mBIyyuZyqYw0QHy8Mabjc-OAaVOrar5wxSaZq0EzeZvmQhnAft2tnvxjQ__&amp;Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA">pregnancy complications</a> and enhance the risk of spontaneous abortion, stillbirth or sudden infant death syndrome. Moreover, nicotine can increase heart rate by 10-15 beats/minute and blood pressure by 5-10 mm Hg and thus poses a risk for <a href="https://www.jacc.org/doi/abs/10.1016/S0735-1097(97)00079-X">cardiovascular disease</a>. Nicotine is not recommended for children and associated with a high risk of overdose. Precautions should be taken for breast feeding mothers and diabetics and interaction with medications should be evaluated. If choosing a lozenge instead of the patch, be aware that it might contain soy allergens.
&nbsp;
How to apply nicotine patches
<ol>
<li>Start at the right dose. Unless advised differently, we recommend the lowest dose.</li>
<li>Do not wear more than one patch at once.</li>
<li>Replace the patch after 24 hours.</li>
<li>Put the patch on clean, dry, hair-free skin on the upper body, avoiding irritated or damaged skin.</li>
<li>Thoroughly wash your hands with soap after handling the patch.</li>
<li>Put the patch on a different area of your upper body each day.</li>
</ol>
The patch can be kept on in the shower. Anecdotal tips recommend wearing a standard plaster below the nicotine patch if you are worried about absorbing too much nicotine at once or about the adhesive of the nicotine patch.
&nbsp;
Conclusion
So far, it was shown that nicotine patches helped four patients with Long COVID. We are not aware of any published scientific data of patients where it did not help or worsened Long COVID symptoms. There are no high-quality clinical trials, and the nicotinic hypothesis remains disputed.
Of all the alternative solutions with low scientific evidence we explored, nicotine patches are among the least expensive and don&rsquo;t require invasive procedures such as surgery. If you want to try whether nicotine replacement therapies help with your Long COVID symptoms, we recommend talking to a health care professional about the potential risks and benefits of nicotine to your health.

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From our community: Do nicotine patches help with Long COVID symptoms?

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