The Emerging Role of Nicotine in the Integrative Treatment of Long COVID

Long COVID, a perplexing constellation of symptoms persisting weeks to months after acute SARS-CoV-2 infection, has challenged conventional medical paradigms. Affecting an estimated 10-30% of those infected with COVID-19, it manifests as fatigue, cognitive impairment (“brain fog”), dyspnea, and autonomic dysfunction, including postural orthostatic tachycardia syndrome (POTS).¹

There is certainly a growing need for therapies that bridge traditional pharmacology with integrative strategies. Among the more unconventional options, nicotine – delivered via low-dose transdermal patches – has surfaced as a potential tool. While the idea may sound wacky, emerging evidence and clinical anecdotes suggest it warrants exploration, especially when it’s within our scope of practice.

That being said, we also need to recognize that there’s a potential for addiction even at low doses; and as a stimulant and vasoconstrictor, nicotine has the potential to make matters worse.

The Long COVID Conundrum

The pathophysiology of long COVID remains elusive, but hypotheses point to persistent inflammation, immune dysregulation, mitochondrial dysfunction, and autonomic nervous system disruption.^2-3 Studies have identified autoantibodies targeting G-protein-coupled receptors in some patients, hinting at an autoimmune component akin to dysautonomias like POTS.⁴ Others propose lingering viral reservoirs or spike protein interactions with nicotinic acetylcholine receptors (nAChRs), which regulate inflammation and neural signaling. ⁵

It appears that nicotine competes with spike proteins at the receptor sites, “crowding out” the spike proteins and returning homeostasis (with a minor buzz).

Conventional treatments, such as beta-blockers for tachycardia or corticosteroids for inflammation, offer partial relief, but often fall short of addressing the full symptom spectrum and carry a host of side effects. While acupuncture can modulate autonomic tone via vagal stimulation, and nutritional support (e.g., magnesium for fatigue) has shown promise,⁶ the combination may not be enough, prompting exploration of novel adjuncts like nicotine.

Nicotine’s Unexpected Mechanism

Nicotine, a plant-derived alkaloid infamous for its role in tobacco addiction, is a potent agonist of nAChRs found throughout the nervous system and immune cells. Its therapeutic potential hinges on the “cholinergic anti-inflammatory pathway,” where nAChR activation – particularly the alpha-7 subtype – dampens pro-inflammatory cytokines like TNF-alpha and IL-6.⁷

This mechanism, first described in sepsis models, may counter the chronic inflammation seen in long COVID.⁸ Additionally, nicotine’s stimulatory effect on parasympathetic signaling could mitigate the sympathetic overdrive observed in POTS and related autonomic symptoms.⁹

A believable hypothesis, advanced by Leitzke in a 2023 Bioelectronic Medicine case series, posits that SARS-CoV-2 spike proteins bind nAChRs, impairing neuromodulation.¹⁰ Nicotine, by competitively binding these receptors, might displace this interference, restoring function as described earlier.

In Leitzke’s report, five long-COVID patients treated with low-dose nicotine patches (7.5 mg/24 h) reported rapid improvements in fatigue, dyspnea, and cognitive clarity – some within 48 hours. While not all had confirmed POTS, the overlap with autonomic symptoms suggests broader relevance.

Clinical Observations and Anecdotes

Beyond formal studies, patient-driven experimentation has sparked interest. Posts on platforms like X and long COVID forums from 2023-2024 describe individuals using nicotine patches (3.5-7 mg/day) with mixed results. Some report reduced brain fog and energy crashes, particularly when paired with heart rate-lowering agents like ivabradine or propranolol to offset nicotine’s stimulatory effects.¹¹

One X user noted, “7 mg patch plus ivabradine — no tachycardia flare, and I can think again.” Others, however, experienced palpitations or nausea, underscoring the need for personalization.

In my practice, needling points like PC 6 (Neiguan) , ST 36 (Zusanli) or auricular Shenmen can calm sympathetic hyperactivity, mirroring nicotine’s proposed action. Could nicotine amplify these effects? Current studies are too sparse to say definitively, but the synergy is certainly possible. (That’s why it’s called the “practice” of medicine.)

Evidence and Limitations

The evidence base for nicotine in long COVID remains sparse, but promising. Leitzke’s series, while compelling, lacks controls and scale – hardly a foundation for widespread adoption.¹⁰ A 2022 trial in Critical Care tested nicotine patches (14 mg/day) in acute COVID-19 patients on ventilators, finding no benefit over placebo, but this acute context differs from long COVID’s chronicity and shouldn’t dampen our enthusiasm.¹²

Preclinical studies bolster the anti-inflammatory rationale: A 2015 paper showed nicotine reduced autoantibody production in lupus models, suggesting a precedent for immune-mediated conditions.¹³

I’m not a fan of smoking, and nicotine has its own issues like the possibility to exacerbate tachycardia, a core POTS feature. Side effects – nausea, insomnia, skin irritation – are common, and while dependence is unlikely with low-dose patches in non-smokers, it’s a theoretical concern.¹⁴

The absence of randomized, controlled trials (as of February 2025) leaves us reliant on case reports and patient narratives – valuable, but not definitive.

Interestingly, cigarette smokers are five times more likely to develop influenza than non-smokers,¹⁵ but COVID doesn’t operate like a typical flu virus. A 2020 cohort study of 8.3 million people¹⁶ concluded a “markedly decreased risk of both COVID-19 disease and ICU admission in smokers,” which is counterintuitive, but supports my thesis.

Integrating Nicotine for Patients Suffering From POTS

In an integrative framework, nicotine isn’t a standalone fix, but a potential adjunctive therapy. First-line treatments – hydration (2-3 L/day), salt loading (10-12 g/day), compression garments, and recumbent exercise – remain foundational for POTS and long COVID, backed by decades of research.¹⁷ Acupuncture, with its evidence for fatigue and orthostatic relief, complements these.¹⁸

Nicotine patches might fit here, titrated cautiously (e.g., 3.5-7 mg/day) under medical supervision, especially for patients with refractory autonomic or cognitive symptoms. A sample protocol could pair nicotine with:

• Acupuncture: Weekly sessions targeting autonomic points (e.g., PC 6, CV 17, auricular Shenmen and Zero Point) to enhance parasympathetic tone.
• Nutrition: An anti-inflammatory diet (e.g., omega-3s, turmeric), plus oral or transdermal magnesium¹⁹ (200-400 mg/day) to support neural repair.
• Medication: Low-dose propranolol (10-20 mg) to blunt tachycardia, per Autonomic Neuroscience guidelines.²⁰

Patient response guides adjustment: Improvement in fatigue or brain fog within 1-2 weeks signals potential efficacy; worsening tachycardia or side effects necessitate re-evaluation.

The Road Ahead

Nicotine’s value in long COVID treatment is an exciting proposition ... promising, yet unproven. Its integrative appeal lies in addressing inflammation and autonomic dysfunction, areas in which conventional options often lag. However, without RCTs, it remains experimental; best reserved for cases unresponsive to standard care. As practitioners, we must balance innovation with caution, grounding novel therapies in patient safety and basic principles.

For now, nicotine patches offer a curious footnote in the long COVID story – one that challenges us to rethink old tools for new problems. As research evolves, so too will our understanding of where it fits in the integrative toolbox.

References

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