What is the evidence for using nicotine for long COVID?

Nicotine for Long COVID: Current Evidence and Recommendations

There is insufficient evidence to support the use of nicotine or nicotine replacement therapy for the treatment of long COVID, and it should not be recommended due to its adverse cardiopulmonary effects and addictive potential. 1

Current Evidence on Nicotine and COVID-19

Potential Anti-inflammatory Mechanisms

Nicotine has demonstrated anti-inflammatory properties in animal models that could theoretically be relevant to COVID-19:

• Nicotine activates the cholinergic anti-inflammatory pathway through α7 nicotinic acetylcholine receptors (α7nAChRs) 1, 2
• In animal models of acute lung injury, nicotine decreased:
  • Lung vascular permeability
  • Leukocyte infiltration
  • Proinflammatory cytokine concentrations 1

Clinical Evidence

Despite theoretical benefits, clinical evidence does not support nicotine use in COVID-19:

• A randomized, double-blind, placebo-controlled trial of nicotine patches in critically ill COVID-19 patients on mechanical ventilation found:

  • No reduction in 28-day mortality (28% in nicotine group vs. 28% in placebo group)
  • No improvement in ventilator-free days 3

• This high-quality clinical trial provides the strongest evidence against nicotine use in severe COVID-19, contradicting earlier hypotheses based on animal models or observational data 3

Risks of Nicotine Use

Nicotine presents significant risks that outweigh any theoretical benefits:

• Adverse cardiopulmonary effects 1
• High addiction potential 1
• May increase ACE2 receptor expression, potentially increasing viral entry 1
• May trigger cytokine release including IL-2, IL-6, and TNF-α, potentially worsening cytokine storm in COVID-19 1

Conflicting Epidemiological Data

The relationship between smoking, nicotine, and COVID-19 outcomes shows mixed results:

• Some epidemiological reports suggest lower incidence of COVID-19 in smokers 4, 5
• However, stronger evidence indicates tobacco use is associated with severe COVID-19 outcomes 6
• Pre-existing comorbidities in tobacco users (cardiovascular diseases, diabetes, respiratory diseases) further aggravate disease manifestations 6

Recommendations for Clinical Practice

1. Do not recommend nicotine or nicotine replacement therapy for long COVID treatment 1

2. For patients who smoke and have COVID-19 or long COVID:

   • Strongly encourage smoking cessation 1
   • Consider standard nicotine replacement therapy only as part of a smoking cessation strategy, not as COVID-19 treatment 1

3. For research purposes:

   • Further investigation into nicotine-containing medications at doses without strong cardiopulmonary effects may be warranted 1
   • Any such research should carefully distinguish between pure nicotine effects versus smoking effects 4

Important Caveats

• The dose-dependent response of nicotine means different doses may have different effects 4
• The effects of nicotine alone differ from those of cigarette smoke, which contains many other harmful compounds 1, 4
• Any theoretical benefit of nicotine's anti-inflammatory properties is outweighed by the demonstrated lack of clinical efficacy and known harms 1, 3

In conclusion, while early hypotheses suggested nicotine might help with COVID-19 through anti-inflammatory mechanisms, the highest quality clinical evidence shows no benefit in severe COVID-19, and there is no evidence supporting its use specifically for long COVID.