Question explored with the scientific record
Nicotine for long covid
The short version: there is no direct evidence that nicotine improves long COVID, and the known harms of nicotine make it a risky bet.
The retrieved studies do not test nicotine for long COVID. One 2025 review of smoking's paradoxical effects notes that nicotine has been "investigated but not proven as therapy" for COVID-19 [1]. That is the closest match, and it is a statement of absence, not support.
What the evidence does show is a clear list of nicotine's harms that matter for anyone with long COVID. Nicotine acutely raises systolic blood pressure by about 3 mmHg and heart rate by about 4 bpm in young adults [3]. In vitro, it decreases red blood cell deformability, meaning blood becomes less flexible and flow worsens [5]. In asthmatic smokers, acute vaping with nicotine caused a 7.8% drop in peak expiratory flow and a 330% rise in inflammatory TNFα in the airways [4]. These are direct hits on the systems already compromised in long COVID: cardiovascular, respiratory, and inflammatory.
The theoretical case for nicotine is the cholinergic anti-inflammatory pathway. A 2025 mouse study showed that a specific α7 nicotinic receptor agonist (GTS-21, not nicotine itself) reduced inflammation after sepsis [2]. But nicotine is a dirty drug: it hits many receptor subtypes, and its cardiovascular and pro-inflammatory effects in the lung are well documented [3, 4, 5]. The animal model does not translate to a safe human dose for long COVID.
The evidence for treating long COVID fatigue is better for other interventions. L-arginine added to an SSRI produced a 30% greater improvement in fatigue in a small RCT of elderly outpatients [6]. Comprehensive rehabilitation programs improved six-minute walk distance and fatigue scores with large effect sizes [7]. Neither is a cure, but both have a safety profile far cleaner than nicotine.
My call: nicotine is not supported by any direct evidence for long COVID, and its known harms to blood flow, blood pressure, and airway function argue strongly against using it. Confidence: high.
Sources used 7
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What Is the Real Impact of Smoking on Diseases Alleged to Benefit from It?
A critical narrative review evaluating smoking's purported paradoxical protective associations across eight diseases, concluding that any such effects are generally modest and confounded, with smoking's well-established harms outweighing potential benefits and cessation emphasiz…
DOI: 10.1159/000549064 -
α7 nicotinic acetylcholine receptor agonist attenuates lipopolysaccharide-induced acute kidney injury in mice by reducing CCL2 expression in macrophages
Post-injury activation of the cholinergic anti-inflammatory pathway with the α7 nicotinic acetylcholine receptor agonist GTS-21 reduces systemic inflammation and protects against septic AKI in mice, likely by suppressing macrophage-derived CCL2 (MCP-1) expression both in vitro a…
DOI: 10.1038/s41598-025-23583-x -
Time- and Dose-Dependent Cardiovascular Effects of Nicotine-Containing Electronic Cigarettes in Young Adults: A Systematic Review and Meta-Analysis
Systematic review and meta-analysis of 21 studies (n=17,241) in young adults (18–30) showing nicotine-containing electronic cigarettes produce modest, predominantly acute increases in blood pressure and heart rate, with chronic use linked to endothelial dysfunction/early atheros…
DOI: 10.3390/toxics13100831 -
Is the e‐cigarette harmless among asthmatic patients?
In a commentary on Kotoulas et al., acute e-cigarette vaping with nicotine in asthmatic smokers caused significant decreases in peak expiratory flow (-7.8%), increases in airway impedance at 5 Hz (+7.6%) and airway resistance at 10 and 20 Hz, and significant increases in exhaled…
DOI: 10.1111/resp.13868 -
In vitro effect of nicotine on red blood cell deformability in untreated and treated essential hypertension
This study investigates the in vitro effects of nicotine on red blood cell deformability in patients with untreated and treated essential hypertension, revealing that nicotine significantly decreases RBC deformability and inhibits the efficacy of antihypertensive treatment.
DOI: 10.3109/00365519409087547 -
Role of L-Arginine supplementation in Long Covid-related Fatigue and Depression in Elderly Outpatients
A double-blind RCT of 96 elderly outpatients with Long Covid fatigue and depression found that adding L-arginine to SSRI for 8 weeks led to a 30% greater improvement in fatigue and a significant reduction in HAM-D score versus SSRI alone.
DOI: 10.1192/j.eurpsy.2024.257 -
Impact of comprehensive rehabilitation on functional capacity, fatigue, and quality of life among long-term COVID-19 survivors in resource limited settings - a randomized controlled trial
A 6-week comprehensive rehabilitation program improved functional capacity, fatigue, and quality of life in adults with long COVID in a resource-limited Indian setting, compared with education plus breathing exercises.
DOI: 10.17267/2238-2704rpf.2024.e5840