Abstract
Background: Cholinergic anti-inflammatory pathway endogenously controls inflammatory processes through activation of the α7-nicotinic acetylcholine receptor (α7nAChR). Varenicline, used in smoking cessation therapy, is a full α7nAChR agonist with anti-inflammatory effects. In this study, the frequency of coronavirus disease (COVID-19) was evaluated in patients using varenicline as a smoking cessation treatment.
Methods: In this retrospective cross-sectional study, records of the 111 patients admitted to Smoking Cessation Outpatient Clinic of Dokuz Eylul University Faculty of Medicine during the COVID-19 pandemic were evaluated. The development of COVID-19 disease according to the status of the patients being positive for SARS-COV-2 was evaluated comparatively in patients who received varenicline or not. Additionally, the disease symptoms were questioned.
Results: SARS-CoV-2 PCR positivity was not detected in any of 38 patients who regularly used varenicline out of 68 patients evaluated. SARS-CoV-2 PCR positivity was detected in 13 (43.3%) of 30 patients who received other treatments or irregularly used varenicline (p<0.001).
Conclusions: Patients under smoking cessation treatment did not develop COVID-19 during the period of varenicline use compared to non-users suggesting that the medication may have a protective role in the development of COVID-19 which might be further investigated by clinical trials.
Supporting Institution
None (Self-funded)
Project Number
None (Self-funded)
Thanks
The authors acknowledge Dr. Ahmet Naci Emecen (Dokuz Eylul Univ., Izmir) for statistical consulting.
References
- 1. Organization WH. Therapeutics and COVID-19: living guideline n.d.:1–98.
- 2. Conti P, Ronconi G, Caraffa A, Gallenga C, Ross R, Frydas I, et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by COVID-19: anti-inflammatory strategies. J Biol Regul Homeost Agents 2020;34.
- 3. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical fatures of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497–506.
- 4. Mehta P, Mcauley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, et al. Correspondence COVID-19 : consider cytokine storm syndromes and immunosuppression. Lancet 2020;6736:19–20.
- 5. Gruner L. Covid-19 Illnes in Native and immunosuppressed states. Lung 2020;21:22–5.
- 6. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 2020;46:846–8.
- 7. Yang Z, Liu J, Zhou Y, Zhao X, Zhao Q, Liu J. The effect of corticosteroid treatment on patients with coronavirus infection: a systematic review and meta-analysis. J Infect 2020;81:e13–20.
- 8. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054–62.
- 9. Geng Y-J, Wei Z-Y, Qian H-Y, Huang J, Lodato R, Castriotta RJ. Pathophysiological Characteristics and Therapeutic Approaches for Pulmonary Injury and Cardiovascular Complications of Coronavirus Disease 2019. Cardiovasc Pathol 2020;47:107228.
- 10. Russell B, Moss C, Rigg A, Hemelrijck M Van. COVID-19 and treatment with NSAIDs and corticosteroids : should we be limiting their use in the clinical setting ? Ecancer 2020;14:1–3.
- 11. Pavlov VA, Wang H, Czura CJ, Friedman SG, Tracey KJ. The cholinrgic anti-inflammatory pathway: a missing link in neuroimmunomodulation. Mol Med 2003;9:125–34.
- 12. Baris E, Arici M.A. Possible Therapeutic Role of Cholinergic Agonists on COVID-19 related inflammatory response. J Basic Clin Heal Sci 2021;5:102–8.
- 13. Pinder N, Bruckner T, Lehmann M, Motsch J, Brenner T, Larmann J, et al. Effect of physostigmine on recovery from septic shock following intra-abdominal infection – Results from a randomized, double-blind, placebo-controlled, monocentric pilot trial (Anticholium® per Se). J Crit Care 2019;52:126–35.
- 14. Zimmermann JB, Pinder N, Bruckner T, Lehmann M, Motsch J, Brenner T, et al. Adjunctive use of physostigmine salicylate (Anticholium®) in perioperative sepsis and septic shock: Study protocol for a randomized, double-blind, placebo-controlled, monocentric trial (Anticholium® per Se). Trials 2017;18:1–10.
- 15. Coe JW, Brooks PR, Vetelino MG, Wirtz MC, Arnold EP, Huang J, et al. Varenicline: An α4β2 Nicotinic Receptor Partial Agonist for Smoking Cessation. J Med Chem 2005;48:3474–7.
- 16. Mihalak KB, Carroll FI, Luetje CW. Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors. Mol Pharmacol 2006;70:801–5.
- 17. Chen S, Bennet L, McGregor AL. Delayed Varenicline Administration Reduces Inflammation and Improves Forelimb Use Following Experimental Stroke. J Stroke Cerebrovasc Dis 2017;26:2778–87.
- 18. Ikonomidis I, Marinou M, Vlastos D, Kourea K, Andreadou I, Liarakos N, et al. Effects of varenicline and nicotine replacement therapy on arterial elasticity, endothelial glycocalyx and oxidative stress during a 3-month smoking cessation program. vol. 262. 2017.
- 19. Koga M, Kanaoka Y, Tashiro T, Hashidume N, Kataoka Y, Yamauchi A. Varenicline is a smoking cessation drug that blocks alveolar expansion in mice intratracheally administrated porcine pancreatic elastase. J Pharmacol Sci 2018;137:224–9.
- 20. Baris E, Efe H, Gumustekin M, Arici MA, Tosun M. Varenicline Prevents LPS-Induced Inflammatory Response via Nicotinic Acetylcholine Receptors in RAW 264.7 Macrophages. Front Mol Biosci 2021;8:912.
- 21. Rinott E, Kozer E, Shapira Y, Bar-Haim A, Youngster I. Ibuprofen use and clinical outcomes in COVID-19 patients. Clin Microbiol Infect 2020;26:1259.e5-1259.e7.
- 22. Wang J, Li R, Peng Z, Zhou W, Hu B, Rao X, et al. GTS-21 Reduces Inflammation in Acute Lung Injury by Regulating M1 Polarization and Function of Alveolar Macrophages. Shock 2019;51:389–400.
- 23. Iida M, Iida H, Takenaka M, Tanabe K, Iwata K. Preventive effect of varenicline on impairment of endothelial function in cerebral vessels induced by acute smoking in rats. J Anesth 2012;26:928–31.
- 24. Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res 2020;178:104787.
- 25. Krause RM, Buisson B, Bertrand S, Corringer P-J, Galzi J-L, Changeux J-P, et al. Ivermectin: A positive allosteric effector of the α7 neuronal nicotinic acetylcholine receptor. Mol Pharmacol 1998;53:283–94.
Sigara Bırakma Tedavisi Olarak Vareniklin Kullanan Hastalarda COVID-19 Insidansının Retrospektif Değerlendirilmesi
Abstract
Giriş ve Amaç: Kolinerjik anti-inflamatuar yol, α7-nikotinik asetilkolin reseptörünün (α7nAChR) aktivasyonu ile inflamatuar süreçlerin endojen kontrolünü sağlamaktadır. Sigarayı bırakma tedavisinde kullanılan vareniklin, bir α7nAChR’lerine agonist etkisi ile anti-inflamatuvar etkiler ortaya çıkarmaktadır. Bu çalışmada sigara bırakma tedavisi olarak vareniklin kullanan hastalarda koronavirüs hastalığı (COVID-19) görülme sıklığı değerlendirilmiştir.
Yöntemler: Bu retrospektif kesitsel çalışmada, COVID-19 pandemisi sırasında Dokuz Eylül Üniversitesi Tıp Fakültesi Sigara Bırakma Polikliniği'ne başvuran 111 hastanın kayıtları değerlendirilmiştir. SARS-COV-2 PCR pozitif olan hastalarda COVID-19 gelişimi ve hastalık belirtileri, vareniklin kullanan ve kullanmayan hastalarda karşılaştırmalı olarak değerlendirilmiştir.
Bulgular: Değerlendirilen 68 hastadan düzenli olarak vareniklin kullanan 38 hastada SARS-CoV-2 PCR pozitifliği saptanmamıştır. Sigara bırakma amacıyla farklı tedavileri alan veya düzensiz vareniklin kullanan 30 hastanın 13'ünde (%43,3) SARS-CoV-2 PCR pozitifliği saptanmıştır (p<0,001).
Sonuç: Sigarayı bırakma tedavisi gören hastalarda, vareniklin kullanmayanlara hastalara kıyasla düzenli vareniklin kullanımı süresince COVID-19 gelişmemesi, bu da ilacın COVID-19 gelişiminde koruyucu bir rolü olabileceğini düşündürmektedir.
Project Number
None (Self-funded)
References
- 1. Organization WH. Therapeutics and COVID-19: living guideline n.d.:1–98.
- 2. Conti P, Ronconi G, Caraffa A, Gallenga C, Ross R, Frydas I, et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by COVID-19: anti-inflammatory strategies. J Biol Regul Homeost Agents 2020;34.
- 3. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical fatures of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497–506.
- 4. Mehta P, Mcauley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, et al. Correspondence COVID-19 : consider cytokine storm syndromes and immunosuppression. Lancet 2020;6736:19–20.
- 5. Gruner L. Covid-19 Illnes in Native and immunosuppressed states. Lung 2020;21:22–5.
- 6. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 2020;46:846–8.
- 7. Yang Z, Liu J, Zhou Y, Zhao X, Zhao Q, Liu J. The effect of corticosteroid treatment on patients with coronavirus infection: a systematic review and meta-analysis. J Infect 2020;81:e13–20.
- 8. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054–62.
- 9. Geng Y-J, Wei Z-Y, Qian H-Y, Huang J, Lodato R, Castriotta RJ. Pathophysiological Characteristics and Therapeutic Approaches for Pulmonary Injury and Cardiovascular Complications of Coronavirus Disease 2019. Cardiovasc Pathol 2020;47:107228.
- 10. Russell B, Moss C, Rigg A, Hemelrijck M Van. COVID-19 and treatment with NSAIDs and corticosteroids : should we be limiting their use in the clinical setting ? Ecancer 2020;14:1–3.
- 11. Pavlov VA, Wang H, Czura CJ, Friedman SG, Tracey KJ. The cholinrgic anti-inflammatory pathway: a missing link in neuroimmunomodulation. Mol Med 2003;9:125–34.
- 12. Baris E, Arici M.A. Possible Therapeutic Role of Cholinergic Agonists on COVID-19 related inflammatory response. J Basic Clin Heal Sci 2021;5:102–8.
- 13. Pinder N, Bruckner T, Lehmann M, Motsch J, Brenner T, Larmann J, et al. Effect of physostigmine on recovery from septic shock following intra-abdominal infection – Results from a randomized, double-blind, placebo-controlled, monocentric pilot trial (Anticholium® per Se). J Crit Care 2019;52:126–35.
- 14. Zimmermann JB, Pinder N, Bruckner T, Lehmann M, Motsch J, Brenner T, et al. Adjunctive use of physostigmine salicylate (Anticholium®) in perioperative sepsis and septic shock: Study protocol for a randomized, double-blind, placebo-controlled, monocentric trial (Anticholium® per Se). Trials 2017;18:1–10.
- 15. Coe JW, Brooks PR, Vetelino MG, Wirtz MC, Arnold EP, Huang J, et al. Varenicline: An α4β2 Nicotinic Receptor Partial Agonist for Smoking Cessation. J Med Chem 2005;48:3474–7.
- 16. Mihalak KB, Carroll FI, Luetje CW. Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors. Mol Pharmacol 2006;70:801–5.
- 17. Chen S, Bennet L, McGregor AL. Delayed Varenicline Administration Reduces Inflammation and Improves Forelimb Use Following Experimental Stroke. J Stroke Cerebrovasc Dis 2017;26:2778–87.
- 18. Ikonomidis I, Marinou M, Vlastos D, Kourea K, Andreadou I, Liarakos N, et al. Effects of varenicline and nicotine replacement therapy on arterial elasticity, endothelial glycocalyx and oxidative stress during a 3-month smoking cessation program. vol. 262. 2017.
- 19. Koga M, Kanaoka Y, Tashiro T, Hashidume N, Kataoka Y, Yamauchi A. Varenicline is a smoking cessation drug that blocks alveolar expansion in mice intratracheally administrated porcine pancreatic elastase. J Pharmacol Sci 2018;137:224–9.
- 20. Baris E, Efe H, Gumustekin M, Arici MA, Tosun M. Varenicline Prevents LPS-Induced Inflammatory Response via Nicotinic Acetylcholine Receptors in RAW 264.7 Macrophages. Front Mol Biosci 2021;8:912.
- 21. Rinott E, Kozer E, Shapira Y, Bar-Haim A, Youngster I. Ibuprofen use and clinical outcomes in COVID-19 patients. Clin Microbiol Infect 2020;26:1259.e5-1259.e7.
- 22. Wang J, Li R, Peng Z, Zhou W, Hu B, Rao X, et al. GTS-21 Reduces Inflammation in Acute Lung Injury by Regulating M1 Polarization and Function of Alveolar Macrophages. Shock 2019;51:389–400.
- 23. Iida M, Iida H, Takenaka M, Tanabe K, Iwata K. Preventive effect of varenicline on impairment of endothelial function in cerebral vessels induced by acute smoking in rats. J Anesth 2012;26:928–31.
- 24. Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res 2020;178:104787.
- 25. Krause RM, Buisson B, Bertrand S, Corringer P-J, Galzi J-L, Changeux J-P, et al. Ivermectin: A positive allosteric effector of the α7 neuronal nicotinic acetylcholine receptor. Mol Pharmacol 1998;53:283–94.
Details
| Primary Language | English |
|---|---|
| Subjects | Clinical Sciences, Infectious Diseases |
| Journal Section | Araştırma Makalesi |
| Authors | |
| Project Number | None (Self-funded) |
| Publication Date | March 27, 2024 |
| Published in Issue | Year 2024 Volume: 11 Issue: 1 |
