From nicotine to the cholinergic anti-inflammatory reflex – Can nicotine alleviate the dysregulated inflammation in COVID-19?

References

• Andersson U, Ottestad W, Tracey K. 2020. Extracellular HMGB1: A therapeutic target in severe pulmonary inflammation including COVID-19? Mol Med. 26(1):42.
   PubMed Web of Science ®Google Scholar
• Argenziano M, Bruce S, Slater C, Tiao J, Baldwin M, Barr R, Chang B, Chau K, Choi J, Gavin N, et al. 2020. Characterization and clinical course of 1000 patients with coronavirus disease 2019 in New York: Retrospective case series. BMJ. 369:1–9.
   Google Scholar
• Azar K, Shen Z, Romanelli R, Lockhart S, Smits K, Robinson S, Brow S, Pressman A. 2020. Disparities in outcomes among COVID-19 patients in a large health care system in California: Study estimates the COVID-19 infection fatality rate at U.S. county level. Health Aff. 39(7):1253–1262.
   PubMed Web of Science ®Google Scholar
• Bhargava A, Fukushima E, Levine M, Zhao W, Tanveer F, Szpunar S, Saravolatz L. 2020. Predictors for severe COVID-19 infection. Clin Infect Dis May. 30:1–7.
   Google Scholar
• Bi X, Su Z, Yan H, Du J, Wang J, Chen L, Peng M, Chen S, Shen B, Li J. 2020. Prediction of severe illness due to COVID-19 based on an analysis of initial fibrinogen to albumin ratio and platelet count. Platelets. 31(5):674–679.
   PubMed Web of Science ®Google Scholar
• Borovikova L, Ivanova S, Zhang M, Yang H, Botchkina G, Watkins L, Wang H, Abumrad N, Eaton J, Tracey K. 2000. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 405(6785):458–462.
   PubMed Web of Science ®Google Scholar
• Buckner F, McCulloch D, Atluri V, Blain M, McGuffin S, Nalla A, Huang M, Greninger A, Jerome K, Cohen S, et al. 2020. Clinical features and outcomes of 105 hospitalized patients with COVID-19 in Seattle, Washington. Clin Infect Dis May. 22:1–7.
   Google Scholar
• Calabrese C, Rajendram P, Sacha G, Calabrese L. 2020. Practical aspects of targeting IL-6 in COVID-19 disease. Cleveland Clin J Med. 2020:1–5.
   Google Scholar
• Cao M, Zhang D, Wang Y, Lu Y, Zhu X, Li Y, Xue H, Lin Y, Zhang M, Sun Y, et al. 2020. Clinical features of patients infected with the 2019 novel coronavirus (COVID-19) in Shanghai, China. Resp Med. DOI:https://doi.org/10.1101/2020.03.04.20030395.
   Google Scholar
• CDC COVID-19 Response Team. 2020. Preliminary estimates of the prevalence of selected underlying health conditions among patients with coronavirus disease 2019-United States, February 12–March 28, 2020. MMWR. 69:382–386.
   PubMed Web of Science ®Google Scholar
• Changeux J, Amoura Z, Rey F, Miyara M. 2020. A nicotinic hypothesis for COVID-19 with preventive and therapeutic implications. C R Biol. 343(1):33–39.
   PubMed Web of Science ®Google Scholar
• Chellasamy S, Kumar S, Wei H. 2020. A computational insight of the improved nicotine binding with ACE2-SARS-CoV-2 complex with its clinical impact. Biomolecules. arXiv:2004.14943.
   Google Scholar
• Chen L, Long X, Xu Q, Tan J, Wang G, Cao Y, Wei J, Luo H, Zhu H, Huang L, et al. 2020. Elevated serum levels of S100A8/A9 and HMGB1 at hospital admission are correlated with inferior clinical outcomes in COVID-19 patients. Cell Mol Immunol. 17(9):992–994.
   PubMed Web of Science ®Google Scholar
• Chen L, Yu J, He W, Chen L, Yuan G, Dong F, Chen W, Cao Y, Yang J, Cai L, et al. 2020. Risk factors for death in 1859 subjects with COVID-19. Leukemia. 34(8):2173–2183.
   PubMed Web of Science ®Google Scholar
• Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, et al. 2020. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet. 395(10223):507–513.
   PubMed Web of Science ®Google Scholar
• Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, Ma K, Xu D, Yu H, Wang H, et al. 2020. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: Retrospective study. BMJ. 368:1–10.
   Google Scholar
• Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M. 2020. The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev. 53:25–32.
   PubMed Web of Science ®Google Scholar
• COVID-19 Treatment Guidelines Panel. 2020a. Immune-based therapy under evaluation for treatment of COVID-19. Bethesda (MD): National Institutes of Health; [accessed 2020 Sep 17]. https://www.covid19treatmentguidelines.nih.gov/immune-based-therapy/immunomodulators/interleukin-6-inhibitors/
   Google Scholar
• COVID-19 Treatment Guidelines Panel. 2020b. Coronavirus disease 2019 (COVID-19) treatment guidelines. Bethesda (MD): National Institutes of Health; [accessed 2020 Dec 9]. https://www.covid19treatmentguidelines.nih.gov/
   Google Scholar
• de Melo G, Lazarini F, Larrous F, Feige L, Kergoat L, Marchio A, Pineau P, Lecuit M, Lledo P, Changeux J, et al. 2020. Anti-COVID-19 efficacy of ivermectin in the golden hamster. bioRxiv. DOI:https://doi.org/10.1101/2020.11.21.392639.
   Google Scholar
• Entezari M, Javdan M, Antoine DJ, Morrow DMP, Sitapara R, Patel V, Wang M, Sharma L, Gorasiya S, Zur M, et al. 2014. Inhibition of extracellular HMGB1 attenuates hyperoxia-induced inflammatory acute lung injury. Redox Biol. 2:314–322.
   PubMed Web of Science ®Google Scholar
• Fajgenbaum D, June C. 2020. Cytokine storm. N Engl J Med. 383(23):2255–2273.
   PubMed Web of Science ®Google Scholar
• Fan E, Beitler J, Brochard L, Calfee C, Ferguson N, Slutsky A, Brodie D. 2020. COVID-19-associated acute respiratory distress syndrome: Is a different approach to management warranted? Lancet Resp Med. 8(8):816–821.
   PubMed Web of Science ®Google Scholar
• Farsalinos K, Angelopoulou A, Alexandris N, Poulas K. 2020. COVID-19 and the nicotinic cholinergic system. Eur Respir J. 56(1):2001589.
   PubMed Web of Science ®Google Scholar
• Farsalinos K, Eliopoulos E, Leonidas D, Papadopoulos G, Tzartos S, Poulas K. 2020a. Molecular modelling and docking experiments examining the interaction between SARS-CoV-2 spike glycoprotein and neuronal nicotinic acetylcholine receptors. Preprints. DOI:https://doi.org/10.20944/preprints202005.0365.v1.
   Google Scholar
• Farsalinos K, Eliopoulos E, Leonidas D, Papadopoulos G, Tzartos S, Poulas K. 2020b. Nicotinic cholinergic system and COVID-19: In silico identification of an interaction between SARS-CoV-2 and nicotinic receptors with potential therapeutic targeting implications. Int J Mol Sci. 21(16):5807.
   Web of Science ®Google Scholar
• Feng Y, Ling Y, Bai T, Xie Y, Huang J, Li J, Xiong W, Yang D, Chen R, Lu F, et al. 2020. COVID-19 with different severities: A multicenter Study of Clinical Features. Am J Respir Crit Care Med. 201(11):1380–1388.
   PubMed Web of Science ®Google Scholar
• Gavin W, Campbell E, Zaidi S, Gavin N, Dbeibo L, Beeler C, Kuebler K, Abdel-Rahman A, Luetkemeyer M, Kara A. 2020. Clinical characteristics, outcomes and prognosticators in adult patients hospitalized with COVID-19. Am J Infect Control. 49(2):158–165.
   Web of Science ®Google Scholar
• Gonzalez-Rubio J, Navarro-Lopez C, Lopez-Najera E, Lopez-Najera A, Jimenez-Diaz L, Navarro-Lopez J, Najera A. 2020. Cytokine release syndrome (CRS) and nicotine in COVID-19 patients: Trying to calm the storm. Front Immunol. 11:1359.
   PubMed Web of Science ®Google Scholar
• Goyal P, Choi J, Pinheiro L, Schenck E, Chen R, Jabri A, Satlin M, Campion T, Nahid M, Ringel J, et al. 2020. Clinical characteristics of Covid-19 in New York City. N Engl J Med. 382(24):2372–2374.
   PubMed Web of Science ®Google Scholar
• Gu T, Mack J, Salvatore M, Sankar S, Valley T, Singh K, Nallamothu B, Kheterpal S, Lisabeth L, Fritsche L, et al. 2020. COVID-19 outcomes, risk factors and associations by race: A comprehensive analysis using electronic health records data in Michigan Medicine. MedRxiv. DOI:https://doi.org/10.1101/2020.06.16.20133140.
   Google Scholar
• Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, Liu L, Shan H, Lei C, Hui D, et al. 2020. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 382(18):1708–1720.
   PubMed Web of Science ®Google Scholar
• Hartmann-Boyce J, Lindson N. 2020. The role of nicotine in COVID-19 infection. Oxford (UK): CEBM (Centre for Evidence-Based Medicine); [accessed 2020 Aug 8]. https://www.cebm.net/covid-19/nicotine-replacement-therapy/
   Google Scholar
• Hartmann-Boyce J, Morris E, Goyder C, Kinton J, Perring J, Nunan D, Mahtani K, Buse J, Prato S, Ji L, et al. 2020. Diabetes and COVID-19: Risks, management, and learnings from other national disasters. Diabetes Care. 43(8):1695–1703.
   PubMed Web of Science ®Google Scholar
• Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens T, Herrler G, Wu N, Nitsche A, et al. 2020. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 181(2):271–280.
   PubMed Web of Science ®Google Scholar
• Hreggvidsdottir H, Ostberg T, Wähämaa H, Schierbeck H, Aveberger A, Klevenvall L, Palmblad K, Ottosson L, Andersson U, Harris H. 2009. The alarmin HMGB1 acts in synergy with endogenous and exogenous danger signals to promote inflammation. J Leukoc Biol. 86(3):655–662.
   PubMed Web of Science ®Google Scholar
• Hu L, Chen S, Fu Y, Gao Z, Long H, Ren H, Zuo Y, Wang J, Li H, Xu Q, et al. 2020. Risk factors associated with clinical outcomes in 323 coronavirus disease 2019 (COVID-19) hospitalized patients in Wuhan. China Clin Infect Dis. 3:1–10.
   Google Scholar
• Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, et al. 2020. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 395(10223):497–506.
   PubMed Web of Science ®Google Scholar
• Ji D, Zhang D, Xu J, Chen Z, Yang T, Zhao P, Chen G, Cheng G, Wang Y, Bi J, et al. 2020. Prediction for progression risk in patients with COVID-19 pneumonia: The CALL score. Clin Infect Dis. 71(6):1393–1399.
   PubMed Web of Science ®Google Scholar
• Jin J, Bai P, He W, Wu F, Liu X, Han D, Liu S, Yang J. 2020. Gender differences in patients with COVID-19: Focus on severity and mortality. Front Publ Health. 9:152.
   Google Scholar
• Kalligeros M, Shehadeh F, Mylona E, Benitez G, Beckwith C, Chan P, Mylonakis E. 2020. Association of obesity with disease severity among patients with coronavirus disease 2019. Obesity. 28(7):1200–1204.
   PubMed Web of Science ®Google Scholar
• Kang R, Chen R, Zhang Q, Hou W, Wu S, Cao L, Huang J, Yu Y, Fan X, Yan Z, et al. 2014. HMGB1 in health and disease. Mol Aspects Med. 40:1–116.
   PubMed Web of Science ®Google Scholar
• Karanasos A, Aznaouridis K, Latsios G, Synetos A, Plitaria S, Tousoulis D, Toutouzas K. 2020. Impact of smoking status on disease severity and mortality of hospitalized patients with COVID-19 infection: A systematic review and meta-analysis. Nicotine Tob Res. 22(9):1657–1659.
   PubMed Web of Science ®Google Scholar
• Kim E, Chin B, Kang C, Kim N, Kang Y, Choi J, Oh D, Kim J, Koh B, Kim S, et al. 2020. Clinical course and outcomes of patients with Severe Acute Respiratory Syndrome corona-virus 2 infection: A preliminary report of the first 28 patients from the Korean Cohort Study on COVID-19. J Korean Med Sci. 35:e142.
   PubMed Web of Science ®Google Scholar
• Kitagawa H, Takenouchi T, Azuma R, Wesnes K, Kramer W, Clody D, Burnett A. 2003. Safety, pharmacokinetics, and effects on cognitive function of multiple doses of GTS-21 in healthy, male volunteers. Neuropsychopharmacology. 28(3):542–551.
   PubMed Web of Science ®Google Scholar
• Klang E, Kassim G, Soffer S, Freeman R, Levin M, Reich D. 2020. Severe obesity as an independent risk factor for COVID‐19 mortality in hospitalized patients younger than 50. Obesity. 28(9):1595–1599.
   PubMed Web of Science ®Google Scholar
• Kox M, Pompe J, Peters E, Vaneker M, van der Laak J, van der Hoeven J, Scheffer G, Hoedemaekers C, Pickkers P. 2011. α7 Nicotinic acetylcholine receptor agonist GTS-21 attenuates ventilator-induced TNFα production and lung injury. Br J Anaesth. 107(4):559–566.
   PubMed Web of Science ®Google Scholar
• Krause R, Buisson B, Bertrand S, Corringer P, Galzi K, Changeux J, Bertrand D. 1998. Ivermectin: A positive allosteric effector of the α7 neuronal nicotinic acetylcholine receptor. Mol Pharmacol. 53(2):283–294.
   PubMed Web of Science ®Google Scholar
• Kuderer N, Choueiri T, Shah D, Shyr Y, Rubinstein S, Rivera R, Shete S, Hsu C, Desai A, de Lima Lopes G, et al. 2020. Clinical impact of COVID-19 on patients with cancer (CCC19): A cohort study. Lancet. 395(10241):1907–1918.
   PubMed Web of Science ®Google Scholar
• Lee D, Gardner R, Porter D, Louis C, Ahmed N, Jensen M, Grupp S, Mackall C. 2014. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 124(2):188–195.
   PubMed Web of Science ®Google Scholar
• Leung J, Yang C, Sin D. 2020. COVID-19 and nicotine as a mediator of ACE-2. Eur Respir J. 55(6):2001261.
   PubMed Web of Science ®Google Scholar
• Li R, Pei S, Chen B, Song Y, Zhang T, Yang W, Shaman J. 2020. Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2). Science. 368(6490):489–493.
   PubMed Web of Science ®Google Scholar
• Li X, Xu S, Yu M, Wang K, Tao Y, Zhou Y, Shi J, Zhou M, Wu B, Yang Z, et al. 2020. Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan. J Allergy Clin Immunol. 146(1):110–118.
   PubMed Web of Science ®Google Scholar
• Liu D, Wang Y, Wang J, Liu J, Yue Y, Liu W, Zhang F, Wang Z. 2020. Characteristics and outcomes of a sample of patients with COVID-19 identified through social media in Wuhan, China: Observational study. J Med Internet Res. 22(8):e20108.
   PubMed Web of Science ®Google Scholar
• Liu J, Li S, Liu J, Liang B, Wang X, Wang H, Li W, Tong Q, Yi J, Zhao L, et al. 2020. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine. 55:102763.
   PubMed Web of Science ®Google Scholar
• Lu B, Kwan K, Levine Y, Olofsson P, Yang H, Li J, Joshi S, Wang H, Andersson U, Chavan S, et al. 2014. α7 Nicotinic acetylcholine receptor signaling inhibits inflammasome activation by preventing mitochondrial DNA release. Mol Med. 20:350–358.
   PubMed Web of Science ®Google Scholar
• Ma K, Liu Z, Cao C, Liu M, Liao J, Zou J, Kong L, Wan K, Zhang J, Wang Q, et al. 2020. COVID-19 myocarditis and severity factors: An adult cohort study. Medrxiv. 2020:1–60.
   Google Scholar
• Mavropoulos S, Khan N, Levy A, Faliks B, Sison C, Pavlov V, Zhang Y, Ojamaa K. 2017. Nicotinic acetylcholine receptor-mediated protection of the rat heart exposed to ischemia reperfusion. Mol Med. 23(1):120–133.
   PubMedGoogle Scholar
• Mazloom R. 2020. Feasibility of therapeutic effects of the cholinergic anti-inflammatory pathway on COVID-19 symptoms. J Neuroimmune Pharmacol. 15(2):165–166.
   PubMed Web of Science ®Google Scholar
• Moon H, Cao Y, Yang J, Lee J, Choi H, Jin Y. 2015. Lung epithelial cell-derived extracellular vesicles activate macrophage-mediated inflammatory responses via ROCK1 pathway. Cell Death Dis. 6:e2016.
   PubMed Web of Science ®Google Scholar
• Ni Y, Tian F, Lu Z, Yang G, Fu H, Wang J, Yan X, Zhao Y, Wang Y, Jiang T. 2011. Protective effect of nicotine on lipopolysaccharide-induced acute lung injury in mice. Respiration. 81(1):39–46.
   PubMed Web of Science ®Google Scholar
• Pandey S, Pathak S, Pandey A, Salunke A, Chawla J, Sharma A, Sharma S, Thivari P, Ratna H. 2020. Ivermectin in COVID-19: What do we know? Diabetes Metab Syndr. 14(6):1921–1922.
   PubMed Web of Science ®Google Scholar
• Patanavanich R, Glantz S. 2020. Smoking is associated with COVID-19 progression: A meta-analysis. medRxiv. 2020:1–16.
   Google Scholar
• Patel V, Dial K, Wu J, Gauthier A, Wu W, Lin M, Espey M, Thoma D, Ashby C, Mantell L. 2020. Dietary anti-oxidants significantly attenuate hyperoxia-induced acute inflammatory lung injury by enhancing macrophage function via reducing the accumulation of airway HMGB1. Int J Mol Sci. 21(3):977.
   Web of Science ®Google Scholar
• Patel V, Sitapara R, Gore A, Phan B, Sharma L, Sampat V, Li J, Yang H, Chavan S, Wang H, et al. 2013. High Mobility Group Box-1 mediates hyperoxia-induced impairment of Pseudomonas aeruginosa clearance and inflammatory lung injury in mice. Am J Respir Cell Mol Biol. 48(3):280–287.
   PubMed Web of Science ®Google Scholar
• Pavlov V, Ochani M, Yang L, Gallowitsch-Puerta M, Ochani K, Lin X, Levi J, Parrish W, Rosas-Ballina M, Czura C, et al. 2007. Selective α7 nicotinic acetylcholine receptor agonist GTS-21 improves survival in murine endotoxemia and severe sepsis. Crit Care Med. 35:1139–1144.
   PubMed Web of Science ®Google Scholar
• Pavlov V, Wang H, Czura C, Friedman S, Tracey K. 2003. The cholinergic anti-inflammatory pathway: A missing link in neuroimmunomodulation. Mol Med. 9(5–8):125–134.
   PubMed Web of Science ®Google Scholar
• Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, Xie C, Ma K, Shang K, Wang W, et al. 2020. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 71(15):762–768.
   PubMed Web of Science ®Google Scholar
• Rafikov R, Nair V, Sinari S, Babu H, Sullivan J, Yuan J, Desai A, Rafikova O. 2019. Gender difference in damage-mediated signaling contributes to pulmonary arterial hypertension. Antioxid Redox Signal. 31(13):917–932.
   PubMed Web of Science ®Google Scholar
• Rentsch C, Kidwai-Khan F, Tate JP, Park L, King J, Skanderson M, Hauser R, Schultze A, Jarvis C, Holodniy M, et al. 2020. Covid-19 testing, hospital admission, and intensive care among 2,026,227 United States veterans aged 54-75 years. MedRxiv. 2020:1–32.
   Google Scholar
• Rothan H, Byrareddy S. 2020. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun. 109:102433.
   PubMed Web of Science ®Google Scholar
• Şenkal N, Meral R, Medetalibeyoğlu A, Konyaoğlu H, Kose M, Tukek T. 2020. Association between chronic ACE inhibitor exposure and decreased odds of severe disease in patients with COVID-19. Anatol J Cardiol. 24(1):21–29.
   PubMed Web of Science ®Google Scholar
• Sinha P, Matthay M, Calfee C. 2020. Is a “cytokine storm” relevant to COVID-19? JAMA Intern Med. 180(9):1152–1154.
   PubMed Web of Science ®Google Scholar
• Sitapara R, Gauthier A, Patel V, Lin M, Zur M, Ashby C, Mantell L. 2020. The α7 nicotinic acetylcholine receptor agonist GTS-21 improves bacterial clearance in mice by restoring hyperoxia-compromised macrophage function. Mol Med. 26(1):98.
   PubMed Web of Science ®Google Scholar
• Sitapara R, Gauthier A, Valdés-Ferrer S, Lin M, Patel V, Wang M, Martino A, Perron J, Ashby C, Tracey K. 2020. The α7 nicotinic acetylcholine receptor agonist, GTS-21, attenu-ates hyperoxia-induced acute inflammatory lung injury by alleviating the accumulation of HMGB1 in the airways and the circulation. Mol Med. 26:63.
   PubMed Web of Science ®Google Scholar
• Soares R, Mattos L, Raposo L. 2020. Risk factors for hospitalization and mortality due to COVID-19 in Espírito Santo State, Brazil. Am J Trop Med Hyg. 103(3):1184–1190.
   PubMed Web of Science ®Google Scholar
• Tabata S, Imai K, Kawano S, Ikeda M, Kodama T, Miyoshi K, Obinata H, Mimura S, Kodera T, Kitagaki M, et al. 2020. The clinical characteristics of COVID-19: A retrospective analysis of 104 patients from the outbreak on board the Diamond Princess cruise ship in Japan. MedRxiv. 2020:1–21.
   Google Scholar
• Tarnawski L, Reardon C, Caravaca A, Rosas-Ballina M, Tusche M, Drake A, Hudson L, Hanes W, Li J, Parrish W, et al. 2018. Adenylyl cyclase-6 mediates inhibition of TNF in the inflammatory reflex. Front Immunol. 9:2648.
   PubMed Web of Science ®Google Scholar
• Tindle H, Newhouse P, Freiberg M. 2020. Beyond smoking cessation: Investigating medicinal nicotine to prevent and treat COVID-19. Nicotine Tob Res. 22(9):1669–1671.
   PubMed Web of Science ®Google Scholar
• To K, Tsang O, Leung W, Tam A, Wu T, Lung D, Yip C, Cai J, Chan J, Chik T, et al. 2020. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: An observational cohort study. Lancet Infect Dis. 20(5):565–574.
   PubMed Web of Science ®Google Scholar
• Tracey K. 2007. Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest. 117(2):289–296.
   PubMed Web of Science ®Google Scholar
• Uteshev V. 2014. The therapeutic promise of positive allosteric modulation of nicotinic receptors. J Med Virol. 92:797–806.
   Google Scholar
• Wan S, Xiang Y, Fang W, Zheng Y, Li B, Hu Y, Lang C, Huang D, Sun Q, Xiong Y, et al. 2020. Clinical features and treatment of COVID‐19 patients in northeast Chongqing. Eur J Phar-Macol. 727:181–185.
   Google Scholar
• Wang B, Wang Z, Zhao J, Zeng X, Wu M, Wang S, Wang T. 2020. Epidemiological and clinical course of 483 patients with COVID-19 in Wuhan, China: A single-center, retrospective study from the mobile cabin hospital. Eur J Clin Microbiol Infect Dis. 39(12):2309–2315.
   PubMed Web of Science ®Google Scholar
• Wang H, Cai D, Chen Z, Wang Y. 2020. GTS-21 promotes α7nAChR to alleviate intestinal ischemia-reperfusion-induced apoptosis and inflammation of enterocytes. Med Sci Monit. 26:e921618-1–e921618-7.
   Web of Science ®Google Scholar
• Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, Li J, Wang H, Yang H, Ulloa L, et al. 2003. Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation. Nature. 421(6921):384–388.
   PubMed Web of Science ®Google Scholar
• Wang K, Zhang Z, Yu M, Tao Y, Xie M. 2020. 15-day mortality and associated risk factors for hospitalized patients with COVID-19 in Wuhan, China: An ambispective observational cohort study. Intensive Care Med. 46(7):1472–1474.
   PubMed Web of Science ®Google Scholar
• Wang M, Gauthier A, Daley L, Dial K, Wu J, Woo J, Lin M, Ashby C, Mantell L. 2019. The role of HMGB1, a nuclear damage-associated molecular pattern molecule, in the pathogenesis of lung diseases. Antioxid Redox Signal. 31(13):954–993.
   PubMed Web of Science ®Google Scholar
• Wang R, Pan M, Zhang X, Han M, Fan X, Zhao F, Miao M, Xu J, Guan M, Deng X, et al. 2020. Epidemiological and clinical features of 125 hospitalized patients with COVID-19 in Fuyang, Anhui, China. Int J Infect Dis. 95:421–428.
   PubMed Web of Science ®Google Scholar
• Ward N, Waxman A, Homer R, Mantell L, Einarsson O, Du Y, Elias J. 2000. Interleukin-6-induced protection in hyperoxic acute lung injury. Am J Respir Cell Mol Biol. 22(5):535–542.
   PubMed Web of Science ®Google Scholar
• Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, Huang H, Zhang L, Zhou X, Du C, et al. 2020. Risk factors associated with acute respiratory distress syndrome and death in patients with Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 180(7):934–943.
   PubMed Web of Science ®Google Scholar
• Wu H, Li L, Su X. 2014. Vagus nerve through α7nAChR modulates lung infection and inflammation: Models, cells, and signals. BioMed Res Intl. 2014:283525.
   PubMed Web of Science ®Google Scholar
• Xu Y, Li Y, Zeng Q, Lu Z, Li Y, Wu W, Dong S, Huang G, Wang X. 2020. Clinical characteristics of SARS-CoV-2 pneumonia compared to controls in Chinese Han population. Medrxiv. 2020:1–20.
   Google Scholar
• Yang H, Liu H, Zeng Q, Imperato G, Addorisio M, Li J, He M, Cheng K, Al-Abed Y, Harris H, et al. 2019. Inhibition of HMGB1/RAGE-mediated endocytosis by HMGB1 antagonist box A, anti-HMGB1 antibodies, and cholinergic agonists suppresses inflammation. Mol Med. 25:13.
   PubMed Web of Science ®Google Scholar
• Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, et al. 2020. Clinical course and outcomes of critically-ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet Resp Med. 8(5):475–481.
   PubMed Web of Science ®Google Scholar
• Yanover C, Mizrahi B, Kalkstein N, Marcus K, Akiva P, Barer Y, Shalev V, Chodick G. 2020. What factors increase the risk of complications in SARS-CoV-2-infected patients? A cohort study in a Nationwide Israeli Health Organization. JMIR Public Health Surveill. 6(3):e20872.
   PubMedGoogle Scholar
• Yao Q, Wang P, Wang X, Qie G, Meng M, Tong X, Bai X, Ding M, Liu W, Liu K, et al. 2020. Retrospective study of risk factors for severe SARS-Cov-2 infections in hospitalized adult patients. Polish Arch Intern Med. 130:390–399.
   PubMedGoogle Scholar
• Zemskova M, Kurdyukov S, James J, McClain N, Rafikov R, Rafikova O. 2020. Sex-specific stress response and HMGB1 release in pulmonary endothelial cells. PLoS One. 15(4):e0231267.
   PubMed Web of Science ®Google Scholar
• Zhang J, Dong X, Cao Y, Yuan Y, Yang Y, Yan Y, Akdis C, Gao Y. 2020. Clinical characteristics of 140 patients infected with SARS‐CoV‐2 in Wuhan. China Allergy. 75(7):1730–1741.
   PubMed Web of Science ®Google Scholar
• Zheng Y, Xiong C, Liu Y, Qian X, Tang Y, Liu L, Leung E, Wang M. 2020. Epidemiological and clinical characteristics analysis of COVID-19 in the surrounding areas of Wuhan, Hubei Province in 2020. Pharmacol Res. 157:104821.
   PubMed Web of Science ®Google Scholar
• Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, et al. 2020. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet. 395(10229):1054–1062.
   PubMed Web of Science ®Google Scholar