Association Between Smoking and SARS-CoV-2 Infection: Cross-sectional Study of the EPICOVID19 Internet-Based Survey

Federica Prinelli, Fabrizio Bianchi, Gaspare Drago, Silvia Ruggieri, Aleksandra Sojic, Nithiya Jesuthasan, Sabrina Molinaro, Luca Bastiani, Stefania Maggi, Marianna Noale, Massimo Galli, Andrea Giacomelli, Raffaele Antonelli Incalzi, Fulvio Adorni, Fabio Cibella, EPICOVID19 Working Group, Fulvio Adorni, Massimo Andreoni, Raffaele Antonelli Incalzi, Luca Bastiani, Fabrizio Bianchi, Mauro Di Bari, Loredana Fortunado, Massimo Galli, Andrea Giacomelli, Nithiya Jesuthasan, Stefania Maggi, Claudio Mastroianni, Sabrina Molinaro, Marianna Noale, Gabriele Pagani, Claudio Pedone, Carla Pettenati, Federica Prinelli, Stefano Rusconi, Aleksandra Sojic, Marcello Tavio, Caterina Trevisan, Federica Prinelli, Fabrizio Bianchi, Gaspare Drago, Silvia Ruggieri, Aleksandra Sojic, Nithiya Jesuthasan, Sabrina Molinaro, Luca Bastiani, Stefania Maggi, Marianna Noale, Massimo Galli, Andrea Giacomelli, Raffaele Antonelli Incalzi, Fulvio Adorni, Fabio Cibella, EPICOVID19 Working Group, Fulvio Adorni, Massimo Andreoni, Raffaele Antonelli Incalzi, Luca Bastiani, Fabrizio Bianchi, Mauro Di Bari, Loredana Fortunado, Massimo Galli, Andrea Giacomelli, Nithiya Jesuthasan, Stefania Maggi, Claudio Mastroianni, Sabrina Molinaro, Marianna Noale, Gabriele Pagani, Claudio Pedone, Carla Pettenati, Federica Prinelli, Stefano Rusconi, Aleksandra Sojic, Marcello Tavio, Caterina Trevisan

Abstract

Background: Several studies have reported a low prevalence of current smoking among hospitalized COVID-19 cases; however, no definitive conclusions can be drawn.

Objective: We investigated the association of tobacco smoke exposure with nasopharyngeal swab (NPS) test results for SARS-CoV-2 infection and disease severity accounting for possible confounders.

Methods: The nationwide, self-administered, cross-sectional web-based Italian National Epidemiological Survey on COVID-19 (EPICOVID19) was administered to an Italian population of 198,822 adult volunteers who filled in an online questionnaire between April 13 and June 2, 2020. For this study, we analyzed 6857 individuals with known NPS test results. The associations of smoking status and the dose-response relationship with a positive NPS test result and infection severity were calculated as odds ratios (ORs) with 95% CIs by means of logistic and multinomial regression models adjusting for sociodemographic, clinical, and behavioral characteristics.

Results: Out of the 6857 individuals (mean age 47.9 years, SD 14.1; 4516/6857, 65.9% female), 63.2% (4334/6857) had never smoked, 21.3% (1463/6857) were former smokers, and 15.5% (1060/6857) were current smokers. Compared to nonsmokers, current smokers were younger, were more educated, were less affected by chronic diseases, reported COVID-19-like symptoms less frequently, were less frequently hospitalized, and less frequently tested positive for COVID-19. In multivariate analysis, current smokers had almost half the odds of a positive NPS test result (OR 0.54, 95% CI 0.45-0.65) compared to nonsmokers. We also found a dose-dependent relationship with tobacco smoke: mild smokers (adjusted OR [aOR] 0.76, 95% CI 0.55-1.05), moderate smokers (aOR 0.56, 95% CI 0.42-0.73), and heavy smokers (aOR 0.38, 95% CI 0.27-0.53). This inverse association also persisted when considering the severity of the infection. Current smokers had a statistically significantly lower probability of having asymptomatic (aOR 0.50, 95% CI 0.27-0.92), mild (aOR 0.65, 95% CI 0.53-0.81), and severe infections (aOR 0.27, 95% CI 0.17-0.42) compared to those who never smoked.

Conclusions: Current smoking was negatively associated with SARS-CoV-2 infection with a dose-dependent relationship. Ad hoc experimental studies are needed to elucidate the mechanisms underlying this association.

Trial registration: ClinicalTrials.gov NCT04471701; https://ichgcp.net/clinical-trials-registry/NCT04471701.

Keywords: COVID-19; SARS-CoV-2; cross-sectional design; dose-response relationship; infection severity; nasopharyngeal swab testing; self-reported; smoking habit; web-based survey.

Conflict of interest statement

Conflicts of Interest: None declared.

©Federica Prinelli, Fabrizio Bianchi, Gaspare Drago, Silvia Ruggieri, Aleksandra Sojic, Nithiya Jesuthasan, Sabrina Molinaro, Luca Bastiani, Stefania Maggi, Marianna Noale, Massimo Galli, Andrea Giacomelli, Raffaele Antonelli Incalzi, Fulvio Adorni, Fabio Cibella, EPICOVID19 Working Group. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 28.04.2021.

Figures

Figure 1
Figure 1
Flowchart of participant recruitment and eligibility for the EPICOVID19 (Italian National Epidemiological Survey on COVID-19) study. NPS: nasopharyngeal swab.
Figure 2
Figure 2
Adjusted odds ratios and relative 95% CIs for smoking status, intensity, and duration (N=6857). Odds ratios were adjusted for age, sex, education, occupation, area of residence, heart diseases, lung diseases, hypertension, metabolic and oncological diseases, contact with confirmed or suspected COVID-19 cases, living area, crowding index, and living with at-risk cohabitants. Dots and vertical lines indicate adjusted odds ratios and 95% CIs, respectively. Mild smokers: ≤10 cigarettes/day for 10 cigarettes/day for 10 cigarettes/day for ≥15 years. cig: cigarettes.
Figure 3
Figure 3
Adjusted odds ratios for positive SARS-CoV-2 tests by smoke-related variables: intensity, duration, and pack-years of smoking (N=6857). Odds ratios were adjusted for age, sex, education, occupation, area of residence, heart diseases, lung diseases, hypertension, metabolic and oncological diseases, contact with COVID-19 cases, living area, crowding index, and living with at-risk cohabitants. Dots and vertical lines indicate adjusted odds ratios and 95% CIs, respectively. cig: cigarettes.

References

    1. Smoking and COVID-19. World Health Organization. 2020. Jun 30, [2020-06-30]. .
    1. Xu X, Chen P, Wang J, Feng J, Zhou H, Li X, Zhong W, Hao P. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci. 2020 Mar;63(3):457–460. doi: 10.1007/s11427-020-1637-5.
    1. Zhang H, Rostami MR, Leopold PL, Mezey JG, O’Beirne SL, Strulovici-Barel Y, Crystal RG. Expression of the SARS-CoV-2 ACE2 receptor in the human airway epithelium. Am J Respir Crit Care Med. 2020 Jul 15;202(2):219–229. doi: 10.1164/rccm.202003-0541oc.
    1. Berlin I, Thomas D, Le Faou AL, Cornuz J. COVID-19 and smoking. Nicotine Tob Res. 2020 Aug 24;22(9):1650–1652. doi: 10.1093/ntr/ntaa059.
    1. Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, Liu L, Shan H, Lei C, Hui DS, Du B, Li L, Zeng G, Yuen K, Chen R, Tang C, Wang T, Chen P, Xiang J, Li S, Wang J, Liang Z, Peng Y, Wei L, Liu Y, Hu Y, Peng P, Wang J, Liu J, Chen Z, Li G, Zheng Z, Qiu S, Luo J, Ye C, Zhu S, Zhong N, China Medical Treatment Expert Group for Covid-19 Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708–1720. doi: 10.1056/NEJMoa2002032.
    1. Cummings MJ, Baldwin MR, Abrams D, Jacobson SD, Meyer BJ, Balough EM, Aaron JG, Claassen J, Rabbani LE, Hastie J, Hochman BR, Salazar-Schicchi J, Yip NH, Brodie D, O'Donnell MR. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: A prospective cohort study. Lancet. 2020 Jun;395(10239):1763–1770. doi: 10.1016/s0140-6736(20)31189-2.
    1. Parra-Bracamonte GM, Lopez-Villalobos N, Parra-Bracamonte FE. Clinical characteristics and risk factors for mortality of patients with COVID-19 in a large data set from Mexico. Ann Epidemiol. 2020 Dec;52:93–98.e2. doi: 10.1016/j.annepidem.2020.08.005.
    1. Yanover C, Mizrahi B, Kalkstein N, Marcus K, Akiva P, Barer Y, Shalev V, Chodick G. 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. 2020 Aug 25;6(3):e20872. doi: 10.2196/20872.
    1. Miyara M, Tubach F, Martinez V, Morelot-Panzini C, Pernet J, Haroche J, Lebbah S, Morawiec E, Gorochov G, Caumes E, Hausfater P, Combes A, Similowski T, Amoura Z. Low rate of daily smokers in patients with symptomatic COVID-19. medRxiv. doi: 10.1101/2020.06.10.20127514. Preprint posted online on June 12, 2020.
    1. Hamer M, Kivimäki M, Gale CR, Batty GD. Lifestyle risk factors, inflammatory mechanisms, and COVID-19 hospitalization: A community-based cohort study of 387,109 adults in UK. Brain Behav Immun. 2020 Jul;87:184–187. doi: 10.1016/j.bbi.2020.05.059.
    1. Gaibazzi D, Tuttolomondo A, Guidorossi A, Botti A, Tedeschi A, Martini C, Mattioli M. Smoking prevalence is low in symptomatic patients admitted for COVID-19. medRxiv. doi: 10.1101/2020.05.05.20092015. Preprint posted online on June 13, 2020.
    1. Lodigiani C, Iapichino G, Carenzo L, Cecconi M, Ferrazzi P, Sebastian T, Kucher N, Studt J, Sacco C, Bertuzzi A, Sandri MT, Barco S, Humanitas COVID-19 Task Force Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res. 2020 Jul;191:9–14. doi: 10.1016/j.thromres.2020.04.024.
    1. Inciardi RM, Adamo M, Lupi L, Cani D, Di Pasquale M, Tomasoni D, Italia L, Zaccone G, Tedino C, Fabbricatore D, Curnis A, Faggiano P, Gorga E, Lombardi CM, Milesi G, Vizzardi E, Volpini M, Nodari S, Specchia C, Maroldi R, Bezzi M, Metra M. Characteristics and outcomes of patients hospitalized for COVID-19 and cardiac disease in Northern Italy. Eur Heart J. 2020 May 14;41(19):1821–1829. doi: 10.1093/eurheartj/ehaa388.
    1. Tsigaris P, Teixeira da Silva JA. Smoking prevalence and COVID-19 in Europe. Nicotine Tob Res. 2020 Aug 24;22(9):1646–1649. doi: 10.1093/ntr/ntaa121.
    1. Pagani G, Conti F, Giacomelli A, Bernacchia D, Rondanin R, Prina A, Scolari V, Gandolfi CE, Castaldi S, Marano G, Ottomano C, Boracchi P, Biganzoli E, Galli M. Seroprevalence of SARS-CoV-2 significantly varies with age: Preliminary results from a mass population screening. J Infect. 2020 Dec;81(6):e10–e12. doi: 10.1016/j.jinf.2020.09.021.
    1. Israel A, Feldhamer I, Lahad A, Levin-Zamir DG, Lavie G. Smoking and the risk of COVID-19 in a large observational population study. medRxiv. doi: 10.1101/2020.06.01.20118877. Preprint posted online on June 5, 2020.
    1. Rentsch CT, Kidwai-Khan F, Tate JP, Park LS, King JT, Skanderson M, Hauser RG, Schultze A, Jarvis CI, Holodniy M, Lo Re V, Akgun KM, Crothers K, Taddei TH, Freiberg MS, Justice AC. Covid-19 testing, hospital admission, and intensive care among 2,026,227 United States veterans aged 54-75 years. medRxiv. doi: 10.1101/2020.04.09.20059964. Preprint posted online on April 14, 2020.
    1. Russo P, Bonassi S, Giacconi R, Malavolta M, Tomino C, Maggi F. COVID-19 and smoking: Is nicotine the hidden link? Eur Respir J. 2020 Jun;55(6):2001116. doi: 10.1183/13993003.01116-2020.
    1. Farsalinos K, Barbouni A, Poulas K, Polosa R, Caponnetto P, Niaura R. Current smoking, former smoking, and adverse outcome among hospitalized COVID-19 patients: A systematic review and meta-analysis. Ther Adv Chronic Dis. 2020;11:1–14. doi: 10.1177/2040622320935765.
    1. Usman MS, Siddiqi TJ, Khan MS, Patel UK, Shahid I, Ahmed J, Kalra A, Michos ED. Is there a smoker's paradox in COVID-19? BMJ Evid Based Med. 2020 Aug 11;:1–6. doi: 10.1136/bmjebm-2020-111492.
    1. Grines CL, Topol EJ, O'Neill WW, George BS, Kereiakes D, Phillips HR, Leimberger JD, Woodlief LH, Califf RM. Effect of cigarette smoking on outcome after thrombolytic therapy for myocardial infarction. Circulation. 1995 Jan 15;91(2):298–303. doi: 10.1161/01.cir.91.2.298.
    1. Leung JM, Yang CX, Tam A, Shaipanich T, Hackett T, Singhera GK, Dorscheid DR, Sin DD. ACE-2 expression in the small airway epithelia of smokers and COPD patients: Implications for COVID-19. Eur Respir J. 2020 May;55(5):2000688. doi: 10.1183/13993003.00688-2020.
    1. Grundy EJ, Suddek T, Filippidis F, Majeed A, Coronini-Cronberg S. Smoking, SARS-CoV-2 and COVID-19: A review of reviews considering implications for public health policy and practice. Tob Induc Dis. 2020;18:58. doi: 10.18332/tid/124788.
    1. Adorni F, Prinelli F, Bianchi F, Giacomelli A, Pagani G, Bernacchia D, Rusconi S, Maggi S, Trevisan C, Noale M, Molinaro S, Bastiani L, Fortunato L, Jesuthasan N, Sojic A, Pettenati C, Tavio M, Andreoni M, Mastroianni C, Antonelli Incalzi R, Galli M. Self-reported symptoms of SARS-CoV-2 infection in a nonhospitalized population in Italy: Cross-sectional study of the EPICOVID19 web-based survey. JMIR Public Health Surveill. 2020 Sep 18;6(3):e21866. doi: 10.2196/21866.
    1. COVID-19 repository - Dipartimento di Protezione Civile [Webpage in Italian] GitHub. 2020. [2020-03-30].
    1. Bastiani L, Fortunato L, Pieroni S, Bianchi F, Adorni F, Prinelli F, Giacomelli A, Pagani G, Maggi S, Trevisan C, Noale M, Jesuthasan N, Sojic A, Pettenati C, Andreoni M, Antonelli Incalzi R, Galli M, Molinaro S. Rapid COVID-19 screening based on self-reported symptoms: Psychometric assessment and validation of the EPICOVID19 short diagnostic scale. J Med Internet Res. 2021 Jan 06;23(1):e23897. doi: 10.2196/23897.
    1. Noale M, Trevisan C, Maggi S, Antonelli Incalzi R, Pedone C, Di Bari M, Adorni F, Jesuthasan N, Sojic A, Galli M, Giacomelli A, Molinaro S, Bianchi F, Mastroianni C, Prinelli F, On Behalf Of The Epicovid Working Group The association between influenza and pneumococcal vaccinations and SARS-CoV-2 infection: Data from the EPICOVID19 web-based survey. Vaccines (Basel) 2020 Aug 23;8(3):471. doi: 10.3390/vaccines8030471.
    1. National Health Interview Survey – Adult tobacco use information. Centers for Disease Prevention and Control. 2017. Aug 29, [2017-08-29]. .
    1. Romagnani P, Gnone G, Guzzi F, Negrini S, Guastalla A, Annunziato F, Romagnani S, De Palma R. The COVID-19 infection: Lessons from the Italian experience. J Public Health Policy. 2020 Sep;41(3):238–244. doi: 10.1057/s41271-020-00229-y.
    1. Annuario Statistico Italiano 2019. Rome, Italy: Istituto nazionale di statistica (Istat); 2019. [2019-01-31]. .
    1. Yang JJ, Song M, Yoon H, Lee H, Lee Y, Lee S, Choi J, Lee J, Kang D. What are the major determinants in the success of smoking cessation: Results from the Health Examinees study. PLoS One. 2015;10(12):e0143303. doi: 10.1371/journal.pone.0143303.
    1. Williamson EJ, Walker AJ, Bhaskaran K, Bacon S, Bates C, Morton CE, Curtis HJ, Mehrkar A, Evans D, Inglesby P, Cockburn J, McDonald HI, MacKenna B, Tomlinson L, Douglas IJ, Rentsch CT, Mathur R, Wong AYS, Grieve R, Harrison D, Forbes H, Schultze A, Croker R, Parry J, Hester F, Harper S, Perera R, Evans SJW, Smeeth L, Goldacre B. Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020 Aug;584(7821):430–436. doi: 10.1038/s41586-020-2521-4.
    1. Miyara M, Tubach F, Pourcher V, Morelot-Panzini C, Pernet J, Haroche J, Lebbah S, Morawiec E, Gorochov G, Caumes E, Hausfater P, Combes A, Similowski T, Amoura Z. Low rate of daily active tobacco smoking in patients with symptomatic COVID-19. Qeios. doi: 10.32388/wpp19w.4. Preprint posted online on May 9, 2020.
    1. Hopkinson NS, Rossi N, El-Sayed Moustafa J, Laverty AA, Quint JK, Freidin M, Visconti A, Murray B, Modat M, Ourselin S, Small K, Davies R, Wolf J, Spector TD, Steves CJ, Falchi M. Current smoking and COVID-19 risk: Results from a population symptom app in over 2.4 million people. Thorax. 2021 Jan 05;:1–9. doi: 10.1136/thoraxjnl-2020-216422.
    1. Vardavas C, Nikitara K. COVID-19 and smoking: A systematic review of the evidence. Tob Induc Dis. 2020;18:20. doi: 10.18332/tid/119324.
    1. Patanavanich R, Glantz SA. Smoking is associated with COVID-19 progression: A meta-analysis. Nicotine Tob Res. 2020 Aug 24;22(9):1653–1656. doi: 10.1093/ntr/ntaa082.
    1. Lippi G, Henry BM. Active smoking is not associated with severity of coronavirus disease 2019 (COVID-19) Eur J Intern Med. 2020 May;75:107–108. doi: 10.1016/j.ejim.2020.03.014.
    1. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CH, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Mar;579(7798):270–273. doi: 10.1038/s41586-020-2012-7.
    1. Alifano M, Alifano P, Forgez P, Iannelli A. Renin-angiotensin system at the heart of COVID-19 pandemic. Biochimie. 2020 Jul;174:30–33. doi: 10.1016/j.biochi.2020.04.008.
    1. Brake SJ, Barnsley K, Lu W, McAlinden KD, Eapen MS, Sohal SS. Smoking upregulates angiotensin-converting enzyme-2 receptor: A potential adhesion site for novel coronavirus SARS-CoV-2 (COVID-19) J Clin Med. 2020 Mar 20;9(3):841. doi: 10.3390/jcm9030841.
    1. Oakes JM, Fuchs RM, Gardner JD, Lazartigues E, Yue X. Nicotine and the renin-angiotensin system. Am J Physiol Regul Integr Comp Physiol. 2018 Nov 01;315(5):R895–R906. doi: 10.1152/ajpregu.00099.2018.
    1. Verdecchia P, Cavallini C, Spanevello A, Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur J Intern Med. 2020 Jun;76:14–20. doi: 10.1016/j.ejim.2020.04.037.
    1. Engin AB, Engin ED, Engin A. Two important controversial risk factors in SARS-CoV-2 infection: Obesity and smoking. Environ Toxicol Pharmacol. 2020 Aug;78:103411. doi: 10.1016/j.etap.2020.103411.
    1. Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, Huan Y, Yang P, Zhang Y, Deng W, Bao L, Zhang B, Liu G, Wang Z, Chappell M, Liu Y, Zheng D, Leibbrandt A, Wada T, Slutsky AS, Liu D, Qin C, Jiang C, Penninger JM. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005 Aug;11(8):875–879. doi: 10.1038/nm1267.
    1. McGonagle D, Sharif K, O'Regan A, Bridgewood C. The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev. 2020 Jun;19(6):102537. doi: 10.1016/j.autrev.2020.102537.
    1. Garufi G, Carbognin L, Orlandi A, Tortora G, Bria E. Smoking habit and hospitalization for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related pneumonia: The unsolved paradox behind the evidence. Eur J Intern Med. 2020 Jul;77:121–122. doi: 10.1016/j.ejim.2020.04.042.
    1. Hedenstierna G, Chen L, Hedenstierna M, Lieberman R, Fine DH. Nitric oxide dosed in short bursts at high concentrations may protect against COVID-19. Nitric Oxide. 2020 Oct 01;103:1–3. doi: 10.1016/j.niox.2020.06.005.
    1. Alla F, Berlin I, Nguyen-Thanh V, Guignard R, Pasquereau A, Quelet S, Schwarzinger M, Arwidson P. Tobacco and COVID-19: A crisis within a crisis? Can J Public Health. 2020 Dec;111(6):995–999. doi: 10.17269/s41997-020-00427-x.
    1. Griffith GJ, Morris TT, Tudball MJ, Herbert A, Mancano G, Pike L, Sharp GC, Sterne J, Palmer TM, Davey Smith G, Tilling K, Zuccolo L, Davies NM, Hemani G. Collider bias undermines our understanding of COVID-19 disease risk and severity. Nat Commun. 2020 Nov 12;11(1):5749. doi: 10.1038/s41467-020-19478-2. doi: 10.1038/s41467-020-19478-2.
    1. Balabanski LL. An international review of tobacco use and the COVID-19 pandemic: Examining hospitalization, asymptomatic cases, and severity. medRxiv. doi: 10.1101/2020.06.12.20129478. Preprint posted online on June 16, 2020.
    1. Italian Ministry of Health, Report 2018. Activities for Smoking Prevention. Rome, Italy: Italian Ministry of Health; 2018. [2018-12-31]. .

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere