Publish in this journal
Journal Information
Letter to the Editor
Full text access
Available online 20 March 2021
Smoker, Former Smoker and COVID-19: Nicotine Does Not Protect Against SARS-CoV-2
Fumador, exfumador y COVID-19: la nicotina no protege contra el SARS-CoV-2
Carlos Andrés Jiménez-Ruiza, Daniel López-Padillab, Adolfo Alonso-Arroyoc, Rafael Aleixandre-Benaventd, Segismundo Solano-Reinab, José Ignacio de Granda-Orivee,
Corresponding author

Corresponding author.
a Unidad Especializada de Tabaquismo de la Comunidad de Madrid, Hospital Clínico San Carlos, Madrid, Spain
b Servicio de Neumología, Hospital General Universitario Gregorio Marañón, Madrid, Spain
c Departamento de Historia de la Ciencia y Documentación, Universidad de Valencia, Valencia, Spain
d Ingenio (CSIC-UPV), UISYS, Joint Research Unit, Universitat de Valencia, Valencia, Spain
e Servicio de Neumología, Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain
Article information
Full Text
Download PDF
Figures (1)
Full Text
To the Editor,

We would like to thank Moril et al.1 for their interest in our paper and for prompting us to explore the topic further. The spike protein is responsible for facilitating the entry of SARS-CoV-2 into human cells and requires priming by protease TMPRSS2 to allow fusion of the viral and cellular membranes.2 The receptor used by the spike protein is the angiotensin-converting enzyme 2 (ACE2),2 which is expressed in different cell strains, as well as in the lung, where there is a gradient of ACE2 expression (higher expression in the upper respiratory tract [nasal epithelium] and lower in the alveolar pneumocytes).2 It has been suggested that a higher expression of ACE2 could contribute to increased SARS-CoV-2 viral infectivity.2 As Moril et al. mention,1 active smokers with chronic obstructive pulmonary disease have a higher level of expression of ACE2 than former smokers and former smokers have a higher level than never smokers,1,2 while a decrease in ACE2 expression has been observed in the bronchial epithelial cells of former smokers compared with active smokers.1,2 Not all authors have obtained the same results. Lee et al.3 did not identify any differences in ACE2 expression based on age, sex, or smoking status, and suggest that smoking is not a protective factor, but rather a risk factor for Covid-19 disease progression. Voinsky et al.4 did not find higher ACE2 and TMPRSS2 expression in smokers or never smokers, but they did observe higher expression of TMPRSS4 (that encodes a protease for cell entry similar to TMPRSS2) in smokers compared to never smokers, suggesting that they may be at increased risk for Covid-19 infection. Regarding the comment of Moril et al.1 on the possibility of a better prognosis in smokers, Takagi, in Japan,5 carried out a meta-regression that showed a positive association between the prevalence of smoking and Covid-19 infection independent of other co-variables, so the hypothesis that smokers have a better disease prognosis is not supported. In a new meta-analysis of our data,6 we classified patients as smokers or former smokers (only 5 articles differentiated former smokers) (Fig. 1). Former smokers clearly showed similarly poor progression, while current smokers showed a clear tendency to worse progression but without statistical significance. The same results were obtained in the meta-analysis of Patanavanich et al.7 (only 8 articles divided smokers into categories). Most of the studies included in the meta-analysis have significant limitations: they are mostly retrospective and have significant selection and data biases and lack a comparative group, making it difficult to establish causality. We reaffirm that smokers and former smokers have a worse Covid-19 progression, including higher mortality, and that nicotine cannot be considered a protective factor in any way.

Fig. 1.

Being a former smoker or an active smoker is a risk factor for worse Covid-19 progression.

M. Moril, H. Peña.
Fumador, exfumador y COVID-19.
I.H. Heijink, T.L. Hackett, S.D. Pouwels.
Effects of cigarettes smoking on SARS-CoV-2 receptor ACE2 expression in the respiratory epithelium.
I.T. Lee, T. Nakayama, C.T. Wu, Y. Goltsev, S. Jiang, P.A. Gall, et al.
ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs.
Nat Commun, 11 (2020), pp. 5453
I. Voinsky, D. Gurwitz.
Smoking and COVID-19: similar bronchial ACE2 and TMPRSS2 expression and higher TMPRSS4 expression in current versus never smokers.
H. Takagi.
Systematic review of the prevalence of current smoking among hospitalized COVID-19 patients in China: could nicotine be a therapeutic option?.
Intern Emerg Med, 15 (2020), pp. 1601-1603
C.A. Jiménez-Ruiz, D. López-Padilla, A. Alonso-Arroyo, R. Aleixandre-Benavent, S. Solano-Reina, J.I. De Granda-Orive.
COVID-19 and smoking: a systematic review and meta-analysis of the evidence.
Arch Bronconeumol, 57 (2020), pp. 21-34
R. Patanavanich, S.A. Glantz.
Smoking is associated with worse outcomes of COVID-19 particularly among younger adults: a systematic review and meta-analysis.

Please cite this article as: Jiménez-Ruiz CA, López-Padilla D, Alonso-Arroyo A, Aleixandre-Benavent R, Solano-Reina S, de Granda-Orive JI. Fumador, exfumador y COVID-19: la nicotina no protege contra el SARS-CoV-2. Arch Bronconeumol. 2021.

Copyright © 2021. SEPAR
Archivos de Bronconeumología

Subscribe to our newsletter

Article options

Are you a health professional able to prescribe or dispense drugs?