COPD and smoking
Chronic Obstructive Pulmonary Disease (COPD) is a common and preventable dysfunction of the lung associated with limitation in airflow. It is a complex disease associated with abnormalities of the airway and/or alveoli which is predominantly caused by exposure to noxious gases and particulates over a long period. A meta-analysis of 15 studies, including a total of 2473 confirmed COVID-19 cases showed that COPD patients were at a higher risk of more severe disease (calculated RR 1.88) and with 60% higher mortality (Alqahtani 2020). Unfortunately, the numbers in this review were very small and only 58 (2.3%) had COPD.
A meta-analysis of 5 early studies comprising 1399 patients observed only a trend but no significant association between active smoking and severity of COVID-19 (Lippi 2020). However, other authors have emphasized that current data do not allow to draw firm conclusions about the association of severity of COVID-19 with smoking status (Berlin 2020). In a more recent review, current smokers were 1.45 times more likely to have severe complications compared to former and never smokers. Current smokers also had a higher mortality rate (Alqahtani 2020).
Ever-smoking increased pulmonary ACE2 expression by 25% (Cai 2020). The significant smoking effect on ACE2 pulmonary expression may suggest an increased risk for viral binding and entry of SARS-CoV-2 into the lungs of smokers. Cigarette smoke triggers an increase in ACE2 positive cells by driving secretory cell expansion (Smith 2020). The overabundance of ACE2 in the lungs of smokers may partially explain a higher vulnerability of smokers.
However, it’s not that easy – both quitting smoking and finding clinical correlations to the above cell experiments. Within a surveillance center primary care sentinel network, multivariate logistic regression models were used to identify risk factors for positive SARS-CoV-2 tests (Lusignan 2020). Of note, active smoking was associated with decreased odds (yes, decreased: adjusted OR 0.49, 95% CI 0.34–0.71). According to the authors, their findings should not be used to conclude that smoking prevents SARS-CoV-2 infection, or to encourage ongoing smoking. Several explanations are given, such as selection bias (smokers are more likely to have a cough, more frequent testing could increase the proportion of smokers with negative results). Active smoking might also affect RT-PCR test sensitivity.
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Alqahtani JS, Oyelade T, Aldhahir AM, et al. Prevalence, Severity and Mortality associated with COPD and Smoking in patients with COVID-19: A Rapid Systematic Review and Meta-Analysis. PLoS One. 2020 May 11;15(5):e0233147. PubMed: https://pubmed.gov/32392262. Full-text: https://doi.org/10.1371/journal.pone.0233147
Cai G, Bosse Y, Xiao F, Kheradmand F, Amos CI. Tobacco Smoking Increases the Lung Gene Expression of ACE2, the Receptor of SARS-CoV-2. Am J Respir Crit Care Med. 2020 Apr 24. PubMed: https://pubmed.gov/32329629. Full-text: https://doi.org/10.1164/rccm.202003-0693LE
Lippi G, Henry BM. Active smoking is not associated with severity of coronavirus disease 2019 (COVID-19). Eur J Intern Med. 2020 Mar 16. PubMed: https://pubmed.gov/32192856. Full-text: https://doi.org/10.1016/j.ejim.2020.03.014
Lusignan S, Dorward J, Correa A, et al. Risk factors for SARS-CoV-2 among patients in the Oxford Royal College of General Practitioners Research and Surveillance Centre primary care network: a cross-sectional study. Lancet Inf Dis 2020, May 15. Full-text: https://doi.org/10.1016/S1473-3099(20)30371-6
Smith JC, Sauswille EL, Girish V, et al. Cigarette smoke exposure and inflammatory signaling increase the expression of the SARS-CoV-2 receptor ACE2 in the respiratory tract. Development Cell, May 16, 2020. Full-text: https://doi.org/10.1016/j.devcel.2020.05.012