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COPD and smoking

Co-morbidities | 461

However, a careful investigation (Coate 2020) suggested that the interaction of diabetes and SARS-CoV-2 is mediated by systemic inflammation and/or metabolic changes in other organs such as liver, muscle or adipose tissue (and not by a direct infection of β cells in the pancreas).

References

Barron E, Bakhai C, Kar P, et al. Associations of type 1 and type 2 diabetes with COVID-19related mortality in England: a whole-population study. Lancet Diabetes Endocrinol. 2020 Oct;8(10):813-822. PubMed: https://pubmed.gov/32798472. Full-text: https://doi.org/10.1016/S2213-8587(20)30272-2 Cheng X, Liu YM, Li H, et al. Metformin Is Associated with Higher Incidence of Acidosis, but

Not Mortality, in Individuals with COVID-19 and Pre-existing Type 2 Diabetes. Cell

Metab. 2020 Oct 6;32(4):537-547.e3. PubMed: https://pubmed.gov/32861268. Full-text: https://doi.org/10.1016/j.cmet.2020.08.013 Coate KC, Cha , Shrestha S. SARS-CoV-2 Cell Entry Factors ACE2 and TMPRSS2 are Expressed in the Microvasculature and Ducts of Human Pancreas but are Not Enriched in β Cells.

Cell Metabolism November 13, 2020. Full-text: https://doi.org/10.1016/j.cmet.2020.11.006 Gerstein HC, Thorpe KE, Taylor DW, Haynes RB. The effectiveness of hydroxychloroquine in

patients with type 2 diabetes mellitus who are refractory to sulfonylureas--a random-

ized trial. Diabetes Res Clin Pract. 2002 Mar;55(3):209-19. PubMed: https://pubmed.gov/11850097. Full-text: https://doi.org/10.1016/s0168-8227(01)00325-4 Holman N, Knighton P, Kar P, et al. Risk factors for COVID-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort study. Lancet

Diabetes Endocrinol. 2020 Oct;8(10):823-833. PubMed: https://pubmed.gov/32798471. Fulltext: https://doi.org/10.1016/S2213-8587(20)30271-0 Hussain A, Bhowmik B, do Vale Moreira NC. COVID-19 and diabetes: Knowledge in progress.

Diabetes Res Clin Pract. 2020 Apr;162:108142. PubMed: https://pubmed.gov/32278764. Fulltext: https://doi.org/10.1016/j.diabres.2020.10814 Kumar A, Arora A, Sharma P, et al. Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis. Diabetes Metab Syndr. 2020 May 6;14(4):535-545. PubMed: https://pubmed.gov/32408118. Full-text: https://doi.org/10.1016/j.dsx.2020.04.044 Rekedal LR, Massarotti E, Garg R, et al. Changes in glycosylated hemoglobin after initiation of

hydroxychloroquine or methotrexate treatment in diabetes patients with rheumatic

diseases. Arthritis Rheum. 2010 Dec;62(12):3569-73. PubMed: https://pubmed.gov/20722019. Full-text: https://doi.org/10.1002/art.27703 Zhu L, She ZG, Cheng X, et al. Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes. Cell Metab. 2020 Jun 2;31(6):10681077.e3. PubMed: https://pubmed.gov/32369736. Full-text: https://doi.org/10.1016/j.cmet.2020.04.021

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 se-

462 | CovidReference.com

vere 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.

References

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 Berlin I, Thomas D, Le Faou AL, Cornuz J. COVID-19 and smoking. Nicotine Tob Res. 2020 Apr 3. pii: 5815378. PubMed: https://pubmed.gov/32242236. Full-text: https://doi.org/10.1093/ntr/ntaa059 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.2020030693LE de 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