key: cord-0918236-mo9p50ot
authors: Lombardi, Carlo; Roca, Elena; Ventura, Laura; Cottini, Marcello
title: SMOKING AND COVID-19, THE PARADOX TO DISCOVER:An Italian retrospective, observational study in hospitalized and non-hospitalized patients
date: 2020-11-12
journal: Med Hypotheses
DOI: 10.1016/j.mehy.2020.110391
sha: f1da8f72a92f895aaee1a28ce852e55aa1392535
doc_id: 918236
cord_uid: mo9p50ot

nan

We have read with great interest the article published on Medical Hypotheses by de Bernardis & Busà about the putative role for the tobacco mosaic virus in smokers' resistance to COVID-19 (1) . We agree with the Authors and we also believe that smoking has a complex and not yet clear link with COVID-19. We considered 2 cohorts of 601 patients from 2 Northern Italian cities (Brescia and Bergamo) most affected by the SARS-CoV-2 infection : one concerning patients admitted to our hospital in Brescia, and another one concerning non-hospitalized patients evaluated at the territorial medicine level in Bergamo. The aim of the study was to assess whether or not there was a correlation between current active smoking and severity of COVID-19 disease. 299 consecutive hospitalized COVID-19 patients (M/F = 208 (70%)/ 91(30%) were included and among these 46 (15%) were current active smokers. The mean age was 68.8 years (±11.7). The patients who died as a consequence of COVID-19 disease were 87 (29%). Table I patients (3,4) . We agree with the Authors and we also found no significant correlation between active smoking and severity of COVID-19 disease. We believe that our study can add important information about the link between smoking and COVID-19 in Italian hospitalized and non-hospitalized patients too.

Probably the link between smoking and COVID-19 is not simple and does not concern a single factor.

If it is true that smoking increases the expression of ACE2 receptors to which the SARS-Cov-2 attaches, it is equally true that up regulation of this enzyme can decrease the risk of developing serious systemic complications of coronavirus infection (5,6). This is due to the fact that ACE2 converts angiotensin II (ANG II) to Angiotensin 1-7 (ANG 1-7) thus decreasing the powerful pro inflammatory effect of ANG II (7, 8) . Other Authors have confirmed that ACE2 mitigates pro inflammatory effects by decreasing the circulating amount of ANG II (9) . Moreover, studies in mice have shown that in smokers there is an upregulation of ACE2 which protects from the development of the Acute Respiratory Distress Syndrome (ARDS) (10, 11) . Consequently, studies have hypothesized that the up-regulation of this enzyme may protect patients from severe lung damage and that this also occurs in patients with COVID-19 (11).

Although it seems like a paradox, the latest scientific evidences are in favour of the hypothesis that smoking is not associated with the severity of COVID-19 patients. Our case series is interesting because it reports the data of hospitalized and non-hospitalized patients, confirming the nonassociation between smoking and COVID-19 disease. Future studies will be need to confirm this hypothesis and to discover the underlying pathophysiological mechanisms. 

A putative role for the tobacco mosaic virus in smokers' resistance to COVID-19

Smoking habit and hospitalization for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related pneumonia: The unsolved paradox behind the evidence

The paradox of the low prevalence of current smokers among COVID-19 patients hospitalized in non-intensive care wards: results from an istalian multicentre case-control study

Active smoking is not associated with severity of coronavirus disease 2019 (COVID-19)

ACE-2 expression in the small airway epithelia of smokers and COPD patients: implications for COVID-19

Cigarette smoke triggers the expansion of a subpopulation of respiratory epithelial cells that express the SARS-CoV-2 receptor ACE2

Angiotensin-Converting Enzyme 2 and Antihypertensives (Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors) in Coronavirus Disease

A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome

Angiotensin-converting enzyme 2 protects from severe acute lung failure

The discovery of angiotensin-converting enzyme 2 and its role in acute lung injury in mice

Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics