key: cord-287682-97fquq16 authors: Daubin, Cédric; Justet, Aurélien; Vabret, Astrid; Bergot, Emmanuel; Terzi, Nicolas title: Is a COPD patient protected against SARS-CoV-2 virus? date: 2020-10-03 journal: Med Mal Infect DOI: 10.1016/j.medmal.2020.09.015 sha: doc_id: 287682 cord_uid: 97fquq16 nan We would like to draw attention to the relationship between SARS-CoV-2 and chronic obstructive pulmonary disease (COPD). Considering the mode of transmission via droplets, and the virulence of SARS-Cov-2, we had anticipated that COPD patients would be at increased risk of SARS-CoV-2 infection. However, among 392 patients with documented SARS-Cov-2 infection admitted to two French University Hospitals between the 15 March and the 15 April 2020, only 22 (5.6%) patients had a documented COPD. All COPD patients were former or active smokers. In the entire cohort, 82 (21%) patients were admitted in medical ICU for ventilatory support (i.e., requiring mechanical invasive ventilation in 59 cases and non-invasive ventilation or high-flow oxygen therapy in 23 cases, respectively), including 5 patients (6%) with a documented COPD (GOLD stage I (n=2), II (n=1), III (n=1), unclassified for 1 patient). Two patients required high-flow oxygen therapy only and 3 patients needed non-invasive ventilation. All COPD patients except 1 survived and were discharged from the hospital. Even if this observation is concordant with the low prevalence of 4 % in COPD patients diagnosed with SARS-CoV-2 infection in a recent Italian cohort [1] , this result is quite surprising since COPD patients admitted in ICU have many SARS-CoV-2 risk factors (i.e., male, overweight, arterial hypertension, chronic cardiopathy and diabetes mellitus). In addition, cigarette smoke and COPD were reported to up-regulate Angiotensin-converting enzyme 2 (ACE-2) expression, which plays a key role in the pathogenesis of SARS-CoV-2 in lower airways [2] . Therefore, how can one explain that COPD patients are under-represented in patients with We could hypothesize that the low prevalence of COPD patients in intensive care settings could be the consequence of pre-existing poor prognosis and decisions to limit the treatment to palliative care. Furthermore, patients with chronic respiratory diseases are likely to be more aware of viral epidemics and are more sensitive to containment and barrier actions than the general population. Another explication could come from COVID 19 pathophysiology. Cell entry of SARS-CoV-2 is a multi-step process in which ACE-2 and the transmembrane protease serine 2 (TMPRSS2) for S protein priming play a crucial role. Considering a significant inverse relationship between ACE-2 gene expression and the severity of COPD [2] , one hypothesis could be that COPD protects against SARS-CoV-2 through a TMPRSS2 inhibitor activity or by an a downregulation of the inflammatory pathway limiting severe forms of infection. Interestingly, as reported by Halpin et al., inhaled corticosteroids, used by COPD patients can reduce the risk of viral infection. Indeed, budesonide was reported as a promising antiviral and anti-inflammatory drug candidate for the treatment of human rhinovirus infection [3] . In-vitro experiments showed that inhaled formoterol alone or in combination with bronchodilators (i.e., glycopyrronium and budesonide) inhibited HCoV-229E replication partly by inhibiting receptor expression and/or endosomal function and modulated infection-induced inflammation. Inhaled corticosteroids also reduced the expression of transmembrane serine protease TMPRSS4 and TMPRSS11, which facilitates viral entry and proliferation in human bronchial epithelial cells in-vitro. Therefore, inhaled corticosteroids in combination with bronchodilators could limit expression or activity of transmenbrane serine protease TMPRSS2 which facilitates SARS-CoV-2 entry in cells. Surprisingly current smokers (i.e., a large part of COPD patients) could be protected against SARS-CoV-2 infection [4] . In-vivo models support that chronic cigarette smoke exposure could downregulate ACE 2 expression in lungs via a mechanism dependent of Angiotensine II and Angiotensine II type 1 Receptor [5] . This result suggests a potential protector effect of nicotine against SARS-CoV-2 cell entry via a possible role of nicotinic acetylcholine receptors [4] . Whether cigarette smoking or nicotine do or do not provide a benefit effect warrants further studies. Understanding why and how remains a challenge for researchers. COVID-19 Lombardy ICU Network. Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV Admitted to ICUs of the Lombardy Region Sin DD (2020) ACE-2 Expression in the Small Airway Epithelia of Smokers and COPD Patients: Implications for COVID-19 Inhaled corticosteroids and COVID-19: a systematic review and clinical perspective Low incidence of daily active smokers in patients with symptomatic COVID19 Nicotine and the reninangiotensin system The authors declare that they have no conflicts of interest.