Abstract
BackgroundHow cigarette smoke (CS) and chronic obstructive pulmonary disease (COPD) affect severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection and severity is controversial. We investigated the effects of COPD and CS on the expression of SARS-CoV-2 entry receptor ACE2 in vivo in COPD patients and controls and in CS-exposed mice, and the effects of CS on SARS-CoV-2 infection in human bronchial epithelial cells in vitro.MethodsWe quantified: (1) pulmonary ACE2 protein levels by immunostaining and ELISA, and both ACE2 and/or TMPRSS2 mRNA levels by RT-qPCR in two independent human cohorts; and (2) pulmonary ACE2 protein levels by immunostaining and ELISA in C57BL/6 WT mice exposed to air or CS for up to 6 months. The effects of CS exposure on SARS-CoV-2 infection were evaluated after in vitro infection of Calu-3 cells and differentiated human bronchial epithelial cells (HBECs), respectively.ResultsACE2 protein and mRNA levels were decreased in peripheral airways from COPD patients versus controls but similar in central airways. Mice exposed to CS had decreased ACE2 protein levels in their bronchial and alveolar epithelia versus air-exposed mice. CS treatment decreased viral replication in Calu-3 cells, as determined by immunofluorescence staining for replicative double-stranded RNA (dsRNA) and western blot for viral N protein. Acute CS exposure decreased in vitro SARS-CoV-2 replication in HBECs, as determined by plaque assay and RT-qPCR.ConclusionsACE2 levels were decreased in both bronchial and alveolar epithelial cells from COPD patients versus controls, and from CS-exposed versus air-exposed mice. CS-pre-exposure potently inhibited SARS-CoV-2 replication in vitro. These findings urge to investigate further the controversial effects of CS and COPD on SARS-CoV-2 infection.
Highlights
How cigarette smoke (CS) and chronic obstructive pulmonary disease (COPD) affect severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection and severity is controversial
We found that the longer the CS exposure, the lower the levels of angiotensin-converting enzyme 2 (ACE2) staining in both bronchial (Fig. 2A, B) and alveolar (Fig. 2A, C) epithelial cells
The magnitude of ACE2 expression found in the central and peripheral airways from our study subjects is in line with that found in CS-exposed mice had decreased ACE2+ cells in both alveolar and bronchial epithelial cells versus air-exposed mice, with the lowest number of ACE2+ cells found after six months of CS exposure
Summary
How cigarette smoke (CS) and chronic obstructive pulmonary disease (COPD) affect severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection and severity is controversial. Coronavirus disease-19 (COVID-19), is an acute and heterogeneous clinical condition caused by the newly identified severe acute respiratory syndrome Coronavirus 2 (SARS-CoV2) [1]. The disease is characterized by a mild presentation of respiratory symptoms and/or in a variable proportion gastrointestinal, neurologic, and cutaneous symptoms [2]. The disease can lead to lethal acute respiratory distress syndrome. The elderly and patients with comorbidities (mainly cardio/respiratory diseases, diabetes, and kidney failure) are at the highest risk of poor prognosis and death from COVID-19 [3]. COPD is one of the most frequent non-communicable chronic conditions affecting millions
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