Abstract
Background: 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 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. Methods: We 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. Results: ACE2 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. Conclusions: ACE2 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.
| Original language | English (US) |
|---|---|
| Article number | 275 |
| Journal | BMC Pulmonary Medicine |
| Volume | 21 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 2021 |
Funding
The Asthma and Airway Disease Research Center (University of Arizona) provided funds for the design of the study and collection, analysis, and interpretation of data; FP is supported by grants from the NIH/NHLBI (HL149744), Flight Attendants Medical Research Institute (#YFAC141004) and NIH/NHLBI (HL132523), that supported the the design of the study and collection, analysis, and interpretation of data; SB is supported by University of Padova DOR funds that supported the collection of the samples. SKC is supported by a UA RII COVID-19 seed grant (#002196) and a grant from NIGMS (1R01GM136853) that supported the analysis of the samples and data analysis; CAT is supported by UA TRIF grant and NIDDK R00 DK103126 that supported the analysis of the samples. FDM is supported by grants from NIH/NHLBI (HL139054, HL091889, HL132523, HL130045, HL098112, HL056177), the NIH/NIEHS (ES006614), the NIH/NIAID (AI126614), and the NIH/ Office of Director (OD023282) that supported the writing of the manuscript. We are grateful to Jen Uhrlaub, for assistance the in the University of Arizona BSL3 suites, and to Drs. Xinxin Ding and Weiguo Han for their assistance with the smoke exposures, and the Southwest Environmental Health Sciences Center (SWEHSC). M. Contoli has received personal fees from Chiesi, AstraZeneca, Boehringer-Ingelheim, Alk-Abello, GSK, Novartis, Zambon, and scientific grants from Chiesi and University of Ferrara, Italy. A. Papi: Board membership, consultancy, payment for lectures, grants for research, travel expenses reimbursement from GSK, AZ, Boehringer Ingelheim, Chiesi Farmaceutici, TEVA, Mundipharma, Zambon, Novartis, Menarini, Sanofi,Roche, Edmondpharma, Fondazione Maugeri, Fondazione Chiesi. None of the other authors have competing conflicts of interest to declare.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
