Evidence map›Paper›PMID 34425811›Full record

ArticleBMC pulmonary medicine2021

Paradoxical effects of cigarette smoke and COPD on SARS-CoV-2 infection and disease.

M Tomchaney, M Contoli, J Mayo, S Baraldo, S Li, C R Cabel, D A Bull, S Lick, J Malo, S Knoper and 12 more

Open access · goldAbstract read
In one paragraph

Article in BMC pulmonary medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.9field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 17 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 7 institutions in 2 countries.

M Tomchaney *Asthma and Airway Disease Research Center, University of Arizona, Tucson, AZ, 85719, USA.
M Contoli *Respiratory Unit, Department of Translational Medicine, University of Ferrara, Ferrara, Italy.
J MayoAsthma and Airway Disease Research Center, University of Arizona, Tucson, AZ, 85719, USA.
S BaraldoDepartment of Cardiological, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy.
S LiDepartment of Immunobiology, University of Arizona College of Medicine, Tucson, USA.
C R CabelDepartment of Cellular and Molecular Medicine, University of Arizona Cancer Center, Tucson, USA.
D A BullThoracic Surgery, University of Arizona, Tucson, USA.
S LickThoracic Surgery, University of Arizona, Tucson, USA.
J MaloThoracic Surgery, University of Arizona, Tucson, USA.
S KnoperThoracic Surgery, University of Arizona, Tucson, USA.
S S KimThoracic Surgery, Northwester University, Chicago, IL, USA.
J TramAsthma and Airway Disease Research Center, University of Arizona, Tucson, AZ, 85719, USA.
J Rojas-QuinteroBrigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
M KraftAsthma and Airway Disease Research Center, University of Arizona, Tucson, AZ, 85719, USA.
J G LedfordAsthma and Airway Disease Research Center, University of Arizona, Tucson, AZ, 85719, USA.
Y TesfaigziBrigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
F D MartinezAsthma and Airway Disease Research Center, University of Arizona, Tucson, AZ, 85719, USA.
C A ThorneDepartment of Cellular and Molecular Medicine, University of Arizona Cancer Center, Tucson, USA.
F KheradmandBaylor College of Medicine, Houston, TX, USA.
S K CamposDepartment of Immunobiology, University of Arizona College of Medicine, Tucson, USA.
A PapiRespiratory Unit, Department of Translational Medicine, University of Ferrara, Ferrara, Italy.
F PolverinoAsthma and Airway Disease Research Center, University of Arizona, Tucson, AZ, 85719, USA. francy@email.arizona.edu.
University of Arizona · USHarvard University · USUniversity of Ferrara · ITBaylor College of Medicine · USNorthwest University · USUniversity of Arizona Cancer CenterUniversity of Padua · IT

Funding

Wisconsin Infant Study Cohort (WISC) ECHO Pediatric Follow-UpUH3OD023282 · OD · UNIVERSITY OF WISCONSIN-MADISON · PI James E. Gern · 2018 to 2026
$64.8M
SOUTHWEST ENVIRONMENTAL HEALTH SCIENCES CENTERP30ES006694 · NIEHS · UNIVERSITY OF ARIZONA · PI George S Watts · 1994 to 2026
$36.7M
ORBEX: Primary Prevention of Asthma and Wheezing in Children-CCC Lead ApplicationU01HL130045 · NHLBI · UNIVERSITY OF ARIZONA · PI MARTINEZ, FERNANDO D · 2016 to 2020
$22.4M
Controlling and preventing Asthma progression and Severity in Kids (CASK)U01AI126614 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI PHIPATANAKUL, WANDA · 2016 to 2023
$21.0M
Wisconsin Infant Study Cohort (WISC) ECHO Pediatric Follow-UpUG3OD023282 · OD · UNIVERSITY OF WISCONSIN-MADISON · PI GERN, JAMES E. · 2016 to 2024
$19.3M
Early Origins of Chronic Lung Disease: Outcomes into the Fifth Decade of LifeR01HL132523 · NHLBI · UNIVERSITY OF ARIZONA · PI Stefano Guerra, Fernando D Martinez · 2016 to 2026
$15.1M
Natural History of Asthma from Birth to Early Adult LifeR01HL056177 · NHLBI · UNIVERSITY OF ARIZONA · PI GUERRA, STEFANO, MARTINEZ, FERNANDO D · 1996 to 2015
$14.4M
Integrative Cancer Scholars Training GrantT32CA009213 · NCI · UNIVERSITY OF ARIZONA · PI CAREW, JENNIFER S, CURIEL-LEWANDROWSKI, CLARA · 1985 to 2024
$8.6M
Arizona/Duke Clinical Center for AsthmaNetU10HL098112 · NHLBI · UNIVERSITY OF ARIZONA · PI KRAFT, MONICA, MARTINEZ, FERNANDO D · 2009 to 2015
$4.7M
Defining mechanisms of CC16 on epithelial-driven host responses to pathogensR01HL142769 · NHLBI · UNIVERSITY OF ARIZONA · PI Julie Gunnells Ledford · 2019 to 2026
$4.2M
B cell-adaptive Immune Profile in Emphysema-predominant COPDR01HL149744 · NHLBI · UNIVERSITY OF ARIZONA · PI POLVERINO, FRANCESCA · 2020 to 2024
$3.4M
Regulation of Asthmatic Inflammation by Non-Muscle MLCKR01HL091889 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI GARCIA, JOE G. N., WANG, TING · 2008 to 2018
$3.2M
NCI NIH HHS T32 CA009213NHLBI NIH HHS HL056177NHLBI NIH HHS HL091889NHLBI NIH HHS HL098112NHLBI NIH HHS HL130045NHLBI NIH HHS HL132523NHLBI NIH HHS HL139054NHLBI NIH HHS HL149744NHLBI NIH HHS R01 HL056177NHLBI NIH HHS R01 HL091889NHLBI NIH HHS R01 HL132523NHLBI NIH HHS R01 HL142769NHLBI NIH HHS R01 HL149744NHLBI NIH HHS U01 HL130045NHLBI NIH HHS U10 HL098112NHLBI NIH HHS UG1 HL139054NIAID NIH HHS U01 AI126614NIDDK NIH HHS DK103126NIDDK NIH HHS K99 DK103126NIDDK NIH HHS R00 DK103126NIEHS NIH HHS ES006614NIEHS NIH HHS P30 ES006694NIGMS NIH HHS GM136853NIGMS NIH HHS R01 GM136853NIH HHS UG3 OD023282NIH HHS UH3 OD023282
6 · The paper itself

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.

Indexed as

SmokeAgedAged, 80 and overAngiotensin-Converting Enzyme 2AnimalsBronchiCell Line, TumorCigarette SmokingCOVID-19FemaleHumansMaleMiceMiddle AgedNicotianaPatient AcuityAngiotensin-Converting Enzyme 2RNA, MessengerSerine EndopeptidasesSmokeTMPRSS2 protein, humanTMPRSS2 protein, mouse

Identifiers

PMID34425811
PMCPMC8381712
OpenAlexW3194469786

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.