ArticleScience advances2021
Age-dependent regulation of SARS-CoV-2 cell entry genes and cell death programs correlates with COVID-19 severity.
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In one paragraph
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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48citing papers in PubMed, 1 pooled it
4.0field-weighted citation impact, top 5% of its field
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
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Corrections and comments
- Update of
Authors and funding
31 authors at 5 institutions in 1 country.
Zintis IndeMolecular and Integrative Physiological Sciences Program, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID 0000-0001-5564-1698
Ben A CrokerDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0002-0885-3599
Clarence YappHarvard Program in Therapeutic Science, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-1144-5710
Gaurav N JoshiMolecular and Integrative Physiological Sciences Program, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID 0000-0002-6789-6783
Johan SpetzMolecular and Integrative Physiological Sciences Program, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID 0000-0002-5216-9786
Cameron FraserMolecular and Integrative Physiological Sciences Program, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Xingping QinMolecular and Integrative Physiological Sciences Program, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID 0000-0003-3263-0843
Le XuDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0001-6321-5023
Brian DeskinMolecular and Integrative Physiological Sciences Program, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID 0000-0001-7850-5146
Elisa GhelfiMolecular and Integrative Physiological Sciences Program, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID 0000-0002-2592-6374
Gabrielle WebbMolecular and Integrative Physiological Sciences Program, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID 0000-0002-3151-136X
Aaron F CarlinDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0002-1669-8066
Yanfang Peipei ZhuDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0001-6908-0860
Sandra L LeibelDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0001-6867-2477
Aaron F GarretsonDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0003-3855-4482
Alex E ClarkDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0003-1687-416X
Jason M DuranDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0003-1666-2319
Victor PretoriusDepartment of Surgery, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0001-6360-4002
Laura E Crotty-AlexanderDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0002-5091-2660
Chendi LiDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Jamie Casey LeeDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0001-5465-3670
Chhinder SodhiDepartment of Surgery, Johns Hopkins University, Baltimore, MD, USA.
David J HackamDepartment of Surgery, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0001-5195-8807
Xin SunDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Aaron N HataDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0002-6127-318X
Lester KobzikMolecular and Integrative Physiological Sciences Program, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Jeffrey MillerMolecular and Integrative Physiological Sciences Program, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID 0000-0001-7718-1581
Jin-Ah ParkMolecular and Integrative Physiological Sciences Program, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID 0000-0002-8930-9287
Douglas BrownfieldMolecular and Integrative Physiological Sciences Program, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID 0000-0003-4769-1518
Hongpeng JiaDepartment of Surgery, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0001-6783-7532
Kristopher A SarosiekMolecular and Integrative Physiological Sciences Program, Harvard T.H. Chan School of Public Health, Boston, MA, USA. sarosiek@hsph.harvard.edu.ORCID 0000-0002-4618-5085
University of California San Diego · USHarvard University · USJohns Hopkins University · USMassachusetts General Hospital · USSanford Burnham Prebys Medical Discovery Institute · US
Funding
Translational Research Support CoreP30ES000002 · NIEHS · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI Marc G Weisskopf · 1985 to 2026
$44.6MTraining Program in Molecular and Integrative Physiological SciencesT32HL007118 · NHLBI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI LU, QUAN · 1985 to 2025
$14.3MSystems Pharmacology of Therapeutic and Adverse Responses to ImmuneCheckpoint and Small Molecule DrugsU54CA225088 · NCI · HARVARD MEDICAL SCHOOL · PI SORGER, PETER KARL · 2018 to 2022
$10.8MThe role of ACE2 in Influenza viral infection mediated immune compromise and subsequent bacterial lung infectionR01AI148446 · NIAID · JOHNS HOPKINS UNIVERSITY · PI JIA, HONGPENG · 2020 to 2024
$2.9MDevelopmental regulation of apoptosis as a modifiable driver of radiotherapy-induced neurocognitive impairment in pediatric patientsR37CA248565 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Kristopher Andrew Sarosiek · 2020 to 2026
$2.6MPhysics of bronchial epithelial unjammingR01HL148152 · NHLBI · HARVARD SCHOOL OF PUBLIC HEALTH · PI FREDBERG, JEFFREY J, PARK, JIN-AH · 2019 to 2022
$2.2MDefining the roles of RIPK1 and RIPK3 in emergency hematopoiesisR01HL124209 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CROKER, BEN ADAM · 2015 to 2019
$2.2MIdentifying targetable apoptotic vulnerabilities for the treatment of AL amyloidosisR01DK125263 · NIDDK · HARVARD SCHOOL OF PUBLIC HEALTH · PI SAROSIEK, KRISTOPHER ANDREW · 2020 to 2023
$1.4MDeconvolution of pro- and anti-viral responses to Dengue virus and Zika Virus infectionsK08AI130381 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CARLIN, AARON F. · 2019 to 2023
$1.0MSupplement to "New ACE2 activator and its prodrug as novel therapeutic regents for inflammatory pulmonary diseases"R21AI149321 · NIAID · JOHNS HOPKINS UNIVERSITY · PI JIA, HONGPENG · 2020 to 2021
$892kReverse Engineering the Alveolus: From cellular to microenvironment specification during developmentR00HL127267 · NHLBI · MAYO CLINIC ROCHESTER · PI BROWNFIELD, DOUGLAS GLENN · 2019 to 2021
$747kRegulation of Apoptotic Priming and Competence in Healthy and Cancerous CellsR00CA188679 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI SAROSIEK, KRISTOPHER ANDREW · 2017 to 2019
$747kAmerican Heart Association-American Stroke AssociationNCI NIH HHS F32 CA250231NCI NIH HHS K99 CA188679NCI NIH HHS R00 CA188679NCI NIH HHS R37 CA248565NCI NIH HHS U54 CA225088NHLBI NIH HHS R00 HL127267NHLBI NIH HHS R01 HL124209NHLBI NIH HHS R01 HL148152NHLBI NIH HHS T32 HL007118NIAID NIH HHS K08 AI130381NIAID NIH HHS R01 AI148446NIAID NIH HHS R21 AI149321NIDDK NIH HHS R01 DK125263NIEHS NIH HHS P30 ES000002NIH HHS 3R21 AI149321-01S1NIH HHS R01 CA248565Wellcome Trust
Abstract
Novel coronavirus disease 2019 (COVID-19) severity is highly variable, with pediatric patients typically experiencing less severe infection than adults and especially the elderly. The basis for this difference is unclear. We find that mRNA and protein expression of angiotensin-converting enzyme 2 (ACE2), the cell entry receptor for the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19, increases with advancing age in distal lung epithelial cells. However, in humans, ACE2 expression exhibits high levels of intra- and interindividual heterogeneity. Further, cells infected with SARS-CoV-2 experience endoplasmic reticulum stress, triggering an unfolded protein response and caspase-mediated apoptosis, a natural host defense system that halts virion production. Apoptosis of infected cells can be selectively induced by treatment with apoptosis-modulating BH3 mimetic drugs. Notably, epithelial cells within young lungs and airways are more primed to undergo apoptosis than those in adults, which may naturally hinder virion production and support milder COVID-19 severity.
Indexed as
AgedAge FactorsAngiotensin-Converting Enzyme 2AnimalsApoptosisCells, CulturedChlorocebus aethiopsCOVID-19FemaleGene Expression ProfilingHumansInfantLungMaleMiceMice, Inbred C57BLAngiotensin-Converting Enzyme 2
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