Evidence map›Paper›PMID 33654293›Full record

SynthesisNature medicine2021

Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics.

Christoph Muus, Malte D Luecken, Gökcen Eraslan, Lisa Sikkema, Avinash Waghray, Graham Heimberg, Yoshihiko Kobayashi, Eeshit Dhaval Vaishnav, Ayshwarya Subramanian, Christopher Smillie and 106 more

Open access · hybridAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Nature medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 227 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
227citing papers in PubMed, 2 pooled it
22.4field-weighted citation impact, top 1% 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

227 citing papers in PubMed, 2 syntheses or guidelines pooled it, 364 citations in OpenAlex.

  1. Pooled it
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  12. Expression of angiotensin-converting enzyme 2, transmembrane serine protease 2, and sirtuin 1 proteins in lungs of different age groups.Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia · 2026
    Article
  13. Review
  14. Metagenomic Data Preprocessing and Quality Control.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
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  20. Article

167 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

116 authors at 20 institutions in 14 countries.

Christoph Muus *Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. muus@broadinstitute.org.ORCID http://orcid.org/0000-0003-2779-0893
Malte D Luecken *Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany. malte.luecken@helmholtz-muenchen.de.ORCID http://orcid.org/0000-0001-7464-7921
Gökcen Eraslan *Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Lisa Sikkema *Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany.ORCID http://orcid.org/0000-0001-9686-6295
Avinash Waghray *Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.
Graham Heimberg *Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Yoshihiko Kobayashi *Department of Cell Biology, Duke University Medical School, Durham, NC, USA.
Eeshit Dhaval Vaishnav *Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-3720-8051
Ayshwarya Subramanian *Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-4134-7612
Christopher Smillie *Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Karthik A Jagadeesh *Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Elizabeth Thu Duong *Division of Respiratory Medicine, Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-7122-4448
Evgenij Fiskin *Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Elena Torlai Triglia *Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-6059-0116
Meshal Ansari *Comprehensive Pneumology Center (CPC)/Institute of Lung Biology and Disease (ILBD), Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.ORCID http://orcid.org/0000-0002-8819-7965
Peiwen Cai *Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Brian Lin *Departments of Internal Medicine and Pediatrics, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8851-3534
Justin Buchanan *Center for Epigenomics, University of California San Diego School of Medicine, La Jolla, CA, USA.
Sijia Chen *Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Jian Shu *Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Adam L Haber *Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Hattie Chung *Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Daniel T Montoro *Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Taylor AdamsPulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT, USA.
Hananeh AlieeInstitute of Computational Biology, Helmholtz Zentrum München, Munich, Germany.
Samuel J AllonBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Zaneta AndrusivovaSciLifeLab, Department of Gene Technology, KTH Royal Institute of Technology, Stockolm, Sweden.
Ilias AngelidisComprehensive Pneumology Center (CPC)/Institute of Lung Biology and Disease (ILBD), Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.
Orr AshenbergKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Kevin BasslerDepartment for Genomics & Immunoregulation, LIMES-Institute, University of Bonn, Bonn, Germany.
Christophe BécavinUniversité Côte d'Azur, CNRS, IPMC, Sophia-Antipolis, France.
Inbal BenharKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Joseph BergenstråhleSciLifeLab, Department of Gene Technology, KTH Royal Institute of Technology, Stockolm, Sweden.
Ludvig BergenstråhleSciLifeLab, Department of Gene Technology, KTH Royal Institute of Technology, Stockolm, Sweden.
Liam BoltWellcome Sanger Institute, Hinxton, UK.
Emelie BraunDivision of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Linh T BuiTranslational Genomics Research Institute, Phoenix, AZ, USA.
Steven CalloriDepartment of Medicine, Boston University School of Medicine, Boston, MA, USA.
Mark ChaffinPrecision Cardiology Laboratory, The Broad Institute, Cambridge, MA, USA.
Evgeny ChichelnitskiyInstitute of Transplant Immunology, Hannover Medical School, MHH, Hannover, Germany.
Joshua ChiouBiomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA.
Thomas M ConlonComprehensive Pneumology Center (CPC)/Institute of Lung Biology and Disease (ILBD), Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.
Michael S CuocoKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Anna S E CuomoEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK.
Marie DeprezUniversité Côte d'Azur, CNRS, IPMC, Sophia-Antipolis, France.
Grant DuclosBoston University School of Medicine, Boston, MA, USA.
Denise FineBoston University Medical Center, Boston, MA, USA.
David S FischerInstitute of Computational Biology, Helmholtz Zentrum München, Munich, Germany.
Shila GhazanfarCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Astrid GillichDepartment of Biochemistry and Wall Center for Pulmonary Vascular Disease, Stanford, CA, USA.
Bruno GiottiGenetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Joshua GouldKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Minzhe GuoDivisions of Pulmonary Biology; Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Austin J GutierrezTranslational Genomics Research Institute, Phoenix, AZ, USA.
Arun C HabermannDivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Tyler HarveyKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Peng HeWellcome Sanger Institute, Hinxton, UK.
Xiaomeng HouCenter for Epigenomics, University of California-San Diego School of Medicine, La Jolla, CA, USA.
Lijuan HuDivision of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Yan HuDivision of Pulmonary Sciences and Critical Care Medicine, School of Medicine, University of Colorado, Aurora, CO, USA.
Alok JaiswalKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Lu JiLi Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, SAR, China.
Peiyong JiangLi Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, SAR, China.
Theodoros S KapellosGenomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Christin S KuoDivision of Pulmonary Medicine, Department of Pediatrics, Stanford University, Stanford, CA, USA.
Ludvig LarssonSciLifeLab, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden.
Michael A Leney-GreeneKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Kyungtae LimGurdon Institute, University of Cambridge, Cambridge, UK.
Monika LitviňukováCellular Genetics Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Leif S LudwigKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Soeren LukassenCharité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Wendy LuoKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Henrike MaatzCardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
Elo MadissoonEuropean Molecular Biology Laboratory-European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, UK.
Lira MamanovaWellcome Sanger Institute, Hinxton, UK.
Kasidet ManakongtreecheepBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Sylvie LeroyPulmonology Department, Université Côte d'Azur, CHU Nice, Nice, France.
Christoph H MayrHelmholtz Zentrum München, Institute of Lung Biology and Disease, Group Systems Medicine of Chronic Lung Disease, Member of the German Center for Lung Research (DZL), Munich, Germany.
Ian M MbanoAfrica Health Research Institute, Durban, South Africa.
Alexi M McAdamsDepartment of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear, Boston, MA, USA.
Ahmad N NabhanDepartment of Biochemistry and Wall Center for Pulmonary Vascular Disease, Stanford, CA, USA.
Sarah K NyquistBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Lolita PenlandDepartment of Biochemistry and Wall Center for Pulmonary Vascular Disease, Stanford, CA, USA.
Olivier B PoirionCenter for Epigenomics, University of California-San Diego School of Medicine, La Jolla, CA, USA.
Sergio PoliPulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT, USA.
CanCan QiDepartment of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Rachel QueenBiosciences Institute, Faculty of Medical Sciences, Newcastle University, International Centre for Life, Newcastle upon Tyne, UK.
Daniel ReichartDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
Ivan RosasPulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT, USA.
Jonas C SchuppSection of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine, New Haven, CT, USA.
Conor V SheaDivision of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
Xingyi ShiDivision of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
Rahul SinhaInstitute for Stem Cell Biology and Regenerative Medicine, Stanford Medicine, Stanford, CA, USA.
Rene V SitDepartment of Biochemistry and Wall Center for Pulmonary Vascular Disease, Stanford, CA, USA.
Kamil SlowikowskiBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Michal SlyperKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Neal P SmithCenter for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, USA.
Alex SountoulidisDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Maximilian StrunzComprehensive Pneumology Center (CPC) and Institute of Lung Biology and Disease (ILBD), Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.
Travis B SullivanLahey Hospital & Medical Center, Burlington, MA, USA.
Dawei SunGurdon Institute, University of Cambridge, Cambridge, UK.
Carlos Talavera-LópezCellular Genetics Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
Peng TanKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jessica TantivitBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Kyle J TravagliniDepartment of Biochemistry and Wall Center for Pulmonary Vascular Disease, Stanford, CA, USA.
Nathan R TuckerPrecision Cardiology Laboratory, The Broad Institute, Cambridge, MA, USA.
Katherine A VernonBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Marc H WadsworthBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Julia WaldmanKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Xiuting WangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ke XuDivision of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
Wenjun YanCenter for Brain Science, Harvard University, Cambridge, MA, USA.
William ZhaoDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Carly G K ZieglerBroad Institute of MIT and Harvard, Cambridge, MA, USA.
NHLBI LungMap Consortium
Human Cell Atlas Lung Biological Network
Broad Institute · USBoston University · USHelmholtz Zentrum München · DEUniversity of California San Diego · USHarvard University · USUniversity of Rochester Medical Center · USWellcome Sanger Institute · GBMassachusetts General Hospital · USCenter for Vascular Biology Research · USCentre National de la Recherche Scientifique · FRIcahn School of Medicine at Mount Sinai · USScience for Life Laboratory · SEUniversity of Cambridge · GBYale University · USCentre for Life · GBEuropean Bioinformatics Institute · GBKarolinska Institutet · SEMax Delbrück Center · DEStanford University · USUniversity Medical Center Groningen · NL

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
RP5: Chemical proteomic discovery of small-molecule probes for autophagy proteinsU19AI142784 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI VIRGIN, HERBERT W · 2019 to 2023
$36.9M
Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Ramnik J Xavier · 1991 to 2026
$35.3M
Tissue resident macrophages regulate proteostasis in the aging lungP01AG049665 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI GR Scott Budinger · 2015 to 2026
$26.9M
Technology CoreU19AI135964 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI RICHARD G WUNDERINK · 2018 to 2026
$24.7M
LABORATORY OF DEVELOPMENTAL BIOLOGYR24HD000836 · NICHD · UNIVERSITY OF WASHINGTON · PI Ian Amos Glass · 1995 to 2026
$16.9M
TriState SenNET (Lung and Heart) Tissue Map and Atlas consortiumU54AG075931 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TOREN FINKEL, Melanie Koenigshoff · 2021 to 2026
$14.0M
BioRepository for INvestigation of Diseases of the Lung (BRINDL) - Phase IIIU01HL148861 · NHLBI · UNIVERSITY OF ROCHESTER · PI GLORIA S PRYHUBER · 2019 to 2026
$9.7M
Defining Pathways from Gene Mutation to Heart FailureR01HL080494 · NHLBI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI CHEN, CHRISTOPHER S, SEIDMAN, CHRISTINE E · 2005 to 2024
$9.4M
Systematic dissection of gut cellular circuits [at single cell resolution]RC2DK114784 · NIDDK · BROAD INSTITUTE, INC. · PI ASHENBERG, ORR, GRAHAM, DANIEL BARTHOLOMEW · 2017 to 2021
$9.0M
The Human Lung BioMolecular Multi-Scale Atlas Program (HuBMAP-Lung)U54HL165443 · NHLBI · UNIVERSITY OF ROCHESTER · PI PRYHUBER, GLORIA S · 2022 to 2025
$8.0M
Lung Macrophage Programming in Acute Lung InjuryR35HL140039 · NHLBI · NATIONAL JEWISH HEALTH · PI JANSSEN, WILLIAM · 2018 to 2024
$6.4M
British Heart Foundation SP/19/1/34461Medical Research Council MR/P009581/1Medical Research Council MR/S005579/1Medical Research Council MR/S035826/1Medical Research Council MR/S035907/1NHLBI NIH HHS F32 HL149290NHLBI NIH HHS K08 HL130595NHLBI NIH HHS K08 HL146943NHLBI NIH HHS R01 HL080494NHLBI NIH HHS R01 HL119215NHLBI NIH HHS R01 HL127349NHLBI NIH HHS R01 HL130938NHLBI NIH HHS R01 HL133153NHLBI NIH HHS R01 HL141380NHLBI NIH HHS R01 HL145372NHLBI NIH HHS R01 HL146519NHLBI NIH HHS R01 HL146557NHLBI NIH HHS R35 HL140039NHLBI NIH HHS R56 HL135124NHLBI NIH HHS U01 HL122700NHLBI NIH HHS U01 HL145550NHLBI NIH HHS U01 HL145567NHLBI NIH HHS U01 HL148856NHLBI NIH HHS U01 HL148861NHLBI NIH HHS U01 HL148867NHLBI NIH HHS U54 HL165443NIAID NIH HHS U19 AI116482NIAID NIH HHS U19 AI135964NIAID NIH HHS U19 AI142784NIAID NIH HHS U24 AI118672NIA NIH HHS P01 AG049665NICHD NIH HHS R24 HD000836NIDDK NIH HHS P30 DK043351NIDDK NIH HHS R01 DK117263NIDDK NIH HHS RC2 DK114784NIGMS NIH HHS T32 GM007753Wellcome Trust
6 · The paper itself

Abstract

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2

Indexed as

Virus InternalizationAdultAgedAged, 80 and overAlveolar Epithelial CellsAngiotensin-Converting Enzyme 2Cathepsin LCOVID-19Datasets as TopicDemographyFemaleGene Expression ProfilingHost-Pathogen InteractionsHumansLungMaleACE2 protein, humanAngiotensin-Converting Enzyme 2Cathepsin LCTSL protein, humanSerine EndopeptidasesTMPRSS2 protein, human

Identifiers

PMID33654293
PMCPMC9469728
OpenAlexW3134181354

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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.