Evidence map›Paper›PMID 34081912›Full record

ArticleCell metabolism2021

SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment.

Chien-Ting Wu, Peter V Lidsky, Yinghong Xiao, Ivan T Lee, Ran Cheng, Tsuguhisa Nakayama, Sizun Jiang, Janos Demeter, Romina J Bevacqua, Charles A Chang and 11 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 231 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
231citing papers in PubMed, 10 pooled it
19.4field-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

231 citing papers in PubMed, 10 syntheses or guidelines pooled it, 359 citations in OpenAlex.

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  10. Impaired glucose regulation, SARS-CoV-2 infections and adverse COVID-19 outcomes.Translational research : the journal of laboratory and clinical medicine · 2022
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  15. Type 1 Diabetes Mellitus Pathogenesis: Mechanisms, Early Diagnostic Strategies, and Emerging Therapeutic Approaches.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026
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171 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 5 institutions in 3 countries.

Chien-Ting WuBaxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Peter V LidskyDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Yinghong XiaoDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Ivan T LeeDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Ran ChengBaxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biology, Stanford University, Stanford, CA, USA.
Tsuguhisa NakayamaDepartment of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA; Department of Otorhinolaryngology, Jikei University School of Medicine, Tokyo, Japan.
Sizun JiangDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Janos DemeterBaxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Romina J BevacquaDepartment of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Charles A ChangDepartment of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford ChEM-H, Stanford University, Stanford, CA 94305, USA.
Robert L WhitenerDepartment of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Anna K StalderInstitute of Pathology, University of Basel, Schönbeinstrasse 40, 4003 Basel, Switzerland.
Bokai ZhuDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Han ChenDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Yury GoltsevDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Alexandar TzankovInstitute of Pathology, University of Basel, Schönbeinstrasse 40, 4003 Basel, Switzerland.
Jayakar V NayakDepartment of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Garry P NolanDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Matthias S MatterInstitute of Pathology, University of Basel, Schönbeinstrasse 40, 4003 Basel, Switzerland. Electronic address: matthias.matter@usb.ch.
Raul AndinoDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: raul.andino@ucsf.edu.
Peter K JacksonBaxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford ChEM-H, Stanford University, Stanford, CA 94305, USA. Electronic address: pjackson@stanford.edu.
Stanford University · USUniversity of Basel · CHUniversity of California, San Francisco · USStanford Medicine · USJikei University School of Medicine · JP

Funding

Supplement to Enhance Wellness and Resiliency in the Graduate EnvironmentT32GM007276 · NIGMS · STANFORD UNIVERSITY · PI MORRISON, ASHBY J. · 1985 to 2023
$32.9M
Stanford Islet Research CoreP30DK116074 · NIDDK · STANFORD UNIVERSITY · PI Seung K Kim · 2017 to 2026
$19.5M
Spatial-Genomic Integrative Multi-Species Analysis of Lymph Node MetastasisU54CA209971 · NCI · STANFORD UNIVERSITY · PI NOLAN, GARRY P, PLEVRITIS, SYLVIA KATINA · 2016 to 2021
$11.0M
Mapping the CPLANE interactome, an extensive protein interaction network underlying human ciliopathiesR01HD085901 · NICHD · UNIVERSITY OF TEXAS AT AUSTIN · PI EDWARD M MARCOTTE, John B Wallingford · 2016 to 2026
$6.2M
Mechanisms of Ciliary Signaling Controlling Obesity and Metabolic DiseaseR01GM121565 · NIGMS · STANFORD UNIVERSITY · PI JACKSON, PETER KENT · 2017 to 2025
$4.3M
Defining Mechanisms of Viral Persistence in Situ at the Single-Cell LevelR01AI149672 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI ESTES, JACOB D · 2020 to 2024
$4.0M
Fatty Acid Signaling via GPCRs in Primary Cilia Controls Adipogenesis and Insulin Secretion, Regulating Obesity and DiabetesR01DK127665 · NIDDK · STANFORD UNIVERSITY · PI JACKSON, PETER KENT, KIM, SEUNG K · 2021 to 2024
$2.0M
NCI NIH HHS U54 CA209971NIAID NIH HHS R01 AI149672NICHD NIH HHS R01 HD085901NIDDK NIH HHS P30 DK116074NIDDK NIH HHS R01 DK127665NIGMS NIH HHS R01 GM121565NIGMS NIH HHS T32 GM007276
6 · The paper itself

Abstract

Emerging evidence points toward an intricate relationship between the pandemic of coronavirus disease 2019 (COVID-19) and diabetes. While preexisting diabetes is associated with severe COVID-19, it is unclear whether COVID-19 severity is a cause or consequence of diabetes. To mechanistically link COVID-19 to diabetes, we tested whether insulin-producing pancreatic β cells can be infected by SARS-CoV-2 and cause β cell depletion. We found that the SARS-CoV-2 receptor, ACE2, and related entry factors (TMPRSS2, NRP1, and TRFC) are expressed in β cells, with selectively high expression of NRP1. We discovered that SARS-CoV-2 infects human pancreatic β cells in patients who succumbed to COVID-19 and selectively infects human islet β cells in vitro. We demonstrated that SARS-CoV-2 infection attenuates pancreatic insulin levels and secretion and induces β cell apoptosis, each rescued by NRP1 inhibition. Phosphoproteomic pathway analysis of infected islets indicates apoptotic β cell signaling, similar to that observed in type 1 diabetes (T1D). In summary, our study shows SARS-CoV-2 can directly induce β cell killing.

Indexed as

Virus InternalizationA549 CellsAdultAgedAged, 80 and overAngiotensin-Converting Enzyme 2Antigens, CDApoptosisApoptosis Regulatory ProteinsCase-Control StudiesCOVID-19Diabetes MellitusFemaleHost-Pathogen InteractionsHumansInsulinACE2 protein, humanAngiotensin-Converting Enzyme 2Antigens, CDApoptosis Regulatory ProteinsCD71 antigenInsulinNeuropilin-1NRP1 protein, humanReceptors, TransferrinReceptors, VirusSerine EndopeptidasesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2TMPRSS2 protein, humanACE2apoptosisCOVID-19insulinneuropilin 1pancreatic beta cellphosphoproteomicsSARS-CoV-2SARS-CoV-2 spike proteintype 1 diabetes

Identifiers

PMID34081912
PMCPMC8130512
OpenAlexW3163131652

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.