Evidence map›Paper›PMID 34307198›Full record

ArticleFrontiers in cellular and infection microbiology2021

SARS-CoV-2 Infects Endothelial Cells

Fengming Liu, Kun Han, Robert Blair, Kornelia Kenst, Zhongnan Qin, Berin Upcin, Philipp Wörsdörfer, Cecily C Midkiff, Joseph Mudd, Elizaveta Belyaeva and 13 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in cellular and infection microbiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed, 1 pooled it
10.3field-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

109 citing papers in PubMed, 1 synthesis or guideline pooled it, 147 citations in OpenAlex.

  1. Pooled it
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  7. SARS-CoV-2 uptake and inflammatory response in senescent endothelial cells are regulated by the BSG/VEGFR2 pathway.Proceedings of the National Academy of Sciences of the United States of America · 2025
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49 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

23 authors at 4 institutions in 2 countries.

Fengming LiuDivision of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, United States.
Kun HanDivision of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, United States.
Robert BlairDivision of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, United States.
Kornelia KenstInstitute of Anatomy and Cell Biology, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Zhongnan QinDivision of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, United States.
Berin UpcinInstitute of Anatomy and Cell Biology, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Philipp WörsdörferInstitute of Anatomy and Cell Biology, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Cecily C MidkiffDivision of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, United States.
Joseph MuddDivision of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, United States.
Elizaveta BelyaevaDepartment of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, United States.
Nicholas S MilliganDepartment of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, United States.
Tyler D RorisonDepartment of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, United States.
Nicole WagnerInstitute of Anatomy and Cell Biology, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Jochen BodemInstitute of Virology, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Lars DölkenInstitute of Virology, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Bertal H AktasDivision of Hematology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
Richard S Vander HeideDepartment of Pathology, LSU Health Sciences Center, New Orleans, LA, United States.
Xiao-Ming YinDepartment of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, United States.
Jay K KollsDepartments of Medicine and Pediatrics, Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, LA, United States.
Chad J RoyDivision of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, United States.
Jay RappaportDivision of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, United States.
Süleyman ErgünInstitute of Anatomy and Cell Biology, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Xuebin QinDivision of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, United States.
Tulane University · USUniversity of Würzburg · DEHarvard University · USLouisiana State University Health Sciences Center New Orleans · US

Funding

Tulane NPRC SPF Sheltered Outdoor Enclosure ExpansionP51OD011104 · OD · TULANE UNIVERSITY OF LOUISIANA · PI L Lee HAMM · 2012 to 2026
$142.4M
Mechanisms and Therapeutic Targeting of CD4 Down regulation in African Green MonkeysR21OD031229 · OD · TULANE UNIVERSITY OF LOUISIANA · PI MUDD, JOSEPH CHRISTOPHER · 2021 to 2022
$611k
Protein Synthesis Inhibitors as anti-T. Cruzi agentsR21AI154196 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI AKTAS, BERTAL H. · 2020 to 2021
$494k
Generation and Characterization of a Novel Cell Subpopulation Ablation ModelR21OD024931 · OD · TULANE UNIVERSITY OF LOUISIANA · PI QIN, XUEBIN · 2018 to 2019
$450k
NIAID NIH HHS R21 AI154196NIH HHS P51 OD011104NIH HHS R21 OD024931NIH HHS R21 OD031229
6 · The paper itself

Abstract

SARS-CoV-2 infection can cause fatal inflammatory lung pathology, including thrombosis and increased pulmonary vascular permeability leading to edema and hemorrhage. In addition to the lung, cytokine storm-induced inflammatory cascade also affects other organs. SARS-CoV-2 infection-related vascular inflammation is characterized by endotheliopathy in the lung and other organs. Whether SARS-CoV-2 causes endotheliopathy by directly infecting endothelial cells is not known and is the focus of the present study. We observed 1) the co-localization of SARS-CoV-2 with the endothelial cell marker CD31 in the lungs of SARS-CoV-2-infected mice expressing hACE2 in the lung by intranasal delivery of adenovirus 5-hACE2 (Ad5-hACE2 mice) and non-human primates at both the protein and RNA levels, and 2) SARS-CoV-2 proteins in endothelial cells by immunogold labeling and electron microscopic analysis. We also detected the co-localization of SARS-CoV-2 with CD31 in autopsied lung tissue obtained from patients who died from severe COVID-19. Comparative analysis of RNA sequencing data of the lungs of infected Ad5-hACE2 and Ad5-empty (control) mice revealed upregulated KRAS signaling pathway, a well-known pathway for cellular activation and dysfunction. Further, we showed that SARS-CoV-2 directly infects mature mouse aortic endothelial cells (AoECs) that were activated by performing an aortic sprouting assay prior to exposure to SARS-CoV-2. This was demonstrated by co-localization of SARS-CoV-2 and CD34 by immunostaining and detection of viral particles in electron microscopic studies. Moreover, the activated AoECs became positive for ACE-2 but not quiescent AoECs. Together, our results indicate that in addition to pneumocytes, SARS-CoV-2 also directly infects mature vascular endothelial cells

Indexed as

COVID-19SARS-CoV-2AnimalsDisease Models, AnimalEndothelial CellsHumansLungMiceMice, Transgenicanimal modelsaorta ringendothelial cell infectionhACE2SARS-CoV-2

Identifiers

PMID34307198
PMCPMC8292147
OpenAlexW3181607748

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.