Evidence map›Paper›PMID 38597954›Full record

ArticleThe Journal of experimental medicine2024

Interstitial macrophages are a focus of viral takeover and inflammation in COVID-19 initiation in human lung.

Timothy Ting-Hsuan Wu, Kyle J Travaglini, Arjun Rustagi, Duo Xu, Yue Zhang, Leonid Andronov, SoRi Jang, Astrid Gillich, Roozbeh Dehghannasiri, Giovanny J Martínez-Colón and 15 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
9.1field-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

36 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
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  3. Review
  4. Article
  5. Extra gene coding capacity of SARS-CoV-2 provides a virus engineering platform for in vitro and in vivo applications.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Single-Cell Insights Into Macrophage Subtypes in Pulmonary Infections.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Associations of Prepandemic Lung Function and Structure with COVID-19 Outcomes: The C4R Study.American journal of respiratory and critical care medicine · 2025
    Article
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

25 authors at 6 institutions in 1 country.

Timothy Ting-Hsuan Wu *Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-6869-362X
Kyle J Travaglini *Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-3164-6448
Arjun Rustagi *Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-6921-1012
Duo XuDepartment of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-0483-8719
Yue ZhangDepartment of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-2955-7780
Leonid AndronovDepartment of Chemistry, Stanford University, Stanford, CA, USA.ORCID 0000-0002-4213-5363
SoRi JangDepartment of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-9156-552X
Astrid GillichDepartment of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-7016-0494
Roozbeh DehghannasiriDepartment of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0001-7413-3437
Giovanny J Martínez-ColónDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0001-6792-8004
Aimee BeckDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-4762-6417
Daniel Dan LiuInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine , Stanford, CA, USA.ORCID 0000-0003-0100-5973
Aaron J WilkDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-1430-5852
Maurizio MorriChan Zuckerberg Biohub , San Francisco, CA, USA.ORCID 0009-0003-5577-4265
Winston L TropeDepartment of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-0927-0405
Rob BiermanDepartment of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0001-8513-7425
Irving L WeissmanInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine , Stanford, CA, USA.ORCID 0000-0002-9077-7467
Joseph B ShragerDepartment of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-0859-0589
Stephen R QuakeChan Zuckerberg Biohub , San Francisco, CA, USA.
Christin S KuoDepartment of Pediatrics, Pulmonary Medicine, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0001-9227-5578
Julia SalzmanDepartment of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0001-7630-3436
W E MoernerDepartment of Chemistry, Stanford University, Stanford, CA, USA.ORCID 0000-0002-2830-209X
Peter S KimDepartment of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0001-6503-4541
Catherine A BlishDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0001-6946-7627
Mark A KrasnowDepartment of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-1976-5471
Stanford University · USHoward Hughes Medical Institute · USStanford Medicine · USChan Zuckerberg Initiative (United States) · USStratford University · USVA Palo Alto Health Care System · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007365 · NIGMS · STANFORD UNIVERSITY · PI CHUA, KATRIN F · 1985 to 2021
$33.8M
Supplement to Enhance Wellness and Resiliency in the Graduate EnvironmentT32GM007276 · NIGMS · STANFORD UNIVERSITY · PI MORRISON, ASHBY J. · 1985 to 2023
$32.9M
Medical Scientist Training ProgramT32GM145402 · NIGMS · STANFORD UNIVERSITY · PI Katrin F. Chua · 2022 to 2026
$10.0M
Diabetes, Endocrinology and Metabolism Training GrantT32DK007217 · NIDDK · STANFORD UNIVERSITY · PI Justin Pierce Annes, David Matthew Maahs · 1987 to 2026
$7.2M
EMERGING INFECTIOUS DISEASEST32AI007502 · NIAID · STANFORD UNIVERSITY · PI Prasanna Jagannathan, DAVID A. RELMAN · 1995 to 2026
$6.8M
Single-Molecule Imaging for Cell Biology and Super-Resolution MicroscopyR35GM118067 · NIGMS · STANFORD UNIVERSITY · PI MOERNER, WILLIAM E · 2016 to 2025
$6.2M
Computational- and experimental- driven discovery of splicing regulation and circRNA functionR35GM139517 · NIGMS · STANFORD UNIVERSITY · PI Julia Salzman · 2021 to 2026
$2.9M
Modeling early SARS-CoV-2 pathogenesis in human lung organoids and slice culturesK08AI163369 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RUSTAGI, ARJUN · 2022 to 2025
$772k
Howard Hughes Medical InstituteNIAID NIH HHS K08 AI163369NIAID NIH HHS T32 AI007502NIDDK NIH HHS T32 DK007217NIGMS NIH HHS R35 GM118067NIGMS NIH HHS R35 GM139517NIGMS NIH HHS T32 GM007276NIGMS NIH HHS T32 GM007365NIGMS NIH HHS T32 GM145402NIH HHS T32 AI007502
6 · The paper itself

Abstract

Early stages of deadly respiratory diseases including COVID-19 are challenging to elucidate in humans. Here, we define cellular tropism and transcriptomic effects of SARS-CoV-2 virus by productively infecting healthy human lung tissue and using scRNA-seq to reconstruct the transcriptional program in "infection pseudotime" for individual lung cell types. SARS-CoV-2 predominantly infected activated interstitial macrophages (IMs), which can accumulate thousands of viral RNA molecules, taking over 60% of the cell transcriptome and forming dense viral RNA bodies while inducing host profibrotic (TGFB1, SPP1) and inflammatory (early interferon response, CCL2/7/8/13, CXCL10, and IL6/10) programs and destroying host cell architecture. Infected alveolar macrophages (AMs) showed none of these extreme responses. Spike-dependent viral entry into AMs used ACE2 and Sialoadhesin/CD169, whereas IM entry used DC-SIGN/CD209. These results identify activated IMs as a prominent site of viral takeover, the focus of inflammation and fibrosis, and suggest targeting CD209 to prevent early pathology in COVID-19 pneumonia. This approach can be generalized to any human lung infection and to evaluate therapeutics.

Indexed as

COVID-19HumansInflammationLungMacrophagesRNA, ViralSARS-CoV-2RNA, Viral

Identifiers

PMID38597954
PMCPMC11009983
OpenAlexW4394677483

What OpenQuestion holds

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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.