Evidence map›Paper›PMID 35353667›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2022

SARS-CoV-2 infection of airway cells causes intense viral and cell shedding, two spreading mechanisms affected by IL-13.

Cameron B Morrison, Caitlin E Edwards, Kendall M Shaffer, Kenza C Araba, Jason A Wykoff, Danielle R Williams, Takanori Asakura, Hong Dang, Lisa C Morton, Rodney C Gilmore and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
16.3field-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

72 citing papers in PubMed, 109 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. SARS-CoV-2 drives upregulation of EpCAM in respiratory epithelial cells with hypercellular profile during severe COVID-19.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Integrated Evaluation ofPharmaceuticals (Basel, Switzerland) · 2026
    Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Type 2 immune responses are associated with less severe COVID-19 in a hospitalized cohort.The journal of allergy and clinical immunology. Global · 2025
    Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

12 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

14 authors at 1 institution in 1 country.

Cameron B MorrisonMarsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0000-0002-4031-9521
Caitlin E EdwardsDepartment of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0000-0003-4228-2192
Kendall M ShafferMarsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0000-0002-1052-2975
Kenza C ArabaMarsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Jason A WykoffMarsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Danielle R WilliamsDepartment of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Takanori AsakuraMarsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0000-0003-3122-6937
Hong DangMarsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Lisa C MortonMarsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Rodney C GilmoreMarsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0000-0002-3821-8422
Wanda K O'NealMarsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Richard C BoucherMarsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Ralph S BaricDepartment of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0000-0001-6827-8701
Camille EhreMarsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0000-0002-0046-0096
University of North Carolina at Chapel Hill · US

Funding

Vector CoreP30DK065988 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Scott H Randell · 2004 to 2026
$26.5M
The Biophysics of Mucus Hydration and Adhesion/CohesionP01HL108808 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BOUCHER, RICHARD CHARLES · 2012 to 2021
$23.9M
Broad-spectrum antiviral GS-5734 to treat MERS-CoV and related emerging CoVR01AI132178 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BARIC, RALPH S, SHEAHAN, TIMOTHY PATRICK · 2017 to 2021
$7.0M
Determinants of Coronavirus Fidelity in Replication and PathogenesisR01AI108197 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BARIC, RALPH S, DENISON, MARK R · 2013 to 2022
$6.5M
NHLBI NIH HHS P01 HL108808NIAID NIH HHS R01 AI108197NIAID NIH HHS R01 AI132178NIDDK NIH HHS P30 DK065988
6 · The paper itself

Abstract

Muco-obstructive lung diseases are typically associated with high risks of COVID-19 severity; however, allergic asthma showed reduced susceptibility. To investigate viral spread, primary human airway epithelial (HAE) cell cultures were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and host–virus interactions were examined via electron microscopy, immunohistochemistry, RNA in situ hybridization, and gene expression analyses. In HAE cell cultures, angiotensin-converting enzyme 2 (ACE2) expression governed cell tropism and viral load and was up-regulated by infection. Electron microscopy identified intense viral egress from infected ciliated cells and severe cytopathogenesis, culminating in the shedding of ciliated cells packed with virions, providing a large viral reservoir for spread and transmission. Intracellular stores of MUC5AC, a major airway mucin involved in asthma, were rapidly depleted, likely to trap viruses. To mimic asthmatic airways, HAE cells were treated with interleukin-13 (IL-13), which reduced viral titers, viral messenger RNA, and cell shedding, and significantly diminished the number of infected cells. Although mucus hyperproduction played a shielding role, IL-13–treated cells maintained a degree of protection despite the removal of mucus. Using Gene Expression Omnibus databases, bulk RNA-sequencing analyses revealed that IL-13 up-regulated genes controlling glycoprotein synthesis, ion transport, and antiviral processes (albeit not the typical interferon-induced genes) and down-regulated genes involved in cilial function and ribosomal processing. More precisely, we showed that IL-13 reduced ACE2 expression, intracellular viral load, and cell-to-cell transmission while increasing the cilial keratan sulfate coating. In conclusion, intense viral and cell shedding caused by SARS-CoV-2 infection was attenuated by IL-13, which affected viral entry, replication, and spread.

Indexed as

COVID-19Interleukin-13SARS-CoV-2Angiotensin-Converting Enzyme 2GlycoproteinsHumansRespiratory SystemACE2 protein, humanAngiotensin-Converting Enzyme 2GlycoproteinsIL13 protein, humanInterleukin-13asthmahuman airway epithelial cellsIL-13 cytokineinfectionSARS-CoV-2

Identifiers

PMID35353667
PMCPMC9169748
OpenAlexW4220670893

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.