Variable susceptibility of intestinal organoid–derived monolayers to SARS-CoV-2 infection Article Swipe
Kyung Ku Jang
,
Maria E. Kaczmarek
,
Simone Dallari
,
Ying-Han Chen
,
Takuya Tada
,
Jordan E. Axelrad
,
Nathaniel R. Landau
,
Kenneth A. Stapleford
,
Ken Cadwell
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pbio.3001592
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pbio.3001592
Gastrointestinal effects associated with Coronavirus Disease 2019 (COVID-19) are highly variable for reasons that are not understood. In this study, we used intestinal organoid–derived cultures differentiated from primary human specimens as a model to examine interindividual variability. Infection of intestinal organoids derived from different donors with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) resulted in orders of magnitude differences in virus replication in small intestinal and colonic organoid–derived monolayers. Susceptibility to infection correlated with angiotensin I converting enzyme 2 ( ACE2 ) expression level and was independent of donor demographic or clinical features. ACE2 transcript levels in cell culture matched the amount of ACE2 in primary tissue, indicating that this feature of the intestinal epithelium is retained in the organoids. Longitudinal transcriptomics of organoid-derived monolayers identified a delayed yet robust interferon signature, the magnitude of which corresponded to the degree of SARS-CoV-2 infection. Interestingly, virus with the Omicron variant spike (S) protein infected the organoids with the highest infectivity, suggesting increased tropism of the virus for intestinal tissue. These results suggest that heterogeneity in SARS-CoV-2 replication in intestinal tissues results from differences in ACE2 levels, which may underlie variable patient outcomes.
Related Topics
Concepts
Organoid
Biology
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Coronavirus disease 2019 (COVID-19)
Microbiology
2019-20 coronavirus outbreak
Virology
Cell biology
Infectious disease (medical specialty)
Disease
Pathology
Medicine
Outbreak
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1371/journal.pbio.3001592
- OA Status
- gold
- Cited By
- 33
- References
- 89
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4220953727
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4220953727Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1371/journal.pbio.3001592Digital Object Identifier
- Title
-
Variable susceptibility of intestinal organoid–derived monolayers to SARS-CoV-2 infectionWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2022Year of publication
- Publication date
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2022-03-31Full publication date if available
- Authors
-
Kyung Ku Jang, Maria E. Kaczmarek, Simone Dallari, Ying-Han Chen, Takuya Tada, Jordan E. Axelrad, Nathaniel R. Landau, Kenneth A. Stapleford, Ken CadwellList of authors in order
- Landing page
-
https://doi.org/10.1371/journal.pbio.3001592Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1371/journal.pbio.3001592Direct OA link when available
- Concepts
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Organoid, Biology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Coronavirus disease 2019 (COVID-19), Microbiology, 2019-20 coronavirus outbreak, Virology, Cell biology, Infectious disease (medical specialty), Disease, Pathology, Medicine, OutbreakTop concepts (fields/topics) attached by OpenAlex
- Cited by
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33Total citation count in OpenAlex
- Citations by year (recent)
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2025: 5, 2024: 9, 2023: 13, 2022: 6Per-year citation counts (last 5 years)
- References (count)
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89Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| cited_by_percentile_year.max | 99 |
| cited_by_percentile_year.min | 98 |
| corresponding_author_ids | https://openalex.org/A5036106449, https://openalex.org/A5033817459, https://openalex.org/A5051423416, https://openalex.org/A5043758952, https://openalex.org/A5070782543, https://openalex.org/A5015505636, https://openalex.org/A5032974783, https://openalex.org/A5081605770, https://openalex.org/A5033086866 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 9 |
| corresponding_institution_ids | https://openalex.org/I57206974 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.7900000214576721 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.96646331 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |