Evidence map›Paper›PMID 35038898›Full record

ArticlemBio2022

Human Nasal Epithelial Cells Sustain Persistent SARS-CoV-2 Infection

Akshamal M Gamage, Kai Sen Tan, Wharton O Y Chan, Zhe Zhang Ryan Lew, Jing Liu, Chee Wah Tan, Deepa Rajagopalan, Quy Xiao Xuan Lin, Le Min Tan, Prasanna Nori Venkatesh and 6 more

Open access · goldAbstract read
In one paragraph

Article in mBio, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.0field-weighted citation impact, top 7% 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

28 citing papers in PubMed, 31 citations in OpenAlex.

  1. Review
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  13. Article
  14. Interactions of SARS-CoV-2 with Human Target Cells-A Metabolic View.International journal of molecular sciences · 2024
    Review
  15. Article
  16. COVID-19: a multi-organ perspective.Frontiers in cellular and infection microbiology · 2024
    Review
  17. Article
  18. Article
  19. Infection of primary nasal epithelial cells differentiates among lethal and seasonal human coronaviruses.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  20. 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

16 authors at 4 institutions in 1 country.

Akshamal M Gamage *Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
Kai Sen Tan *Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Wharton O Y Chan *Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
Zhe Zhang Ryan Lew *Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Jing LiuDepartment of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Chee Wah TanProgramme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
Deepa RajagopalanLaboratory of Systems Biology and Data Analytics, Genome Institute of Singaporegrid.418377.e, Singapore.
Quy Xiao Xuan LinLaboratory of Systems Biology and Data Analytics, Genome Institute of Singaporegrid.418377.e, Singapore.
Le Min TanLaboratory of Systems Biology and Data Analytics, Genome Institute of Singaporegrid.418377.e, Singapore.
Prasanna Nori VenkateshLaboratory of Systems Biology and Data Analytics, Genome Institute of Singaporegrid.418377.e, Singapore.
Yew Kwang OngDepartment of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Mark ThongDepartment of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Raymond Tzer Pin LinDepartment of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Shyam PrabhakarLaboratory of Systems Biology and Data Analytics, Genome Institute of Singaporegrid.418377.e, Singapore.
De Yun WangDepartment of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Lin-Fa WangProgramme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.ORCID 0000-0003-2752-0535
National University of Singapore · SGGenome Institute of Singapore · SGDuke-NUS Medical School · SGSingHealth Duke-NUS Academic Medical Centre · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The dynamics of SARS-CoV-2 infection in COVID-19 patients are highly variable, with a subset of patients demonstrating prolonged virus shedding, which poses a significant challenge for disease management and transmission control. In this study, the long-term dynamics of SARS-CoV-2 infection were investigated using a human well-differentiated nasal epithelial cell (NEC) model of infection. NECs were observed to release SARS-CoV-2 virus onto the apical surface for up to 28 days postinfection (dpi), further corroborated by viral antigen staining. Single-cell transcriptome sequencing (sc-seq) was utilized to explore the host response from infected NECs after short-term (3-dpi) and long-term (28-dpi) infection. We identified a unique population of cells harboring high viral loads present at both 3 and 28 dpi, characterized by expression of cell stress-related genes DDIT3 and ATF3 and enriched for genes involved in tumor necrosis factor alpha (TNF-α) signaling and apoptosis. Remarkably, this sc-seq analysis revealed an antiviral gene signature within all NEC cell types even at 28 dpi. We demonstrate increased replication of basal cells, absence of widespread cell death within the epithelial monolayer, and the ability of SARS-CoV-2 to replicate despite a continuous interferon response as factors likely contributing to SARS-CoV-2 persistence. This study provides a model system for development of therapeutics aimed at improving viral clearance in immunocompromised patients and implies a crucial role for immune cells in mediating viral clearance from infected epithelia.

Indexed as

COVID-19Antiviral AgentsEpithelial CellsHumansPost-Acute COVID-19 SyndromeSARS-CoV-2Antiviral AgentsCOVID-19nasal epithelial cellsSARS-CoV-2single-cell sequencingviral persistence

Identifiers

PMID35038898
PMCPMC8764519
OpenAlexW4206503382

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.