ArticleJCI insight2020
Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers.
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.
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.
Who cites it
153 citing papers in PubMed, 230 citations in OpenAlex.
- SARS-CoV-2 spike-armed vesicular stomatitis virus recapitulates severe COVID-19 acute respiratory distress syndrome in mice.iScience · 2026Article
- Pathogenicity Difference Between Male and Female mice by Recent SARS-CoV-2/2025.Current microbiology · 2026Article
- Revisiting endothelial tropism of SARS-CoV-2 using a cell-specific hACE2 mouse model.Microbiology spectrum · 2026Article
- SARS-CoV-2 Spike Protein Induces Time-Dependent and Brain-Region-Specific Alterations in Ferroptosis Markers: A Preliminary Study in K18-hACE2 Mice.International journal of molecular sciences · 2026Article
- Article
- Neuroinflammatory and transcriptional dynamics during SARS-CoV-2 infection in KRT18-hACE2 mouse brain.Frontiers in immunology · 2026Article
- Translating animal models of SARS-CoV-2 infection to vascular, neurological and gastrointestinal manifestations of COVID-19.Disease models & mechanisms · 2025Review
- Sustained Lung Inflammation Post-SARS-CoV-2 Infection in Mice Is Associated with Increased Pulmonary T Cells.European journal of immunology · 2025Article
- Article
- Differential patterns of cross-protection against antigenically distinct variants in small animal models of SARS-CoV-2 infection.Npj viruses · 2025Article
- Guinea Pigs Are Not a Suitable Model to Study Neurological Impacts of Ancestral SARS-CoV-2 Intranasal Infection.Viruses · 2025Article
- Effector CD8 T cell differentiation in primary and breakthrough SARS-CoV-2 infection in mice.Communications biology · 2025Article
- Interferon Regulatory Factor 3 Exacerbates the Severity of COVID-19 in Mice.Critical care explorations · 2025Article
- ACE2, From the Kidney to SARS-CoV-2: Donald Seldin Award Lecture 2023.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Partially hydrolyzed guar gum attenuates symptoms and modulates the gut microbiota in a model of SARS-CoV-2 infection.Gut microbiome (Cambridge, England) · 2025Article
- Pathogenesis and virulence of coronavirus disease: Comparative pathology of animal models for COVID-19.Virulence · 2024Review
- The lethal K18-hACE2 knock-in mouse model mimicking the severe pneumonia of COVID-19 is practicable for antiviral development.Emerging microbes & infections · 2024Article
- Utilizing HCoV-OC43 to better understand the neurological impact of COVID-19.Brain, behavior, & immunity - health · 2024Article
- Upregulation of inflammatory genes and pathways links obesity to severe COVID-19.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- CCL2-mediated endothelial injury drives cardiac dysfunction in long COVID.Nature cardiovascular research · 2024Article
93 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The emergence of SARS-CoV-2 has created an international health crisis, and small animal models mirroring SARS-CoV-2 human disease are essential for medical countermeasure (MCM) development. Mice are refractory to SARS-CoV-2 infection owing to low-affinity binding to the murine angiotensin-converting enzyme 2 (ACE2) protein. Here, we evaluated the pathogenesis of SARS-CoV-2 in male and female mice expressing the human ACE2 gene under the control of the keratin 18 promoter (K18). In contrast to nontransgenic mice, intranasal exposure of K18-hACE2 animals to 2 different doses of SARS-CoV-2 resulted in acute disease, including weight loss, lung injury, brain infection, and lethality. Vasculitis was the most prominent finding in the lungs of infected mice. Transcriptomic analysis from lungs of infected animals showed increases in transcripts involved in lung injury and inflammatory cytokines. In the low-dose challenge groups, there was a survival advantage in the female mice, with 60% surviving infection, whereas all male mice succumbed to disease. Male mice that succumbed to disease had higher levels of inflammatory transcripts compared with female mice. To our knowledge, this is the first highly lethal murine infection model for SARS-CoV-2 and should be valuable for the study of SARS-CoV-2 pathogenesis and for the assessment of MCMs.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.