Evidence map›Paper›PMID 40686017›Full record

ArticleJournal of medical virology2025

Dissecting Sex-Specific Pathology in K18-hACE2 Transgenic Mice Infected With Different SARS-CoV-2 Variants.

Elysia A Masters, Weichun Tang, Insung Kang, Martina Kosikova, Jennifer H Hanks, Lana Elkins, Hyung-Joon Kwon, Uriel Ortega-Rodriguez, Binsheng Gong, Kelly E Mercer and 1 more

Abstract read
In one paragraph

Article in Journal of medical virology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Modeling the Exposome in Murine Cardiovascular Disease.JACC. Basic to translational science · 2026
    Review
  3. Review
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

11 authors.

Elysia A MastersDivision of Systems Biology, National Center for Toxicological Research, United States Food and Drug Administration, Jefferson, Arkansas, USA.
Weichun TangDivision of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, USA.
Insung KangDivision of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, USA.
Martina KosikovaDivision of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, USA.
Jennifer H HanksToxicologic Pathology Associates, Jefferson, Arkansas, USA.
Lana ElkinsToxicologic Pathology Associates, Jefferson, Arkansas, USA.
Hyung-Joon KwonDivision of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, USA.
Uriel Ortega-RodriguezDivision of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, USA.
Binsheng GongDivision of Bioinformatics and Biostatistics, National Center for Toxicological Research, United States Food and Drug Administration, Jefferson, Arkansas, USA.
Kelly E MercerDivision of Systems Biology, National Center for Toxicological Research, United States Food and Drug Administration, Jefferson, Arkansas, USA.
Hang XieDivision of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, USA.

Funding

Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Suzanne AW Fuqua · 2007 to 2026
$73.9M
Tissue Analysis & Molecular Imaging CoreP30DK056338 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI Hashem B El-Serag · 2001 to 2026
$28.3M
Translational Research Support CoreP30ES030285 · NIEHS · BAYLOR COLLEGE OF MEDICINE · PI Cheryl L. Walker · 2019 to 2026
$14.7M
NCI NIH HHS P30 CA125123NIDDK NIH HHS P30 DK056338NIEHS NIH HHS P30 ES030285This study was supported by the FDA Office of Women's Health fund (22-01-0001) to Hang Xie and Kelly E. Mercer. The authors sincerely appreciate the support of the FDA/CBER Biosafety team and White Oak Vivarium staff in this study. This manuscript reflects the views of the authors and does not necessarily reflect those of the U.S. Food and Drug Administration. Any mention of commercial products is for clarification only and is not intended as approval, endorsement, or recommendation. Sequencing was performed at the Genomic & RNA Profiling Core at Baylor University by Dr. Daniel C. Kraushaar and his team (Emily Ricco, Stacy Nguyen, and Victoria Rodriguez). Funding for Baylor's Genomic & RNA Profiling Core comes from P30 Digestive Disease Center Support Grant (NIDDK-DK56338) and P30 Cancer Center Support Grant (NCI-CA125123), P30 Center for Precision Environmental Health (NIEHS-5P30ES030285-03), NIH S10 grant (1S10OD02346901).
6 · The paper itself

Abstract

Sex-biased differences in COVID-19 outcomes in relation to individual SARS-CoV-2 variants are not well understood. In this study, lungs and nasal cavities of age-matched female and male K18-hACE2 transgenic mice were collected for dissecting sex-specific differences in pathology after infection of SARS-CoV-2 614 G, Delta, or Omicron variant. Overall, Delta infection induced the most severe inflammation and pathology in nasal cavity and lung followed by the 614 G, then Omicron variant. Sex differences in host responses to SARS-CoV-2 infection were variant-specific. Delta-infected males showed increased pulmonary infiltration of CD163+ "M2" macrophages, Ly6G+ neutrophils, and NKR-P1C + NK cells during early onset of infection, and elevated lung inflammatory cytokines such as IL-10, IL-6, and IP-10 than Delta-infected females. Conversely, females had increased lung CD4 + T cell recruitment after Omicron infection and significantly elevated lung MCP-1 secretion after Delta infection than males. Lung spatial transcriptomics data revealed that Delta-infected females had enriched gene pathways related to humoral immune response and interferon signaling, while males had enriched pathways associated with extracellular matrix production, chemokine signaling, and cell chemotaxis. Taken together, this study highlights the complex infection dynamics with respect to individual SARS-CoV-2 variants and underscores the importance of sex as a confounding factor for COVID-19 pathology.

Indexed as

Angiotensin-Converting Enzyme 2COVID-19SARS-CoV-2AnimalsCytokinesDisease Models, AnimalFemaleHumansLungMacrophagesMaleMiceMice, TransgenicSex FactorsAngiotensin-Converting Enzyme 2CytokinesCOVID‐19K18‐hACE2 transgenic mousepathologySARS‐CoV‐2sex differencesspatial transcriptomics

Identifiers

PMID40686017
PMCPMC12277941

What OpenQuestion holds

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LicenceCC BY
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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.