Evidence map›Paper›PMID 42776388›Full record

ArticleGeroScience2026

Intestinal oxysterol remodeling underlies severe COVID-19 in an aged hamster model.

AhmedElmontaser Mergani, Katrin Wirz, Wencke Reineking, Armina Richter, Victoria Lechler, Veronika Pilchová, Theresa Störk, Lukas Mathias Michaely, Isabel Zdora, Manuela Buettner and 5 more

Abstract read
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In one paragraph

Article in GeroScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

15 authors.

AhmedElmontaser Mergani *Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover Foundation, Hanover, Germany.
Katrin Wirz *Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover Foundation, Hanover, Germany.
Wencke ReinekingDepartment of Pathology, University of Veterinary Medicine Hannover Foundation, Hanover, Germany.
Armina RichterResearch Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover Foundation, Hanover, Germany.
Victoria LechlerResearch Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover Foundation, Hanover, Germany.
Veronika PilchováResearch Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover Foundation, Hanover, Germany.
Theresa StörkDepartment of Pathology, University of Veterinary Medicine Hannover Foundation, Hanover, Germany.
Lukas Mathias MichaelyDepartment of Pathology, University of Veterinary Medicine Hannover Foundation, Hanover, Germany.
Isabel ZdoraDepartment of Pathology, University of Veterinary Medicine Hannover Foundation, Hanover, Germany.
Manuela BuettnerInstitute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany.
Asisa VolzInstitute of Virology, University of Veterinary Medicine Hannover Foundation, Hanover, Germany.
Andre BleichInstitute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany.
Wolfgang BaumgärtnerDepartment of Pathology, University of Veterinary Medicine Hannover Foundation, Hanover, Germany.
Claudia SchulzResearch Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover Foundation, Hanover, Germany.
Maren von Köckritz-BlickwedeResearch Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover Foundation, Hanover, Germany. maren.von.koeckritz-blickwede@tiho-hannover.de.ORCID http://orcid.org/0000-0001-7712-9767

Funding

Niedersächsische Ministerium für Wissenschaft und Kultur 14-76403-184
6 · The paper itself

Abstract

Age is a critical determinant of COVID-19 severity, yet the underlying metabolic mechanisms driving disease progression remain poorly understood. Using a well-characterized Syrian hamster model, we investigated how aging shapes intestinal and systemic sterol metabolism during SARS-CoV-2 infection. Young (7-10 weeks) and aged (12 months) hamsters were intranasally infected, and clinical outcomes were integrated with virological, histopathological, and lipidomic profiles across intestinal tissues, lungs, and serum. Despite comparable pulmonary pathology, aged hamsters exhibited significantly higher intestinal viral loads and more pronounced clinical decline than young counterparts. We identified a clear age-dependent divergence in sterol responses: young hamsters mounted a robust systemic induction of antiviral side-chain oxysterols, notably 25-hydroxycholesterol (25-HC) and 27-hydroxycholesterol (27-HC), in both intestinal tissues and serum. In contrast, this protective response was markedly blunted in aged animals. Moreover, aged hosts displayed a selective accumulation of ring oxysterols, particularly colonic 4β-hydroxycholesterol (4β-HC), which correlated positively with viral burden and clinical severity. Correlation analyses revealed a functional intestinal-systemic axis, where gut-derived and circulating side-chain oxysterols were inversely associated with lung cholesterol levels and clinical scores. These findings suggest that youthful metabolic responses may limit viral spread and disease progression by reducing cellular entry through modulation of pulmonary cholesterol homeostasis, while oxysterols may additionally exert direct antiviral effects-a defense mechanism that diminishes with advancing age. Collectively, these findings identify the intestine as a potential contributor to the systemic metabolic alterations associated with age-dependent COVID-19 severity and suggest oxysterol pathways as promising candidates for future mechanistic investigations and therapeutic exploration.

Indexed as

25-HydroxycholesterolHost–pathogen interactionIntestinal barrierLipidomicsSARS-CoV-2Sterol metabolism

Identifiers

PMID42776388

What OpenQuestion holds

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Registered trials

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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.