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Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
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Animal Models for Long COVID: Current Advances, Limitations, and Future Directions.

Yu Zhang1, Huan Chen2, Yumeng Li1

  • 1Department of Biosafety, School of Basic Medicine, Army Medical University, Chongqing, China.

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|February 21, 2025
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Summary

Long COVID (LC) is a chronic, disabling condition needing better animal models. This review assesses current models for replicating LC symptoms and guides future research for effective treatments.

Keywords:
COVID‐19Long COVIDSARS‐CoV‐2animal models

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Area of Science:

  • Virology
  • Immunology
  • Pathology

Background:

  • Long COVID (LC) is a significant public health concern with chronic, systemic, and disabling effects.
  • Understanding LC mechanisms requires foundational scientific studies for developing treatments.
  • There is a critical need for animal models that accurately mimic human LC clinical features.

Purpose of the Study:

  • To review pathological changes in extrapulmonary systems affected by LC using clinical epidemiological data.
  • To critically evaluate existing animal models (nonhuman primates, mice, hamsters) for their ability to replicate persistent LC symptoms.
  • To identify areas for improvement in developing next-generation animal models for LC research.

Main Methods:

  • Integration of clinical epidemiological data on Long COVID.
  • Critical examination of current animal models for Long COVID symptom replication.
  • Identification of research gaps in animal model development for chronic post-viral syndromes.

Main Results:

  • LC affects multiple extrapulmonary systems, with pathological changes documented.
  • Existing animal models show limitations in fully recapitulating the diverse and persistent symptoms of human LC.
  • Specific areas for enhancing animal model fidelity to human LC manifestations were identified.

Conclusions:

  • Improved animal models are essential for advancing Long COVID research.
  • Next-generation models will accelerate understanding of viral infection chronicity.
  • Enhanced models are crucial for pandemic preparedness and developing effective therapeutic strategies.