Having reliable preclinical models is crucial for better understanding COVID-19 and advancing the development of effective treatments. In this context, IRTA-CReSA, in collaboration with IrsiCaixa, the Institute for Biomedical Research (IRB), and the Comparative Medicine and Bioimaging Centre of Catalonia (CMCiB), has published a study in the scientific journal mBio, presenting a new mouse model that more accurately replicates the disease caused by SARS-CoV-2 in humans.

Until now, the animal models used developed severe neurological effects that led to the death of the mice, a pattern that did not reflect the virus’s behavior in humans. This new model, however, avoids these brain alterations and mimics an infection focused on the lungs and respiratory tract, as it commonly occurs in humans. This advancement allows for more precise study of the disease’s progression, evaluation of new therapeutic strategies, and further research into persistent COVID.

A milder infection focused on the respiratory system

The goal of the Virology and Cellular Immunology Group at IrsiCaixa, supported by IRTA-CReSA, was to create a model that better represents the human response to SARS-CoV-2 infection. To achieve this, the IRB team inserted the human ACE2 gene—the virus’s entry point into cells—into a specific area of the mouse genome. This modification allows the gene to be primarily expressed in the lungs and respiratory tract, as in humans, facilitating viral access, infection of cells, and viral replication, thereby reproducing the real dynamics of infection in the human respiratory system.

When these mice are infected with SARS-CoV-2, they do not show brain damage but do exhibit active viral replication in the lungs and respiratory tract, accompanied by inflammation. Unlike previous models, the mice do not die but develop a milder form of the disease and eventually recover. This represents a significant breakthrough for preclinical research, providing a model that more accurately mimics the disease’s reality in humans.

A step forward in combating COVID-19 and persistent COVID

This new model is an essential tool for better understanding how the virus operates within the body and for testing new preventive and therapeutic strategies. Despite significant advancements in vaccination, effective antivirals are still needed to prevent severe forms of the disease or reverse its effects.

Additionally, this model opens new avenues for studying persistent COVID, a condition affecting thousands of people who continue to experience symptoms months or even years after the infection. Better understanding this reality is crucial for developing specific treatments and improving the quality of life for those affected.

Pons-Grífols A, Tarrés-Freixas F, Pérez M, Riveira-Muñoz E, Raïch-Regué D, Perez-Zsolt D, Muñoz-Basagoiti J, Tondelli B, Pradenas E, Izquierdo-Useros N, Capdevila S, Vergara-Alert J, Urrea V, Carrillo J, Ballana E, Forrow S, Clotet B, Segalés J, Trinité B, Blanco J. 0. A human-ACE2 knock-in mouse model for SARS-CoV-2 infection recapitulates respiratory disorders but avoids neurological disease associated with the transgenic K18-hACE2 model. mBio 0:e00720-25.

https://doi.org/10.1128/mbio.00720-25

About the author of this post:

Eduard Cecilia

Comunicació. Centre de Recerca en Sanitat Animal (IRTA-CReSA). Programa de Sanitat Animal IRTA. eduard.cecilia@irta.cat

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