Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression

Area of Science:

• Virology
• Immunology
• Genomics

Background:

• Mouse models are crucial for studying human diseases like COVID-19.
• The accuracy of mouse models in recapitulating human transcriptional profiles during SARS-CoV-2 infection is debated.

Purpose of the Study:

• To compare transcriptional responses in SARS-CoV-2 infected human lungs with those in commonly used mouse models.
• To evaluate the relevance of mouse models for COVID-19 research, particularly concerning immune responses.

Main Methods:

• RNA-sequencing (RNA-Seq) data from human studies and mouse models were analyzed.
• Bioinformatics approaches were used to compare differentially expressed genes (DEGs) between species.
• Immune signatures and inflammatory pathways were specifically analyzed for concordance.

Main Results:

• Overlap of single-copy orthologue differentially expressed genes (scoDEGs) between human and mouse studies was generally low (15-35%).
• Poor gene overlap was attributed to species-specific expression differences, not experimental variables.
• Significant concordance was observed in immune signatures and inflammatory pathways between humans and mice.

Conclusions:

• Despite poor overall gene expression overlap, mouse models effectively capture key immune and inflammatory responses relevant to COVID-19.
• These models are considered representative and relevant for investigating the immunity and immunopathology of SARS-CoV-2 infection.