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Obesity fosters severe disease outcomes in a mouse model of coronavirus infection associated with transcriptomic abnormalities
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  • Pallavi Rai,
  • Jeffrey M. Marano,
  • Lin Kang,
  • Sheryl Coutermarsh-Ott,
  • Andrea Daamen,
  • Peter Lipsky E,
  • James Weger-Lucarelli
Pallavi Rai
Virginia-Maryland College of Veterinary Medicine Department of Biomedical Sciences and Pathobiology
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Jeffrey M. Marano
Center for Emerging Zoonotic and Arthropod-borne Pathogens Virginia Tech
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Lin Kang
Virginia-Maryland College of Veterinary Medicine Department of Biomedical Sciences and Pathobiology
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Sheryl Coutermarsh-Ott
Virginia-Maryland College of Veterinary Medicine Department of Biomedical Sciences and Pathobiology
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Andrea Daamen
AMPEL BioSolutions LLC
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Peter Lipsky E
AMPEL BioSolutions LLC
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James Weger-Lucarelli
Virginia-Maryland College of Veterinary Medicine Department of Biomedical Sciences and Pathobiology

Corresponding Author:[email protected]

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Abstract

Obesity has been identified as an independent risk factor for severe outcomes in humans with coronavirus disease 2019 (COVID-19) and other infectious diseases. Here, we established a mouse model of COVID-19 using the murine betacoronavirus, mouse hepatitis virus 1 (MHV-1). C57BL/6 and C3H/HeJ mice exposed to MHV-1 developed mild and severe disease, respectively. Obese C57BL/6 mice developed clinical manifestations similar to those of lean controls. In contrast, all obese C3H/HeJ mice succumbed by 8 days post-infection, compared to a 50% mortality rate in lean controls. Notably, both lean and obese C3H/HeJ mice exposed to MHV-1 developed lung lesions consistent with severe human COVID-19, with marked evidence of diffuse alveolar damage (DAD). To identify early predictive biomarkers of worsened disease outcomes in obese C3H/HeJ mice, we sequenced RNA from whole blood 2 days post-infection and assessed changes in gene and pathway expression. Many pathways uniquely altered in obese C3H/HeJ mice post-infection aligned with those found in humans with severe COVID-19. Furthermore, we observed altered gene expression related to the unfolded protein response and lipid metabolism in infected obese mice compared to their lean counterparts, suggesting a role in the severity of disease outcomes. This study presents a novel model for studying COVID-19 and elucidating the mechanisms underlying severe disease outcomes in obese and other hosts.
01 Feb 2024Submitted to Journal of Medical Virology
02 Feb 2024Submission Checks Completed
02 Feb 2024Assigned to Editor
02 Feb 2024Review(s) Completed, Editorial Evaluation Pending
06 Feb 2024Reviewer(s) Assigned
05 Mar 2024Editorial Decision: Revise Major
15 Mar 20241st Revision Received
20 Mar 2024Reviewer(s) Assigned
24 Mar 2024Review(s) Completed, Editorial Evaluation Pending