Obesity and metabolic dysfunction drive sex-associated differential disease profiles in hACE2-mice challenged with SARS-CoV-2.
iScience
; 25(10): 105038, 2022 Oct 21.
Article
in English
| MEDLINE | ID: covidwho-2007777
ABSTRACT
Severe outcomes from SARS-CoV-2 infection are highly associated with preexisting comorbid conditions like hypertension, diabetes, and obesity. We utilized the diet-induced obesity (DIO) model of metabolic dysfunction in K18-hACE2 transgenic mice to model obesity as a COVID-19 comorbidity. Female DIO, but not male DIO mice challenged with SARS-CoV-2 were observed to have shortened time to morbidity compared to controls. Increased susceptibility to SARS-CoV-2 in female DIO was associated with increased viral RNA burden and interferon production compared to males. Transcriptomic analysis of the lungs from all mouse cohorts revealed sex- and DIO-associated differential gene expression profiles. Male DIO mice after challenge had decreased expression of antibody-related genes compared to controls, suggesting antibody producing cell localization in the lung. Collectively, this study establishes a preclinical comorbidity model of COVID-19 in mice where we observed sex- and diet-specific responses that begin explaining the effects of obesity and metabolic disease on COVID-19 pathology.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Type of study:
Cohort study
/
Observational study
/
Prognostic study
Language:
English
Journal:
IScience
Year:
2022
Document Type:
Article
Affiliation country:
J.isci.2022.105038
Similar
MEDLINE
...
LILACS
LIS