Adenovirus transduction to express human ACE2 causes obesity-specific morbidity in mice, impeding studies on the effect of host nutritional status on SARS-CoV-2 pathogenesis

• Published in: Virology (New York, N.Y.) N.Y.), 2021-11, Vol.563, p.98-106
• Main Authors: Rai, Pallavi, Chuong, Christina, LeRoith, Tanya, Smyth, James W., Panov, Julia, Levi, Moshe, Kehn-Hall, Kylene, Duggal, Nisha K., Lucarelli, James-Weger
• Format: Article
• Language: English
• Subjects: Animals; Chlorocebus aethiops; Comorbidity; COVID-19; COVID-19 - epidemiology; Diet-induced obesity; Disease Models, Animal; Female; hACE2; HEK293 Cells; Humans; Male; Mice; Mice, Inbred C57BL; Morbidity; Obesity - epidemiology; Pathology; Replication-defective adenovirus; Tissue; Vero Cells
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2021.08.014

The COVID-19 pandemic has paralyzed the global economy and resulted in millions of deaths globally. People with co-morbidities like obesity, diabetes and hypertension are at an increased risk for severe COVID-19 illness. This is of overwhelming concern because 42% of Americans are obese, 30% are pre-diabetic and 9.4% have clinical diabetes. Here, we investigated the effect of obesity on disease severity following SARS-CoV-2 infection using a well-established mouse model of diet-induced obesity. Diet-induced obese and lean control C57BL/6 N mice, transduced for ACE2 expression using replication-defective adenovirus, were infected with SARS-CoV-2, and monitored for lung pathology, viral titers, and cytokine expression. No significant differences in tissue pathology or viral replication was observed between AdV transduced lean and obese groups, infected with SARS-CoV-2, but certain cytokines were expressed more significantly in infected obese mice compared to the lean ones. Notably, significant weight loss was observed in obese mice treated with the adenovirus vector, independent of SARS-CoV-2 infection, suggesting an obesity-dependent morbidity induced by the vector. These data indicate that the adenovirus-transduced mouse model of SARS-CoV-2 infection, as described here and elsewhere, may be inappropriate for nutrition studies. •Lean and obese C57BL/6 N mice transduced with a replication-defective adenovirus encoding human ACE2 became susceptible to SARS-CoV-2 infection.•High levels of infectious virus and viral RNA were detected in the lungs of infected lean and obese mice.•Inoculation with the adenovirus vector at this dose caused an obesity-specific morbidity in C57BL/6 N mice.