tetano
Editor, Senior Moderator
JACC Basic Transl Sci
. 2026 Oct;11(10):101691.
doi: 10.1016/j.jacbts.2026.101691.
Mahmoud Gheblawi 1 , Mobin Khoramjoo 1 , Mohamed Elaish 2 , Kaiming Wang 3 , Lakshmi Puttagunta 4 , Faqi Wang 5 , Pavel Zhabyeyev 5 , Natacha S Ogando 6 , Ratnadeep Basu 7 , Anran Zhang 7 , Colombo Daniele 8 , Franca Del Nonno 8 , Enrico Girardi 9 , Monica De Gaspari 10 , Cristina Basso 10 , Brian Chiu 11 , Kodjovi D Mlaga 12 , Rohan John 13 , James W Scholey 14 , Qiumin Tan 15 , Ram Prasad 16 , Justin R Wright 17 , Regina Lamendella 17 , Christopher Power 6 , David H Evans 18 , Emilia Liana Falcone 19 , Ryan S Noyce 18 , Josef M Penninger 20 , Zamaneh Kassiri 21 , Tom C Hobman 22 , Maria B Grant 16 , Gavin Y Oudit 23
Affiliations Expand
Angiotensin-converting enzyme 2 (ACE2), the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is ubiquitously expressed and contributes to cardiovascular, metabolic, and gastrointestinal homeostasis. In this study, we observed ACE2 loss in organs of patients with COVID-19 and in SARS-CoV-2-infected cells. In aged, obese, and diabetic mice, SARS-CoV-2 infection caused greater morbidity, persistent pulmonary infection, intestinal and metabolic disruption, and impaired cardiac Wnt and interferon-γ signaling. ACE2-deficient obese-diabetic mice showed cardiovascular, intestinal, metabolic, and neurobehavioral abnormalities, providing a complementary model to examine ACE2-associated disruption in metabolic disease. Exploratory metabolic profiling identified shared disruptions in taurine, tryptophan, and microbiota-derived metabolites across clinical and preclinical samples. These findings identify metabolic disease as a modifier of SARS-CoV-2 susceptibility and support ACE2-associated dysregulation as one contributor to selected infection-related sequelae.
Keywords: cardiovascular disease; coronavirus infection; gut microbiota; interferon gamma; post-COVID-19 condition; tryptophan.
. 2026 Oct;11(10):101691.
doi: 10.1016/j.jacbts.2026.101691.
Obesity and Diabetes Increase SARS-CoV-2 Susceptibility Through Angiotensin-Converting Enzyme 2, Immunologic, and Gut Microbial Dysregulation
Mahmoud Gheblawi 1 , Mobin Khoramjoo 1 , Mohamed Elaish 2 , Kaiming Wang 3 , Lakshmi Puttagunta 4 , Faqi Wang 5 , Pavel Zhabyeyev 5 , Natacha S Ogando 6 , Ratnadeep Basu 7 , Anran Zhang 7 , Colombo Daniele 8 , Franca Del Nonno 8 , Enrico Girardi 9 , Monica De Gaspari 10 , Cristina Basso 10 , Brian Chiu 11 , Kodjovi D Mlaga 12 , Rohan John 13 , James W Scholey 14 , Qiumin Tan 15 , Ram Prasad 16 , Justin R Wright 17 , Regina Lamendella 17 , Christopher Power 6 , David H Evans 18 , Emilia Liana Falcone 19 , Ryan S Noyce 18 , Josef M Penninger 20 , Zamaneh Kassiri 21 , Tom C Hobman 22 , Maria B Grant 16 , Gavin Y Oudit 23
Affiliations Expand
- PMID: 42937414
- DOI: 10.1016/j.jacbts.2026.101691
Abstract
Angiotensin-converting enzyme 2 (ACE2), the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is ubiquitously expressed and contributes to cardiovascular, metabolic, and gastrointestinal homeostasis. In this study, we observed ACE2 loss in organs of patients with COVID-19 and in SARS-CoV-2-infected cells. In aged, obese, and diabetic mice, SARS-CoV-2 infection caused greater morbidity, persistent pulmonary infection, intestinal and metabolic disruption, and impaired cardiac Wnt and interferon-γ signaling. ACE2-deficient obese-diabetic mice showed cardiovascular, intestinal, metabolic, and neurobehavioral abnormalities, providing a complementary model to examine ACE2-associated disruption in metabolic disease. Exploratory metabolic profiling identified shared disruptions in taurine, tryptophan, and microbiota-derived metabolites across clinical and preclinical samples. These findings identify metabolic disease as a modifier of SARS-CoV-2 susceptibility and support ACE2-associated dysregulation as one contributor to selected infection-related sequelae.
Keywords: cardiovascular disease; coronavirus infection; gut microbiota; interferon gamma; post-COVID-19 condition; tryptophan.