SARS-CoV-2 infection induces persistent adipose tissue damage in aged golden Syrian hamsters

• Published in: Cell death & disease 2023-02, Vol.14 (2), p.75-16, Article 75
• Main Authors: Bogard, Gemma, Barthelemy, Johanna, Hantute-Ghesquier, Aline, Sencio, Valentin, Brito-Rodrigues, Patricia, Séron, Karin, Robil, Cyril, Flourens, Anne, Pinet, Florence, Eberlé, Delphine, Trottein, François, Duterque-Coquillaud, Martine, Wolowczuk, Isabelle
• Format: Article
• Language: English
• Subjects: 13; 13/51; 38; 45/77; 631/443/7; 692/420/254; Adipocytes; Adipose tissue; Adipose Tissue, White - pathology; Age; Animals; Antibodies; Biochemistry; Biomedical and Life Sciences; Body fat; Cell Biology; Cell Culture; Coronaviruses; COVID-19; COVID-19 - pathology; Cricetinae; Disease Models, Animal; Dyslipidemia; Immunology; Infections; Insulin; Insulin resistance; Life Sciences; Lipid metabolism; Macrophages; Mesocricetus; Risk factors; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Viral diseases
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-023-05574-w

Coronavirus disease 2019 (COVID-19, caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2)) is primarily a respiratory illness. However, various extrapulmonary manifestations have been reported in patients with severe forms of COVID-19. Notably, SARS-CoV-2 was shown to directly trigger white adipose tissue (WAT) dysfunction, which in turn drives insulin resistance, dyslipidemia, and other adverse outcomes in patients with COVID-19. Although advanced age is the greatest risk factor for COVID-19 severity, published data on the impact of SARS-CoV-2 infection on WAT in aged individuals are scarce. Here, we characterized the response of subcutaneous and visceral WAT depots to SARS-CoV-2 infection in young adult and aged golden hamsters. In both age groups, infection was associated with a decrease in adipocyte size in the two WAT depots; this effect was partly due to changes in tissue’s lipid metabolism and persisted for longer in aged hamsters than in young-adult hamsters. In contrast, only the subcutaneous WAT depot contained crown-like structures (CLSs) in which dead adipocytes were surrounded by SARS-CoV-2-infected macrophages, some of them forming syncytial multinucleated cells. Importantly, older age predisposed to a unique manifestation of viral disease in the subcutaneous WAT depot during SARS-CoV-2 infection; the persistence of very large CLSs was indicative of an age-associated defect in the clearance of dead adipocytes by macrophages. Moreover, we uncovered age-related differences in plasma lipid profiles during SARS-CoV-2 infection. These data suggest that the WAT’s abnormal response to SARS-CoV-2 infection may contribute to the greater severity of COVID-19 observed in elderly patients.