Hyperglycemia in Acute COVID-19 is Characterized by Insulin Resistance and Adipose Tissue Infectivity by SARS-CoV-2

Reiterer, Moritz; Rajan, Mangala; Gómez-Banoy, Nicolás; Lau, Jennifer D.; Gomez-Escobar, Luis G.; Ma, Lunkun; Gilani, Ankit; Alvarez-Mulett, Sergio; Sholle, Evan T.; Chandar, Vasuretha; Bram, Yaron; Hoffman, Katherine; Bhardwaj, Priya; Piloco, Phoebe; Rubio-Navarro, Alfonso; Uhl, Skyler; Carrau, Lucia; Houhgton, Sean; Redmond, David; Shukla, Alpana P.; Goyal, Parag; Brown, Kristy A.; tenOever, Benjamin R.; Alonso, Laura C.; Schwartz, Robert E.; Schenck, Edward J.; Safford, Monika M.; Lo, James C.

Individuals infected with SARS-CoV-2 who also display hyperglycemia suffer from longer hospital stays, higher risk of developing acute respiratory distress syndrome (ARDS), and increased mortality. Nevertheless, the pathophysiological mechanism of hyperglycemia in COVID-19 remains poorly characterized. Here, we show that hyperglycemia is similarly prevalent among patients with ARDS independent of COVID-19 status. Yet, among patients with ARDS and COVID-19, insulin resistance is the prevalent cause of hyperglycemia, independent of glucocorticoid treatment, which is unlike patients with ARDS but without COVID-19, where pancreatic beta cell failure predominates. A screen of glucoregulatory hormones revealed lower levels of adiponectin in patients with COVID-19. Hamsters infected with SARS-CoV-2 demonstrated a strong antiviral gene expression program in the adipose tissue and diminished expression of adiponectin. Moreover, we show that SARS-CoV-2 can infect adipocytes. Together these data suggest that SARS-CoV-2 may trigger adipose tissue dysfunction to drive insulin resistance and adverse outcomes in acute COVID-19.