Hyperglycemia in acute COVID-19 is characterized by insulin resistance and adipose tissue infectivity by SARS-CoV-2

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. [Display omitted] •Hyperglycemia is highly prevalent in acute respiratory distress syndrome ± COVID-19•Insulin resistance is the main cause for hyperglycemia in patients with severe COVID-19•Patients with COVID-19 and hamsters infected with SARS-CoV-2 have decreased adiponectin•SARS-CoV-2 can directly infect human and mouse adipocytes Here, Reiterer et al. report that hyperglycemia in critically ill patients with COVID-19 is caused mainly by insulin resistance and is associated with decreased circulating adiponectin. SARS-CoV-2 is shown to directly infect human adipocytes, trigger an inflammatory antiviral response in the adipose tissue, and cause its dysfunction.