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.

感染 SARS-CoV-2 并表现出高血糖的个体住院时间更长，患急性呼吸窘迫综合征 (ARDS) 的风险更高，死亡率也更高。然而，COVID-19 高血糖的病理生理机制仍不清楚。在这里，我们发现高血糖在 ARDS 患者中同样普遍存在，与 COVID-19 状态无关。然而，在 ARDS 和 COVID-19 患者中，胰岛素抵抗是高血糖的普遍原因，与糖皮质激素治疗无关，这与 ARDS 患者但没有 COVID-19 的患者不同，后者以胰腺 β 细胞衰竭为主。葡萄糖调节激素筛查显示，COVID-19 患者的脂联素水平较低。感染 SARS-CoV-2 的仓鼠在脂肪组织中表现出强大的抗病毒基因表达程序，并且脂联素的表达减少。此外，我们发现 SARS-CoV-2 可以感染脂肪细胞。这些数据共同表明，SARS-CoV-2 可能会引发脂肪组织功能障碍，从而导致胰岛素抵抗和急性 COVID-19 的不良后果。