SARS-CoV-2 directly infects the human pancreatic islet cells. a Pancreatic tissue sections from the deceased control subject were stained by multi-label IF for SARS-CoV-2 S1 protein (S, green), glucagon (α, red), insulin (β, cyan), and somatostatin (δ, yellow) (n = 10 images examined in total). Scale bars, 50 μm. b Pancreatic tissue sections from the COVID-19 autopsy samples (the prototypic SARS-CoV-2 strain-infected) were stained by multi-label IF for SARS-CoV-2 S1 protein (S, green), glucagon (α, red), insulin (β, cyan), and somatostatin (δ, yellow) (n = 10 images examined in total). Scale bars, 200 μm. c Representative multi-label IF image from the magnified section of (b). Inset highlights SARS-CoV-2 viral antigen scattered in a severely damaged and necrotic islet. Scale bars, 50 μm. c The serial section from the same pancreatic tissue stained for H&E and the same necrotic islet was magnified and circled (blue) to clearly observe its pathological changes. The islet structure is disorganized, with cellular swelling and degeneration observed in the internal regions. Cytoplasmic eosinophilia is intensified, and nuclear swelling is evident. The pentagon-marked area (☆) indicates significant necrosis of islet cells, with nuclear pyknosis, karyolysis, and loss of original cellular structure, leaving only homogeneously stained eosinophilic areas. d, e Representative multi-label IF image from the magnified section of (a). Inset highlights SARS-CoV-2 viral antigen co-localized with islet endocrine cells. Scale bars, 50 μm. COVID-19, coronavirus disease 2019; H&E, hematoxylin and eosin; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. f–i Quantification of the percentage of glucagon+ α, insulin+ β, somatostatin+ δ, and SARS-CoV-2 S protein+ cells, as well as S protein+glucagon+ α, S protein+insulin+ β, and S protein+somatostatin+ δ cells, in control human pancreatic tissues and the COVID-19 patients pancreatic tissues (n = 10 images/group). Data are presented as mean ± SD. p Values were calculated by paired or unpaired two-tailed Student’s t test. *p < 0.05, **p < 0.01, and ***p < 0.001