**9. COVID-19 and Pancreas; Diabetes**

Diabetes is the most prevalent co-morbidity in COVID-19, second only to obesity. If those with diabetes do contract COVID-19, they are indeed likely to develop more severe form of the disease particularly if the diabetes is uncontrolled [56–68]. Data from Wuhan, China confirms that approximately 20% of severe cases of COVID-19 do show diabetes, as co morbidity [36]. According to reports from India, of the first 125 deaths on COVID-19, 56% had diabetes, 47% had hypertension, and over a third had both diabetes and hypertension [57]. An Indian study of 231 patients of COVID-19 infections, 21.2% had co-morbidities of which diabetes mellitus and hypertension was the most common [58]. In some stable diabetic patients with COVID-19, there was rapid worsening of glycaemic control requiring high insulin dose. Possibility of pancreatic affection due to virus is postulated as high level of ACE2 was found in the pancreatic islet beta cells [59–61].

Wang et al demonstrated that 9 of 52 admitted patients in Wuhan with COVID-19 pneumonia developed pancreatic injury as evidenced by abnormality in serum amylase or lipase levels [62]. After viral entry into the beta cells, there is a downregulation of ACE2 leading to increased angiotensin level, which also impairs insulin secretion [63]. Possible mechanisms on pancreatic injury include (i) direct cytopathic effect of SARS-CoV-2 replication, (ii) systemic response to respiratory failure, and (iii) harmful immune response induced by SARS-CoV-2 infection [62].

An important feature of type 2 diabetes is low grade inflammation. There is long term immune system imbalance, metabolic syndrome, or nutrient excess associated with obesity [64, 65]. Also, in individuals with diabetes, there is an exaggeration of pro-inflammatory responses, especially IL-1, IL-6 and TNF-alpha. This may be further worsened in those with severe COVID-19. Prolonged hyperglycaemia alters the host immune system. Dysfunctions in leukocytes, monocyte and macrophage chemotaxis and phagocytosis, and damaged specific immunity have also been reported in subjects with diabetes [66, 67]. Moreover, diabetes shares common features promoting disease progression with infectious disorders such as proinflammatory state and endothelial dysfunction [68].
