Fig. 1. Potential pathogenic mechanisms in patients with T2DM and COVID-19.

Lightning bolts indicate mechanisms that are accentuated in patients with type 2 diabetes mellitus (T2DM). Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)^7,239 can lead to increased levels of inflammatory mediators in the blood, including lipopolysaccharide^240,241, inflammatory cytokines^9,43,242,243 and toxic metabolites. Modulation of natural killer cell activity (increased^9,39,50 or decreased^242,244) and IFNγ production can increase the interstitial and/or vascular permeability for pro-inflammatory products^243,245,246. In addition, infection with SARS-CoV-2 leads to increased reactive oxygen species (ROS) production^243,247,248. These effects lead to lung fibrosis²⁴⁹, acute lung damage and acute respiratory distress syndrome (ARDS)^9,250. ROS production and viral activation of the renin–angiotensin–aldosterone system (RAAS)^249,251 (via increased angiotensin II expression) cause insulin resistance^39,252, hyperglycaemia²⁵³ and vascular endothelial damage^243,254,255, all of which contribute to cardiovascular events, thromboembolism and disseminated intravascular coagulation (DIC). Infection also causes increases in the clotting components fibrinogen^60,256 and D-dimer^43,242,257, leading to increases in blood viscosity^146,243 and vascular endothelial damage, and associated cardiovascular events, thromboembolism and DIC. COVID-19, coronavirus disease 2019.