The second wave of COVID-19 results in outbreak of mucormycosis: diabetes and immunological perspective.

Hyperglycaemia impairs the motility of phagocytes and also decreases the oxidative and non-oxidative mechanism of killing the causative pathogen. Chronic hyperglycemia also leads to the formation of advanced glycation end-products (AGE), which leads to cross-linking between key proteins of inflammation and connective tissue such as collagen which makes tissue susceptible to immunological dysregulation. The receptor for AGE (RAGE) is expressed on various inflammatory cells including neutrophils and its activation by AGEs leads to activation of many down signaling pathways which ultimately leads to impairment of the inflammatory response. Hyperglycemia also increases serum Nitric Oxide (NO), which decreases neutrophil motility and reduces the synthesis and release of various inflammatory mediators such as TNF-α and IL-1β, IL-6. It also decreases the expression of adhesion molecules such as LFA-1 and ICAM-2, on neutrophils. Steroids cause immunosuppression majorly by inhibiting the NF-κB pathway which is a transcription factor involved in the synthesis of many immunological mediators such as Interleukins, cytokines, chemokines, etc., and various adhesion molecules.