Fig. 1.

Proposed 2 phase model of innate immune priming in response to SARS-Cov-2 infection in aging, diabetic and/or obese patients. Comparison of the sequence of events between vulnerable (left sequence) and non-vulnerable (right sequence) patients. Vulnerable patients show increased glycation of proteins because of age, obesity and hyper glycaemia resulting in the generation of circulating negatively charged macromolecules, specifically proteins. In these vulnerable patients the lungs are primed to produce an inflammatory state as the result of the interaction of these circulating anionic macromolecules with RAGE. This further upregulates expression of RAGE in the lungs of these patients in a positive feedback loop. Patients with this primed inflammatory state subsequently over-react to viral infection, inducing an inflammatory spiral in Phase 2 resulting in a cytokine storm and enhanced morbidity and mortality. In non-vulnerable patients there is no phase 1 and the patient recovers from viral infection (phase 2) with little or no symptoms. Thicker arrows highlight pathways that are upregulated in vulnerable patients.