SARS-CoV-2 Spike protein binding of glycated serum albumin - its potential role in the pathogenesis of the COVID-19 clinical syndromes and bias towards individuals with pre-diabetes/type 2 diabetes & metabolic diseases

Since the immune response to SARS-CoV2 infection requires antibody recognition of the Spike protein, we used MagMix, a semi-automated magnetic rack to reproducibly isolate patient plasma proteins bound to a pre-fusion stabilised Spike and nucleocapsid proteins conjugated to magnetic beads. Once eluted, MALDI-ToF mass spectrometry identified a range of immunoglobulins, but also in Spike protein magnetic beads we found a high affinity for human serum albumin. Careful mass comparison revealed a preferential capture of advanced glycation end product (AGE) glycated human serum albumin by the pre-fusion Spike protein.

The ability of bacteria and viruses to surround themselves with serum proteins is a recognised process of immune evasion. A lower serum albumin concentration is a reported feature of COVID-19 patients with severe symptoms and high probability of death. This binding preference of the Spike protein for AGE glycated serum albumin may contribute to immune evasion and influence the severity & pathology of SARS-COV2 towards acute respiratory distress. Thus, it can be hypothesised, contributing to the symptom severity bias and mortality risk for the elderly and those with (pre)diabetic and atherosclerotic/metabolic diseases who contract SARS-CoV2 infections.