Role of SARS-CoV-2 Spike-Protein-Induced Activation of Microglia and Mast Cells in the Pathogenesis of Neuro-COVID

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). About 45% of COVID-19 patients experience several symptoms a few months after the initial infection and develop post-acute sequelae of SARS-CoV-2 (PASC), referred to as Long-COVID, characterized by persistent physical and mental fatigue. However, the exact pathogenetic mechanisms affecting the brain are still not well-understood. There is increasing evidence of neurovascular inflammation in the brain. However, the precise role of the neuroinflammatory response that contributes to the disease severity of COVID-19 and long COVID pathogenesis is not clearly understood. Here, we review the reports that the SARS-CoV-2 spike protein can cause blood-brain barrier (BBB) dysfunction and damage neurons either directly, or via activation of brain mast cells and microglia and the release of various neuroinflammatory molecules. Moreover, we provide recent evidence that the novel flavanol eriodictyol is particularly suited for development as an effective treatment alone or together with oleuropein and sulforaphane (ViralProtek (R)), all of which have potent anti-viral and anti-inflammatory actions.

Automated summary

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, and approximately 45% of patients experience long-term fatigue and neurovascular inflammation. The spike protein of SARS-CoV-2 can disrupt the blood-brain barrier, damage neurons, and activate brain mast cells and microglia, resulting in the release of neuroinflammatory molecules. Recent evidence suggests that the flavanol eriodictyol, along with oleuropein and sulforaphane, may be effective in treating COVID-19 and its long-term consequences.