Circulating virus, cytokines, DAMPs, and PAMPs could act on endothelial cells, leading to inflammation and opening of the BBB. These factors could cause inflammation in vascular mural cells and brain resident myeloid cells (microglia and macrophages). The resulting cytokine production could lead to the cytokine sickness, a potential cause of encephalopathy in COVID-19.

Bowdoin College

Entry of  SARSCoV-2 into the blood has been described with widely ranging frequencies (1% to 41%) . There are a few possible mechanisms of entry through the BBB:

1. Circulating SARS-CoV-2, associated cytokines, DAMPs, and PAMPs could act on endothelial cells leading to inflammation and opening of the BBB. 

2. Comorbidities often seen in COVID-19, like cardiovascular risk or pre-existing neurological diseases, could, alone or in combination with cytokines, increase BBB permeability. 

3. SARS-CoV-2 could enter the brain through the median eminence of the hypothalamus and other circumventricular organs, brain regions with a leaky BBB due to openings in the capillary wall. The hypothalamus could serve as a gateway to the entire brain. 


SARS-CoV-2 Entry Through the Blood Brain Barrier (BBB)

Iadecola C.., Anrather J., & Kamel H. (2020). Effects of COVID-19 on the Nervous System. Cell, 183(1), 16-27. https://doi.org/10.1016/j.cell.2020.08.028


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