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.