SARS‐CoV‐2 induces blood‐brain barrier and choroid plexus barrier impairments and vascular inflammation in mice

Abstract

AbstractThe coronavirus disease of 2019 (COVID‐19) pandemic has led to more than 700 million confirmed cases and nearly 7 million deaths. Although severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) virus mainly infects the respiratory system, neurological complications are widely reported in both acute infection and long‐COVID cases. Despite the success of vaccines and antiviral treatments, neuroinvasiveness of SARS‐CoV‐2 remains an important question, which is also centered on the mystery of whether the virus is capable of breaching the barriers into the central nervous system. By studying the K18‐hACE2 infection model, we observed clear evidence of microvascular damage and breakdown of the blood‐brain barrier (BBB). Mechanistically, SARS‐CoV‐2 infection caused pericyte damage, tight junction loss, endothelial activation and vascular inflammation, which together drive microvascular injury and BBB impairment. In addition, the blood‐cerebrospinal fluid barrier at the choroid plexus was also impaired after infection. Therefore, cerebrovascular and choroid plexus dysfunctions are important aspects of COVID‐19 and may contribute to neurological complications both acutely and in long COVID.