SARS-COV-2 induces blood-brain barrier and choroid plexus barrier impairments and vascular inflammation in mice (preprint)

The coronavirus disease of 2019 (COVID-19) pandemic that has led to more than 700 million confirmed cases and near 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 as an important question, which is also centered on the mystery 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 the neurological complications both acutely and in long COVID.

Investigation of Interaction Between the Spike Protein of SARS-CoV-2 and ACE2-Expressing Cells Using an In Vitro Cell Capturing System (preprint)

Background: The Interaction between severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2 ) spike protein with Angiotensin converting enzyme 2 (ACE2) on the host cells is a crucial step for the viral entry and infection. Therefore, investigating the molecular mechanism underlying the interaction is of great importance for the prevention of the infection of SARS-CoV-2. In this study, we aimed to establish a virus-free in vitro system to study the interaction between the spike protein and host cells of SARS-CoV-2.Results: Our results show that ACE2-overexpressing HEK293T cells are captured by immobilized spike protein, and the cell capturing process can be inhibited by the receptor binding domain of the spike protein or antibodies against S protein. Furthermore, spike protein variant with D614G mutant show a higher cell capturing ability than wild type spike protein. In addition, the captured cells can be eluted as living cells for further investigation.Conclusions: This study provides a new in vitro system for investigating the interaction between SARS-CoV-2 and host cells and purifying ACE2-expressing cells.