SARS-CoV-2 disrupts the integrity of a human blood-brain barrier model in the absence of infection, 2026, Jmii et al.

[Chandelier]

SARS-CoV-2 disrupts the integrity of a human blood-brain barrier model in the absence of infection

Spoiler: Authors

Jmii, Habib; Haverty, Ruth; Rochfort, Keith D; Fletcher, Nicola F

Abstract
Neurological symptoms are recognized in patients with COVID-19, and include anosmia, ageusia, cognitive impairments as well as more severe complications including encephalitis and ischemic strokes.
Furthermore, persistent cognitive impairment including ‘brain fog’ is recognised as part of the long COVID syndrome.
While SARS-CoV-2 has been shown to infect cells of the central nervous system (CNS) in vitro and in vivo, it is unclear whether direct infection of the CNS or indirect mechanisms including activation of the coagulation cascade or immune activation are the key drivers of COVID-19 neuropathology.
We investigated whether inactivated SARS-CoV-2, or spike protein, can disrupt the integrity of the blood-brain barrier (BBB) and characterised neuroinflammation in the absence of infection.

Using an in vitro model of the BBB composed of primary human microvascular endothelial cells, astrocytes, pericytes and microglia, we observed BBB disruption following exposure of the model to SARS-CoV-2 or spike protein.
Importantly, loss of BBB integrity was observed in response to luminal (mimicking ‘blood side’) or abluminal (‘brain side’) exposure to inactivated virus or spike protein.
Transcriptional upregulation of a range of chemokines, inflammatory cytokines and adhesion factors, and release of inflammatory cytokines from BBB models was also observed in response to luminal or abluminal SARS-CoV-2 or spike protein exposure.

These data indicate that BBB disruption and immune activation in vitro occurs in response to SARS-CoV-2 in the absence of infection, highlighting the importance of the host immune system in BBB disruption during SARS-CoV-2 infection.

Web | DOI | PDF | Journal of NeuroVirology | Open Access

 

[jnmaciuch]

I have a few concerns with the methodology. First, even from the first figure, it’s clear that this setup gives you quite a bit of variability between runs. Compare y axis values for the media controls between 1B and 1D.

Second, I worry that the negative control condition is insufficient. It’s spent cell culture medium. So theoretically the effects we’re seeing here could be due to something that is not specific to SARS-CoV-2 or the spike protein at all. Maybe that’s just what happens when you have add in a high concentration of any protein. I would have liked to see an additional negative control, maybe something like another pathogen that typically doesn’t interact with these cell types.