Blood-brain barrier penetration of non-replicating SARS-CoV-2 and S1 Variants of Concern induce neuroinflammation... 2023 Erickson et al

[Andy]

Full title: Blood-brain barrier penetration of non-replicating SARS-CoV-2 and S1 Variants of Concern induce neuroinflammation which is accentuated in a mouse model of Alzheimer’s disease

Abstract

COVID-19 and especially Long COVID are associated with severe CNS symptoms and may place persons at risk to develop long-term cognitive impairments. Here, we show that two non-infective models of SARS-CoV-2 can cross the blood-brain barrier (BBB) and induce neuroinflammation, a major mechanism underpinning CNS and cognitive impairments, even in the absence of productive infection. The viral models cross the BBB by the mechanism of adsorptive transcytosis with the sugar N-acetylglucosamine being key. The delta and omicron variants cross the BBB faster than the other variants of concern, with peripheral tissue uptake rates also differing for the variants. Neuroinflammation induced by icv injection of S1 protein was greatly enhanced in young and especially in aged SAMP8 mice, a model of Alzheimer’s disease, whereas sex and obesity had little effect.

Open access, https://www.sciencedirect.com/science/article/abs/pii/S0889159123000107

 

[SNT Gatchaman]

The viral models cross the BBB by the mechanism of adsorptive transcytosis with the sugar N-acetylglucosamine being key.

The mechanism by which SARS-PV and VLPs cross the BBB is similar to that of S1 as evidenced by WGA [wheatgerm agglutinin] enhancing viral transport across the BBB. Adsorptive transcytosis (transport across the BBB) is the classic method by which viruses enter cells and cross the BBB and depends on interactions between the viral attachment glycoproteins of the virus and the glycoproteins and glycolipids of the targeted cell.

For a mini-review article on transcytosis, see Transcytosis to Cross the Blood Brain Barrier, New Advancements and Challenges (2019, Frontiers in Neuroscience) —

In polarized cells, unidirectional transcytosis refers to the transport of macromolecules from apical to basolateral plasma membranes. Steps along this pathway include endocytosis, intracellular vesicular trafficking and exocytosis. The first of these steps may involve adsorptive (charge dependent) or receptor-mediated internalization. Positively charged molecules such as polymers, cationic lipids, albumin and nanoparticles may interact with the negatively charged cell membrane and internalize through adsorptive endocytosis.

 

[SNT Gatchaman]

See also prior report from same group: The S1 protein of SARS-CoV-2 crosses the blood–brain barrier in mice (2020, Nature Neuroscience)

 

[duncan]

Covid crosses the BBB.

Then what? Does it have a tropism for different parts of the brain? Is it indiscriminate as it ravages like 9th century Goths? Do symptoms mirror neurosyphilis or neurolyme? What time frames are involved? What happens in 6 months? 6 Years?

Ive read atrophies of grey matter, white matter too. Various degrees of cognitive impairment ranging from brain fog to dementia.

I'd like to know what I can expect. But neurology is kind of hit or miss. Half the time no one is minding the shop. 50% is my experience. We know what to expect with neurosyphilis. NeuroLyme ask 10 neurologist you'll get ten different spiels.

Is there any group charged with pulling together all the academic bits and pieces to at least have a go at characterizing what happens to the average patient when her covid pierces the BBB? Or are we blithely siloing ourselves into ignorance?