SARS-CoV-2 S1 … produces a protracted priming of the neuroinflammatory, physiological, and behavioral responses…, 2024, Frank+

[SNT Gatchaman]

SARS-CoV-2 S1 subunit produces a protracted priming of the neuroinflammatory, physiological, and behavioral responses to a remote immune challenge: A role for corticosteroids
Frank; Ball; Hopkins; Kelley; Kuzma; Thompson; Fleshner; Maier

Long COVID is a major public health consequence of COVID-19 and is characterized by multiple neurological and neuropsychatric symptoms. SARS-CoV-2 antigens (e.g., spike S1 subunit) are found in the circulation of Long COVID patients, have been detected in post-mortem brain of COVID patients, and exhibit neuroinflammatory properties. Considering recent observations of chronic neuroinflammation in Long COVID patients, the present study explores the idea that antigens derived from SARS-CoV-2 might produce a long-term priming or sensitization of neuroinflammatory processes, thereby potentiating the magnitude and/or duration of the neuroinflammatory response to future inflammatory insults.

Rats were administered S1 or vehicle intra-cisterna magna and 7d later challenged with vehicle or LPS. The neuroinflammatory, physiological, and behavioral responses to LPS were measured at various time points post-LPS. We found that prior S1 treatment potentiated many of these responses to LPS suggesting that S1 produces a protracted priming of these processes. Further, S1 produced a protracted reduction in basal brain corticosteroids.

Considering the anti-inflammatory properties of corticosteroids, these findings suggest that S1 might disinhibit innate immune processes in brain by reducing antiinflammatory drive, thereby priming neuroinflammatory processes. Given that hypocortisolism is observed in Long COVID, we propose that similar S1-induced innate immune priming processes might play role in the pathophysiology of Long COVID.

Link | PDF (Brain, Behavior, and Immunity)

 

[SNT Gatchaman]

In rats.

The present set of findings provide evidence that the SARS-CoV-2 S1 antigen produces a protracted priming or sensitization of neuroinflammatory processes, which lowers the threshold for activation of those processes. Thus, upon exposure to a future proinflammatory condition such as pathogen exposure or stress, the neuroinflammatory response and its physiological and behavioral sequelae will be potentiated. The S1 antigen also reduces corticosteroids in the brain, which suggests a possible mechanism whereby S1-induced hypocortisolism produces a disinhibition of brain innate inflammatory processes or immune cells (microglia) because of reduced anti-inflammatory drive. Priming of microglia and/or neuroinflammatory processes might thus reflect this state of disinhibition. Considering that SARS-CoV-2 antigens 1) are detected in the circulation of Long COVID patients, 2) cross the blood–brain barrier and are found in post-mortem brains of COVID patients, and 3) exhibit proinflammatory properties, we propose that SARS-CoV-2 antigens might play a role in the pathophysiology of Long COVID due to the long-term priming of innate immune proinflammatory processes.

 

[Eleanor]

Given that hypocortisolism is observed in Long COVID

is it though?

 

[Creekside]

The neuroinflammatory, physiological, and behavioral responses to LPS were measured at various time points post-LPS.

I wonder if anyone has tested the psychological and behavioral changes of lab animals that have been exposed to temporary "feel worse" treatments. If they associate "feeling worse" with eating--especially if they can taste the substance--or being injected or whatever, that would possibly affect their behavior in the future. I find it hard to place much trust in "the rats spend less time grooming their cagemates" type of findings.