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

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)

 

In rats.