SARS-COV-2-DRIVEN EPIDERMAL GROWTH FACTOR RECEPTOR SIGNALING AND THE COVID19-ASSCOCIATED PSYCHOSIS/SCHIZOPHRENIA

Abstract Background COVID-19 presents a wide range of symptoms, including respiratory issues and, intriguingly, neurological and psychiatric manifestations such as delirium and psychosis as well. Pathological studies reveal that the cytokine storm, particularly involving the activation of the epidermal growth factor receptor (EGFR), plays a crucial role in viral replication and the development of lung fibrosis. Notably, the spike domain of SARS-CoV-2 mimics EGF and directly triggers EGFR activation before inflammation occurs, suggesting new therapeutic options involving anti-EGFR kinase inhibitors to combat COVID-19 fibrosis. However, this finding regarding the biological activity of the spike protein also raises concerns about current and future psychiatric disorders associated with COVID-19. Method Recombinant EGF or SARS-CoV-2 spike protein is subcutaneously administered to neonatal mice, hamsters, and rats during their postnatal period. After 2-3 months, these animals undergo neurobehavioral tests and physiological recordings with institutional authorization. Results We are exploring the connections between EGFR signaling and schizophrenia, revealing significant molecular associations of the EGFR system in the blood and brain tissue of patients. Animal models exposed to EGF or the other EGFR ligands during perinatal stages exhibit various behavioral endophenotypes relevant to schizophrenia, including abnormalities in ASSR, d/fMMN, P300, ABR, and frontotemporal connectivity. The animal models also exhibit behavioral changes, especially an increase in dopaminergic activity post-puberty and neuronal hyperactivity in the auditory cortex, correlating with the onset of their behavioral impairments. Discussion & Conclusion This comprehensive discussion with the EGF animal model delves into the neuropsychiatric implications of prognostic symptoms of COVID-19 and their interaction with the EGFR system. However, the severity and prevalence of neurological/ psychiatric symptoms vary among COVID- 19 patients, and not all individuals with the virus experience CNS involvement. Further studies will help clarify the role of EGFR signaling in psychiatric symptoms and consequences in the context of COVID-19.