A study on mice infected with a SARS-CoV-2 variant that does not infect the brain reveals persistent neurological deficits, suggesting that these may be similar to neurodegenerative diseases. The research shows that even after recovery from nasal infection, mice exhibit reduced tyrosine hydroxylase (TH) expression in the olfactory bulb and decreased neurotransmitter levels in the substantia nigra. These changes are accompanied by increased pro-inflammatory cytokines and neurobehavioral changes. RNA sequencing indicates persistent microglia activation, similar to human neurodegenerative diseases. Antiviral treatments reduced viral load and lung inflammation but did not prevent neurological abnormalities. The study also found decreased TH expression in the substantia nigra of deceased COVID-19 patients, suggesting a link between SARS-CoV-2 infection and neurodegenerative processes. The findings indicate that chronic inflammation may contribute to long-term neurological dysfunction, highlighting the complex role of the immune response in post-acute sequelae of COVID-19.A study on mice infected with a SARS-CoV-2 variant that does not infect the brain reveals persistent neurological deficits, suggesting that these may be similar to neurodegenerative diseases. The research shows that even after recovery from nasal infection, mice exhibit reduced tyrosine hydroxylase (TH) expression in the olfactory bulb and decreased neurotransmitter levels in the substantia nigra. These changes are accompanied by increased pro-inflammatory cytokines and neurobehavioral changes. RNA sequencing indicates persistent microglia activation, similar to human neurodegenerative diseases. Antiviral treatments reduced viral load and lung inflammation but did not prevent neurological abnormalities. The study also found decreased TH expression in the substantia nigra of deceased COVID-19 patients, suggesting a link between SARS-CoV-2 infection and neurodegenerative processes. The findings indicate that chronic inflammation may contribute to long-term neurological dysfunction, highlighting the complex role of the immune response in post-acute sequelae of COVID-19.