Neurocircuitry hypothesis and clinical experience treating neuropsychiatric symptoms of post-acute sequelae of SARS-CoV-2 (PASC).

Persistent symptoms following COVID-19 infection have been termed post-acute sequelae of SARS-CoV-2 infection (PASC). Many of these symptoms are neuropsychiatric, such as inattention, impaired memory, and executive dysfunction; these are often colloquially termed "brain fog". These symptoms are common and often persist long after the acute phase. The pattern of these deficits combined with laboratory, neuroimaging, electroencephalographic and neuropsychological data suggest that these symptoms may be driven by direct and indirect damage to the frontal-subcortical neural networks. Here, we review this evidence, share our clinical experience at an academic medical center, and discuss potential treatment implications. While the exact etiology remains unknown, a neurocircuit-informed understanding of PASC can help guide pharmacology, neuromodulation, physical and psychological therapeutic approaches.