Biological correlates of the neuropsychiatric symptoms in SARS-CoV-2 infection: an updated review

Abstract

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) appeared in early 2019 and swiftly became a pandemic causing extensive morbidity and mortality. Many studies have recognized the neuropathological changes in the brain and hypothesized the possible link with cognitive dysfunction, neuropsychiatric symptoms and behavioral disturbances. Potential biological mechanisms may include direct neuronal micro-invasion, disturbances in the neuro-immuno-endocrine system and possibly alteration of neuronal excitability. SARS-CoV-2 facilitates down-regulation of the ACE2 (Angiotensin-2) receptors which could alter inflammatory response through various cellular and neurophysiological systems leading to disturbance in the hypo-thalamopituitary–adrenal (HPA) axis, escalation of the oxidative stress and disruption of the homeostasis of the neurotransmitter system, including serotonin, dopamine and GABA (gamma-aminobutyric acid), eventually resulting in the emergence of neuropsychiatric symptoms. Psychiatric symptoms that emerged are many, some of which may be unique to SARS-CoV-2 infection. These neuropsychiatric symptoms are acute or chronic with possibly distinct etiopathogenesis. This article discusses the possible biological correlates and neurobiology of the psychiatric symptoms of SARS-CoV-2 and their impact on the brain and behavior.