SARS-CoV-2 Psychiatric Sequelae: A Review of Neuroendocrine Mechanisms and Therapeutic Strategies

Abstract

From the earliest days of the COVID-19 pandemic, there have been reports of significant neurological and psychological symptoms following SARS-CoV-2 infection. This narrative review is designed to examine the potential psychoneuroendocrine pathogenic mechanisms by which SARS-CoV-2 elicits psychiatric sequelae, as well as to posit potential pharmacologic strategies to address and reverse these pathologies. Following a brief overview of neurological and psychological sequelae from previous viral pandemics, we address mechanisms by which SARS-CoV-2 could enter or otherwise elicit changes in the CNS. We then examine the hypothesis that COVID-19-induced psychiatric disorders result from challenges to the neuroendocrine system, in particular the hypothalamic-pituitary-adrenal (HPA) stress axis and monoamine synthesis, physiological mechanisms that are only further enhanced by the pandemic-induced social environment of fear, isolation, and socioeconomic pressure. Finally, we evaluate several FDA-approved therapeutics in the context of COVID-19-induced psychoneuroendocrine disorders.

COVID-19 Vaccine-Associated Transient Global Amnesia: A Disproportionality Analysis of the WHO Safety Database

“…( Inzitari, 2005 ). In addition, during the pandemic, COVID-19 infection itself, ( Werner et al, 2020 ; Hornick et al, 2022 ), increased stress induced by social distancing, uncertainty concerning the future, and the fear of getting infected could trigger TGA. ( Ramanathan and Wachsman, 2021 ).…”

“…An increased incidence of TGA has been suggested since the beginning of the COVID-19 pandemic, but still has to be confirmed, pertaining to COVID-19 infection itself or the stress induced by the constraints endured by the population. ( Werner et al, 2020 ; Ramanathan and Wachsman, 2021 ; Hornick et al, 2022 ). Yet, the association of TGA with various drugs (e.g.…”

Biobehavioral Implications of Covid-19 for Transplantation and Cellular Therapy Recipients

“…The Covid-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has claimed the lives of over 5 ½ million people worldwide as of January 28 th , 2022 ( 1 , 2 ). Resulting public health measures have significantly altered the social environment, increasing social isolation and feelings of loneliness ( 2 ). The pandemic has also precipitated economic hardship and financial strife ( 3 ).…”

“…They are already vulnerable due to their intense treatment regimens accompanied by prolonged hospitalizations, high risk of medical complications, and immediate and long-term medical comorbidities ( 6 , 7 ). TCT recipients also have heightened risk for clinically significant distress and poor psychological function due to pandemic conditions ( 2 , 8 , 9 ).…”

“…Both psychological stress and viral infection can disrupt the HPA system and affect fatigue and sleep disruption directly through alternations in cortisol or indirectly via modulation of immune pathways ( 2 , 10 , 76 ). Further, HPA axis dysregulation and inflammatory processes can disrupt circadian rhythms, which has been linked to poor QOL among HCT recipients ( 77 ) and heightened fatigue and sleep disruption among other cancer populations ( 78 ).…”