Biological and Psychological Factors Determining Neuropsychiatric Outcomes in COVID-19

Abstract

Purpose of Review We present biological and psychological factors implicated in psychiatric manifestations of SARS-CoV-2, as well as its neuroinvasive capability and immune pathophysiology. Recent Findings Preexisting mental illness leads to worse clinical outcomes in COVID-19. The presence of the virus was reported in the cerebrospinal fluid (CSF) and brain tissue post-mortem. Most common psychiatric manifestations include delirium, mood disorders, anxiety disorders, and posttraumatic stress disorder. “Long-COVID” non-syndromal presentations include “brain-fogginess,” autonomic instability, fatigue, and insomnia. Summary SARS-CoV-2 infection can trigger prior vulnerabilities based on the priming of microglia and other cells, induced or perpetuated by aging and mental and physical illnesses. COVID-19 could further induce priming of neuroimmunological substrates leading to exacerbated immune response and autoimmunity targeting structures in the central nervous system (CNS), in response to minor immune activating environmental exposures, including stress, minor infections, allergens, pollutants, and traumatic brain injury.

Alteration of the blood-brain barrier by COVID-19 and its implication in the permeation of drugs into the brain

“…SARS-CoV-2 is a positive-sense, single-stranded RNA virus with a spherical and spiked protein envelope of about 60-140 nm, belonging to the betacoronavirus genus ( Welcome and Mastorakis, 2021 ). Among the main structural proteins, there is the spike (S) glycoprotein, which is a type I transmembrane protein, composed of the S1 subunit responsible for binding to the receptor on the surface of the host cell and the S2 subunit responsible for the fusion of membranes and viral penetration ( Tizenberg et al, 2021 ; Takeda, 2022 ). SARS-CoV-1 and SARS-CoV-2 share 79% identity with each other ( Lu et al, 2020 ; Chen Z. et al, 2021 ); however, SARS-CoV-2 has shown higher binding affinity to human angiotensin-converting enzyme 2 (ACE2), which has been identified as the primary mechanism of cellular infection ( Tizenberg et al, 2021 ).…”

Rationale, design, and methods: A randomized placebo-controlled trial of an immunomodulatory probiotic intervention for Veterans with PTSD

“…Moreover, efforts outlined as part of this clinical trial are aimed at increasing understanding regarding inflammation, the gut microbiome, autonomic functioning (i.e., HRV), and PTSD symptoms. Such knowledge is expected to highlight multiple potential interventions for PTSD, as well as other mental health-related conditions that involve inappropriate inflammation and dysregulated autonomic function, for example long-COVID [ 61 ]. Also of note, Reber et al recently completed an animal study in which mice were treated with a heat-killed preparation of an immunoregulatory environmental microorganism, Mycobacterium vaccae NCTC 11659 [ 62 ].…”

Neurogenic Interventions for Fear Memory via Modulation of the Hippocampal Function and Neural Circuits

“…Previous studies have demonstrated that upregulated responsivity of the amygdala and ACC reduces the responsiveness of the mPFC and the hippocampal function. A recent case study has reported that healthcare workers, veterans, and children may currently be particularly vulnerable to PTSD and stress- or fear-related disorders due to the COVID-19 pandemic [ 98 ]. In addition, there have been reports of successful cases of anxiety and stress relief by prescribing therapeutic drugs to such individuals [ 99 , 100 ].…”