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Brain Fog: a Narrative Review of the Most Common Mysterious Cognitive Disorder in COVID-19

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Abstract

It has been more than three years since COVID-19 impacted the lives of millions of people, many of whom suffer from long-term effects known as long-haulers. Notwithstanding multiorgan complaints in long-haulers, signs and symptoms associated with cognitive characteristics commonly known as “brain fog” occur in COVID patients over 50, women, obesity, and asthma at excessive. Brain fog is a set of symptoms that include cognitive impairment, inability to concentrate and multitask, and short-term and long-term memory loss. Of course, brain fog contributes to high levels of anxiety and stress, necessitating an empathetic response to this group of COVID patients. Although the etiology of brain fog in COVID-19 is currently unknown, regarding the mechanisms of pathogenesis, the following hypotheses exist: activation of astrocytes and microglia to release pro-inflammatory cytokines, aggregation of tau protein, and COVID-19 entry in the brain can trigger an autoimmune reaction. There are currently no specific tests to detect brain fog or any specific cognitive rehabilitation methods. However, a healthy lifestyle can help reduce symptoms to some extent, and symptom-based clinical management is also well suited to minimize brain fog side effects in COVID-19 patients. Therefore, this review discusses mechanisms of SARS-CoV-2 pathogenesis that may contribute to brain fog, as well as some approaches to providing therapies that may help COVID-19 patients avoid annoying brain fog symptoms.

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Abbreviations

ACE2:

Angiotensin-converting enzyme 2

AD:

Alzheimer’s disease

ANA:

Antinuclear antibodies

ANCA:

Antineutrophil cytoplasmic antibodies

AOSD:

Adult-onset Still’s disease

ASD:

Autism spectrum disorders

BBB:

Blood-brain barrier

CA:

Carnosic acid

CFS:

Chronic fatigue syndrome

CNS:

Central nervous system

COVID-19:

Coronavirus disease 2019

ED:

Emergency department

DSF:

Disulfiram

FTD:

Frontotemporal dementia

GPX1:

Glutathione peroxidase 1

GSH:

Glutathione

GSTM1:

Glutathione S-transferase mu 1

IIM:

Idiopathic inflammatory myopathies

KEAP1:

Kelch-like ECH-associated protein 1

MC:

Mast cell

nEVs:

Neuron-enriched extracellular vesicles

NF-κβ:

Nuclear factor kappa beta

NFL:

Neurofilament light chain

NLRP3:

NLR family pyrin domain–containing 3

NRF2:

Nuclear factor erythroid-related factor 2

NRP1:

Neuropilin-1

OCR:

Oxygen consumption rate

OPC:

Oligodendrocyte progenitor cells

POTS:

Postural orthostatic tachycardia syndrome

ROS:

Reactive oxygen species

SARS-CoV-2:

Severe acute respiratory syndrome coronavirus 2

SLE:

Systemic lupus erythematosus

SM:

Systemic mastocytosis

SOD:

Superoxide dismutase

SR:

Coronavirus spike protein receptor

THT:

Thioflavin T aggregation assay

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  1. Deputy of Research and Technology, Babol University of Medical Sciences, Babol, Iran

    Mahsa Aghajani Mir

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Aghajani Mir, M. Brain Fog: a Narrative Review of the Most Common Mysterious Cognitive Disorder in COVID-19. Mol Neurobiol (2023). https://doi.org/10.1007/s12035-023-03715-y

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