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Review
. 2023 Sep-Oct;14(5):549-564.
doi: 10.32598/bcn.2022.3202.1. Epub 2023 Sep 1.

Probable Neuropsychological and Cognitive Complications Due to Cytokine Storm in Patients With COVID-19

Zahra Keshtgar  1 , Gholamreza Chalabianloo  2 , Niloofar Esmaeili  3
Affiliations
Review

Probable Neuropsychological and Cognitive Complications Due to Cytokine Storm in Patients With COVID-19

Zahra Keshtgar et al. Basic Clin Neurosci. 2023 Sep-Oct.

Abstract

Introduction: COVID-19 (coronavirus disease 2019) was first identified in China in December 2019 and is rapidly spreading worldwide as a pandemic. Since COVID-19 causes mild to severe acute respiratory syndrome, most studies in this context have focused on pathogenesis primarily in the respiratory system. However, evidence shows that the central nervous system (CNS) may also be affected by COVID-19. Since COVID-19 is spreading, it is necessary to study its possible cognitive effects on COVID-19 patients and their recovery.

Methods: The articles used in this study were searched by keywords, such as cytokine storm and COVID-19, COVID-19 and executive dysfunction, cognitive disorder, and COVID-19, central nervous system (CNS) and COVID-19, coronavirus, neuroinvasion in Science Direct, Scopus, PubMed, Embase, and Web of Science databases based on preferred reporting items for systematic reviews and meta-analysis (PRISMA) checklist. The study evaluates all observational studies published between December 2019 and April 2021 in peer-reviewed journals, including cross-sectional, cohort, case-control studies, case reports, and case series. The search result was 106 articles, of which 73 articles related to COVID-19, the stages of infection by this virus, its effect on the nervous system and neurological symptoms, the cytokine storm caused by this infection, and the possible cognitive consequences caused by this virus in patients, has been reviewed. Other articles were not checked due to their limited relevance to the topic under discussion.

Results: Studies showed that neurons may be directly affected by severe acute respiratory syndrome coronavirus (SARS-CoV)-1 and SARS-CoV-2. Furthermore, various studies indicated that systemic inflammation (so-called "cytokine storm") is also responsible for brain damage induced by infection with SARS-CoV-1 and SARS-CoV-2. In such a way that these patients showed elevated levels of interleukin (IL-), 6, 8, and 10 and of tumor necrosis factor-alpha (TNF-α) in their blood.

Conclusion: Various cognitive defects have been observed following an increased level of cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6, 8. Therefore, due to the increased level of these pro-inflammatory factors in the brains of these patients, cognitive deficits can be expected, which need further investigation.

Keywords: COVID-19; Cognitive impairments; Coronavirus; Cytokine storm; Neuroinvasin; Neuropsychological complications; Routes of dissemination.

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Conflict of interest statement

All authors declared no conflict of interest.

Figures

Figure 1.
Figure 1.
Cytokine storm in SARS-CoV-2 infection (Chen et al., 2019)
Figure 2.
Figure 2.
An overview of SARS-CoV-2 Infection effects on the body’s organs Note: Like the SARS-CoV-1 virus, the cellular receptor for SARS-CoV-2 is the ACE2 (Hoffmann et al., 2020), which is highly expressed in the olfactory bulb, eyes, heart, vascular, kidney (Harmer et al., 2002), liver, lung, and nasopharynx.
Figure 3.
Figure 3.
Different routes of cytokines release in severe COVID-19 patients through direct viral proliferation in infected cells (AEC2) or an indirect process involving neuro-immunopathology (Gu et al., 2005; Xu et al., 2005; Gue et al., 2008; Li et al., 2016b; Chen et al., 2019, Chen et al., 2020a
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