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Review
. 2023 Jun:10:100074.
doi: 10.1016/j.dscb.2023.100074. Epub 2023 Apr 5.

COVID-19 delirium and encephalopathy: Pathophysiology assumed in the first 3 years of the ongoing pandemic

Kyohei Otani  1   2 , Haruko Fukushima  1 , Kunitaka Matsuishi  1
Affiliations
Review

COVID-19 delirium and encephalopathy: Pathophysiology assumed in the first 3 years of the ongoing pandemic

Kyohei Otani et al. Brain Disord. 2023 Jun.

Abstract

Background: The coronavirus disease (COVID-19) continues to spread worldwide. It has a high rate of delirium, even in young patients without comorbidities. Infected patients required isolation because of the high infectivity and virulence of COVID-19. The high prevalence of delirium in COVID-19 primarily results from encephalopathy and neuroinflammation caused by acute respiratory distress syndrome (ARDS)-associated cytokine storm. Acute respiratory distress syndrome has been linked to delirium and psychotic symptoms in the subacute phase (4 to 12 weeks), termed post-acute COVID-19 syndrome (PACS), and to brain fog, cognitive dysfunction, and fatigue, termed "long COVID," which persists beyond 12 weeks. However, no review article that mentions "COVID-19 delirium" have never been reported.

Basic procedures: This narrative review summarizes data on delirium associated with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and related neurological symptoms of persistent post-infection illness (PACS or long COVID) after persistence of cognitive dysfunction. Thus, we describe the pathophysiological hypothesis of COVID-19 delirium and its continuation as long COVID. This review also describes the treatment of delirium complicated by COVID-19 pneumonia.

Main findings: SARS-CoV-2 infection is associated with encephalopathy and delirium. An association between COVID-19 infection and Alzheimer's disease has been suggested, and studies are being conducted from multiple facets including genetics, cytology, and postmortem study.

Principal conclusions: This review suggests that COVID-19 has important short and long-term neuropsychiatric effects. Several hypotheses have been proposed that highlight potential neurobiological mechanisms as causal factors, including neuronal-inflammatory pathways by cytokine storm and cellular senescence, and chronic inflammation.

Keywords: COVID-19; Cognitive impairment; Delirium; Encephalopathy; Long COVID; microglia.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig 1
Fig. 1
The timeline from COVID-19-related encephalopathy or delirium (acute phase) to Past-acute COVID-19 syndrome (subacute phase) to long COVID (chronic phase).
Fig 2
Fig. 2
Inflammatory mechanisms in COVID-19 delirium. Cytokines are classified as interleukins (ILs), hematopoietic factors (colony-stimulating factor (CSF), erythropoietin (EPO), thrombopoietin (TPO)), interferons (IFN), tumor necrosis factors (TNF), growth factors (epidermal growth factor (EGF), fibroblast growth factor (FGF), prostaglandin E2(PDG2)), and chemokines (IL-8, CCL2, CXCL10 etc.).
See this image and copyright information in PMC

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