Long-term cognitive dysfunction after the COVID-19 pandemic: a narrative review

Abstract

Introduction: SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has brought a conglomerate of novel chronic disabling conditions described as ‘Long COVID/Post-COVID-19 Syndrome’. Recent evidence suggests that the multifaceted nature of this syndrome results in both pulmonary and extrapulmonary sequelae,chronic dyspnoea, persistent fatigue, and cognitive dysfunction being the most common, debilitating symptoms. Several mechanisms engender or exacerbate cognitive impairment, including central nervous system and extra-central nervous system causes, although the exact mechanism remains unclear. Both hospitalized and non-hospitalized patients may suffer varying degrees of cognitive impairment, ranging from fatigue and brain fog to prolonged deficits in memory and attention, detrimental to the quality-of-life years post-recovery. The aim of this review is to understand the underlying mechanisms, associations, and attempts for prevention with early intervention of long-term cognitive impairment post-COVID-19. Methodology: A systematic search was conducted through multiple databases such as Medline, National Library of Medicine, Ovid, Scopus database to retrieve all the articles on the long-term sequalae of cognitive dysfunction after SARS-CoV-2 infection. The inclusion criteria included all articles pertinent to this specific topic and exclusion criteria subtracted studies pertaining to other aetiologies of cognitive dysfunction. This search was carefully screened for duplicates and the relevant information was extracted and analysed. Results/discussion: To date, the exact pathogenesis, and underlying mechanisms behind cognitive dysfunction in COVID-19, remain unclear, hindering the development of adequate management strategies. However, the proposed mechanisms suggested by various studies include direct damage to the blood-brain barrier, systemic inflammation, prolonged hypoxia, and extended intensive care admissions. However, no clear-cut guidelines for management are apparent. Conclusion: This review of the COVID-19 pandemic has elucidated a new global challenge which is affecting individuals’ quality of life by inducing long-term impaired cognitive function. The authors have found that comprehensive evaluations and interventions are crucial to address the cognitive sequelae in all COVID-19 patients, especially in patients with pre-existing cognitive impairment. Nevertheless, the authors recommend further research for the development of relevant, timely neurocognitive assessments and treatment plans.

SARS‐CoV‐2 induces blood‐brain barrier and choroid plexus barrier impairments and vascular inflammation in mice

“…5 For example, delayed verbal memory, impaired immediate verbal memory and learning, depression, and posttraumatic stress disorder symptoms were reported after 2 months following the infection, 6 and long-term cognitive dysfunctions were still seen at 7 months post-COVID. 7 The blood-brain barrier (BBB), situated at the interface between the circulation and brain parenchyma, is specialized to prevent the invasion of parasites, 8 bacterial, 9 and viral pathogens. 10,11 The BBB comprises the brain microvascular endothelial cells, which are sealed together by the tight junctions and reinforced by extracellular basement membrane structures, perivascular mural cells, as well as astrocytic end feet.…”

“…The neurological symptoms may persist long after infection, and develop into the Post‐acute Sequelae of COVID‐19 (PASC) 5 . For example, delayed verbal memory, impaired immediate verbal memory and learning, depression, and posttraumatic stress disorder symptoms were reported after 2 months following the infection, 6 and long‐term cognitive dysfunctions were still seen at 7 months post‐COVID 7 …”

Breaking through the noise: how to unveil the cognitive impact of long COVID on pre-existing conditions with executive dysfunctions?

“…In studies focused on the interplay of specific cognitive disorders with COVID-19, neurodegenerative dementia is the most actively studied, with parallels drawn from neuropathology to animal models ( 10 , 11 ). Recently, a detailed cognitive and neuroimaging evaluation of patients with pre-existing dementia, 1 year following SARS-CoV-2 infection, showed a worsening of cognitive symptoms with a specific pattern of decreased attention, executive dysfunctions, delayed information processing speed, mood changes, and memory impairment, indicating an underlying disruption of frontal subcortical networks ( 12 ).…”