The Infected Lungs and Brain Interface in COVID-19: The Impact on Cognitive Function

Abstract

Many coronavirus disease 2019 (COVID-19)-recovered patients report signs and symptoms and are experiencing neurological, psychiatric, and cognitive problems. However, the exact prevalence and outcome of cognitive sequelae is unclear. Even though the severe acute respiratory syndrome coronavirus 2 has target brain cells through binding to angiotensin-converting enzyme 2 (ACE2) receptor in acute infection, several studies indicate the absence of the virus in the brain of many COVID-19 patients who developed neurological disorders. Thus, the COVID-19 mechanisms for stimulating cognitive dysfunction may include neuroinflammation, which is mediated by a sustained systemic inflammation, a disrupted brain barrier, and severe glial reactiveness, especially within the limbic system. This review explores the interplay of infected lungs and brain in COVID-19 and its impact on the cognitive function.

Peripheral inflammation and neurocognitive impairment: correlations, underlying mechanisms, and therapeutic implications

“…Compared to aging, chronic diseases (e.g., IBD and silicosis) are characterized by significantly different peripheral immune profiles, such as increased IL1β + DCs and monocytes, enrichment of γδ T-cell subsets, and up-regulated expression of HLA-DR, a marker of T-cell (CD3 + , CD4 + , and CD8 + ) activation ( Brilland et al, 2019 ; Boland et al, 2020 ; Mitsialis et al, 2020 ). Acute inflammatory stress also differs from chronic peripheral inflammation in the initial phase, the former is often accompanied by short-term exacerbations and intense immune cell activation, aggregation, and inflammatory storm formation, often with highly activated macrophages, neutrophils, and mast cells mediating activation of innate intrinsic immunity, e.g., COVID-19 and surgically-induced aseptic injury ( Joaquim et al, 2022 ; Bhuiyan et al, 2023 ). Some acute inflammatory events can be followed by transformation into chronic inflammatory processes, e.g., long COVID-19, with long-term neurocognitive effects ( Joaquim et al, 2022 ).…”

“…Acute inflammatory stress also differs from chronic peripheral inflammation in the initial phase, the former is often accompanied by short-term exacerbations and intense immune cell activation, aggregation, and inflammatory storm formation, often with highly activated macrophages, neutrophils, and mast cells mediating activation of innate intrinsic immunity, e.g., COVID-19 and surgically-induced aseptic injury ( Joaquim et al, 2022 ; Bhuiyan et al, 2023 ). Some acute inflammatory events can be followed by transformation into chronic inflammatory processes, e.g., long COVID-19, with long-term neurocognitive effects ( Joaquim et al, 2022 ). Unlike chronic inflammation, in acute inflammation, after the pathogen is removed or stress is blocked, damaged tissue is healed and the body’s inflammatory status and immunity returns to normal.…”

Exploring the Impact of Coronavirus Disease 2019 on Dementia: A Review

“…The virus causes microvascular changes or damage to lung function resulting in impaired flow of oxygen to the brain with subsequent impaired cognitive function. [43][44][45][46] COVID-19 has an additional risk dimension when it comes to Alzheimer's disease (AD), as COVID-19 has been shown to exacerbate the main pathological components of AD, such as beta-amyloid neurotoxicity and pathological tau accumulation. [47][48][49][50][51] It has also been suggested that COVID-19 might impair amyloid processing and mimic cerebrospinal fluid and serum biomarkers of AD, with decreased amyloid beta loads even in cognitively typical patients.…”

The importance of neuroendocrine immunology pathways in course of COVID-19

“…Furthermore, Joaquim and colleagues reviewed neurological manifestations of COVID-19 that included deficits in executive/visuospatial functions (i.e., rapid visual attention, immediate recall, information processing speed), working memory, verbal learning, language, orientation, and abstraction [8]. Interestingly, the authors highlighted how cognitive impairment was not linked only to the acute phase of SARS-CoV-2 infection.…”