Delirium and neuropsychological outcomes in critically Ill patients with COVID-19: a cohort study

Ragheb, Jacqueline; McKinney, Amy; Zierau, Mackenzie; Brooks, Joseph; Hill-Caruthers, Maria; Iskander, Mina; Ahmed, Yusuf; Lobo, Remy; Mentz, Graciela; Vlisides, Phillip E.

doi:10.1136/bmjopen-2021-050045

Cited by 31 publications

(29 citation statements)

References 47 publications

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“…Supporting this concept, ∼70% of intensive care unit COVID-19 patients presented delirium symptoms that were likely connected to the underlying anti-cholinergic mechanisms [ 123 ], and associated with neuropsychological impairments. These symptoms lasted several months after discharge, based on data collected from a single-center cohort that supported previous findings of higher delirium incidence in critically ill patients with COVID-19 [ 126 ]. Further, COVID-19-induced delirium was correlated to the higher inflammatory response and 70% of COVID-19 patients with delirium were females [ 126 ].…”

Section: Future Prospects For Elucidating Post-covid Attention Defici...supporting

confidence: 85%

“…These symptoms lasted several months after discharge, based on data collected from a single-center cohort that supported previous findings of higher delirium incidence in critically ill patients with COVID-19 [ 126 ]. Further, COVID-19-induced delirium was correlated to the higher inflammatory response and 70% of COVID-19 patients with delirium were females [ 126 ]. This adds up to the consistent reports of increased risk of dementia in aged patients under long-term anticholinergic medications [ 88 ].…”

Section: Future Prospects For Elucidating Post-covid Attention Defici...supporting

confidence: 85%

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Cholinergic blockade of neuroinflammation: from tissue to RNA regulators

2022

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Inflammatory stimuli and consequent pro-inflammatory immune responses may facilitate neurodegeneration and threaten survival following pathogen infection or trauma, but potential controllers preventing these risks are incompletely understood. Here, we argue that small RNA regulators of acetylcholine (ACh) signaling, including microRNAs and transfer RNA fragments may tilt the balance between innate and adaptive immunity, avoid chronic inflammation and prevent the neuroinflammation-mediated exacerbation of many neurological diseases. While the restrictive permeability of the blood-brain barrier protects the brain from peripheral immune events, this barrier can be disrupted by inflammation and is weakened with age. The consequently dysregulated balance between pro- and anti-inflammatory processes may modify the immune activities of brain microglia, astrocytes, perivascular macrophages, oligodendrocytes and dendritic cells, leading to neuronal damage. Notably, the vagus nerve mediates the peripheral cholinergic anti-inflammatory reflex and underlines the consistent control of body-brain inflammation by pro-inflammatory cytokines, which affect cholinergic functions; therefore, the disruption of this reflex can exacerbate cognitive impairments such as attention deficits and delirium. RNA regulators can contribute to re-balancing the cholinergic network and avoiding its chronic deterioration, and their activities may differ between men and women and/or wear off with age. This can lead to hypersensitivity of aged patients to inflammation and higher risks of neuroinflammatory-driven cholinergic impairments such as delirium and dementia following COVID-19 infection. The age- and sex-driven differences in post-transcriptional RNA regulators of cholinergic elements may hence indicate new personalized therapeutic options for neuroinflammatory diseases.

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Section: Future Prospects For Elucidating Post-covid Attention Defici...supporting

confidence: 85%

Section: Future Prospects For Elucidating Post-covid Attention Defici...supporting

confidence: 85%

Cholinergic blockade of neuroinflammation: from tissue to RNA regulators

2022

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“…Studies have found that 30% to 51.8% of critically ill COVID-19 patients had at least one episode of hyperactive delirium, which is substantially higher than the pre-pandemic incidence of 12.7% in critically ill patients [50,54,55]. The reason behind this high rate of agitation in COVID-19 patients is unclear; this could be related to the greater severity of COVID-19 lung injury and higher levels of ventilatory support, the frequent use of prone positioning, a relatively higher incidence of young individuals needing critical care during early COVID-19 surges, crisis staffing with providers less experienced in effective sedation management, decreased family visitation, or perhaps biological mechanisms unique to SARS-CoV-2 infection [50,[55][56][57][58].…”

Section: Epidemiology and Presentationmentioning

confidence: 99%

Therapeutic Approaches to the Neurologic Manifestations of COVID-19

2022

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As of May 2022, there have been more than 527 million infections with severe acute respiratory disease coronavirus type 2 (SARS-CoV-2) and over 6.2 million deaths from Coronavirus Disease 2019 (COVID-19) worldwide. COVID-19 is a multisystem illness with important neurologic consequences that impact long-term morbidity and mortality. In the acutely ill, the neurologic manifestations of COVID-19 can include distressing but relatively benign symptoms such as headache, myalgias, and anosmia; however, entities such as encephalopathy, stroke, seizures, encephalitis, and Guillain-Barre Syndrome can cause neurologic injury and resulting disability that persists long after the acute pulmonary illness. Furthermore, as many as one-third of patients may experience persistent neurologic symptoms as part of a Post-Acute Sequelae of SARS-CoV-2 infection (Neuro-PASC) syndrome. This Neuro-PASC syndrome can affect patients who required hospitalization for COVID-19 or patients who did not require hospitalization and who may have had minor or no pulmonary symptoms. Given the large number of individuals affected and the ability of neurologic complications to impair quality of life and productivity, the neurologic manifestations of COVID-19 are likely to have major and long-lasting personal, public health, and economic consequences. While knowledge of disease mechanisms and therapies acquired prior to the pandemic can inform us on how to manage patients with the neurologic manifestations of COVID-19, there is a critical need for improved understanding of specific COVID-19 disease mechanisms and development of therapies that target the neurologic morbidities of COVID-19. This current perspective reviews evidence for proposed disease mechanisms as they inform the neurologic management of COVID-19 in adult patients while also identifying areas in need of further research.

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“…In critically ill patients, delirium is associated with a higher mortality independently from the severity of the main underlying disease and of the preexisting individual risk factors ( 12 ). Studies on large cohorts of ICUs patients have reported delirium to be highly prevalent and prolonged ( 15 ) with patients also showing persistent neuropsychological dysfunctions even after discharge ( 16 ). However, delirium is highly prevalent in mechanically ventilated patients ( 17 ), even though delirium rate in ICU seems to be declining in recent years ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

Factors Associated With Severity of Delirium Complicating COVID-19 in Intensive Care Units

et al. 2022

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The clinical outcome of the disease provoked by the SARS-CoV-2 infection, COVID-19, is largely due to the development of interstitial pneumonia accompanied by an Acute Respiratory Distress Syndrome (ARDS), often requiring ventilatory support therapy in Intensive Care Units (ICUs). Current epidemiologic evidence is demonstrating that the COVID-19 prognosis is significantly influenced by its acute complications. Among these, delirium figures as one of the most frequent and severe, especially in the emergency setting, where it shows a significantly negative prognostic impact. In this regard, the aim of our study is to identify clinical severity factors of delirium complicating COVID-19 related-ARDS. We performed a comparative and correlation analysis using demographics, comorbidities, multisystemic and delirium severity scores and anti-delirium therapy in two cohorts of ARDS patients with delirium, respectively, due to COVID-19 (n = 40) or other medical conditions (n = 39). Our results indicate that delirium in COVID-19-related ARDS is more severe since its onset despite a relatively less severe systemic condition at the point of ICU admission and required higher dosages of antipsychotic and non-benzodiazepinic sedative therapy respect to non-COVID patients. Finally, the correlation analysis showed a direct association between the male gender and maximum dosage of anti-delirium medications needed within the COVID-19 group, which was taken as a surrogate of delirium severity. Overall, our results seem to indicate that pathogenetic factors specifically associated to severe COVID-19 are responsible for the high severity of delirium, paving the way for future research focused on the mechanisms of the cognitive alterations associated with COVID-19.

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Delirium and neuropsychological outcomes in critically Ill patients with COVID-19: a cohort study

Cited by 31 publications

References 47 publications

Cholinergic blockade of neuroinflammation: from tissue to RNA regulators

Cholinergic blockade of neuroinflammation: from tissue to RNA regulators

Therapeutic Approaches to the Neurologic Manifestations of COVID-19

Factors Associated With Severity of Delirium Complicating COVID-19 in Intensive Care Units

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