(Kiosk 3) Case Studies Suggesting Multifactorial Etiology for Delirium in COVID-19 Encephalopathy

Case Diagnosis: Delirium secondary to COVID-19 has been observed in 70-80% of patients admitted to the ICU.

Case Description or Program Description: Patient A underwent mechanical ventilation and sedation, patient B did not receive either intervention. Patient A demonstrated an elevated neutrophil-predominant NLR at delirium onset which peaked during symptom course, then downtrended at delirium resolution. Additional findings include hyponatremia prior to delirium onset with improvement at resolution, although a weak association with clinical presentation. For Patient B, the NLR was lower at delirium onset then peaked to even higher levels at delirium resolution. Additional findings include hypernatremia with closer association to symptoms, elevated C-reactive protein, and elevated interleukin-6.

Setting: Acute inpatient rehabilitation

Assessment/Results: While NLR in patient A demonstrated a positive correlation with delirium onset to suggest neutrophil-mediated neuronal inflammation, patient B findings suggest an alternative mechanism for pathophysiology of COVID-19 delirium which may involve other mediators including metabolic derangements, cytokine activation, and platelet-derived factors.

Discussion (relevance): Initial hypothesis for central nervous system (CNS) involvement suggested neuronal and/or hematogenous viral dissemination with secondary contributors including hypoxemia, inflammation, hypercoagulability, medications, and immobility. The pathophysiology of delirium in COVID-19 is poorly understood, however it coincides with severity of disease and mechanical ventilation with sedation. Complications of COVID-19 are risk factors for delirium such as respiratory failure and infection, systemic organ dysfunction, and disseminated intravascular coagulation. Neutrophil-to-lymphocyte ratio (NLR) has shown to have predictive value for need to intubate, outcome measures, and risk of delirium. Here, we present two patients where the first case demonstrates a close association between delirium and NLR, while the second case follows an alternative pattern which may implicate a multifactorial etiology for COVID-19 delirium.

Conclusions: Delirium is associated with increased length of hospital stay, and significant morbidity and mortality in patients with COVID-19. Our case studies support a hypothesis that pathophysiology of COVID-19 delirium is likely a multifactorial process.