Abstract
Background: Critical illness with COVID-19 is associated with increased delirium duration and severity, and delirium is associated with poor health outcomes. The pathophysiology of delirium in this population is not well understood but neuroinflammation is hypothesized to play a key role.
 Objective: To evaluate the relationship between biomarkers of systemic inflammation and delirium in critically ill patients with COVID-19.
 Design: Observational retrospective data extraction study from March 1, 2020 – June 7, 2020. Biomarker levels and delirium occurrence were assessed up to the first 14 days in the intensive care unit (ICU).
 Setting: Two large, urban, academic referral hospitals in Indianapolis, IN
 Patients: Two hundred thirty-five patients admitted to the ICU with a positive SARS-Co-V2 PCR test
 Methods and Main Results: A total of 235 consecutive patients admitted to the ICU were included in the analysis. The cohort had a mean age of 58.6 years (SD: 15.4), 43.4% were female, 45.9% were African American, with median Acute Physiology and Chronic Evaluation-II score of 18.0 (IQR: 13.0 -15.0). Delirium occurred in 176 (79.1%). Increased levels of C-Reactive Protein (CRP) were associated with increased odds of delirium and coma (OR: 1.27, 95% CI: 1.08, 1.49, p=0.004). Increased levels of D-dimer were not associated with increased odds of delirium/coma (OR: 0.94, 95% CI 0.76, 1.16, p=0.574). Increased levels of ferritin (OR: 1.04, 95% CI 0.84, 1.29, p=0.717) and lactate dehydrogenase (LDH) were also not associated with increased odds of delirium/coma (OR: 0.86, 95% CI 0.70, 1.06, p=0.149). Elevated levels of creatine kinase (CK) levels were associated with lower odds of delirium/coma (OR: 0.71 95% CI 0.52, 0.97, p=0.033).
 Conclusion: Increased levels of biomarkers of inflammation and thrombosis were associated with greater odds of delirium and coma. Further studies are needed to validate these results in a larger population.
 “This project was funded, in part, with support from the NIH NHLBI Short-Term Training Program in Biomedical Sciences Grantfunded, in part by T35HL110854 from the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.”
Highlights
1Indiana University School of Medicine, 2Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Department of Medicine, Indiana University School of Medicine, 3Department of Biostatistics, Indiana University School of Medicine, 4 Eskenazi Hospital Critical Care Recovery Center, Division of Pulmonary and Critical Care, Indiana University School of Background: Critical illness with COVID-19 is associated with increased delirium duration and severity, and delirium is associated with poor health outcomes
Increased levels of CReactive Protein (CRP) were associated with increased odds of delirium and coma (OR: 1.27, 95% CI: 1.08, 1.49, p=0.004)
Increased levels of D-dimer were not associated with increased odds of delirium/coma (OR: 0.94, 95% CI 0.76, 1.16, p=0.574)
Summary
Critical illness with COVID-19 is associated with increased delirium duration and severity, and delirium is associated with poor health outcomes. The pathophysiology of delirium in this population is not well understood but neuroinflammation is hypothesized to play a key role
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