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. 2023 Jan 18;5(1):e0851.
doi: 10.1097/CCE.0000000000000851. eCollection 2023 Jan.

Relationship Among Clinically Obtained Biomarkers of Inflammation, Hypercoagulability, and Macrophage Activation, and Delirium in Critically Ill Patients With COVID-19

Sikandar H Khan  1   2 , Anthony J Perkins  3 , Rosalyn Chi  1 , Sarah Seyffert  1 , Peter Conrad  4 , Heidi Lindroth  5 , Sophia Wang  6 , Malissa Mulkey  7 , Sujuan Gao  3 , Babar Khan  1   2
Affiliations

Relationship Among Clinically Obtained Biomarkers of Inflammation, Hypercoagulability, and Macrophage Activation, and Delirium in Critically Ill Patients With COVID-19

Sikandar H Khan et al. Crit Care Explor. .

Abstract

Critically ill patients with COVID-19 experience high rates of delirium and coma. Whether delirium occurs through novel mechanisms in COVID-19 is not known. We analyzed the relationship among biomarkers of inflammation (C-reactive protein [CRP]), hypercoagulability (d-dimer), and lung macrophage activation (ferritin), and the primary composite outcome of delirium/coma next day. We also measured associations between biomarkers and next day delirium and coma independently, and delirium severity.

Design: Retrospective, observational cohort study.

Setting: ICUs at two large, urban, academic referral hospitals.

Patients: All consecutive adult patients admitted to the ICU from March 1, 2020, to June 7, 2020, with COVID-19 with clinical biomarkers and delirium assessments performed.

Interventions: None.

Measurements and main results: Daily concentrations of CRP, d-dimer, and ferritin were obtained. Coma (assessed by Richmond Agitation-Sedation Scale) and delirium (assessed by Confusion Assessment Method for the ICU/Confusion Assessment Method for the ICU-7) were measured bid. A cohort of 197 ICU patients with COVID-19 were included. Higher d-dimer (odds ratio [OR], 1.57; 95% CI, 1.17-2.12; p < 0.01) and ferritin quartiles (OR, 1.36; 95% CI, 1.02-1.81; p < 0.01) were associated with greater odds of the composite outcome of delirium/coma next day. d-dimer was associated with greater odds of next day delirium (OR, 1.49; 95% CI, 1.14-1.94; p < 0.01) and coma independently (OR, 1.52; 95% CI, 1.08-2.14; p = 0.017). Higher ferritin quartiles were associated with greater odds of next day delirium (OR, 1.33; 95% CI, 1.04-1.70; p = 0.026) and coma independently (OR, 1.59; 95% CI, 1.14-2.23; p < 0.01). Higher CRP quartiles were associated with coma (OR, 1.36; 95% CI, 1.03-1.79; p = 0.030) and delirium severity the next day (β = 0.30; se, 0.07; p ≤ 0.01).

Conclusions: Our hypothesis-generating study found d-dimer and ferritin were associated with delirium/coma the following day, as well as delirium and coma independently. CRP was associated with next day coma and delirium severity. Larger studies to validate these results are needed.

Keywords: COVID-19; biomarkers; coma; critical care; delirium; delirium severity.

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Conflict of interest statement

Dr. S. H. Khan is supported by the National Institute on Aging (K76AG074925). Dr. Wang is supported by the National Institute of Aging (K23 AG062555-03 and P30AG072976-01). Dr. Lindroth is supported by National Institute on Aging (K23AG076662). Dr. B. Khan is supported by the National Institute on Aging (K23AG043476). The remaining authors have disclosed that they do not have any potential conflicts of interest.

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References

    1. Auld SC, Harrington KRV, Adelman MW, et al. : Trends in ICU mortality from coronavirus disease 2019: A tale of three surges. Crit Care Med 2022; 50:245–255 - PMC - PubMed
    1. Carbonell R, Urgeles S, Rodriguez A, et al. : Mortality comparison between the first and second/third waves among 3,795 critical COVID-19 patients with pneumonia admitted to the ICU: A multicentre retrospective cohort study. Lancet Reg Health Eur 2021; 11:100243. - PMC - PubMed
    1. Twigg HL, 3rd, Khan SH, Perkins AJ, et al. : Mortality rates in a diverse cohort of mechanically ventilated patients with novel coronavirus in the urban Midwest. Crit Care Explor 2020; 2:e0187. - PMC - PubMed
    1. Desai AD, Lavelle M, Boursiquot BC, et al. : Long-term complications of COVID-19. Am J Physiol Cell Physiol 2022; 322:C1–C11 - PMC - PubMed
    1. Jin Y, Ji W, Yang H, et al. : Endothelial activation and dysfunction in COVID-19: From basic mechanisms to potential therapeutic approaches. Signal Transduct Target Ther 2020; 5:293. - PMC - PubMed