COVID-19-Related Delirium Associated with Increased Length of Stay and Mortality
Abstract
1. Introduction
2. Materials and Methods
2.1. Delirium Screening and Determination
2.2. Statistical Analysis
2.3. Primary Outcomes
3. Results
3.1. Baseline Characteristics
3.2. Higher Delirium Rates in COVID-19 Patients
3.3. Association of Delirium with Mortality
3.4. Association of Delirium with Length of Stay
3.5. Association of COVID-19 and Delirium with Mortality
4. Discussion
4.1. Effects of COVID-19 and Delirium on Mortality
4.2. Effects of COVID-19 and Delirium on Length of Stay
4.3. Strengths and Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Mohandas, S.; Jagannathan, P.; Henrich, T.J.; Sherif, Z.A.; Bime, C.; Quinlan, E.; Portman, M.A.; Gennaro, M.; Rehman, J.; RECOVER Mechanistic Pathways Task Force. Immune mechanisms underlying COVID-19 pathology and post-acute sequelae of SARS-CoV-2 infection (PASC). eLife 2023, 12, e86014. [Google Scholar] [CrossRef]
- Davitt, E.; Davitt, C.; Mazer, M.B.; Areti, S.S.; Hotchkiss, R.S.; Remy, K.E. COVID-19 disease and immune dysregulation. Best Pract. Res. Clin. Haematol. 2022, 35, 101401. [Google Scholar] [CrossRef]
- Weatherhead, J.E.; Clark, E.; Vogel, T.P.; Atmar, R.L.; Kulkarni, P.A. Inflammatory syndromes associated with SARS-CoV-2 infection: Dysregulation of the immune response across the age spectrum. J. Clin. Investig. 2020, 130, 6194–6197. [Google Scholar] [CrossRef]
- Manjili, R.H.; Zarei, M.; Habibi, M.; Manjili, M.H. COVID-19 as an Acute Inflammatory Disease. J. Immunol. 2020, 205, 12–19. [Google Scholar] [CrossRef] [PubMed]
- Mavraganis, G.; Dimopoulou, M.-A.; Delialis, D.; Bampatsias, D.; Patras, R.; Sianis, A.; Maneta, E.; Stamatelopoulos, K.; Georgiopoulos, G. Clinical implications of vascular dysfunction in acute and convalescent COVID-19: A systematic review. Eur. J. Clin. Investig. 2022, 52, e13859. [Google Scholar] [CrossRef] [PubMed]
- Sullivan, B.N.; Fischer, T. Age-Associated Neurological Complications of COVID-19: A Systematic Review and Meta-Analysis. Front. Aging Neurosci. 2021, 13, 653694. [Google Scholar] [CrossRef] [PubMed]
- Tyson, B.; Shahein, A.; Erdodi, L.; Tyson, L.; Tyson, R.; Ghomi, R.; Agarwal, P. Delirium as a Presenting Symptom of COVID-19. Cogn. Behav. Neurol. 2022, 35, 123–129. [Google Scholar] [CrossRef]
- Martins, S.; Fernandes, L. Delirium in elderly people: A review. Front. Neurol. 2012, 3, 101. [Google Scholar] [CrossRef]
- Cunningham, C. Systemic inflammation and delirium: Important co-factors in the progression of dementia. Biochem. Soc. Trans. 2011, 39, 945–953. [Google Scholar] [CrossRef]
- Simone, M.J.; Tan, Z.S. The role of inflammation in the pathogenesis of delirium and dementia in older adults: A review. CNS Neurosci. Ther. 2011, 17, 506–513. [Google Scholar] [CrossRef]
- Kaushik, R.; McAvay, G.J.; Murphy, T.E.; Acampora, D.; Araujo, K.; Charpentier, P.; Ferrante, L.E. In-Hospital Delirium and Disability and Cognitive Impairment After COVID-19 Hospitalization. JAMA Network Open 2024, 7, e2419640. [Google Scholar] [CrossRef] [PubMed]
- McCusker, J.; Cole, M.; Abrahamowicz, M.; Primeau, F.; Belzile, E. Delirium Predicts 12-Month Mortality. Arch. Intern. Med. 2002, 162, 457–463. [Google Scholar] [CrossRef] [PubMed]
- Schnorr, T.; Fleiner, T.; Schroeder, H.; Reupke, I.; Woringen, F.; Trumpf, R.; Haussermann, P. Post-discharge Mortality in Patients with Delirium and Dementia: A 3-Year Follow Up Study. Front. Psychiatry 2022, 13, 835696. [Google Scholar] [CrossRef] [PubMed]
- Zazzara, M.B.; Ornago, A.M.; Cocchi, C.; Serafini, E.; Bellelli, G.; Onder, G. A pandemic of delirium: An updated systematic review and meta-analysis of occurrence of delirium in older adults with COVID-19. Eur. Geriatr. Med. 2024, 15, 397–406. [Google Scholar] [CrossRef]
- Aung Thein, M.Z.; Pereira, J.V.; Nitchingham, A.; Caplan, G.A. A call to action for delirium research: Meta-analysis and regression of delirium associated mortality. BMC Geriatr. 2020, 20, 325. [Google Scholar] [CrossRef]
- Titlestad, I.; Haugarvoll, K.; Solvang, S.E.H.; Norekvål, T.M.; Skogseth, R.E.; Andreassen, O.A.; Giil, L.M. Delirium is frequently underdiagnosed among older hospitalised patients despite available information in hospital medical records. Age Ageing 2024, 53, afae006. [Google Scholar] [CrossRef]
- Ragheb, J.; Norcott, A.; Benn, L.; Shah, N.; McKinney, A.; Min, L.; Vlisides, P.E. Barriers to delirium screening and management during hospital admission: A qualitative analysis of inpatient nursing perspectives. BMC Health Serv. Res. 2023, 23, 712. [Google Scholar] [CrossRef]
- Andrew, M.K.; Ye, L.; Hatchette, T.; Haguinet, F.; Santos, G.D.; McElhaney, J.E.; Ambrose, A.; Boivin, G.; Bowie, W.; Chit, A.; et al. The Importance of Frailty in the Assessment of Influenza Vaccine Effectiveness Against Influenza-Related Hospitalization in Elderly People. J. Infect. Dis. 2017, 216, 405–414. [Google Scholar] [CrossRef]
- Bonanad, C.; García-Blas, S.; Tarazona-Santabalbina, F.; Sanchis, J.; Bertomeu-González, V.; Fácila, L.; Cordero, A. The Effect of Age on Mortality in Patients with COVID-19: A Meta-Analysis with 611,583 Subjects. J. Am. Med. Dir. Assoc. 2020, 21, 915–918. [Google Scholar] [CrossRef]
- Tejada-Vera, B.; Kramarow, E.A. COVID-19 Mortality in Adults Aged 65 and Over: United States, 2020. NCHS Data Brief. 2022, 1–8. Available online: https://www.cdc.gov/nchs/products/index.htm (accessed on 12 October 2025).
- Kiely, D.K.; Marcantonio, E.R.; Inouye, S.K.; Shaffer, M.L.; Bergmann, M.A.; Yang, F.M.; Jones, R.N. Persistent delirium predicts greater mortality. J. Am. Geriatr. Soc. 2009, 57, 55–61. [Google Scholar] [CrossRef]
- Ely, E.W.; Shintani, A.; Truman, B.; Speroff, T.; Gordon, S.M.; Harrell Jr, F.E.; Dittus, R.S. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004, 291, 1753–1762. [Google Scholar] [CrossRef]
- Dani, M.; Owen, L.H.; Jackson, T.A.; Rockwood, K.; Sampson, E.L.; Davis, D. Delirium, Frailty, and Mortality: Interactions in a Prospective Study of Hospitalized Older People. J. Gerontol. Ser. A 2018, 73, 415–418. [Google Scholar] [CrossRef] [PubMed]
- Al Huraizi, A.R.; Al-Maqbali, J.S.; Al Farsi, R.S.; Al Zeedy, K.; Al-Saadi, T.; Al-Hamadani, N.; Al Alawi, A.M. Delirium and Its Association with Short- and Long-Term Health Outcomes in Medically Admitted Patients: A Prospective Study. J. Clin. Med. 2023, 12, 5346. [Google Scholar] [CrossRef] [PubMed]
- Dziegielewski, C.; Skead, C.; Canturk, T.; Webber, C.; Fernando, S.M.; Thompson, L.H.; Kyeremanteng, K. Delirium and Associated Length of Stay and Costs in Critically Ill Patients. Crit. Care Res. Pract. 2021, 2021, 6612187. [Google Scholar] [CrossRef] [PubMed]
- Yuan, Y.; Jiao, B.; Qu, L.; Yang, D.; Liu, R. The development of COVID-19 treatment. Front. Immunol. 2023, 14, 1125246. [Google Scholar] [CrossRef]
- Collins, N.; Blanchard, M.R.; Tookman, A.; Sampson, E.L. Detection of delirium in the acute hospital. Age Ageing 2010, 39, 131–135. [Google Scholar] [CrossRef]
- Geriatric Medicine Research Collaborative. Delirium is prevalent in older hospital inpatients and associated with adverse outcomes: Results of a prospective multi-centre study on World Delirium Awareness Day. BMC Med. 2019, 17, 229. [Google Scholar] [CrossRef]
Delirium(−), COVID-19(−) (n = 3926) | Delirium(−), COVID-19(+) (n = 248) | Delirium(+), COVID-19(−) (n = 634) | Delirium(+), COVID-19(+) (n = 64) | p-Values | |
---|---|---|---|---|---|
Age | 77.0 ± 7.9 (76) | 77.1 ± 7.7 (77) | 79.4 ± 8.6 (80.0) | 79.9 ± 8.7 (81) | <0.001 |
Male Gender | 1871 (47.7%) | 117 (47.2%) | 306 (48.3%) | 31 (48.4%) | 0.989 |
Race | |||||
White or Caucasian | 3782 (96.3%) | 240 (96.8%) | 615 (97.0%) | 63 (98.4%) | 0.998 |
Black or African American | 120 (3.1%) | 7 (2.8%) | 17 (2.7%) | 1 (1.6%) | |
Hispanic/Latin American | 6 (0.2%) | 1 (0.4%) | 1 (0.2%) | 0 (0.0%) | |
Smoking Status | |||||
Everyday | 387 (12.8%) | 20 (11.4%) | 62 (12.7%) | 6 (11.1%) | 0.350 |
Former | 1455 (47.9%) | 91 (52.0%) | 207 (42.3%) | 24 (44.4%) | |
Never | 1099 (36.2%) | 61 (34.9%) | 197 (40.3%) | 23 (42.6%) | |
Medicare User | 2254 (57.4%) | 124 (50.0%) | 389 (61.4%) | 32 (50.0%) | 0.975 |
Comorbidity | |||||
Dementia | 70 (1.8%) | 2 (0.8%) | 44 (6.9%) | 4 (6.2%) | <0.001 |
Diabetes | 310 (7.9%) | 30 (12.1%) | 50 (7.9%) | 6 (9.4%) | 0.127 |
Hypertension | 791 (20.1%) | 61 (24.6%) | 124 (19.6%) | 14 (21.9%) | 0.362 |
COPD | 453 (11.5%) | 32 (12.9%) | 74 (11.7%) | 6 (9.4%) | 0.864 |
Obesity | 375 (9.6%) | 29 (11.7%) | 50 (7.9%) | 6 (9.4%) | 0.345 |
Heart Disease | 410 (10.4%) | 31 (12.5%) | 69 (10.9%) | 4 (6.2%) | 0.498 |
Heart Failure | 611 (15.6%) | 37 (14.9%) | 78 (12.3%) | 7 (10.9%) | 0.145 |
Time | Delirium and COVID-19 Status | Death Number (%) | aOR |
---|---|---|---|
30-day Mortality | Delirium(−), COVID-19(−) (n = 3926) | 338 (8.6%) | Reference |
Delirium(−), COVID-19(+) (n = 248) | 46 (18.5%) | 2.86 (1.90–4.19) | |
Delirium(+), COVID-19(−) (n = 634) | 166 (26.2%) | 3.86 (3.01–4.94) | |
Delirium(+), COVID-19(+) (n = 64) | 28 (43.8%) | 8.17 (4.60–14.3) | |
60-day Mortality | Delirium(−), COVID-19(−) (n = 3926) | 480 (12.2%) | Reference |
Delirium(−), COVID-19(+) (n = 248) | 55 (22.2%) | 2.45 (1.69–3.49) | |
Delirium(+), COVID-19(−) (n = 634) | 191 (30.1%) | 3.13 (2.49–3.93) | |
Delirium(+), COVID-19(+) (n = 64) | 28 (43.8%) | 5.21 (2.95–9.08) | |
90-day Mortality | Delirium(−), COVID-19(−) (n = 3926) | 565 (14.4%) | Reference |
Delirium(−), COVID-19(+) (n = 248) | 64 (25.8%) | 2.36 (1.65–3.33) | |
Delirium(+), COVID-19(−) (n = 634) | 216 (34.1%) | 3.11 (2.49–3.87) | |
Delirium(+), COVID-19(+) (n = 64) | 29 (45.3%) | 4.71 (2.68–8.19) | |
180-day Mortality | Delirium(−), COVID-19(−) (n = 3926) | 767 (19.5%) | Reference |
Delirium(−), COVID-19(+) (n = 248) | 72 (29.0%) | 1.93 (1.37–2.69) | |
Delirium(+), COVID-19(−) (n = 634) | 263 (41.5%) | 2.99 (2.43–3.68) | |
Delirium(+), COVID-19(+) (n = 64) | 32 (50.0%) | 4.08 (2.35–7.10) | |
360-day Mortality | Delirium(−), COVID-19(−) (n = 3926) | 996 (25.4%) | Reference |
Delirium(−), COVID-19(+) (n = 248) | 80 (32.3%) | 1.53 (1.09–2.12) | |
Delirium(+), COVID-19(−) (n = 634) | 304 (47.9%) | 2.65 (2.16–3.24) | |
Delirium(+), COVID-19(+) (n = 64) | 34 (53.1%) | 3.12 (1.80–5.43) |
Delirium and COVID-19 Status | LOS [Mean ± Std (Median)] | p-Value |
---|---|---|
Delirium(−), COVID-19(−) (n = 3926) | 5.3 ± 5.1 (4.0) | Reference |
Delirium(−), COVID-19(+) (n = 248) | 5.8 ± 5.9 (4.0) | <0.001 |
Delirium(+), COVID-19(−) (n = 634) | 8.6 ± 9.6 (7.0) | <0.001 |
Delirium(+), COVID-19(+) (n = 64) | 11.6 ± 9.3 (9.0) | <0.001 |
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Bradley, J.; Tang, F.; Panzarella, Z.; Nanney, J.; Bryant, B.; Hammel, I.; Cole, D. COVID-19-Related Delirium Associated with Increased Length of Stay and Mortality. COVID 2025, 5, 175. https://doi.org/10.3390/covid5100175
Bradley J, Tang F, Panzarella Z, Nanney J, Bryant B, Hammel I, Cole D. COVID-19-Related Delirium Associated with Increased Length of Stay and Mortality. COVID. 2025; 5(10):175. https://doi.org/10.3390/covid5100175
Chicago/Turabian StyleBradley, Jerry, Fei Tang, Zachary Panzarella, Jacob Nanney, Bill Bryant, Iriana Hammel, and Darby Cole. 2025. "COVID-19-Related Delirium Associated with Increased Length of Stay and Mortality" COVID 5, no. 10: 175. https://doi.org/10.3390/covid5100175
APA StyleBradley, J., Tang, F., Panzarella, Z., Nanney, J., Bryant, B., Hammel, I., & Cole, D. (2025). COVID-19-Related Delirium Associated with Increased Length of Stay and Mortality. COVID, 5(10), 175. https://doi.org/10.3390/covid5100175