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Published in: Neurocritical Care 1/2022

01-02-2022 | COVID-19 | Original work

Disorders of Consciousness in Hospitalized Patients with COVID-19: The Role of the Systemic Inflammatory Response Syndrome

Authors: Amelia K. Boehme, Kevin Doyle, Kiran T. Thakur, David Roh, Soojin Park, Sachin Agarwal, Angela G. Velazquez, Jennifer A. Egbebike, Caroline Der Nigoghossian, Morgan L. Prust, Jon Rosenberg, Daniel Brodie, Katherine N. Fishkoff, Beth R. Hochmann, Leroy E. Rabani, Natalie H. Yip, Oliver Panzer, Jan Claassen

Published in: Neurocritical Care | Issue 1/2022

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Abstract

Background

Prevalence and etiology of unconsciousness are uncertain in hospitalized patients with coronavirus disease 2019 (COVID-19). We tested the hypothesis that increased inflammation in COVID-19 precedes coma, independent of medications, hypotension, and hypoxia.

Methods

We retrospectively assessed 3203 hospitalized patients with COVID-19 from March 2 through July 30, 2020, in New York City with the Glasgow Coma Scale and systemic inflammatory response syndrome (SIRS) scores. We applied hazard ratio (HR) modeling and mediation analysis to determine the risk of SIRS score elevation to precede coma, accounting for confounders.

Results

We obtained behavioral assessments in 3203 of 10,797 patients admitted to the hospital who tested positive for SARS-CoV-2. Of those patients, 1054 (32.9%) were comatose, which first developed on median hospital day 2 (interquartile range [IQR] 1–9). During their hospital stay, 1538 (48%) had a SIRS score of 2 or above at least once, and the median maximum SIRS score was 2 (IQR 1–2). A fivefold increased risk of coma (HR 5.05, 95% confidence interval 4.27–5.98) was seen for each day that patients with COVID-19 had elevated SIRS scores, independent of medication effects, hypotension, and hypoxia. The overall mortality in this population was 13.8% (n = 441). Coma was associated with death (odds ratio 7.77, 95% confidence interval 6.29–9.65) and increased length of stay (13 days [IQR 11.9–14.1] vs. 11 [IQR 9.6–12.4]), accounting for demographics.

Conclusions

Disorders of consciousness are common in hospitalized patients with severe COVID-19 and are associated with increased mortality and length of hospitalization. The underlying etiology of disorders of consciousness in this population is uncertain but, in addition to medication effects, may in part be linked to systemic inflammation.
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Literature
1.
go back to reference Cummings MJ, Baldwin MR, Abrams D, et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet. 2020;395(10239):1763–70.CrossRef Cummings MJ, Baldwin MR, Abrams D, et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet. 2020;395(10239):1763–70.CrossRef
2.
go back to reference Ellul MA, Benjamin L, Singh B, et al. Neurological associations of COVID-19. Lancet Neurol. 2020;19:767–83.CrossRef Ellul MA, Benjamin L, Singh B, et al. Neurological associations of COVID-19. Lancet Neurol. 2020;19:767–83.CrossRef
3.
go back to reference Koralnik IJ, Tyler KL. COVID-19: a global threat to the nervous system. Ann Neurol. 2020;88:1–11.CrossRef Koralnik IJ, Tyler KL. COVID-19: a global threat to the nervous system. Ann Neurol. 2020;88:1–11.CrossRef
4.
go back to reference Needham EJ, Chou SHY, Coles AJ, Menon DK. Neurological implications of COVID-19 infections. Neurocrit Care. 2020;32:667–71.CrossRef Needham EJ, Chou SHY, Coles AJ, Menon DK. Neurological implications of COVID-19 infections. Neurocrit Care. 2020;32:667–71.CrossRef
5.
go back to reference Paterson RW, Brown RL, Benjamin L, et al. The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings. Brain. 2020;143(10):3104–20.CrossRef Paterson RW, Brown RL, Benjamin L, et al. The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings. Brain. 2020;143(10):3104–20.CrossRef
6.
go back to reference Kotfis K, Williams Roberson S, Wilson JE, et al. COVID-19: ICU delirium management during SARS-CoV-2 pandemic. Crit Care. 2020;24:176.CrossRef Kotfis K, Williams Roberson S, Wilson JE, et al. COVID-19: ICU delirium management during SARS-CoV-2 pandemic. Crit Care. 2020;24:176.CrossRef
7.
go back to reference Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020;77(6):683–90.CrossRef Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020;77(6):683–90.CrossRef
8.
go back to reference Helms J, Kremer S, Merdji H, et al. Neurologic features in severe SARS-CoV-2 infection. N Engl J Med. 2020;382:2268–70.CrossRef Helms J, Kremer S, Merdji H, et al. Neurologic features in severe SARS-CoV-2 infection. N Engl J Med. 2020;382:2268–70.CrossRef
9.
go back to reference Claassen J, Doyle K, Matory A, et al. Detection of brain activation in unresponsive patients with acute brain injury. N Engl J Med. 2019;380:2497–505.CrossRef Claassen J, Doyle K, Matory A, et al. Detection of brain activation in unresponsive patients with acute brain injury. N Engl J Med. 2019;380:2497–505.CrossRef
10.
go back to reference Turgeon AF, Lauzier F, Simard J-F, et al. Mortality associated with withdrawal of life-sustaining therapy for patients with severe traumatic brain injury: a Canadian multicentre cohort study. CMAJ. 2011;183:1581–8.CrossRef Turgeon AF, Lauzier F, Simard J-F, et al. Mortality associated with withdrawal of life-sustaining therapy for patients with severe traumatic brain injury: a Canadian multicentre cohort study. CMAJ. 2011;183:1581–8.CrossRef
11.
go back to reference Elmer J, Torres C, Aufderheide TP, et al. Association of early withdrawal of life-sustaining therapy for perceived neurological prognosis with mortality after cardiac arrest. Resuscitation. 2016;102:127–35.CrossRef Elmer J, Torres C, Aufderheide TP, et al. Association of early withdrawal of life-sustaining therapy for perceived neurological prognosis with mortality after cardiac arrest. Resuscitation. 2016;102:127–35.CrossRef
12.
go back to reference Claassen J, Albers D, Schmidt JM, et al. Nonconvulsive seizures in subarachnoid hemorrhage link inflammation and outcome. Ann Neurol. 2014;75:771–81.CrossRef Claassen J, Albers D, Schmidt JM, et al. Nonconvulsive seizures in subarachnoid hemorrhage link inflammation and outcome. Ann Neurol. 2014;75:771–81.CrossRef
13.
go back to reference Boehme AK, Kapoor N, Albright KC, et al. Predictors of systemic inflammatory response syndrome in ischemic stroke undergoing systemic thrombolysis with intravenous tissue plasminogen activator. J Stroke Cerebrovasc Dis. 2014;23:e271–6.CrossRef Boehme AK, Kapoor N, Albright KC, et al. Predictors of systemic inflammatory response syndrome in ischemic stroke undergoing systemic thrombolysis with intravenous tissue plasminogen activator. J Stroke Cerebrovasc Dis. 2014;23:e271–6.CrossRef
14.
go back to reference Boehme AK, Hays AN, Kicielinski KP, et al. Systemic Inflammatory response syndrome and outcomes in intracerebral hemorrhage. Neurocrit Care. 2016;25:133–40.CrossRef Boehme AK, Hays AN, Kicielinski KP, et al. Systemic Inflammatory response syndrome and outcomes in intracerebral hemorrhage. Neurocrit Care. 2016;25:133–40.CrossRef
15.
go back to reference Szklener S, Korchut A, Godek M, et al. Systemic inflammatory response syndrome in the course of status epilepticus: 7-year, two-center observational study. Epilepsy Res. 2017;137:53–5.CrossRef Szklener S, Korchut A, Godek M, et al. Systemic inflammatory response syndrome in the course of status epilepticus: 7-year, two-center observational study. Epilepsy Res. 2017;137:53–5.CrossRef
16.
go back to reference Hagen M, Sembill JA, Sprügel MI, et al. Systemic inflammatory response syndrome and long-term outcome after intracerebral hemorrhage. Neurol Neuroimmunol Neuroinflamm 2019;6:e588. Hagen M, Sembill JA, Sprügel MI, et al. Systemic inflammatory response syndrome and long-term outcome after intracerebral hemorrhage. Neurol Neuroimmunol Neuroinflamm 2019;6:e588.
17.
go back to reference Boehme AK, Comeau ME, Langefeld CD, et al. Systemic inflammatory response syndrome, infection, and outcome in intracerebral hemorrhage. Neurol Neuroimmunol Neuroinflamm 2017;5:e428. Boehme AK, Comeau ME, Langefeld CD, et al. Systemic inflammatory response syndrome, infection, and outcome in intracerebral hemorrhage. Neurol Neuroimmunol Neuroinflamm 2017;5:e428.
19.
go back to reference Teasdale G, Jennett B. Assessment of coma and impaired. Lancet. 1974;2:81–4.CrossRef Teasdale G, Jennett B. Assessment of coma and impaired. Lancet. 1974;2:81–4.CrossRef
20.
go back to reference Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Crit Care Med. 2003;31:1250–6.CrossRef Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Crit Care Med. 2003;31:1250–6.CrossRef
21.
go back to reference Valeri L, VanderWeele TJ. Mediation analysis allowing for exposure-mediator interactions and causal interpretation: theoretical assumptions and implementation with SAS and SPSS macros. Psychol Methods. 2013;18:137–50.CrossRef Valeri L, VanderWeele TJ. Mediation analysis allowing for exposure-mediator interactions and causal interpretation: theoretical assumptions and implementation with SAS and SPSS macros. Psychol Methods. 2013;18:137–50.CrossRef
22.
go back to reference Sepulveda J, Westblade LF, Whittier S, et al. Bacteremia and blood culture utilization during covid-19 surge in New York City. J Clin Microbiol. 2020;58:e00875-e920.CrossRef Sepulveda J, Westblade LF, Whittier S, et al. Bacteremia and blood culture utilization during covid-19 surge in New York City. J Clin Microbiol. 2020;58:e00875-e920.CrossRef
23.
go back to reference Gofton TE, Bryan YG. Sepsis-associated encephalopathy. Nat Rev Neurol. 2012;8:557–66.CrossRef Gofton TE, Bryan YG. Sepsis-associated encephalopathy. Nat Rev Neurol. 2012;8:557–66.CrossRef
24.
go back to reference Maldonado JR. Neuropathogenesis of delirium: review of current etiologic theories and common pathways. Am J Geriatr Psychiatry. 2013;21:1190–222.CrossRef Maldonado JR. Neuropathogenesis of delirium: review of current etiologic theories and common pathways. Am J Geriatr Psychiatry. 2013;21:1190–222.CrossRef
25.
go back to reference Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19: final report. N Engl J Med. 2020;383(19):1813–26.CrossRef Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19: final report. N Engl J Med. 2020;383(19):1813–26.CrossRef
26.
go back to reference Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033–4.CrossRef Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033–4.CrossRef
27.
go back to reference Cao A, Rohaut B, Le Guennec L, et al. Severe COVID-19-related encephalitis can respond to immunotherapy. Brain. 2020;143:e102. Cao A, Rohaut B, Le Guennec L, et al. Severe COVID-19-related encephalitis can respond to immunotherapy. Brain. 2020;143:e102.
28.
go back to reference Pilotto A, Masciocchi S, Volonghi I, et al. Clinical presentation and outcomes of severe acute respiratory syndrome coronavirus 2-related encephalitis: the ENCOVID multicenter study. J Infect Dis. 2021;223:28–37.CrossRef Pilotto A, Masciocchi S, Volonghi I, et al. Clinical presentation and outcomes of severe acute respiratory syndrome coronavirus 2-related encephalitis: the ENCOVID multicenter study. J Infect Dis. 2021;223:28–37.CrossRef
30.
go back to reference Perrin P, Collongues N, Baloglu S, et al. Cytokine release syndrome-associated encephalopathy in patients with COVID-19. Eur J Neurol. 2021;28:248–58.CrossRef Perrin P, Collongues N, Baloglu S, et al. Cytokine release syndrome-associated encephalopathy in patients with COVID-19. Eur J Neurol. 2021;28:248–58.CrossRef
31.
go back to reference Chaudhry N, Duggal AK. Sepsis associated encephalopathy. Adv Med. 2014;2014:762320. Chaudhry N, Duggal AK. Sepsis associated encephalopathy. Adv Med. 2014;2014:762320.
32.
go back to reference Brower RG, Matthay MA, Morris A, et al. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342:1301–8.CrossRef Brower RG, Matthay MA, Morris A, et al. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342:1301–8.CrossRef
33.
go back to reference Paniz-Mondolfi A, Bryce C, Grimes Z, et al. Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). J Med Virol. 2020;92:699–702.CrossRef Paniz-Mondolfi A, Bryce C, Grimes Z, et al. Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). J Med Virol. 2020;92:699–702.CrossRef
34.
go back to reference Seymour CW, Kahn JM, Cooke CR, et al. Prediction of critical illness during out-of-hospital emergency care. JAMA. 2010;304:747–54.CrossRef Seymour CW, Kahn JM, Cooke CR, et al. Prediction of critical illness during out-of-hospital emergency care. JAMA. 2010;304:747–54.CrossRef
35.
go back to reference Claassen J, Velazquez A, Meyers E, et al. Bedside quantitative electroencephalography improves assessment of consciousness in comatose subarachnoid hemorrhage patients. Ann Neurol. 2016;80:541–53.CrossRef Claassen J, Velazquez A, Meyers E, et al. Bedside quantitative electroencephalography improves assessment of consciousness in comatose subarachnoid hemorrhage patients. Ann Neurol. 2016;80:541–53.CrossRef
36.
go back to reference Oxley TJ, Mocco J, Majidi S, et al. Large-vessel stroke as a presenting feature of Covid-19 in the young. N Engl J Med. 2020;382:e60. Oxley TJ, Mocco J, Majidi S, et al. Large-vessel stroke as a presenting feature of Covid-19 in the young. N Engl J Med. 2020;382:e60.
37.
go back to reference Reith FCM, Van den Brande R, Synnot A, et al. The reliability of the Glasgow Coma Scale: a systematic review. Intensive Care Med. 2016;42:3–15.CrossRef Reith FCM, Van den Brande R, Synnot A, et al. The reliability of the Glasgow Coma Scale: a systematic review. Intensive Care Med. 2016;42:3–15.CrossRef
Metadata
Title
Disorders of Consciousness in Hospitalized Patients with COVID-19: The Role of the Systemic Inflammatory Response Syndrome
Authors
Amelia K. Boehme
Kevin Doyle
Kiran T. Thakur
David Roh
Soojin Park
Sachin Agarwal
Angela G. Velazquez
Jennifer A. Egbebike
Caroline Der Nigoghossian
Morgan L. Prust
Jon Rosenberg
Daniel Brodie
Katherine N. Fishkoff
Beth R. Hochmann
Leroy E. Rabani
Natalie H. Yip
Oliver Panzer
Jan Claassen
Publication date
01-02-2022
Publisher
Springer US
Keywords
COVID-19
Coma
Published in
Neurocritical Care / Issue 1/2022
Print ISSN: 1541-6933
Electronic ISSN: 1556-0961
DOI
https://doi.org/10.1007/s12028-021-01256-7

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