Neurologic manifestations of COVID-19 in critically ill patients: results of the prospective multicenter registry PANDEMIC.
COVID-19
Critically ill
Intensive care
Neurologic manifestations
Journal
Critical care (London, England)
ISSN: 1466-609X
Titre abrégé: Crit Care
Pays: England
ID NLM: 9801902
Informations de publication
Date de publication:
16 07 2022
16 07 2022
Historique:
received:
13
03
2022
accepted:
29
06
2022
entrez:
16
7
2022
pubmed:
17
7
2022
medline:
20
7
2022
Statut:
epublish
Résumé
Neurologic manifestations are increasingly reported in patients with coronavirus disease 2019 (COVID-19). Yet, data on prevalence, predictors and relevance for outcome of neurological manifestations in patients requiring intensive care are scarce. We aimed to characterize prevalence, risk factors and impact on outcome of neurologic manifestations in critically ill COVID-19 patients. In the prospective, multicenter, observational registry study PANDEMIC (Pooled Analysis of Neurologic DisordErs Manifesting in Intensive care of COVID-19), we enrolled COVID-19 patients with neurologic manifestations admitted to 19 German intensive care units (ICU) between April 2020 and September 2021. We performed descriptive and explorative statistical analyses. Multivariable models were used to investigate factors associated with disorder categories and their underlying diagnoses as well as to identify predictors of outcome. Of the 392 patients included in the analysis, 70.7% (277/392) were male and the mean age was 65.3 (SD ± 3.1) years. During the study period, a total of 2681 patients with COVID-19 were treated at the ICUs of 15 participating centers. New neurologic disorders were identified in 350 patients, reported by these centers, suggesting a prevalence of COVID-19-associated neurologic disorders of 12.7% among COVID-19 ICU patients. Encephalopathy (46.2%; 181/392), cerebrovascular (41.0%; 161/392) and neuromuscular disorders (20.4%; 80/392) were the most frequent categories identified. Out of 35 cerebrospinal fluid analyses with reverse transcriptase PCR for SARS-COV-2, only 3 were positive. In-hospital mortality was 36.0% (140/389), and functional outcome (mRS 3 to 5) of surviving patients was poor at hospital discharge in 70.9% (161/227). Intracerebral hemorrhage (OR 6.2, 95% CI 2.5-14.9, p < 0.001) and acute ischemic stroke (OR 3.9, 95% CI 1.9-8.2, p < 0.001) were the strongest predictors of poor outcome among the included patients. Based on this well-characterized COVID-19 ICU cohort, that comprised 12.7% of all severe ill COVID-19 patients, neurologic manifestations increase mortality and morbidity. Since no reliable evidence of direct viral affection of the nervous system by COVID-19 could be found, these neurologic manifestations may for a great part be indirect para- or postinfectious sequelae of the infection or severe critical illness. Neurologic ICU complications should be actively searched for and treated.
Sections du résumé
BACKGROUND
Neurologic manifestations are increasingly reported in patients with coronavirus disease 2019 (COVID-19). Yet, data on prevalence, predictors and relevance for outcome of neurological manifestations in patients requiring intensive care are scarce. We aimed to characterize prevalence, risk factors and impact on outcome of neurologic manifestations in critically ill COVID-19 patients.
METHODS
In the prospective, multicenter, observational registry study PANDEMIC (Pooled Analysis of Neurologic DisordErs Manifesting in Intensive care of COVID-19), we enrolled COVID-19 patients with neurologic manifestations admitted to 19 German intensive care units (ICU) between April 2020 and September 2021. We performed descriptive and explorative statistical analyses. Multivariable models were used to investigate factors associated with disorder categories and their underlying diagnoses as well as to identify predictors of outcome.
RESULTS
Of the 392 patients included in the analysis, 70.7% (277/392) were male and the mean age was 65.3 (SD ± 3.1) years. During the study period, a total of 2681 patients with COVID-19 were treated at the ICUs of 15 participating centers. New neurologic disorders were identified in 350 patients, reported by these centers, suggesting a prevalence of COVID-19-associated neurologic disorders of 12.7% among COVID-19 ICU patients. Encephalopathy (46.2%; 181/392), cerebrovascular (41.0%; 161/392) and neuromuscular disorders (20.4%; 80/392) were the most frequent categories identified. Out of 35 cerebrospinal fluid analyses with reverse transcriptase PCR for SARS-COV-2, only 3 were positive. In-hospital mortality was 36.0% (140/389), and functional outcome (mRS 3 to 5) of surviving patients was poor at hospital discharge in 70.9% (161/227). Intracerebral hemorrhage (OR 6.2, 95% CI 2.5-14.9, p < 0.001) and acute ischemic stroke (OR 3.9, 95% CI 1.9-8.2, p < 0.001) were the strongest predictors of poor outcome among the included patients.
CONCLUSIONS
Based on this well-characterized COVID-19 ICU cohort, that comprised 12.7% of all severe ill COVID-19 patients, neurologic manifestations increase mortality and morbidity. Since no reliable evidence of direct viral affection of the nervous system by COVID-19 could be found, these neurologic manifestations may for a great part be indirect para- or postinfectious sequelae of the infection or severe critical illness. Neurologic ICU complications should be actively searched for and treated.
Identifiants
pubmed: 35842675
doi: 10.1186/s13054-022-04080-3
pii: 10.1186/s13054-022-04080-3
pmc: PMC9287707
doi:
Types de publication
Journal Article
Multicenter Study
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
217Informations de copyright
© 2022. The Author(s).
Références
Oliveira E, Parikh A, Lopez-Ruiz A, et al. ICU outcomes and survival in patients with severe COVID-19 in the largest health care system in central Florida. PLoS ONE. 2021;16(3):e0249038.
pubmed: 33765049
pmcid: 7993561
doi: 10.1371/journal.pone.0249038
Zhang JJY, Lee KS, Ang LW, et al. Risk factors for severe disease and efficacy of treatment in patients infected with COVID-19: a systematic review, meta-analysis, and meta-regression analysis. Clin Infect Dis. 2020;71(16):2199–206.
pubmed: 32407459
pmcid: 7239203
doi: 10.1093/cid/ciaa576
Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020;323(16):1574–81.
pubmed: 32250385
pmcid: 7136855
doi: 10.1001/jama.2020.5394
Chen X, Laurent S, Onur OA, et al. A systematic review of neurological symptoms and complications of COVID-19. J Neurol. 2021;268(2):392–402.
pubmed: 32691236
doi: 10.1007/s00415-020-10067-3
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.
pubmed: 32275288
doi: 10.1001/jamaneurol.2020.1127
Helms J, Kremer S, Merdji H, et al. Neurologic features in severe SARS-CoV-2 infection. N Engl J Med. 2020;382(23):2268–70.
pubmed: 32294339
doi: 10.1056/NEJMc2008597
Kleineberg NN, Knauss S, Gulke E, et al. Neurological symptoms and complications in predominantly hospitalized COVID-19 patients: results of the European multinational Lean European Open Survey on SARS-Infected Patients (LEOSS). Eur J Neurol. 2021. https://doi.org/10.1111/ene.15072 .
doi: 10.1111/ene.15072
pubmed: 34411383
pmcid: 8444823
Berlit P, Bosel J, Gahn G, et al. “Neurological manifestations of COVID-19”—guideline of the German society of neurology. Neurol Res Pract. 2020;2:51.
pubmed: 33283160
pmcid: 7708894
doi: 10.1186/s42466-020-00097-7
Frontera JA, Sabadia S, Lalchan R, et al. A prospective study of neurologic disorders in hospitalized patients with COVID-19 in New York City. Neurology. 2021;96(4):e575–86.
pubmed: 33020166
pmcid: 7905791
doi: 10.1212/WNL.0000000000010979
Liu L, Ni SY, Yan W, et al. Mental and neurological disorders and risk of COVID-19 susceptibility, illness severity and mortality: a systematic review, meta-analysis and call for action. EClinicalMedicine. 2021;40:101111.
pubmed: 34514362
pmcid: 8424080
doi: 10.1016/j.eclinm.2021.101111
Chou SH, Beghi E, Helbok R, et al. Global incidence of neurological manifestations among patients hospitalized with COVID-19—a report for the GCS-NeuroCOVID Consortium and the ENERGY Consortium. JAMA Netw Open. 2021;4(5):e2112131.
pubmed: 33974053
pmcid: 8114143
doi: 10.1001/jamanetworkopen.2021.12131
Cervantes-Arslanian AM, Venkata C, Anand P, et al. Neurologic manifestations of severe acute respiratory syndrome Coronavirus 2 infection in hospitalized patients during the first year of the COVID-19 pandemic. Crit Care Explor. 2022;4(4):e0686.
pubmed: 35492258
pmcid: 9042584
doi: 10.1097/CCE.0000000000000686
Leven Y, Bosel J. Neurological manifestations of COVID-19 - an approach to categories of pathology. Neurol Res Pract. 2021;3(1):39.
pubmed: 34311778
pmcid: 8310775
doi: 10.1186/s42466-021-00138-9
Aghagoli G, Gallo Marin B, Katchur NJ, et al. Neurological involvement in COVID-19 and potential mechanisms: a review. Neurocrit Care. 2021;34(3):1062–71.
pubmed: 32661794
doi: 10.1007/s12028-020-01049-4
Misra S, Kolappa K, Prasad M, et al. Frequency of neurologic manifestations in COVID-19: a systematic review and meta-analysis. Neurology. 2021. https://doi.org/10.1212/WNL.0000000000012930 .
doi: 10.1212/WNL.0000000000012930
pubmed: 34635561
Van Der Jagt M, Kompanje EJ. Prognosis of neurologic complications in critical illness. Handb Clin Neurol. 2017;141:765–83.
doi: 10.1016/B978-0-444-63599-0.00041-7
Lorusso R, Gelsomino S, Parise O, et al. Neurologic injury in adults supported with veno-venous extracorporeal membrane oxygenation for respiratory failure: findings from the extracorporeal life support organization database. Crit Care Med. 2017;45(8):1389–97.
pubmed: 28538440
doi: 10.1097/CCM.0000000000002502
Rubinos C, Ruland S. Neurologic complications in the intensive care unit. Curr Neurol Neurosci Rep. 2016;16(6):57.
pubmed: 27098953
doi: 10.1007/s11910-016-0651-8
Hokkoku K, Erra C, Cuccagna C, et al. Intensive care unit-acquired weakness and positioning-related peripheral nerve injuries in COVID-19: a case series of three patients and the latest literature review. Brain Sci. 2021;11(9):1177.
pubmed: 34573198
pmcid: 8470888
doi: 10.3390/brainsci11091177
Network C-IGobotR, the C-ICUI. Clinical characteristics and day-90 outcomes of 4244 critically ill adults with COVID-19: a prospective cohort study. Intensive Care Med. 2021;47(1):60–73.
doi: 10.1007/s00134-020-06294-x
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.
pubmed: 32442528
pmcid: 7237188
doi: 10.1016/S0140-6736(20)31189-2
Frontera JA, Balcer L, Galetta S. Author Response: a prospective study of neurologic disorders in hospitalized patients with COVID-19 in New York City. Neurology. 2021;96(11):549–50.
pubmed: 33723025
doi: 10.1212/WNL.0000000000011611
Romero-Sanchez CM, Diaz-Maroto I, Fernandez-Diaz E, et al. Neurologic manifestations in hospitalized patients with COVID-19: The ALBACOVID registry. Neurology. 2020;95(8):e1060–70.
pubmed: 32482845
pmcid: 7668545
doi: 10.1212/WNL.0000000000009937
Katsoularis I, Fonseca-Rodriguez O, Farrington P, et al. Risk of acute myocardial infarction and ischaemic stroke following COVID-19 in Sweden: a self-controlled case series and matched cohort study. Lancet. 2021;398(10300):599–607.
pubmed: 34332652
pmcid: 8321431
doi: 10.1016/S0140-6736(21)00896-5
Mateen FJ, Muralidharan R, Shinohara RT, et al. Neurological injury in adults treated with extracorporeal membrane oxygenation. Arch Neurol. 2011;68(12):1543–9.
pubmed: 21825216
pmcid: 7816483
doi: 10.1001/archneurol.2011.209
Nasr DM, Rabinstein AA. Neurologic complications of extracorporeal membrane oxygenation. J Clin Neurol. 2015;11(4):383–9.
pubmed: 26320848
pmcid: 4596114
doi: 10.3988/jcn.2015.11.4.383
Correction to: Influence of the COVID-19 pandemic on treatment times for acute ischemic stroke: the Society of Vascular and Interventional Neurology Multicenter Collaboration. Stroke. 2021;52(3):e104.
Levine RL, LeClerc JR, Bailey JE, et al. Venous and arterial thromboembolism in severe sepsis. Thromb Haemost. 2008;99(5):892–8.
pubmed: 18449418
Pilato F, Profice P, Dileone M, et al. Stroke in critically ill patients. Minerva Anestesiol. 2009;75(5):245–50.
pubmed: 18636061
Wijdicks EF, Scott JP. Stroke in the medical intensive-care unit. Mayo Clin Proc. 1998;73(7):642–6.
pubmed: 9663192
doi: 10.1016/S0025-6196(11)64887-8
Bleck TP, Smith MC, Pierre-Louis SJ, et al. Neurologic complications of critical medical illnesses. Crit Care Med. 1993;21(1):98–103.
pubmed: 8420739
doi: 10.1097/00003246-199301000-00019
Naik-Tolani S, Oropello JM, Benjamin E. Neurologic complications in the intensive care unit. Clin Chest Med. 1999;20(2):423–34.
pubmed: 10386265
doi: 10.1016/S0272-5231(05)70150-7
Rothstein A, Oldridge O, Schwennesen H, et al. Acute cerebrovascular events in hospitalized COVID-19 patients. Stroke. 2020;51(9):e219–22.
pubmed: 32684145
doi: 10.1161/STROKEAHA.120.030995
Li Y, Li M, Wang M, et al. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. Stroke Vasc Neurol. 2020;5(3):279–84.
pubmed: 32616524
pmcid: 7371480
doi: 10.1136/svn-2020-000431
Jain R, Young M, Dogra S, et al. COVID-19 related neuroimaging findings: a signal of thromboembolic complications and a strong prognostic marker of poor patient outcome. J Neurol Sci. 2020;414: 116923.
pubmed: 32447193
pmcid: 7236667
doi: 10.1016/j.jns.2020.116923
Piroth L, Cottenet J, Mariet AS, et al. Comparison of the characteristics, morbidity, and mortality of COVID-19 and seasonal influenza: a nationwide, population-based retrospective cohort study. Lancet Respir Med. 2021;9(3):251–9.
pubmed: 33341155
doi: 10.1016/S2213-2600(20)30527-0
Lang CN, Dettinger JS, Berchtold-Herz M, et al. Intracerebral hemorrhage in COVID-19 patients with pulmonary failure: a propensity score-matched registry study. Neurocrit Care. 2021;34(3):739–47.
pubmed: 33619668
pmcid: 7899797
doi: 10.1007/s12028-021-01202-7
Ibrahim W. Neurological manifestations in coronavirus disease 2019 (COVID-19) patients: a systematic review of literature. CNS Spectr. 2020;21:1–12.
Neumann B, Schmidbauer ML, Dimitriadis K, et al. Cerebrospinal fluid findings in COVID-19 patients with neurological symptoms. J Neurol Sci. 2020;418: 117090.
pubmed: 32805440
pmcid: 7417278
doi: 10.1016/j.jns.2020.117090
Lewis A, Frontera J, Placantonakis DG, et al. Cerebrospinal fluid in COVID-19: a systematic review of the literature. J Neurol Sci. 2021;421: 117316.
pubmed: 33561753
pmcid: 7833669
doi: 10.1016/j.jns.2021.117316
Elsayed HH, Hassaballa AS, Ahmed TA, et al. Variation in outcome of invasive mechanical ventilation between different countries for patients with severe COVID-19: a systematic review and meta-analysis. PLoS ONE. 2021;16(6): e0252760.
pubmed: 34086779
pmcid: 8177443
doi: 10.1371/journal.pone.0252760
Armstrong RA, Kane AD, Kursumovic E, et al. Mortality in patients admitted to intensive care with COVID-19: an updated systematic review and meta-analysis of observational studies. Anaesthesia. 2021;76(4):537–48.
pubmed: 33525063
pmcid: 8013495
doi: 10.1111/anae.15425
Chang R, Elhusseiny KM, Yeh YC, et al. COVID-19 ICU and mechanical ventilation patient characteristics and outcomes—a systematic review and meta-analysis. PLoS ONE. 2021;16(2):e0246318.
pubmed: 33571301
pmcid: 7877631
doi: 10.1371/journal.pone.0246318
Schüttler JMJ, Kapsner LA, Seuchter SA, Binder H, Zöller D, et al. Letalität von Patienten mit COVID-19: Untersuchungen zu Ursachen und Dynamik an deutschen Universitätsklinika. Anästh Intensivmed. 2021;62:244–57.
Karagiannidis C, Mostert C, Hentschker C, et al. Case characteristics, resource use, and outcomes of 10 021 patients with COVID-19 admitted to 920 German hospitals: an observational study. Lancet Respir Med. 2020;8(9):853–62.
pubmed: 32735842
pmcid: 7386882
doi: 10.1016/S2213-2600(20)30316-7
Malik P, Patel K, Pinto C, et al. Post-acute COVID-19 syndrome (PCS) and health-related quality of life (HRQoL)—a systematic review and meta-analysis. J Med Virol. 2022;94(1):253–62.
pubmed: 34463956
doi: 10.1002/jmv.27309
Mikkelsen ME, Still M, Anderson BJ, et al. Society of Critical Care Medicine’s international consensus conference on prediction and identification of long-term impairments after critical illness. Crit Care Med. 2020;48(11):1670–9.
pubmed: 32947467
doi: 10.1097/CCM.0000000000004586
Long Q, Li J, Hu X, et al. Follow-ups on persistent symptoms and pulmonary function among post-acute COVID-19 patients: a systematic review and meta-analysis. Front Med (Lausanne). 2021;8:702635.
doi: 10.3389/fmed.2021.702635
Tay MRJ, Ong PL, Puah SH, et al. Acute functional outcomes in critically ill COVID-19 patients. Front Med (Lausanne). 2020;7:615997.
doi: 10.3389/fmed.2020.615997
Suleyman G, Fadel RA, Malette KM, et al. Clinical characteristics and morbidity associated with Coronavirus disease 2019 in a series of patients in Metropolitan Detroit. JAMA Netw Open. 2020;3(6):e2012270.
pubmed: 32543702
pmcid: 7298606
doi: 10.1001/jamanetworkopen.2020.12270
Rousseau AF, Minguet P, Colson C, et al. Post-intensive care syndrome after a critical COVID-19: cohort study from a Belgian follow-up clinic. Ann Intensive Care. 2021;11(1):118.
pubmed: 34324073
pmcid: 8319705
doi: 10.1186/s13613-021-00910-9