[en] Increasing evidence suggests that infection with Sars-CoV-2 causes neurological deficits in a substantial proportion of affected patients. While these symptoms arise acutely during the course of infection, less is known about the possible long-term consequences for the brain. Severely affected COVID-19 cases experience high levels of proinflammatory cytokines and acute respiratory dysfunction and often require assisted ventilation. All these factors have been suggested to cause cognitive decline. Pathogenetically, this may result from direct negative effects of the immune reaction, acceleration or aggravation of pre-existing cognitive deficits, or de novo induction of a neurodegenerative disease. This article summarizes the current understanding of neurological symptoms of COVID-19 and hypothesizes that affected patients may be at higher risk of developing cognitive decline after overcoming the primary COVID-19 infection. A structured prospective evaluation should analyze the likelihood, time course, and severity of cognitive impairment following the COVID-19 pandemic.
Disciplines :
Neurology
Author, co-author :
HENEKA, Michael ; Department of Neurodegenerative Disease and Geriatric Psychiatry, University of Bonn, Bonn, Germany. michael.heneka@ukbonn.de ; German Center for Neurodegenerative Disease, Bonn, Germany. michael.heneka@ukbonn.de ; Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, 01605, USA. michael.heneka@ukbonn.de
Golenbock, Douglas; German Center for Neurodegenerative Disease, Bonn, Germany
Latz, Eicke; German Center for Neurodegenerative Disease, Bonn, Germany ; Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, 01605, USA ; Institute for Innate Immunity, University of Bonn, Bonn, Germany
Morgan, Dave; Translational Neuroscience, College of Human Medicine, Michigan State University, Grand Rapids, USA
Brown, Robert; Department of Neurology, University of Massachusetts Medical School, Worcester, MA, 01605, USA
External co-authors :
yes
Language :
English
Title :
Immediate and long-term consequences of COVID-19 infections for the development of neurological disease.
Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020:e201127.
Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, et al. Neurologic features in severe SARS-CoV-2 infection. N Engl J Med. 2020: NEJMc2008597.
Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. 2020;6:1–11.
Gonzalez-Pinto T, Luna-Rodriguez A, Moreno-Estebanez A, Agirre-Beitia G, Rodriguez-Antiguedad A, Ruiz-Lopez M. Emergency room neurology in times of COVID-19: malignant ischemic stroke and SARS-COV2 infection. Eur J Neurol. 2020:ene.14286.
Oxley TJ, Mocco J, Majidi S, Kellner CP, Shoirah H, Singh IP, et al. Large-vessel stroke as a presenting feature of Covid-19 in the young. N Engl J Med. 2020;382(20):e60.
Beyrouti R, Adams ME, Benjamin L, Cohen H, Farmer SF, Goh YY, et al. Characteristics of ischaemic stroke associated with COVID-19. J Neurol Neurosurg Psychiatry. 2020:jnnp-2020-323586.
Viguier A, Delamarre L, Duplantier J, Olivot JM, Bonneville F. Acute ischemic stroke complicating common carotid artery thrombosis during a severe COVID-19 infection. J Neuroradiol. 2020:S0150-9861(20)30159-0.
Toscano G, Palmerini F, Ravaglia S, Ruiz L, Invernizzi P, Cuzzoni MG, et al. Guillain-Barre syndrome associated with SARS-CoV-2. N Engl J Med. 2020: NEJMc2009191.
Gutierrez-Ortiz C, Mendez A, Rodrigo-Rey S, San Pedro-Murillo E, Bermejo-Guerrero L, Gordo-Manas R, et al. Miller fisher syndrome and polyneuritis cranialis in COVID-19. Neurology. 2020. https://doi.org/10.1212/WNL. 0000000000009619.
Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020;130:2620–9.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506.
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033–4.
Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010; 304(16):1787–94.
Lindlau A, Widmann CN, Putensen C, Jessen F, Semmler A, Heneka MT. Predictors of hippocampal atrophy in critically ill patients. Eur J Neurol. 2015;22(2):410–5.
Rodriguez-Morales AJ, Cardona-Ospina JA, Gutierrez-Ocampo E, Villamizar-Pena R, Holguin-Rivera Y, Escalera-Antezana JP, et al. Clinical, laboratory and imaging features of COVID-19: a systematic review and meta-analysis. Travel Med Infect Dis. 2020;34:101623.
Girard TD, Thompson JL, Pandharipande PP, Brummel NE, Jackson JC, Patel MB, et al. Clinical phenotypes of delirium during critical illness and severity of subsequent long-term cognitive impairment: a prospective cohort study. Lancet Respir Med. 2018;6(3):213–22.
Sasannejad C, Ely EW, Lahiri S. Long-term cognitive impairment after acute respiratory distress syndrome: a review of clinical impact and pathophysiological mechanisms. Crit Care. 2019;23(1):352.
Zhou L, Zhang M, Wang J, Gao J. Sars-Cov-2: underestimated damage to nervous system. Travel Med Infect Dis. 2020;101642.
Jones HD, Crother TR, Gonzalez-Villalobos RA, Jupelli M, Chen S, Dagvadorj J, et al. The NLRP3 inflammasome is required for the development of hypoxemia in LPS/mechanical ventilation acute lung injury. Am J Respir Cell Mol Biol. 2014;50(2):270–80.
Feng Z, Qi S, Zhang Y, Qi Z, Yan L, Zhou J, et al. Ly6G+ neutrophil-derived miR-223 inhibits the NLRP3 inflammasome in mitochondrial DAMP-induced acute lung injury. Cell Death Dis. 2017;8(11):e3170.
Siu KL, Yuen KS, Castano-Rodriguez C, Ye ZW, Yeung ML, Fung SY, et al. Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC. FASEB J. 2019;33(8):8865–77.
Ding HG, Deng YY, Yang RQ, Wang QS, Jiang WQ, Han YL, et al. Hypercapnia induces IL-1beta overproduction via activation of NLRP3 inflammasome: implication in cognitive impairment in hypoxemic adult rats. J Neuroinflammation. 2018;15(1):4.
Tejera D, Mercan D, Sanchez-Caro JM, Hanan M, Greenberg D, Soreq H, et al. Systemic inflammation impairs microglial Aβ clearance through NLRP3 inflammasome. EMBO J. 2019;38(17):e101064.
Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S, Vieira-Saecker A, et al. NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice. Nature. 2013;493(7434):674–8.
Venegas C, Kumar S, Franklin BS, Dierkes T, Brinkschulte R, Tejera D, et al. Microglia-derived ASC specks cross-seed amyloid-beta in Alzheimer’s disease. Nature. 2017;552(7685):355–61.
Ising C, Venegas C, Zhang S, Scheiblich H, Schmidt SV, Vieira-Saecker A, et al. NLRP3 inflammasome activation drives tau pathology. Nature. 2019; 575(7784):669–73.
