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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Encephalitis Is a Cytokine Release Syndrome: Evidences From Cerebrospinal Fluid Analyses.
Pilotto, Andrea; Masciocchi, Stefano; Volonghi, Irene; De Giuli, Valeria; Caprioli, Francesca; Mariotto, Sara; Ferrari, Sergio; Bozzetti, Silvia; Imarisio, Alberto; Risi, Barbara; Premi, Enrico; Benussi, Alberto; Focà, Emanuele; Castelli, Francesco; Zanusso, Gianluigi; Monaco, Salvatore; Stefanelli, Paola; Gasparotti, Roberto; Zekeridou, Anastasia; McKeon, Andrew; Ashton, Nicholas J; BlennoW, Kaj; Zetterberg, Henrik; Padovani, Alessandro.
  • Pilotto A; Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
  • Masciocchi S; Parkinson's Disease Rehabilitation Centre, FERB ONLUS-S. Isidoro Hospital, Trescore Balneario (BG), Italy.
  • Volonghi I; Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
  • De Giuli V; Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
  • Caprioli F; Neurology Unit, Istituti Ospedalieri, ASST Cremona, Cremona, Italy.
  • Mariotto S; Neurology Unit, Istituti Ospedalieri, ASST Cremona, Cremona, Italy.
  • Ferrari S; Neurology Unit, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
  • Bozzetti S; Neurology Unit, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
  • Imarisio A; Neurology Unit, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
  • Risi B; Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
  • Premi E; Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
  • Benussi A; Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
  • Focà E; Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
  • Castelli F; University Division of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili Hospital, Brescia, Italy.
  • Zanusso G; University Division of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili Hospital, Brescia, Italy.
  • Monaco S; Neurology Unit, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
  • Stefanelli P; Neurology Unit, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
  • Gasparotti R; Department of Infectious Diseases, Italian National Public Health Institute, Rome, Italy.
  • Zekeridou A; Neuroradiology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia and ASST Spedali Civili Hospital, Brescia, Italy.
  • McKeon A; Departments of Laboratory Medicine and Pathology, and Neurology, Mayo Clinic, Rochester, Minnesota, USA.
  • Ashton NJ; Departments of Laboratory Medicine and Pathology, and Neurology, Mayo Clinic, Rochester, Minnesota, USA.
  • BlennoW K; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
  • Zetterberg H; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
  • Padovani A; King's College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, London, United Kingdom.
Clin Infect Dis ; 73(9): e3019-e3026, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1501050
Semantic information from SemMedBD (by NLM)
1. Circumferential Supracrestal Fiberotomy TREATS COVID-19
Subject
Circumferential Supracrestal Fiberotomy
Predicate
TREATS
Object
COVID-19
2. Encephalitis PROCESS_OF Patients
Subject
Encephalitis
Predicate
PROCESS_OF
Object
Patients
3. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
4. TNF protei INTERACTS_WITH C0027836
Subject
TNF protei
Predicate
INTERACTS_WITH
Object
C0027836
5. Microglobulin INTERACTS_WITH Neuroglia
Subject
Microglobulin
Predicate
INTERACTS_WITH
Object
Neuroglia
6. Glial activation COEXISTS_WITH Encephalitis
Subject
Glial activation
Predicate
COEXISTS_WITH
Object
Encephalitis
7. Neuroinflammation COEXISTS_WITH Encephalitis
Subject
Neuroinflammation
Predicate
COEXISTS_WITH
Object
Encephalitis
8. Cytokine Release Syndrome MANIFESTATION_OF Encephalitis
Subject
Cytokine Release Syndrome
Predicate
MANIFESTATION_OF
Object
Encephalitis
9. Circumferential Supracrestal Fiberotomy TREATS COVID-19
Subject
Circumferential Supracrestal Fiberotomy
Predicate
TREATS
Object
COVID-19
10. Encephalitis PROCESS_OF Patients
Subject
Encephalitis
Predicate
PROCESS_OF
Object
Patients
11. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
12. TNF protein, human|TNF INTERACTS_WITH Neuroglia
Subject
TNF protein, human|TNF
Predicate
INTERACTS_WITH
Object
Neuroglia
13. Microglobulin INTERACTS_WITH Neuroglia
Subject
Microglobulin
Predicate
INTERACTS_WITH
Object
Neuroglia
14. Glial activation COEXISTS_WITH Encephalitis
Subject
Glial activation
Predicate
COEXISTS_WITH
Object
Encephalitis
15. Neuroinflammation COEXISTS_WITH Encephalitis
Subject
Neuroinflammation
Predicate
COEXISTS_WITH
Object
Encephalitis
16. Cytokine Release Syndrome MANIFESTATION_OF Encephalitis
Subject
Cytokine Release Syndrome
Predicate
MANIFESTATION_OF
Object
Encephalitis
ABSTRACT

BACKGROUND:

Recent findings indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related neurological manifestations involve cytokine release syndrome along with endothelial activation, blood brain barrier dysfunction, and immune-mediated mechanisms. Very few studies have fully investigated the cerebrospinal fluid (CSF) correlates of SARS-CoV-2 encephalitis.

METHODS:

Patients with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection and encephalitis (COV-Enc), encephalitis without SARS-CoV-2 infection (ENC), and healthy controls (HC) underwent an extended panel of CSF neuronal (neurofilament light chain [NfL], T-tau), glial (glial fibrillary acidic protein [GFAP], soluble triggering receptor expressed on myeloid cells 2 [sTREM2], chitinase-3-like protein 1 [YKL-40]) and inflammatory biomarkers (interleukin [IL]-1ß, IL-6, Il-8, tumor necrosis factor [TNF] α, CXCL-13, and ß2-microglobulin).

RESULTS:

Thirteen COV-Enc, 21 ENC, and 18 HC entered the study. In COV-Enc cases, CSF was negative for SARS-CoV-2 real-time PCR but exhibited increased IL-8 levels independently from presence of pleocytosis/hyperproteinorracchia. COV-Enc patients showed increased IL-6, TNF- α, and ß2-microglobulin and glial markers (GFAP, sTREM2, YKL-40) levels similar to ENC but normal CXCL13 levels. Neuronal markers NfL and T-tau were abnormal only in severe cases.

CONCLUSIONS:

SARS-CoV-2-related encephalitis were associated with prominent glial activation and neuroinflammatory markers, whereas neuronal markers were increased in severe cases only. The pattern of CSF alterations suggested a cytokine-release syndrome as the main inflammatory mechanism of SARS-CoV-2-related encephalitis.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Encephalitis / COVID-19 Type of study: Observational study Limits: Humans Language: English Journal: Clin Infect Dis Journal subject: Communicable Diseases Year: 2021 Document Type: Article Affiliation country: Cid

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Encephalitis / COVID-19 Type of study: Observational study Limits: Humans Language: English Journal: Clin Infect Dis Journal subject: Communicable Diseases Year: 2021 Document Type: Article Affiliation country: Cid