Andrea Pilotto1,2, Stefano Masciocchi1, Irene Volonghi1, Valeria De Giuli3, Francesca Caprioli3, Sara Mariotto4, Sergio Ferrari4, Silvia Bozzetti4, Alberto Imarisio1, Barbara Risi1, Enrico Premi1, Alberto Benussi1, Emanuele Focà5, Francesco Castelli5, Gianluigi Zanusso4, Salvatore Monaco4, Paola Stefanelli6, Roberto Gasparotti7, Anastasia Zekeridou8, Andrew McKeon8, Nicholas J Ashton9,10,11,12, Kaj Blennov9,13, Henrik Zetterberg9,13,14,15, Alessandro Padovani1. 1. Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Italy. 2. Parkinson's Disease Rehabilitation Centre, FERB ONLUS - S. Isidoro Hospital, Trescore Balneario (BG), Italy. 3. Neurology Unit, Istituti Ospedalieri, ASST Cremona, Cremona, Italy. 4. Neurology Unit, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy. 5. University Division of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili Hospital, Brescia, Italy. 6. Department of Infectious Diseases, Italian National Public Health Institute, Rome, Italy. 7. Neuroradiology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia and ASST Spedali Civili Hospital, Brescia, Italy. 8. Departments of Laboratory Medicine and Pathology, and Neurology, Mayo Clinic, Rochester, MN 55906, USA. 9. Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. 10. Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden. 11. King's College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, London, UK. 12. NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK. 13. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 14. Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK. 15. UK Dementia Research Institute at UCL, London, UK.
Abstract
BACKGROUND: Recent findings indicated that 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 CSF correlates of SARS-CoV-2 encephalitis. METHODS: Patients with 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 (NfL, T-tau), glial (GFAP, TREM2, YKL-40) and inflammatory biomarkers (IL-1β, IL-6, Il-8, TNF- α, CXCL-13 and β2-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 β2-microglobulin and glial markers (GFAP, sTREM-2, 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.
BACKGROUND: Recent findings indicated that 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 CSF correlates of SARS-CoV-2 encephalitis. METHODS:Patients with 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 (NfL, T-tau), glial (GFAP, TREM2, YKL-40) and inflammatory biomarkers (IL-1β, IL-6, Il-8, TNF- α, CXCL-13 and β2-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 β2-microglobulin and glial markers (GFAP, sTREM-2, 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.
Authors: Jennifer A Frontera; Allal Boutajangout; Arjun V Masurkar; Rebecca A Betensky; Yulin Ge; Alok Vedvyas; Ludovic Debure; Andre Moreira; Ariane Lewis; Joshua Huang; Sujata Thawani; Laura Balcer; Steven Galetta; Thomas Wisniewski Journal: Alzheimers Dement Date: 2022-01-13 Impact factor: 16.655
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 Journal: Neurocrit Care Date: 2021-06-28 Impact factor: 3.532