Severe COVID-19-related encephalitis can respond to immunotherapy

Cao, Albert; Rohaut, Benjamin; Guennec, Loïc Le; Saheb, Samir; Marois, Clémence; Altmayer, Victor; Carpentier, Vincent T.; Nemlaghi, Safaa; Soulié, Marie; Morlon, Quentin; Berthet-Delteil, Bryan; Bleibtreu, Alexandre; Raux, Mathieu; Weiss, Nicolas; Carvalho, Stéphanie; Sagnes, Sandrine; Dubois, Bruno; Kas, Aurélie; Lamari, Foudil; Brochard, Vanessa Batista; Dupont, Sophie; Lubetzki, Catherine; Seilhean, Danielle; Pradat‐Diehl, Pascale; Rosso, Charlotte; Hoang-Xuân, Khê; Fontaine, Bertrand; Naccache, Lionel; Fossati, Philippe; Arnulf, Isabelle; Dürr, Alexandra; Carpentier, Alexandre; Lehericy, Stéphane; Edel, Yves; Stefano, Anna Luisa Di; Robain, G.; Thoumie, P.; Degos, Bertrand; Sharshar, Tarek; Alamowitch, Sonia; Apartis‐Bourdieu, Emmanuelle; Peretti, Charles‐Siegried; Ursu, Rénata; Dzierzynski, Nathalie; Bourron, Kiyoka Kinugawa; Belmin, Joël; Oquendo, Bruno; Pautas, Éric; Verny, Marc; Delorme, Cécile; Corvol, Jean‐Christophe; Delattre, Jean‐Yves; Samson, Yves; Leder, Sara; Léger, A.; Deltour, Sandrine; Baronnet, Flore; Bombois, Stéphanie; Touat, Mehdi; Idbaïh, Ahmed; Sanson, Marc; Dehais, Caroline; Houillier, Caroline; Laigle‐Donadey, Florence; Psimaras, Dimitri; Alenton, Agusti; Younan, Nadia; Villain, Nicolas; Grabli, David; Amador, Maria del Mar; Bruneteau, Gaëlle; Louapre, Céline; Mariani, Louise‐Laure; Mezouar, Nicolas; Mangone, Graziella; Méneret, Aurélie; Hartmann, Andreas; Tarrano, Clément; Bendetowicz, David; Pradat, Pierre‐François; Baulac, Michel; Sambin, Sara; Salachas, François; Forestier, Nadine Le; Pichit, Phintip; Chochon, F; Hesters, Adèle; Herlin, Bastien; Nguyen, An Hung; Procher, Valerie; Demoule, Alexandre; Morawiec, Élise; Mayaux, Julien; Faure, Morgan; Ewenczyk, Claire; Coarelli, Giulia; Heinzmann, Anna; Charles, Perrine; Stojkovic, Tanya; Masingue, Marion; Bassez, Guillaume; Navarro, Vincent; An, Isabelle; Worbe, Yulia; Debs, Rabab; Musat, Esteban Munoz; Lenglet, Timothée; Lambrecq, Virginie; Hanin, Aurélie; Chougar, Lydia; Shor, Nathalia; Pyatigorskaya, Nadya; Galanaud, Damien; Leclercq, Delphine; Demeret, Sophie; Gassama, Salimata; Degos, Vincent; Jacquens, Alice; Similowski, Thomas; Morélot-Panzini, Capucine; Rotgé, Jean-Yves; Saudreau, Bertrand; Millet, Bruno; Pitron, Victor; Sarni, Nassim; Girault, N.; Maatoug, Redwan; Gales, Ana; Leu, Smaranda; Bayen, É.; Thivard, Lionel; Mokhtari, Karima; Plu, Isabelle; Gonçalves, Bruno; Bottin, Laure; Yger, Marion; Ouvrard, Gaëlle; Haddad, Rebecca; Ketz, Flora; Lafuente, Carmelo; Oasi, Christel; Megabarne, Bruno; Hervé, Dominique; Salman, Haysam; Rametti‐Lacroux, Armelle; Chalançon, Alize; Hervé, Anaïs; Royer, Hugo; Beauzor, Florence; Maheo, Valentine; Laganot, Christelle; Minelli, Camille; Fekete, Aurélie; Grine, Abel; Biet, Marie; Hilab, Rania; Besnard, Aurore; Bouguerra, Meriem; Goudard, Gwen; Houairi, Saida; Al‐Youssef, Saba; Pires, Christine; Oukhedouma, Anissa; Siuda‐Krzywicka, Katarzyna; Malkinson, Tal Seidel; Agguini, Hanane; Douzane, Hassen; Said, Safia; Houot, Marion

doi:10.1093/brain/awaa337

Cited by 60 publications

(98 citation statements)

References 19 publications

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“…CSF oligoclonal bands were tested in 114 patients who did not have a positive CSF SARS-CoV-2 PCR or positive CSF antibodies to SARS-CoV-2 (103 (90%) who had symptoms that localized to the CNS and 11 (10%) who had symptoms that localized to the PNS) [ 9 , 10 , 19 , 20 , 35 , 36 , 42 , 44 , 45 , 58 , 69 , 74 , 79 , 81 , 101 , 112 , 113 , 116 , 117 , 126 , 127 , 130 , 135 , 136 , 147 , 149 , 152 , 154 , 160 , [168] , [169] , [170] , [171] , 177 , 181 , 182 , [185] , [186] , [187] , [188] , 191 , 194 , 203 , 205 , 207 , 209 , 212 , 213 , 215 , 216 , 218 , 233 , 242 , 245 ]. Of these, 35 (31%) had matched CSF and serum bands [ 9 , 35 , 79 , 112 , 113 , 127 , 147 , 170 , 171 , …”

Section: Resultsmentioning

confidence: 99%

“…Autoimmune antibodies were tested in the CSF of 72/430 (17%) patients (60 (83%) of whom were encephalopathic or comatose, 4 (6%) of whom were paraparetic, 3 (4%) of whom had seizures, 3 (4%) of whom had cerebellar symptoms, 1 (1%) of whom had parkinsonism and 1 (1%) of whom was locked-in) [ 10 , 25 , 30 , 34 , 44 , 45 , 74 , 122 , 135 , 136 , 141 , 148 , 154 , 164 , 169 , 171 , 177 , 182 , 185 , 186 , 191 , 193 , 194 , [205] , [206] , [207] , 209 , 213 , 215 , 216 , 220 , 233 , 234 , 242 , 245 , 246 ]. Of the 72 patients who had autoimmune antibodies tested in the CSF, 4 (6%) had positive autoimmune antibodies [ 30 , 169 , 171 , 205 ].…”

Section: Resultsmentioning

confidence: 99%

“…Although CSF testing of biomarkers is not universally available, we identified 58 patients who had CSF biomarkers measured, 46 (79%) of whom had elevation of at least one CSF biomarker suggesting the presence of inflammation, axonal injury, gliosis and Alzheimer-type pathologic changes [ 10 , 24 , 25 , 30 , 31 , 98 , 111 , 119 , 128 , 135 , 136 , 149 , 157 , 165 , 182 , 191 , 205 , 215 , 217 , 227 , 231 , 236 ]. Interestingly, some of these patients had elevation of biomarkers in the CSF, but not the serum, which is similar to ICANS, the neurotoxicity that occurs after treatment with chimeric antigen receptor T-cell therapy [ 10 , 217 , 231 ].…”

Section: Discussionmentioning

confidence: 99%

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Cerebrospinal fluid in COVID-19: A systematic review of the literature

Lewis

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Placantonakis

et al. 2021

Journal of the Neurological Sciences

153

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We sought to review the literature on cerebrospinal fluid (CSF) testing in patients with COVID-19 for evidence of viral neuroinvasion by SARS-CoV-2. Methods: We performed a systematic review of Medline and Embase between December 1, 2019 and November 18, 2020 to identify case reports or series of patients who had COVID-19 diagnosed based on positive SARS-CoV-2 polymerase chain reaction (PCR) or serologic testing and had CSF testing due to a neurologic symptom. Results: We identified 242 relevant documents which included 430 patients with COVID-19 who had acute neurological symptoms prompting CSF testing. Of those, 321 (75%) patients had symptoms that localized to the central nervous system (CNS). Of 304 patients whose CSF was tested for SARS-CoV-2 PCR, there were 17 (6%) whose test was positive, all of whom had symptoms that localized to the central nervous system (CNS). The majority (13/17, 76%) of these patients were admitted to the hospital because of neurological symptoms. Of 58 patients whose CSF was tested for SARS-CoV-2 antibody, 7 (12%) had positive antibodies with evidence of intrathecal synthesis, all of whom had symptoms that localized to the CNS. Of 132 patients who had oligoclonal bands evaluated, 3 (2%) had evidence of intrathecal antibody synthesis. Of 77 patients tested for autoimmune antibodies in the CSF, 4 (5%) had positive findings. Conclusion: Detection of SARS-CoV-2 in CSF via PCR or evaluation for intrathecal antibody synthesis appears to be rare. Most neurological complications associated with SARS-CoV-2 are unlikely to be related to direct viral neuroinvasion.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cerebrospinal fluid in COVID-19: A systematic review of the literature

Lewis

Frontera

Placantonakis

et al. 2021

Journal of the Neurological Sciences

153

152

View full text Add to dashboard Cite

show abstract

“…[ 29 ]. Although we cannot rule out a spontaneous recovery, the impressive and rapid response to immunotherapies argues in favour of a dysimmune mechanism [ 22 ]. In our case, as in most patients with neurological manifestations, CSF analysis showed neither inflammation nor the presence of the virus [ 2 , 5 , 9 ].…”

Section: Discussionmentioning

confidence: 99%

“…At 5.5 months, he was discharged home with only a mild attention deficit disorder, fatigability (walk with a cane for long distances) and a chronic cough (Glasgow outcome scale extended (GOSE) = 6), ( Figure 5 ). Note that this patient has previously been reported in a case series focusing exclusively on therapeutic options in COVID-19 associated encephalitis [ 22 ].…”

Section: Clinical Presentationmentioning

confidence: 95%

Neuroprognostication of Consciousness Recovery in a Patient with COVID-19 Related Encephalitis: Preliminary Findings from a Multimodal Approach

et al. 2020

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Predicting the functional recovery of patients with severe neurological condition due to coronavirus disease 2019 (COVID-19) is a challenging task. Only limited outcome data are available, the pathophysiology is poorly understood, and the time-course of recovery is still largely unknown. Here, we report the case of a patient with COVID-19 associated encephalitis presenting as a prolonged state of unresponsiveness for two months, who finally fully recovered consciousness, functional communication, and autonomy after immunotherapy. In a multimodal approach, a high-density resting state EEG revealed a rich brain activity in spite of a severe clinical presentation. Using our previously validated algorithms, we could predict a possible improvement of consciousness in this patient. This case report illustrates the value of a multimodal approach capitalizing on advanced brain-imaging and bedside electrophysiology techniques to improve prognosis accuracy in this complex and new aetiology.

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Association of Clinical, Biological, and Brain Magnetic Resonance Imaging Findings With Electroencephalographic Findings for Patients With COVID-19

et al. 2021

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Key Points Question Can electroencephalography (EEG), combined with clinical, biological, and magnetic resonance imaging (MRI) analyses, help to better characterize patients with neurologic coronavirus disease 2019 (COVID-19) and diagnose specific COVID-19–related encephalopathy? Findings Neurologic manifestations, biological findings, EEG findings, and brain MRI images were analyzed in a cohort study of 78 adult patients with COVID-19. Nine patients had no identified cause of brain injury, as revealed by biological and MRI findings; their injury was defined as COVID-19–related encephalopathy. Meaning This study suggests that, although neurologic manifestations, EEG findings, and MRI findings may appear heterogeneous and nonspecific, multimodal monitoring may better identify patients with COVID-19–related encephalopathy and guide treatment strategy.

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Severe COVID-19-related encephalitis can respond to immunotherapy

Cited by 60 publications

References 19 publications

Cerebrospinal fluid in COVID-19: A systematic review of the literature

Cerebrospinal fluid in COVID-19: A systematic review of the literature

Neuroprognostication of Consciousness Recovery in a Patient with COVID-19 Related Encephalitis: Preliminary Findings from a Multimodal Approach

Association of Clinical, Biological, and Brain Magnetic Resonance Imaging Findings With Electroencephalographic Findings for Patients With COVID-19

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