Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

Panteleimon G. Takis | Megan L. Nagel | S. Sawcer | W. Paxton | A. Mentzer | A. Venneri | Eglė Savičiūtė | N. Wrobel | Joyce Mitchell | K. Tharmaratnam | R. Salman | M. Noursadeghi | J. Coleman | S. McDonald | J. Child | S. Roberts | L. Merson | R. Bethlehem | M. Dumas | C. Mulholland | T. Veenith | K. Tatham | T. Szakmany | S. Defres | E. Thomson | J. Hiscox | A. Garg | M. Twagira | C. Evans | T. D. de Silva | D. Latawiec | S. Metelmann | R. Thwaites | Maria Mancini | A. Easton | A. Docherty | E. Gkrania-Klotsas | L. Sigfrid | A. Meynert | L. Vincent-Smith | I. Welters | R. Pius | M. Wijesinghe | J. Tanianis-Hughes | G. Koshy | A. Whittington | Clive Graham | J. Minton | R. Vincent | M. Lyttle | P. Lillie | L. Turtle | Krishanthi S Subramaniam | M. Peters | Isabel García-Dorival | V. Sancho-Shimizu | E. Hodel | S. Sriskandan | R. O'Malley | K. Chechi | A. Tamborska | D. Agranoff | M. Zandi | T. Grammatikopoulos | R. Vancheeswaran | Maria-Teresa Cutino-Moguel | G. Koduri | G. Pollakis | P. Bothma | N. Kingston | Richard Smith | A. Fawkes | L. Maslen | C. Fairfield | S. Halpin | H. Hardwick | K. Holden | C. Jackson | L. Norman | O. Swann | A. Hormis | L. McEvoy | S. Knight | D. Hawcutt | P. Dyer | S. Clohisey | S. Panchatsharam | R. Digby | R. Brittain-Long | D. Stuart | Sean S. Keating | J. Pepperell | J. Bernatoniene | A. Elliott | N. Spittle | C. Thompson | S. Laha | P. Andrikopoulos | C. Kerrison | Bhagteshwar Singh | Tristan Dyer | C. Bassford | J. Cupitt | H. Reschreiter | A. Burtenshaw | Marc Hardwick | P. Collini | M. Ellul | Jordan Thomas | C. Dunai | S. Barnass | R. Mulla | S. Dervisevic | S. Kegg | E. Lahnsteiner | A. Palmos | Tim Reynolds | R. Shears | Ross Hendry | Joanne Dalton | Lorna Donnelly | Bobby Ruge | W. Oosthuyzen | S. Lant | G. Rousseau | S. Basude | Sarah J. Cole | N. Bulteel | A. Workman | O. Koch | S. Paddick | P. Papineni | S. Laird | A. Garjani | S. Bakshi | Nigel Chee | J. Sizer | A. Evans | J. Armstrong | B. Small | P. Mansoori | S. Douthwaite | E. Hardy | N. Rae | T. Prince | Innocent G Asiimwe | C. Donohue | T. Leiner | P. Whittaker | R. Wake | P. Ridley | C. Eziefula | E. McGlinchey | N. Carlucci | Benjamin Bach | S. Khoo | S. Moore | Fiona Griffiths | D. Murphy | James Lee | M. Girvan | M. Connor | Murray Wham | M. Ashworth | S. Barlow | Benjamin W. A. Catterall | H. Cox | Oslem Dincarslan | Chris Dunn | L. Finch | P. Gunning | Shadia Khandaker | K. King | Robyn T Kiy | Chrysa Koukorava | L. Lavelle-Langham | Lauren Lett | Lucia A. Livoti | N. Miah | J. Middleton | E. Murphy | Rebekah Penrice-Randal | J. Pilgrim | W. Reynolds | Debby Sales | Agnieska Szemiel | Aislynn Taggart | E. Trochu | E. Wilcock | J. E. Zhang | K. Adeniji | K. Agwuh | D. Ail | A. Alegria | Brian Angus | Doug Atkinson | S. Bari | D. Baxter | N. Best | Vikki Caruth | D. Chambler | S. Chukkambotla | Tom Clark | Chris Dawson | P. Donnison | J. Godden | S. Hartshorn | D. Harvey | M. Hobrok | L. Hodgson | M. Jacobs | A. Kaliappan | V. Kasipandian | Michael R. Kelsey | J. Kendall | I. Kerslake | Susan G. Larkin | J. Little | E. Macnaughton | Ravish Mankregod | Huw Masson | K. McCullough | R. Mcewen | M. Meda | G. Mills | K. Mohandas | Elinoor Moore | P. Morgan | C. Morris | S. Moses | T. Nagarajan | I. Otahal | M. Pais | Hassan Paraiso | Natalie Pattison | M. Phull | S. Pintus | J. Pooni | F. Post | R. Prout | Prad Shanmuga | Anil Sharma | A. Shawcross | N. Staines | T. Stambach | R. Stewart | P. Subudhi | Robert Thompson | A. Tridente | S. Visuvanathan | A. Vuylsteke | S. Waddy | Martin Williams | Lawrence Wilson | S. Winchester | A. Wolverson | B. Yates | Peter Young | Cara Donegan | Anthonia Osagie | Daniella A. Lefteri | L. Flaherty | Nicole Maziere | E. Cass | Anthony Holmes | H. Massey | K. Morrice | Alan Maclean | A. Coutts | Sam Allen | A. Carracedo | G. Sunderland | B. Patel | NicholasS . C. Price | Thomas G Burden | N. Nicholas | L. Norris | M. Samuel | M. Hartmann | C. Collie | Bethany Facer | Catherine Cosgrove | Quen Mok | James P. Stewart | K. Bullock | Lily George | F. Egbe | D. Monssen | H. Rogers | V. Linnett | B. Blackledge | K. Glen | W. Lim | Sonia Liggi | J. Aggleton | J. Mclauchlan | J. Berridge | A. Rose | Erin L. Aldera | Danai Papakonstantinou | M. Olanipekun | A. Fower | Julian L Griffin | P. Jennings | K. Mclean | Chris Green | Louise Macgillivray | D. Chadwick | R. Gregory | Catherine A Shaw | R. L. Jensen | B. Alex | Rebecca G Spencer | S. Boardman | M. Leibowitz | Jacqueline Smith | Sarah Tait | W. Barclay | T. Gilchrist | Lewis W. S. Fisher | J. Limb | Emily Clarke | P. Havalda | L. Cooper | K. Hafezi | K. Ahmed | Sarah McCafferty | N. Martin | Andrew Law | Neil Richardson | Sharon J. Peacock | Pamela J Shaw | M. Shankar-Hari | James Scott-Brown | Lucy Norris | P. Klenerman | Andrew Drummond | David P. Breen | Meera A Chand | N. Basu | M. Broome | G. Carson | D. Price | R. Upthegrove | Andrew Rambaut | Sanjeev Garg | Annette Lake | Gerome Breen | Daniel R Plotkin | J. Baillie | Clark D Russell | Tim Planche | L. Murphy | C. Snelson | David K. Menon | Alan Carson | M. Hotopf | Brendan J. Ryan | S. Irani | Massimo Palmarini | M. Ostermann | M. Wiselka | G. Barlow | P. Openshaw | T. Drake | Debby Bogaert | Graham S. Cooke | C. Gamble | Janet Harrison | David L. Robertson | V. Shaw | Christopher Jones | Chrisopher Fegan | A. Goldsmith | E. Matovu | A. Shah | N. Vallotton | Nicholas A. Barrett | A. Walden | Ewan Harrison | Samreen Ijaz | Gary Leeming | Mbiye A Mpenge | P. Dark | M. Macmahon | S. Jain | J. Underwood | E. Bullmore | I. DuRand | Leonie S. Taams | Nikos Evangelou | Ewen M Harrison | A. M. McIntosh | A. Ashish | A. Finn | D. Fullerton | Rishi Gupta | M. Roberts | Christopher Davis | Matthew R. Lewis | C. Palmieri | Tommy Solomon | M. Beadsworth | C. Berry | J. Howard | M. Nelson | D. Roberts | T. Foster | P. Jezzard | Fernando Zelaya | Maria Zambon | R. S. Tedder | P. Horby | N. Davies | B. Michael | Alasdair J. Coles | Laura J. Booth | Judith Breuer | Katherine Mortimore | Darell Tupper-Carey | Stephen R. Knight | Laura Marsh | Catherine Hartley | L. Tonder | A. Al-Chalabi | M. G. Semple | J. Dunning | Thomas Jackson | T. R. Jones | A. Dushianthan | Timothy Nicholson | Anne-cécile Chiollaz | John‐Paul Taylor | David M. Christmas | R. Clark | Taranprit Saluja | A. Thompson | D. Wootton | W. Greenhalf | Karla Miller | Robyn Williams | Hannah Fox | Laura A. Benjamin | Z. Takáts | Patrick F. Chinnery | Matthew K. O’Shea | Matthias L. Schmid | Adam W. Seed | B. Sargent | S. Pendered | A. Hampshire | Charles Leek | Edward J. Needham | Thomas A Pollak | Kathy Stirrups | G. B. Williams | C. Armour | R. Francis | Yun Huang | Jordan J. Clark | Parul Sharma | Greta K. Wood | Alexander Ren | Emma Norton | Soraya Ebrahimi | Esteban Tato | Marie Held | Claire Hetherington | Alexander Grundmann | Jean-Charles Sanchez | Michael Griffiths | John R Bradley | Jonathan Cavanagh | Angela Vincent | Ana Filipe Da Silva | Gonçalo dos Santos | Tom Fletcher | Antonia Y. Wai | Caroline J. Sands | Janet T. Scott | Charlotte Summers | James Moon | Michael Murphy | Tony Whitehouse | Benjamin Brennan | Adam Sieradzki | Akshay Nair | Alaisdair Coles | Alastair Darby | Alex Dregan | Angela E. Holland | Angela Roberts | Anthony S. David | Arvind Patel | Christopher M. Morris | Christopher M. Allen | C. L. MacIver | Craig J. Smith | Daniel J. van | Daniel Madarshahian | David Cousins | Eugene Duff | Gabriella Lewis | Gavin McDonnell | C. Hannah | Jade D. Harris | James B. Lilleker | J. Amin | Katherine C. Dodd | Mark R. Baker | Masud Husain | Matthew Butler | M. Lunn | Nadine Cossette | Neil A. Harrison | Nicholas Wood | Paul J. Harrison | Peter M. Fernandes | Rahul Batra | Rhys H. Thomas | Ryan McIlwaine | Sandar Kyaw | Savini Gunatilake | Scott Semple | Shahd H. Hamid | Silvia Rota | Simon Keller | Suzanne Barrett | Stella Hughes | Stephen Smith | S. Williams | Sui H. Wong | Thomas M. Jenkins | Victoria Grimbly | V. Newcombe | M. Semple

[1]  Pardis C Sabeti,et al.  Neuropathological features of SARS-CoV-2 delta and omicron variants. , 2023, Journal of neuropathology and experimental neurology.

[2]  J. Kjems,et al.  The brain reacting to COVID-19: analysis of the cerebrospinal fluid proteome, RNA and inflammation , 2023, Journal of Neuroinflammation.

[3]  Wei Jiang,et al.  Infectious diseases, autoantibodies, and autoimmunity. , 2022, Journal of autoimmunity.

[4]  C. Pariante,et al.  Neurogenesis is disrupted in human hippocampal progenitor cells upon exposure to serum samples from hospitalized COVID-19 patients with neurological symptoms , 2022, Molecular psychiatry.

[5]  Z. Al-Aly,et al.  Long-term neurologic outcomes of COVID-19 , 2022, Nature Medicine.

[6]  J. Rivera-Correa,et al.  Autoantibodies during infectious diseases: Lessons from malaria applied to COVID-19 and other infections , 2022, Frontiers in Immunology.

[7]  Kenneth G. C. Smith,et al.  Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses , 2022, Brain : a journal of neurology.

[8]  M. Boldrini,et al.  COVID-19 induces CNS cytokine expression and loss of hippocampal neurogenesis , 2022, Brain : a journal of neurology.

[9]  C. Yasuda,et al.  Morphological, cellular, and molecular basis of brain infection in COVID-19 patients , 2022, Proceedings of the National Academy of Sciences of the United States of America.

[10]  D. Perl,et al.  Neurovascular injury with complement activation and inflammation in COVID-19 , 2022, Brain : a journal of neurology.

[11]  D. Perl,et al.  Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation , 2022, Cell.

[12]  B. Michael,et al.  Immune-Mediated Mechanisms of COVID-19 Neuropathology , 2022, Frontiers in Neurology.

[13]  Peter J Hellyer,et al.  Multivariate profile and acute-phase correlates of cognitive deficits in a COVID-19 hospitalised cohort , 2022, eClinicalMedicine.

[14]  R. Sánchez-Valle,et al.  CSF Biomarkers in COVID-19 Associated Encephalopathy and Encephalitis Predict Long-Term Outcome , 2022, Frontiers in Immunology.

[15]  P. Newton,et al.  Detection and significance of neuronal autoantibodies in patients with meningoencephalitis in Vientiane, Lao PDR , 2022, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[16]  P. Dormitzer,et al.  Modeling SARS-CoV-2: Comparative Pathology in Rhesus Macaque and Golden Syrian Hamster Models , 2022, Toxicologic pathology.

[17]  H. Zhou,et al.  Visualizing in deceased COVID-19 patients how SARS-CoV-2 attacks the respiratory and olfactory mucosae but spares the olfactory bulb , 2021, Cell.

[18]  E. Turillazzi,et al.  SARS‐CoV‐2 and the brain: A review of the current knowledge on neuropathology in COVID‐19 , 2021, Brain pathology.

[19]  P. Marques‐Vidal,et al.  The cytokines HGF and CXCL13 predict the severity and the mortality in COVID-19 patients , 2021, Nature Communications.

[20]  K. Wilson,et al.  Adaptive Immunity and the Risk of Autoreactivity in COVID-19 , 2021, International journal of molecular sciences.

[21]  K. Blennow,et al.  Neurochemical signs of astrocytic and neuronal injury in acute COVID-19 normalizes during long-term follow-up , 2021, EBioMedicine.

[22]  G. Pengas,et al.  Spectrum, risk factors and outcomes of neurological and psychiatric complications of COVID-19: a UK-wide cross-sectional surveillance study , 2021, Brain Communications.

[23]  Panteleimon G. Takis,et al.  Characterisation of in-hospital complications associated with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol UK: a prospective, multicentre cohort study , 2021, The Lancet.

[24]  Siva Sai Krishna Venigalla,et al.  Untangling COVID-19 and autoimmunity: Identification of plausible targets suggests multi organ involvement , 2021, Molecular Immunology.

[25]  D. Quirk,et al.  Tofacitinib in Patients Hospitalized with Covid-19 Pneumonia , 2021, The New England journal of medicine.

[26]  P. Comoglio,et al.  HGF and MET: From Brain Development to Neurological Disorders , 2021, Frontiers in Cell and Developmental Biology.

[27]  D. Kell,et al.  Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin , 2021, Cardiovascular Diabetology.

[28]  R. Domingues,et al.  Cerebrospinal fluid analysis in patients with COVID-19-associated central nervous system manifestations: a systematic review , 2021, Arquivos de Neuro-Psiquiatria.

[29]  A. Khandji,et al.  COVID-19 neuropathology at Columbia University Irving Medical Center/New York Presbyterian Hospital , 2021, medRxiv.

[30]  Y. Crow,et al.  Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19 , 2021, Science Immunology.

[31]  S. Farhadian,et al.  Neuroinvasion of SARS-CoV-2 in human and mouse brain , 2021, The Journal of experimental medicine.

[32]  Jocelyn T. Kim,et al.  Interleukin-8 as a Biomarker for Disease Prognosis of Coronavirus Disease-2019 Patients , 2021, Frontiers in Immunology.

[33]  C. Conrad,et al.  Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19 , 2020, Nature Neuroscience.

[34]  Tony Y. Hu,et al.  Neuropathology and virus in brain of SARS-CoV-2 infected non-human primates , 2020, Nature Communications.

[35]  K. Pahan,et al.  IL-12 p40 monomer is different from other IL-12 family members to selectively inhibit IL-12Rβ1 internalization and suppress EAE , 2020, Proceedings of the National Academy of Sciences.

[36]  K. Blennow,et al.  Complex Autoantibody Responses Occur following Moderate to Severe Traumatic Brain Injury , 2020, The Journal of Immunology.

[37]  Elizabeth B White,et al.  Longitudinal analyses reveal immunological misfiring in severe COVID-19 , 2020, Nature.

[38]  Eric Song,et al.  Longitudinal analyses reveal immunological misfiring in severe COVID-19 , 2020, Nature.

[39]  Maria Thom,et al.  The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings , 2020, Brain : a journal of neurology.

[40]  P. Matthews,et al.  Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study , 2020, The Lancet Psychiatry.

[41]  J. Mege,et al.  Anticardiolipin IgG Autoantibody Level Is an Independent Risk Factor for COVID‐19 Severity , 2020, Arthritis & rheumatology.

[42]  S. Morgello,et al.  Macrothrombosis and stroke in patients with mild Covid‐19 infection , 2020, Journal of Thrombosis and Haemostasis.

[43]  J. Sejvar,et al.  Neurological associations of COVID-19 , 2020, The Lancet Neurology.

[44]  L. Mao,et al.  Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. , 2020, JAMA neurology.

[45]  Edmond J. Breen,et al.  Cytokine levels and associations with symptom severity in male and female children with autism spectrum disorder , 2017, Molecular Autism.

[46]  D. Menon,et al.  Serial Sampling of Serum Protein Biomarkers for Monitoring Human Traumatic Brain Injury Dynamics: A Systematic Review , 2017, Front. Neurol..

[47]  T. Solomon,et al.  Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology , 2016, PloS one.

[48]  T. Solomon,et al.  Post-acute serum eosinophil and neutrophil-associated cytokine/chemokine profile can distinguish between patients with neuromyelitis optica and multiple sclerosis; and identifies potential pathophysiological mechanisms - a pilot study. , 2013, Cytokine.

[49]  T. Solomon,et al.  In enterovirus 71 encephalitis with cardio-respiratory compromise, elevated interleukin 1β, interleukin 1 receptor antagonist, and granulocyte colony-stimulating factor levels are markers of poor prognosis. , 2012, The Journal of infectious diseases.

[50]  R. Balice-Gordon,et al.  Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series , 2010, The Lancet Neurology.

[51]  A. Vincent,et al.  Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan’s syndrome and acquired neuromyotonia , 2010, Brain : a journal of neurology.

[52]  D. Kullmann,et al.  N-methyl-d-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes , 2010, Brain : a journal of neurology.

[53]  B. Segal,et al.  IL-12– and IL-23–modulated T cells induce distinct types of EAE based on histology, CNS chemokine profile, and response to cytokine inhibition , 2008, The Journal of experimental medicine.

[54]  A. Alavi,et al.  Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates. , 2005, Brain : a journal of neurology.

[55]  H. Ljunggren,et al.  The Critical Role of IL‐12p40 in Initiating, Enhancing, and Perpetuating Pathogenic Events in Murine Experimental Autoimmune Neuritis , 2002, Brain pathology.

[56]  B. Winblad,et al.  Neutralizing Antibodies to IL‐18 Ameliorate Experimental Autoimmune Neuritis by Counter‐Regulation of Autoreactive Th1 Responses to Peripheral Myelin Antigen , 2002, Journal of neuropathology and experimental neurology.

[57]  D. Böhning,et al.  Impact of Dexamethasone and Remdesivir on Neurological Complications during COVID-19 , 2022, SSRN Electronic Journal.

[58]  OUP accepted manuscript , 2022, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[59]  OUP accepted manuscript , 2022, Brain.