Antiphospholipid antibodies and neurological manifestations in acute COVID-19: A single-centre cross-sectional study

Laura A. Benjamin; Ross W. Paterson; Rachel Moll; Charis Pericleous; Rachel Brown; Puja R. Mehta; Dilan Athauda; Oliver J. Ziff; Judith Heaney; Anna M. Checkley; Catherine F. Houlihan; Michael Chou; Amanda J. Heslegrave; Arvind Chandratheva; Benedict D. Michael; Kaj Blennow; Vinojini Vivekanandam; Alexander Foulkes; Catherine J. Mummery; Michael P. Lunn; Stephen Keddie; Moira J. Spyer; Tom Mckinnon; Melanie Hart; Francesco Carletti; Hans Rolf Jäger; Hadi Manji; Michael S. Zandi; David J. Werring; Eleni Nastouli; Robert Simister; Tom Solomon; Henrik Zetterberg; Jonathan M. Schott; Hannah Cohen; Maria Efthymiou

EClinicalMedicine (Sep 2021)

Antiphospholipid antibodies and neurological manifestations in acute COVID-19: A single-centre cross-sectional study

Laura A. Benjamin,
Ross W. Paterson,
Rachel Moll,
Charis Pericleous,
Rachel Brown,
Puja R. Mehta,
Dilan Athauda,
Oliver J. Ziff,
Judith Heaney,
Anna M. Checkley,
Catherine F. Houlihan,
Michael Chou,
Amanda J. Heslegrave,
Arvind Chandratheva,
Benedict D. Michael,
Kaj Blennow,
Vinojini Vivekanandam,
Alexander Foulkes,
Catherine J. Mummery,
Michael P. Lunn,
Stephen Keddie,
Moira J. Spyer,
Tom Mckinnon,
Melanie Hart,
Francesco Carletti,
Hans Rolf Jäger,
Hadi Manji,
Michael S. Zandi,
David J. Werring,
Eleni Nastouli,
Robert Simister,
Tom Solomon,
Henrik Zetterberg,
Jonathan M. Schott,
Hannah Cohen,
Maria Efthymiou

Affiliations

Laura A. Benjamin: National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK; Laboratory of Molecular and Cell Biology, UCL, Gower St, Kings Cross, London WC1E 6BT, UK; Brain Infections Group, University of Liverpool, Liverpool, Merseyside, UK; Stroke Research Centre, UCL Queen Square Institute of Neurology, London, UK; Corresponding author at: National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK.
Ross W. Paterson: National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK; UCL Queen Square Institute of Neurology, London, UK; Darent Valley Hospital, Dartford, Kent, UK; UK Dementia Research Institute, London, UK
Rachel Moll: Haemostasis Research Unit, Department of Haematology, UCL, UK; Department of Haematology, University College London Hospitals, UK
Charis Pericleous: Imperial College London, National Heart and Lung Institute, UK
Rachel Brown: National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK; UCL Queen Square Institute of Neurology, London, UK; Department of Infection and Immunity, University College London, UK
Puja R. Mehta: National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK; UCL Queen Square Institute of Neurology, London, UK
Dilan Athauda: National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK; UCL Queen Square Institute of Neurology, London, UK
Oliver J. Ziff: National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK; UCL Queen Square Institute of Neurology, London, UK; Francis Crick Institute, London, UK
Judith Heaney: Department of Clinical Virology, University College London Hospitals NHS Foundation Trust, UK; Advanced Pathogens Diagnostic Unit, University College London Hospitals NHS Foundation Trust, UK
Anna M. Checkley: Hospital of Tropical Medicine, University College London Hospitals, UK
Catherine F. Houlihan: Department of Infection and Immunity, University College London, UK; Department of Clinical Virology, University College London Hospitals NHS Foundation Trust, UK; Advanced Pathogens Diagnostic Unit, University College London Hospitals NHS Foundation Trust, UK
Michael Chou: UCL Queen Square Institute of Neurology, London, UK; Neuroimmunology and CSF Laboratory, National Hospital for Neurology and Neurosurgery, UK
Amanda J. Heslegrave: National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK; UCL Queen Square Institute of Neurology, London, UK; UK Dementia Research Institute, London, UK
Arvind Chandratheva: National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK; Stroke Research Centre, UCL Queen Square Institute of Neurology, London, UK
Benedict D. Michael: Brain Infections Group, University of Liverpool, Liverpool, Merseyside, UK; Veterinary and Ecological Sciences, National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, University of Liverpool, UK; Walton Centre NHS Foundation Trust, Liverpool, UK
Kaj Blennow: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
Vinojini Vivekanandam: National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK; UCL Queen Square Institute of Neurology, London, UK
Alexander Foulkes: National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK
Catherine J. Mummery: National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK; UCL Queen Square Institute of Neurology, London, UK; UK Dementia Research Institute, London, UK
Michael P. Lunn: UCL Queen Square Institute of Neurology, London, UK; Neuroimmunology and CSF Laboratory, National Hospital for Neurology and Neurosurgery, UK
Stephen Keddie: UCL Queen Square Institute of Neurology, London, UK; Neuroimmunology and CSF Laboratory, National Hospital for Neurology and Neurosurgery, UK
Moira J. Spyer: Department of Clinical Virology, University College London Hospitals NHS Foundation Trust, UK; Advanced Pathogens Diagnostic Unit, University College London Hospitals NHS Foundation Trust, UK; Institute of Child Health, UCL, UK
Tom Mckinnon: Department of Immunology and Inflammation, Imperial College London, UK
Melanie Hart: UCL Queen Square Institute of Neurology, London, UK; Neuroimmunology and CSF Laboratory, National Hospital for Neurology and Neurosurgery, UK
Francesco Carletti: National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK
Hans Rolf Jäger: National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK; Stroke Research Centre, UCL Queen Square Institute of Neurology, London, UK
Hadi Manji: National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK
Michael S. Zandi: National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK; UCL Queen Square Institute of Neurology, London, UK
David J. Werring: National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK; Stroke Research Centre, UCL Queen Square Institute of Neurology, London, UK
Eleni Nastouli: Francis Crick Institute, London, UK; Department of Clinical Virology, University College London Hospitals NHS Foundation Trust, UK; Advanced Pathogens Diagnostic Unit, University College London Hospitals NHS Foundation Trust, UK; Institute of Child Health, UCL, UK
Robert Simister: National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK; Stroke Research Centre, UCL Queen Square Institute of Neurology, London, UK
Tom Solomon: Brain Infections Group, University of Liverpool, Liverpool, Merseyside, UK; Veterinary and Ecological Sciences, National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, University of Liverpool, UK; Walton Centre NHS Foundation Trust, Liverpool, UK
Henrik Zetterberg: UCL Queen Square Institute of Neurology, London, UK; UK Dementia Research Institute, London, UK; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
Jonathan M. Schott: National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK; UCL Queen Square Institute of Neurology, London, UK; UK Dementia Research Institute, London, UK
Hannah Cohen: Haemostasis Research Unit, Department of Haematology, UCL, UK; Department of Haematology, University College London Hospitals, UK
Maria Efthymiou: Haemostasis Research Unit, Department of Haematology, UCL, UK; Department of Haematology, University College London Hospitals, UK

Journal volume & issue: Vol. 39
p. 101070

Abstract

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Background: A high prevalence of antiphospholipid antibodies has been reported in case series of patients with neurological manifestations and COVID-19; however, the pathogenicity of antiphospholipid antibodies in COVID-19 neurology remains unclear. Methods: This single-centre cross-sectional study included 106 adult patients: 30 hospitalised COVID-neurological cases, 47 non-neurological COVID-hospitalised controls, and 29 COVID-non-hospitalised controls, recruited between March and July 2020. We evaluated nine antiphospholipid antibodies: anticardiolipin antibodies [aCL] IgA, IgM, IgG; anti-beta-2 glycoprotein-1 [aβ2GPI] IgA, IgM, IgG; anti-phosphatidylserine/prothrombin [aPS/PT] IgM, IgG; and anti-domain I β2GPI (aD1β2GPI) IgG. Findings: There was a high prevalence of antiphospholipid antibodies in the COVID-neurological (73.3%) and non-neurological COVID-hospitalised controls (76.6%) in contrast to the COVID-non-hospitalised controls (48.2%). aPS/PT IgG titres were significantly higher in the COVID-neurological group compared to both control groups (p < 0.001). Moderate-high titre of aPS/PT IgG was found in 2 out of 3 (67%) patients with acute disseminated encephalomyelitis [ADEM]. aPS/PT IgG titres negatively correlated with oxygen requirement (FiO2 R=-0.15 p = 0.040) and was associated with venous thromboembolism (p = 0.043). In contrast, aCL IgA (p < 0.001) and IgG (p < 0.001) was associated with non-neurological COVID-hospitalised controls compared to the other groups and correlated positively with d-dimer and creatinine but negatively with FiO2. Interpretation: Our findings show that aPS/PT IgG is associated with COVID-19-associated ADEM. In contrast, aCL IgA and IgG are seen much more frequently in non-neurological hospitalised patients with COVID-19. Characterisation of antiphospholipid antibody persistence and potential longitudinal clinical impact are required to guide appropriate management. Funding: This work is supported by UCL Queen Square Biomedical Research Centre (BRC) and Moorfields BRC grants (#560441 and #557595). LB is supported by a Wellcome Trust Fellowship (222102/Z/20/Z). RWP is supported by an Alzheimer's Association Clinician Scientist Fellowship (AACSF-20-685780) and the UK Dementia Research Institute. KB is supported by the Swedish Research Council (#2017-00915) and the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), and theUK Dementia Research Institute at UCL. BDM is supported by grants from the MRC/UKRI (MR/V007181/1), MRC (MR/T028750/1) and Wellcome (ISSF201902/3). MSZ, MH and RS are supported by the UCL/UCLH NIHR Biomedical Research Centre and MSZ is supported by Queen Square National Brain Appeal.

Published in EClinicalMedicine

ISSN: 2589-5370 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Medicine (General)
Website: https://www.thelancet.com/journals/eclinm/home

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