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Antiphospholipid antibodies and neurological manifestations in acute COVID-19: A single-centre cross-sectional study.
Benjamin, Laura A; Paterson, Ross W; Moll, Rachel; Pericleous, Charis; Brown, Rachel; Mehta, Puja R; Athauda, Dilan; Ziff, Oliver J; Heaney, Judith; Checkley, Anna M; Houlihan, Catherine F; Chou, Michael; Heslegrave, Amanda J; Chandratheva, Arvind; Michael, Benedict D; Blennow, Kaj; Vivekanandam, Vinojini; Foulkes, Alexander; Mummery, Catherine J; Lunn, Michael P; Keddie, Stephen; Spyer, Moira J; Mckinnon, Tom; Hart, Melanie; Carletti, Francesco; Jäger, Hans Rolf; Manji, Hadi; Zandi, Michael S; Werring, David J; Nastouli, Eleni; Simister, Robert; Solomon, Tom; Zetterberg, Henrik; Schott, Jonathan M; Cohen, Hannah; Efthymiou, Maria.
  • Benjamin LA; National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK.
  • Paterson RW; Laboratory of Molecular and Cell Biology, UCL, Gower St, Kings Cross, London WC1E 6BT, UK.
  • Moll R; Brain Infections Group, University of Liverpool, Liverpool, Merseyside, UK.
  • Pericleous C; Stroke Research Centre, UCL Queen Square Institute of Neurology, London, UK.
  • Brown R; National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK.
  • Mehta PR; UCL Queen Square Institute of Neurology, London, UK.
  • Athauda D; Darent Valley Hospital, Dartford, Kent, UK.
  • Ziff OJ; UK Dementia Research Institute, London, UK.
  • Heaney J; Haemostasis Research Unit, Department of Haematology, UCL, UK.
  • Checkley AM; Department of Haematology, University College London Hospitals, UK.
  • Houlihan CF; Imperial College London, National Heart and Lung Institute, UK.
  • Chou M; National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK.
  • Heslegrave AJ; UCL Queen Square Institute of Neurology, London, UK.
  • Chandratheva A; Department of Infection and Immunity, University College London, UK.
  • Michael BD; National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK.
  • Blennow K; UCL Queen Square Institute of Neurology, London, UK.
  • Vivekanandam V; National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK.
  • Foulkes A; UCL Queen Square Institute of Neurology, London, UK.
  • Mummery CJ; National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK.
  • Lunn MP; UCL Queen Square Institute of Neurology, London, UK.
  • Keddie S; Francis Crick Institute, London, UK.
  • Spyer MJ; Department of Clinical Virology, University College London Hospitals NHS Foundation Trust, UK.
  • Mckinnon T; Advanced Pathogens Diagnostic Unit, University College London Hospitals NHS Foundation Trust, UK.
  • Hart M; Hospital of Tropical Medicine, University College London Hospitals, UK.
  • Carletti F; Department of Infection and Immunity, University College London, UK.
  • Jäger HR; Department of Clinical Virology, University College London Hospitals NHS Foundation Trust, UK.
  • Manji H; Advanced Pathogens Diagnostic Unit, University College London Hospitals NHS Foundation Trust, UK.
  • Zandi MS; UCL Queen Square Institute of Neurology, London, UK.
  • Werring DJ; Neuroimmunology and CSF Laboratory, National Hospital for Neurology and Neurosurgery, UK.
  • Nastouli E; National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK.
  • Simister R; UCL Queen Square Institute of Neurology, London, UK.
  • Solomon T; UK Dementia Research Institute, London, UK.
  • Zetterberg H; National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK.
  • Schott JM; Stroke Research Centre, UCL Queen Square Institute of Neurology, London, UK.
  • Cohen H; Brain Infections Group, University of Liverpool, Liverpool, Merseyside, UK.
  • Efthymiou M; 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.
EClinicalMedicine ; 39: 101070, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1351631
ABSTRACT

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 [aß2GPI] IgA, IgM, IgG; anti-phosphatidylserine/prothrombin [aPS/PT] IgM, IgG; and anti-domain I ß2GPI (aD1ß2GPI) 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.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Language: English Journal: EClinicalMedicine Year: 2021 Document Type: Article Affiliation country: J.eclinm.2021.101070

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Language: English Journal: EClinicalMedicine Year: 2021 Document Type: Article Affiliation country: J.eclinm.2021.101070