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

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 [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.

• Authors: 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, UCLH Queen Square COVID-19 Biomarker Study group
• Journal: EClinicalMedicine (EClinicalMedicine) Vol. 39 Pg. 101070 (Sep 2021) ISSN: 2589-5370 [Electronic] England
• PMID: 34401683 (Publication Type: Journal Article)
• Copyright: © 2021 The Author(s).