Benjamin LA, Paterson RW, Moll R, Pericleous C, Brown R, Mehta PR, Athauda D, Ziff OJ, Heaney J, Checkley AM, Houlihan CF, Chou M, Heslegrave AJ, Chandratheva A, Michael BD, Blennow K, Vivekanandam V, Foulkes A, Mummery CJ, Lunn MP, Keddie S, Spyer MJ, Mckinnon T, Hart M, Carletti F, Jäger HR, Manji H, Zandi MS, Werring DJ, Nastouli E, Simister R, Solomon T, Zetterberg H, Schott JM, Cohen H, Efthymiou M, UCLH Queen Square COVID-19 Biomarker Study group
EClinicalMedicine 39 (-) 101070 [2021-09-00; online 2021-08-12]
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. 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. 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. 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. 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.