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

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 [aβ(2)GPI] IgA, IgM, IgG; anti-phosphatidylserine/prothrombin [aPS/PT] IgM, IgG; and anti-domain I β(2)GPI (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 (FiO(2)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 FiO(2). 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.