Authors:	Hollerbach, Anne Müller-Calleja, Nadine Pedrosa, Denise Canisius, Antje Sprinzl, Martin F. Falter, Tanja Rossmann, Heidi Bodenstein, Marc Werner, Christian Sagoschen, Ingo Münzel, Thomas Schreiner, Oliver Sivanathan, Visvakanth Reuter, Michael Niermann, Johannes Galle, Peter R. Teyton, Luc Ruf, Wolfram Lackner, Karl J.
Title:	Pathogenic lipid-binding antiphospholipid antibodies are associated with severity of COVID-19
Online publication date:	12-Sep-2022
Year of first publication:	2021
Language:	english
Abstract:	Background Coronavirus disease 19 (COVID-19)–associated coagulopathy is a hallmark of disease severity and poor prognosis. The key manifestations of this prothrombotic syndrome—microvascular thrombosis, stroke, and venous and pulmonary clots—are also observed in severe and catastrophic antiphospholipid syndrome. Antiphospholipid antibodies (aPL) are detectable in COVID-19 patients, but their association with the clinical course of COVID-19 remains unproven. Objectives To analyze the presence and relevance of lipid-binding aPL in hospitalized COVID-19 patients. Methods Two cohorts of 53 and 121 patients from a single center hospitalized for PCR-proven severe acute respiratory syndrome–coronavirus 2 infection were analyzed for the presence of aPL and clinical severity of COVID-19. Results We here demonstrate that lipid-binding aPL are common in COVID-19. COVID-19 patients with lipid-binding aPL have higher median concentrations of C-reactive protein and D-dimer, and are more likely to have a critical clinical course and fatal outcome. Lipid-binding aPL isolated from COVID-19 patients target the recently described cell surface complex of lysobisphosphatidic acid (LBPA) with the protein C receptor (EPCR) to induce prothrombotic and inflammatory responses in monocytes and endothelial cells. We show that B1a cells producing lipid-reactive aPL of the IgG isotype circulate in the blood of COVID-19 patients. In vivo, COVID-19 aPL accelerate thrombus formation in an experimental mouse model dependent on the recently delineated signaling pathway involving EPCR-LBPA. Conclusions COVID-19 patients rapidly expand B1a cells secreting pathogenic lipid-binding aPL with broad thrombotic and inflammatory effects. The association with markers of inflammation and coagulation, clinical severity, and mortality suggests a causal role of aPL in COVID-19–associated coagulopathy.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7704
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY-NC
Information on rights of use:	https://creativecommons.org/licenses/by-nc/4.0/
Journal:	Journal of thrombosis and haemostasis 19 9
Pages or article number:	2335 2347
Publisher:	Wiley-Blackwell
Publisher place:	Oxford
Issue date:	2021
ISSN:	1538-7836
Publisher DOI:	10.1111/jth.15455
Appears in collections:	JGU-Publikationen