TY - JOUR T1 - Increased protease-activated receptor 1 autoantibodies are associated with severe COVID-19 JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00379-2022 VL - 8 IS - 4 SP - 00379-2022 AU - Florian Tran AU - Danielle M.M. Harris AU - Alena Scharmacher AU - Hanna Graßhoff AU - Kristina Sterner AU - Susanne Schinke AU - Nadja Käding AU - Jens Y. Humrich AU - Otávio Cabral-Marques AU - Joana P. Bernardes AU - Neha Mishra AU - Thomas Bahmer AU - Jeanette Franzenburg AU - Bimba F. Hoyer AU - Andreas Glück AU - Martina Guggeis AU - Alexander Ossysek AU - Andre Küller AU - Derk Frank AU - Christoph Lange AU - Jan Rupp AU - Jan Heyckendorf AU - Karoline I. Gaede AU - Howard Amital AU - Philip Rosenstiel AU - Yehuda Shoenfeld AU - Gilad Halpert AU - Avi Z. Rosenberg AU - Kai Schulze-Forster AU - Harald Heidecke AU - Gabriela Riemekasten AU - Stefan Schreiber Y1 - 2022/10/01 UR - http://openres.ersjournals.com/content/8/4/00379-2022.abstract N2 - Immune perturbation is a hallmark of coronavirus disease 2019 (COVID-19), with ambiguous roles of various immune cell compartments. Plasma cells, responsible for antibody production, have a two-pronged response while mounting an immune defence with 1) physiological immune response producing neutralising antibodies against protein structures of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 2) potentially deleterious autoantibody generation. Growing evidence hints towards broad activation of plasma cells and the presence of pathological autoantibodies (abs) that mediate immune perturbation in acute COVID-19 [1]. Recently, a systematic screening for abs confirmed induction of diverse functional abs in SARS-CoV-2 infection, targeting several immunomodulatory proteins, including cytokines/chemokines and their respective G-protein coupled receptors (GPCR) [1]. Abs against GPCR act as agonistic and allosteric receptor modulators and are linked to chronic inflammatory diseases [2] and, as we demonstrated recently, disease severity in acute COVID-19 [3].In patients with severe #COVID19, increased levels of autoantibodies against PAR1 were found. These might serve as allosteric agonists of PAR1 on endothelial cells and platelets, and thus might contribute to the pathogenesis of microthrombosis in COVID-19. https://bit.ly/3pqM9VvWe thank M. Rohm, M. Hansen and R. Möhring (Institute of Clinical Molecular Biology, University Medical Center Schleswig-Holstein, Kiel, Germany) for perfect technical assistance. We are indebted to the patients, their families and the hospital staff for support, without whom this study would not have been possible. ER -