%0 Journal Article %A Frank Van De Veerdonk %A Monika Looijen-Salamon %A Michel Van Den Heuvel %A Quirijn Van Der Mast %A Catrien Van Der Meer %A Shoko Vos %A Sarah Van Belle %A Sanne Vermorgen %A Johannes G. Van Der Hoeven %A Mihai G. Netea %A Katrien Grünberg %T Late Breaking Abstract - Plasma cells and endothelitis in COVID-19 lung pathology %D 2020 %R 10.1183/13993003.congress-2020.4148 %J European Respiratory Journal %P 4148 %V 56 %N suppl 64 %X Histopathology is a powerful tool to understand the COVID-19 pathogenesis and come up with rational treatment strategies. We present lung histopathological features of biopsies of fatal COVID-19 cases together with anakinra (Kineret®) Il-1α and IL-1β receptor blocking treatment of the disease. Lung biopsy of 8 cases were scored for alveolar, vascular and inflammatory features on a 4-point scale (none-severe) by 3 lung pathologists; consensus scores were used. Anakinra was given in off-label setting to 3 COVID-19 cases receiving ICU treatment including mechanical ventilation. Lung pathology includes 1. Extensive epithelial damage with regenerative metaplasia with co-localization of neutrophils and macrophages, together with organizing pneumonia and scarring, 2. Alveolar edema, hemorrhage, diffuse alveolar damage and a dominant pattern of acute and chronic arterial thrombosis in all cases as manifestations of vascular leakage and its sequelae, and 3. plasma cell or T cell endothelitis of the pulmonary arteries as a characteristic feature to COVID-19 in six out of eight cases, indicating a role for plasma cells (fig.1) or T cells in its vascular pathology. The temporal heterogeneity of both the epithelial damage and repair and the thrombosis and thrombotic arteriopathy within in all cases indicated ongoing disease. The anakinra-treated cases showed a rapid response with extubation in 2-4 days and a drop in fever and inflammatory parameters. We propose that these distinctive features of COVID-19 are initiated through the IL-1 innate immunity pathway and operated by plasma cells. We further provide proof of concept that the IL-1 receptor antagonist anakinra was beneficial in the late and severe stage of COVID-19 disease.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 4148.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). %U