Plasma Cells and Endothelitis in COVID-19 Lung Pathology

Histopathology is a powerful tool to understand the COVID-19 pathogenesis and come up with rational treatment strategies in real time. 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 score was 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 oedema, haemorrhage, 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 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, 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.Funding: MGN was supported by an ERC Advanced Grant and a Spinoza Grant of the NetherlandsOrganization for Scientific Research (NWO).