ABSTRACT
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®) 11-1 a and IL-1ß 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 orT 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) orT 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.