Giant Cell Arteritis With Medin-Derived Amyloid (AMed) Deposition in a Patient With COVID-19: An Autopsy Case

An 88-year-old man with no past clinical history of polymyalgia rheumatica and symptoms suggestive of giant cell arteritis (GCA), per his family, was found dead outdoors. Antigen testing and real-time PCR confirmed COVID-19 infection. Histopathologic examination revealed granulomatous inflammation consistent with GCA throughout the aorta. Moreover, the medial layer showed widespread amyloid deposits, some of which were phagocytosed by multinucleated GCs and macrophages. Proteomic analysis using laser microdissection and liquid chromatography-tandem mass spectrometry confirmed that the deposits primarily comprise lactadherin, particularly medin peptides. Immunohistochemistry with antisera directed against three medin sequences confirmed immunoreactivity in the amyloid deposits (medin-derived amyloid [AMed]), as well as in the cytoplasm of adjacent histiocytes and multinucleated GCs. In addition, postmortem serum analysis revealed markedly elevated interleukin-6 (IL-6) levels (383 pg/mL; reference ≤ 7.0 pg/mL). These findings suggest that the cause of death was multi-organ failure resulting from a systemic inflammatory response associated with COVID-19. IL-6 is strongly implicated in GCA pathogenesis. By analogy with vasculitides associated with other age-related amyloids, GCA is suggested to result from an immune response targeting AMed deposits. Taken together, GCA in this case may have developed via an immune response to AMed triggered by COVID-19-related IL-6 elevation.