W152 - Massive Microthrombosis in the Heart Muscular Tissues with Decreased ADAMTS13 Activity in a Lethal Case of Acute Heart Failure Following Mrna Vaccination Against covid-19

Hiroyuki Yoshitomi, MD PhD – Department of Immunology, Graduate School of Medicine – Kyoto University; Akihiko Sugimoto, MD – Department of Diagnostic Pathology – Kyoto University Hospital; Sachiko Minamiguchi, MD PhD – Department of Diagnostic Pathology – Kyoto University Hospital; Hironori Haga, MD PhD – Department of Diagnostic Pathology – Kyoto University Hospital; Takamoto Hirota, MD – Department of Cardiology – Osaka Saiseikai Noe Hospital; Kinta Hatakeyama, MD PhD – Department of Pathology – National Cerebral and Cardiovascular Center Hospital; Yoshihiko Ikeda, MD PhD – Department of Pathology – National Cerebral and Cardiovascular Center Hospital; Keiko Ogo, MD PhD – Department of Pathology – National Cerebral and Cardiovascular Center Hospital; Masanori Matsumoto, MD PhD – Department of Blood Transfusion Medicine – Nara Medical University; Hideki Ueno, MD PhD – Department of Immunology, Graduate School of Medicine – Kyoto University

Abstract Text: Myocarditis has been shown to be one of the rare complications following immunization with mRNA vaccines against Covid-19. Although symptoms are mostly mild and self-limiting, lethal cases have also been reported. The pathogenesis of vaccine-associated myocarditis remains largely unknown and lack of appropriate animal models necessitates human immunology approach using samples from real world patients. Here, we performed an in-depth analysis of a case of lethal acute heart failure after the third mRNA vaccination. A previously healthy male in his fifties developed cardiac arrest sixteen hours after vaccination and deceased thirteen days later. Autopsy revealed infiltration of inflammatory cells into myocytes, confirming the diagnosis of myocarditis. Single-cell RNA sequencing of the pericardial effusion revealed a large proportion of macrophages expressing proinflammatory cytokine genes, including IL-1β, IL-6, IL-18 and TNF-α. Elevation of serum inflammatory cytokines at onset as well as the presence of bone marrow hemophagocytosis at autopsy demonstrated the presence of cytokine storm. Infiltration of neutrophils carrying IFN responsive gene signature was evident within the cardiac tissue. Additionally, massively distributed microthrombi were noted within the heart muscle tissues. Serum ADAMTS13 activity at onset was significantly reduced, but autoantibodies against ADAMTS13 were absent. We suspect that low ADAMTS13 activity together with activated neutrophils and vascular endothelial damage caused by the cytokine-storm seemed to coordinately contribute to the formation of microthrombi, resulting in the myocardial ischemia and subsequent cardiac arrest. In conclusion, our study demonstrates a possible involvement of systemic hyperinflammation and thrombosis in a lethal type of vaccine-associated acute heart failure.