Detection of SARS-CoV-2 in bone marrow megakaryocytes and elevated emperipolesis in COVID-19 patients with thrombocytopenia

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BACKGROUND: Thrombocytopenia and altered platelet activation are correlated with COVID-19 severity and mortality. COVID-19 patients have modifications of the platelet and blood-circulating megakaryocyte (MK) transcriptome. OBJECTIVES: To explore the features of bone marrow MKs, which remain poorly characterized in SARS-CoV-2-infected patients, particularly those with thrombocytopenia. METHODS: In this case series study, we analyzed bone marrow samples from a series of 11 COVID-19 patients with thrombocytopenia admitted to the intensive care unit for acute respiratory distress syndrome. Bone marrow sampling, aimed to explore thrombocytopenia's etiology by cytology, allowed us to document bone marrow MK behavior. RESULTS: A reduction in bone marrow cellularity and a decrease in the megakaryocytic lineage were observed, suggesting a central component of the thrombocytopenia. Bone marrow MKs exhibited significantly increased emperipolesis and vacuolization. Moreover, transmission electron microscopy pointed to the presence of viral particles inside bone marrow MKs. Immunolabeling confirmed the presence of 2 SARS-CoV-2 proteins, spike and Orf3a, and double-stranded RNA, suggesting a potential viral replication cycle. CONCLUSION: In this series of COVID-19 patients with thrombocytopenia, we report the presence of SARS-CoV-2 in bone marrow MKs as well as a decrease in MK lineage and an increase in emperipolesis.

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