A proof of evidence supporting abnormal immunothrombosis in severe COVID-19: naked megakaryocyte nuclei increase in the bone marrow and lungs of critically ill patients

Abstract

Coronavirus disease 2019 (COVID-19) is a global public health emergency with many clinical facets, and new knowledge about its pathogenetic mechanisms is deemed necessary; among these, there are certainly coagulation disorders. In the history of medicine, autopsies and tissue sampling have played a fundamental role in order to understand the pathogenesis of emerging diseases, including infectious ones; compared to the past, histopathology can be now expanded by innovative techniques and modern technologies. For the first time in worldwide literature, we provide a detailed postmortem and biopsy report on the marked increase, up to 1 order of magnitude, of naked megakaryocyte nuclei in the bone marrow and lungs from serious COVID-19 patients. Most likely related to high interleukin-6 serum levels stimulating megakaryocytopoiesis, this phenomenon concurs to explain well the pulmonary abnormal immunothrombosis in these critically ill patients, all without molecular or electron microscopy signs of megakaryocyte infection.

Keywords:

• Coronavirus disease 2019 (COVID-19)
• immunothrombosis
• interleukin-6 (IL-6)
• megakaryocytes
• naked megakaryocyte nuclei
• severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Acknowledgements

We thank the Interdepartmental Center for Large Instruments of Modena and Reggio Emilia University, the Pathology Lab of Policlinico Hospital (Modena), and the Laboratory of Toxicology and Advanced Diagnostics of Baggiovara Hospital (Modena).

Authors Contribution

LR conceived, designed and supervised the study, interpreted the data, prepared figures and table with the related legends and wrote the manuscript; GL, WG, LF, CM, and GG performed the experiments and analyzed the data; VN, BL, MC, and TT provided ideas for the research study; SG, ML, TS, and AP performed the literature search; AM revised critically the final version of the manuscript.

Disclosure Statement

The authors report no conflicts of interest.

Supplementary Material

Supplemental data for this article can be accessed on the publisher’s website. Figure S1, Figure S2, Table S1 and related legends are available as supplemental online material.