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

Platelets. 2020 Nov 16;31(8):1085-1089. doi: 10.1080/09537104.2020.1810224. Epub 2020 Aug 28.

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).

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Aged
  • Autopsy
  • Betacoronavirus / immunology
  • Betacoronavirus / pathogenicity*
  • Bone Marrow / immunology
  • Bone Marrow / pathology*
  • Bone Marrow / virology
  • COVID-19
  • Cell Nucleus / immunology
  • Cell Nucleus / pathology
  • Cell Nucleus / virology
  • Coronavirus Infections / complications
  • Coronavirus Infections / immunology
  • Coronavirus Infections / pathology*
  • Coronavirus Infections / virology
  • Critical Illness
  • Cytokine Release Syndrome / complications
  • Cytokine Release Syndrome / immunology
  • Cytokine Release Syndrome / pathology*
  • Cytokine Release Syndrome / virology
  • Disseminated Intravascular Coagulation / complications
  • Disseminated Intravascular Coagulation / immunology
  • Disseminated Intravascular Coagulation / pathology*
  • Disseminated Intravascular Coagulation / virology
  • Fatal Outcome
  • Host-Pathogen Interactions / immunology
  • Humans
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / immunology
  • Lung / immunology
  • Lung / pathology*
  • Lung / virology
  • Male
  • Megakaryocytes / immunology
  • Megakaryocytes / pathology
  • Megakaryocytes / virology
  • Middle Aged
  • Pandemics
  • Pneumonia, Viral / complications
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / pathology*
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Severity of Illness Index
  • Thrombopoiesis / immunology
  • Thrombosis / complications
  • Thrombosis / immunology
  • Thrombosis / pathology*
  • Thrombosis / virology

Substances

  • IL6 protein, human
  • Interleukin-6