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.
Subject(s)
Betacoronavirus/pathogenicity , Bone Marrow/pathology , Coronavirus Infections/pathology , Cytokine Release Syndrome/pathology , Disseminated Intravascular Coagulation/pathology , Lung/pathology , Pneumonia, Viral/pathology , Thrombosis/pathology , Adult , Aged , Autopsy , Betacoronavirus/immunology , Bone Marrow/immunology , Bone Marrow/virology , COVID-19 , Cell Nucleus/immunology , Cell Nucleus/pathology , Cell Nucleus/virology , Coronavirus Infections/complications , Coronavirus Infections/immunology , Coronavirus Infections/virology , Critical Illness , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Disseminated Intravascular Coagulation/complications , Disseminated Intravascular Coagulation/immunology , Disseminated Intravascular Coagulation/virology , Fatal Outcome , Host-Pathogen Interactions/immunology , Humans , Interleukin-6/biosynthesis , Interleukin-6/immunology , Lung/immunology , Lung/virology , Male , Megakaryocytes/immunology , Megakaryocytes/pathology , Megakaryocytes/virology , Middle Aged , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2 , Severity of Illness Index , Thrombopoiesis/immunology , Thrombosis/complications , Thrombosis/immunology , Thrombosis/virologyABSTRACT
Coronavirus Disease 2019 (COVID-19) is an ongoing public health emergency and new knowledge about its immunopathogenic mechanisms is deemed necessary in the attempt to reduce the death burden, globally. For the first time in worldwide literature, we provide scientific evidence that in COVID-19 vasculitis a life-threatening escalation from type 2 T-helper immune response (humoral immunity) to type 3 hypersensitivity (immune complex disease) takes place. The subsequent deposition of immune complexes inside the vascular walls is supposed to induce a severe inflammatory state and a cytokine release syndrome, whose interleukin-6 is the key myokine, from the smooth muscle cells of blood vessels.