COVID-19-Latest: SARS-CoV-2 May Target Red Marrow And Prevent Formation Of New Erythrocytes. Vitamin B12 Supplementation Important
: A new study by scientist from Far Eastern Federal University, Vladivostok-Russia, Pacific State Medical University, Vladivostok-Russia and the International Medical Research Center, Niigata-Japan finds that the SARS-CoV-2 coronavirus might attack the red marrow , thus not only affecting existing erythrocytes in the bloodstream but also the process of the formation of the new ones.
The study findings considers the possible mechanism of the pathogenesis of COVID-19 caused by SARSCOV-2, associated with damage to red blood cells, which the study team attribute to the main key target that triggers a cascade of reactions leading to multiple organ failure.
The study findings present morphological evidence for the presence of pathological forms of erythrocytes characteristic of various anemias in the blood vessels and parenchyma of damaged lungs of patients with COVID-19.
The death of red blood cells leads to cell ischemia and anemia. The defeat of brain neurons, blood vessels and hematotissue barriers in organ systems is a consequence of ischemia due to the impossibility of transferring hemoglobin by damaged erythrocytes and ends at the terminal stages of the development of the disease with their dysfunction. Adaptive erythropoiesis with an increase in erythropoietin secretion is especially dangerous for patients suffering from hypertension, and then it is impossible, since all organs involved in the synthesis of erythropoietin are damaged. In this case, the synthesis of hemoglobin is also disrupted due to a deficiency of iron and cyancobolamin, whereas toxic iron and hemosiderin are deposited in the tissues
The study findings were published in the peer reviewed journal: Archiv EuroMedica
The research was carried out within the framework of the Russian state assignment approval 17.5740.2017 / 6.7, the international Russian-Japanese grant of the FEFU (agreement No. 13- 09-0602-m_a dated 06.11.2013) and the execution of the grant from the Russian Science Foundation 19-14-00260 (2019).
The red blood cells or Erythrocytes are the major target for the SARS-CoV-2, according to the researchers. These red blood cells are responsible in the body for transport of the iron-rich protein hemoglobin carrying the oxygen.
The damage, decline and loss of erythrocytes might cause damage to the brain neurons, blood vessels, and internals, considering they get not enough oxygen.
Importantly in the most severe cases, multiple organ failure can occur, and without one’s own red blood cells, the patient starts to suffocate. Artificial ventilation does not help as there are no cells to the transports oxygen within the body. Effective therapy for such patients is to administer erythrocyte mass and vitamin B12
. The mechanism of recovery of damaged red blood cells is still a mystery for scientists.
According to the study team, early breakdown of red blood cells is the initial reaction of the bo
dy to the SARS COV-2 virus, which scales up gradually.
It was found that some patient can actually ‘feel’ the taste of iron. This occurs because hemoglobin released from erythrocytes in the bloodstream gets into the saliva.
The researchers say most individuals who have a low hemoglobin is at risk. Typically elderly people, patients with high blood pressure, people with obesity and diabetes mellitus, pregnant women, patients with primary and acquired immunodeficiency, with inhibition of hematopoietic function, HIV- and cancer patients are all at risk.
The novel coronavirus enters the epithelium, where it multiplies, then enters the bloodstream and attacks targets, which can be both the internal epithelium (gastrointestinal tract, lungs, genitourinary system) and erythrocytes. Although most frequently we would see the pathology of the respiratory system, lungs, the virus needs epithelial cells only for reproduction.
The study team believes the main target for the virus is the red marrow, where it damages the endothelium, the tissue, which normally regulates the migration of maturing cells into the blood. For this reason, a variety of conditions are affecting the immune system, and megakaryocytes, very large cells of the bone marrow, had been found in the tissues of various organs.
Typically, megakaryocytes become sources of platelets, which are responsible for blood coagulation, but with COVID-19 they clot blood in the vessels.
Dr Galina Reva, Professor of the Department of Fundamental Medicine, School of Biomedicine, FEFU says that lung fibrosis is just the most obvious manifestation of COVID-19, which appears not only as usual scar tissue formation in the affected areas. Since the cause of fibrosis is megakaryocytes "thrown" into the bloodstream, similar processes might occur in the tissues of all parenchymal (dense) organs, which are lungs, liver, spleen, kidneys, pancreas, and thyroid.
Professor Reva said, "This is an aggressive process, though it can be slow and relatively benignant, with no clinical manifestations at the background besides anemia, short breathe, and increased heart rate. Simultaneously, the number of functionally active cells of organs' tissue is shrinking. Sometimes local tissue changes take the form of a large fibrous tumor-like formation. The pathology is very dangerous since clinical signs can appear when these irreversible processes occupy a significant volume of the organ."
According to study team, in order to develop targeted treatments and measures to prevent possible complications after SARS-CoV-2 infections, it is necessary to scrutinize the mechanism behind fibrosis of the lungs tissue, liver, kidneys, and other organs.
Professor Reva said that the SARS-Cov-2 also induces destruction of white pulp in the spleen, the very tissue producing cells responsible for infectious immunity like T-cells, and B-lymphocytes. For this exact reason, secondary infections and existing comorbidities are dangerous risk factors. The body simply too weak to fight back.
Hemolytic anemia in COVID-19, which develops at the first stage as a reaction to the SARS COV-2 viral microorganisms, causes cascading reactions to toxic erythropoietin and hemoglobin released from erythrocytes in the bloodstream, and then to hemosiderin released due to the death of erythrocytes in the tissue. The process ends with a decrease in the synthesis of erythropoietin in the decaying liver and kidneys, in the absence of the necessary vitamin B12 due to the pathology of its secretion in the gastrointestinal tract. The characteristic signs of damage to red blood cells in conditions of infection with COVID-19 indicate disruption of erythropoiesis, with developing iron deficiency and B12 anemia.
The synthesis of hemoglobin lags behind the differentiation of erythrocytes, which in the initial period of the disease induces an increase in the secretion of erythropoietin, which has a hypertensive effect; increases blood viscosity and leads to impaired blood microcirculation, which is why patients with essential hypertension are the main risk group.
This underlies the inability to use erythropoietin-based drugs to treat patients with anemia in the context of COVID-19 infection. Pathological changes in erythrocytes infected with viruses are caused by specific and non-specific processes. Reactions caused by the configuration of the permeability of the plasma membrane of erythrocytes, margination of chromatin in the form of Howell-Jolly bodies, and vacuolization of the cytoplasm are nonspecific. SARS COV-2, like SV40, can be attributed to vacuolizing viruses, but only erythrocytes, since the virus has a particularly peculiar and pronounced character of inducing vacuolization. Specific changes are oxyphilic viral inclusions in cell nuclei, leading to cell destruction through a rapid and deep effect on the synthesis of cellular proteins.
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