ABSTRACT
Determining how hematopoietic stem and progenitor cells (HSPCs) can be infected by viruses is necessary to understand and predict how the immune system will drive the host response. We present here a protocol to analyze the capacity of SARS-CoV-2 to infect different subsets of human HSPCs, inlcuding procedures for SARS-CoV-2 production and titration, isolation of human HSPCs from different sources (bone marrow, umbilical cord, or peripheral blood), and quantification of SARS-Cov-2 infection capacity by RT-qPCR and colony forming unit assay. For complete details on the use and execution of this protocol, please refer to Huerga Encabo et al. (2021).
Subject(s)
Bone Marrow/virology , COVID-19 Nucleic Acid Testing/methods , COVID-19/virology , Colony-Forming Units Assay/methods , Fetal Blood/virology , Hematopoietic Stem Cells/virology , SARS-CoV-2/isolation & purification , COVID-19/pathology , Hematopoietic Stem Cells/pathology , HumansSubject(s)
Angiotensin-Converting Enzyme 2/metabolism , Endothelial Progenitor Cells/pathology , Hematopoietic Stem Cells/pathology , Inflammasomes/immunology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pyroptosis , Spike Glycoprotein, Coronavirus/metabolism , Angiotensin-Converting Enzyme 2/genetics , Endothelial Progenitor Cells/immunology , Endothelial Progenitor Cells/metabolism , Hematopoietic Stem Cells/immunology , Hematopoietic Stem Cells/metabolism , Humans , Spike Glycoprotein, Coronavirus/geneticsABSTRACT
PURPOSE OF REVIEW: In recent history there have been three outbreaks of betacoronavirus infections in humans, with the most recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; causing Coronavirus disease 2019 [COVID-19]) outbreak leading to over two million deaths, with a rapidly rising death toll. Much remains unknown about host cells and tissues affected by coronavirus infections, including the hematopoietic system. Here, we discuss the recent findings examining effects that coronavirus infection or exposure has on hematopoietic cells and the clinical implications for these effects. RECENT FINDINGS: Recent studies have centered on SARS-CoV-2, demonstrating that hematopoietic stem and progenitor cells and mature immune cells may be susceptible to infection and are impacted functionally by exposure to SARS-CoV-2 Spike protein. These findings have important implications regarding hematologic complications arising from COVID-19 and other coronavirus-induced disease, which we discuss here. SUMMARY: Infection with coronaviruses sometimes leads to hematologic complications in patients, and these hematologic complications are associated with poorer prognosis. These hematologic complications may be caused by coronavirus direct infection or impact on primitive hematopoietic cells or mature immune cells, by indirect effects on these cells, or by a combination thereof. It is important to understand how hematologic complications arise in order to seek new treatments to improve patient outcomes.
Subject(s)
COVID-19/metabolism , Hematopoietic Stem Cells/metabolism , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , COVID-19/mortality , COVID-19/pathology , Hematopoietic Stem Cells/pathology , HumansABSTRACT
In December 2019, an emergence of pneumonia was detected in patients infected with a novel coronavirus (CoV) in Wuhan (Hubei, China). The International Committee on Taxonomy of Viruses named the virus severe acute respiratory syndromeCoV2 and the disease CoV disease19 (COVID19). Patients with COVID19 present with symptoms associated with respiratory system dysfunction and hematological changes, including lymphopenia, thrombocytopenia and coagulation disorders. However, to the best of our knowledge, the pathogenesis of COVID19 remains unclear. Therefore, understanding the mechanisms underlying the hematological changes that manifest during COVID19 may aid in the development of treatments and may improve patient prognosis.
Subject(s)
Betacoronavirus , Coronavirus Infections/blood , Pneumonia, Viral/blood , Antibodies, Viral/immunology , Antigen-Antibody Complex/immunology , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Betacoronavirus/immunology , COVID-19 , Cellular Microenvironment , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Coronavirus Infections/therapy , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/prevention & control , Cytokines/blood , Diagnostic Tests, Routine , Endothelium, Vascular/pathology , Hematologic Tests , Hematopoiesis/drug effects , Hematopoietic Stem Cells/pathology , Humans , Hypoalbuminemia/etiology , Liver/physiopathology , Lung/physiopathology , Lymphopenia/etiology , Lymphopenia/physiopathology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Pneumonia, Viral/therapy , Reperfusion Injury/etiology , SARS-CoV-2 , Thrombocytopenia/etiology , Thrombocytopenia/physiopathology , Thrombophilia/etiology , COVID-19 Drug TreatmentSubject(s)
Bone Marrow/pathology , COVID-19/blood , Hematopoietic Stem Cells/pathology , Leukemia, Monocytic, Acute/diagnosis , Lymphocytes/pathology , Monocytes/pathology , Neoplastic Stem Cells/pathology , SARS-CoV-2 , Blood Component Transfusion , COVID-19/diagnosis , COVID-19/pathology , COVID-19 Nucleic Acid Testing , Cell Count , Diagnosis, Differential , Humans , Lymphocyte Count , Male , Middle Aged , Remission, SpontaneousABSTRACT
Thymalin is a polypeptide complex isolated from the thymus and regulating the functions of the immune system. Thymalin is effective in therapy of acute respiratory syndrome, chronic obstructive bronchitis, and other immunopathology. Thymalin increases functional activity of T lymphocytes, but the targeted molecular mechanism of its biological activity requires further study. We studied the influence of thymalin on differentiation of human hematopoietic stem cells (HSC) and expression of CD28 molecule involved in the implementation of antiviral immunity in COVID-19 infection. It was found that thymalin reduced the expression of CD44 (stem cell marker) and CD117 (molecule of the intermediate stage of HSC differentiation) by 2-3 times and increased the expression of CD28 (marker of mature T lymphocytes) by 6.8 times. This indirectly indicates that thymalin stimulated differentiation of CD117+ cells into mature CD28+T lymphocytes. It is known that in patients with severe COVID-19, the number of CD28+, CD4+, CD8+T lymphocytes in the blood decreased, which attested to a pronounced suppression of immunity. It is possible that the antiviral effect of thymalin consists in compensatory stimulation of HSC differentiation into CD28+T lymphocytes at the stage of immunity suppression in unfavorable course of viral infection. Thymalin can be considered as an immunoprotective peptide drug for the prevention of COVID-19.