RESUMEN
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).
Asunto(s)
Médula Ósea/virología , Prueba de Ácido Nucleico para COVID-19/métodos , COVID-19/virología , Ensayo de Unidades Formadoras de Colonias/métodos , Sangre Fetal/virología , Células Madre Hematopoyéticas/virología , SARS-CoV-2/aislamiento & purificación , COVID-19/patología , Células Madre Hematopoyéticas/patología , HumanosAsunto(s)
Enzima Convertidora de Angiotensina 2/metabolismo , Células Progenitoras Endoteliales/patología , Células Madre Hematopoyéticas/patología , Inflamasomas/inmunología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Piroptosis , Glicoproteína de la Espiga del Coronavirus/metabolismo , Enzima Convertidora de Angiotensina 2/genética , Células Progenitoras Endoteliales/inmunología , Células Progenitoras Endoteliales/metabolismo , Células Madre Hematopoyéticas/inmunología , Células Madre Hematopoyéticas/metabolismo , Humanos , Glicoproteína de la Espiga del Coronavirus/genéticaRESUMEN
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.
Asunto(s)
COVID-19/metabolismo , Células Madre Hematopoyéticas/metabolismo , SARS-CoV-2/metabolismo , Glicoproteína de la Espiga del Coronavirus/metabolismo , COVID-19/mortalidad , COVID-19/patología , Células Madre Hematopoyéticas/patología , HumanosRESUMEN
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.
Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/sangre , Neumonía Viral/sangre , Anticuerpos Antivirales/inmunología , Complejo Antígeno-Anticuerpo/inmunología , Antivirales/farmacología , Antivirales/uso terapéutico , Betacoronavirus/inmunología , COVID-19 , Microambiente Celular , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/terapia , Síndrome de Liberación de Citoquinas/sangre , Síndrome de Liberación de Citoquinas/etiología , Síndrome de Liberación de Citoquinas/prevención & control , Citocinas/sangre , Pruebas Diagnósticas de Rutina , Endotelio Vascular/patología , Pruebas Hematológicas , Hematopoyesis/efectos de los fármacos , Células Madre Hematopoyéticas/patología , Humanos , Hipoalbuminemia/etiología , Hígado/fisiopatología , Pulmón/fisiopatología , Linfopenia/etiología , Linfopenia/fisiopatología , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/terapia , Daño por Reperfusión/etiología , SARS-CoV-2 , Trombocitopenia/etiología , Trombocitopenia/fisiopatología , Trombofilia/etiología , Tratamiento Farmacológico de COVID-19Asunto(s)
Médula Ósea/patología , COVID-19/sangre , Células Madre Hematopoyéticas/patología , Leucemia Monocítica Aguda/diagnóstico , Linfocitos/patología , Monocitos/patología , Células Madre Neoplásicas/patología , SARS-CoV-2 , Transfusión de Componentes Sanguíneos , COVID-19/diagnóstico , COVID-19/patología , Prueba de Ácido Nucleico para COVID-19 , Recuento de Células , Diagnóstico Diferencial , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Remisión EspontáneaRESUMEN
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.