RESUMEN
Interferon-induced transmembrane (IFITM) proteins mediate protection against enveloped viruses by blocking membrane fusion at endosomes. IFITM1 and IFITM3 are crucial for protection against influenza, and various single nucleotide polymorphisms altering their function have been linked to disease susceptibility. However, bulk IFITM1 and IFITM3 mRNA expression dynamics and their correlation with clinical outcomes have not been extensively addressed in patients with respiratory infections. In this study, we evaluated the expression of IFITM1 and IFITM3 in peripheral leukocytes from healthy controls and individuals with severe pandemic influenza A(H1N1) or coronavirus disease 2019 (COVID-19). Comparisons between participants grouped according to their clinical characteristics, underlying disease, and outcomes showed that the downregulation of IFITM1 was a distinctive characteristic of severe pandemic influenza A(H1N1) that correlated with outcomes, including mortality. Conversely, increased IFITM3 expression was a common feature of severe pandemic influenza A(H1N1) and COVID-19. Using a high-dose murine model of infection, we confirmed not only the downregulation of IFITM1 but also of IFITM3 in the lungs of mice with severe influenza, as opposed to humans. Analyses in the comparative cohort also indicate the possible participation of IFITM3 in COVID-19. Our results add to the evidence supporting a protective function of IFITM proteins against viral respiratory infections in humans.
Asunto(s)
Antígenos de Diferenciación , COVID-19 , Gripe Humana , Proteínas de la Membrana , Proteínas de Unión al ARN , Animales , Antígenos de Diferenciación/genética , Antígenos de Diferenciación/metabolismo , COVID-19/genética , Humanos , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/genética , Leucocitos/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismoRESUMEN
The kidnapping of the lipid metabolism of the host's cells by severe acute respiratory syndrome (SARS-CoV-2) allows the virus to transform the cells into optimal machines for its assembly and replication. Here we evaluated changes in the fatty acid (FA) profile and the participation of the activity of the desaturases, in plasma of patients with severe pneumonia by SARS-CoV-2. We found that SARS-CoV-2 alters the FA metabolism in the cells of the host. Changes are characterized by variations in the desaturases that lead to a decrease in total fatty acid (TFA), phospholipids (PL) and non-esterified fatty acids (NEFAs). These alterations include a decrease in palmitic and stearic acids (p ≤ 0.009) which could be used for the formation of the viral membranes and for the reparation of the host's own membrane. There is also an increase in oleic acid (OA; p = 0.001) which could modulate the inflammatory process, the cytokine release, apoptosis, necrosis, oxidative stress (OS). An increase in linoleic acid (LA) in TFA (p = 0.03) and a decreased in PL (p = 0.001) was also present. They result from damage of the internal mitochondrial membrane. The arachidonic acid (AA) percentage was elevated (p = 0.02) in the TFA and this can be participated in the inflammatory process. EPA was decreased (p = 0.001) and this may decrease of pro-resolving mediators with increase in the inflammatory process. The total of NEFAs (p = 0.03), PL (p = 0.001), cholesterol, HDL and LDL were decreased, and triglycerides were increased in plasma of the COVID-19 patients. Therefore, SARS-CoV-2 alters the FA metabolism, the changes are characterized by alterations in the desaturases that lead to variations in the TFA, PL, and NEFAs profiles. These changes may favor the replication of the virus but, at the same time, they are part of the defense system provided by the host cell metabolism in its eagerness to repair damage caused by the virus to cell membranes.
RESUMEN
The SARS-CoV-2 pandemic is of hich risk for patients on chronic hemodialysis due to their immunosuppressed state, advanced age, and the coexistence of significant comorbidities, in particular cardiovascular disease, diabetes mellitus, and others. Additionally, they constitute a closed conglomerate since they come to treatment regularly, spending hours in the treatment places, exposed to a possible acquisition of the infection. Finally, going to their treatment regularly prevents them from remaining in home isolation and with potential exposure. These recommendations summarize the interventions proposed by three international organizations and add some suggested by national experts, with the aim to early identify the patients and health personnel at risk and reducing the risk of infection.
La pandemia del SARS-CoV-2 representa un riesgo especial para los pacientes en hemodiálisis crónica por su estado de inmunosupresión, edad avanzada y coexistencia de comorbilidades importantes, en particular patología cardiovascular, diabetes mellitus y otras. Adicionalmente, esta población constituye un conglomerado cerrado ya que los pacientes acuden a tratamiento con regularidad y permanecen horas en los lugares de tratamiento, expuestos a una posible adquisición de la infección. El hecho de acudir necesaria y regularmente a su tratamiento impide que permanezcan en aislamiento domiciliario y con exposición potencial en el traslado. Las presentes recomendaciones resumen las intervenciones propuestas por tres organizaciones internacionales, a las que se agregan algunas sugeridas por expertos nacionales, con el objetivo de identificar precozmente a los pacientes y personal de la salud en riesgo para disminuir el riesgo de infección.
Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Pandemias/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , Diálisis Renal , Insuficiencia Renal Crónica/terapia , Algoritmos , COVID-19 , Desinfección , Diagnóstico Precoz , Humanos , Educación del Paciente como Asunto , Equipo de Protección Personal , Prevención Primaria , SARS-CoV-2Asunto(s)
Humanos , Corticoesteroides , Antioxidantes , Eicosanoides , Mediciones del Volumen Pulmonar , Pentoxifilina , Respiración con Presión Positiva , Respiración Artificial , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Síndrome de Dificultad Respiratoria/terapia , Transporte RespiratorioRESUMEN
Al síndrome de insuficiencia respiratoria progresiva del adulto (SIRPA) se le denomina actualmente síndrome de insuficiencia respiratoria aguda. Es un término descriptivo que se aplica a muchas lesiones pulmonares agudas, infiltrativas y difusas, de tiología diversa, que se acompañan de hipoxemia severa. El SIRPA se caracteriza por lesiones de la membrana alveolo-capilar que consisten en escape de líquidos y elementos formes de los vasos sanguíneos al espacio intersticial y a los alveolos, y permeabilidad vascular aumentada a las proteínas. Los objetivos del tratamiento son mantener la disponibilidad de oxígeno en niveles óptimos (apoyo ventilatorio convencional y no convencional, oxigenación de membrana extracorpórea, gasto cardiaco adecuado) y restricción de líquidos. Otras acciones terapéuticas de esta entidad (decúbito prono, aumento de la precarga ventricular, surfactante exógeno, antioxidante, ketoconazol, eicosanoides y pentoxifilina) están en proceso de evaluación; el empleo de corticoesteroides, es controversial en la actualidad
