Evaluación del impacto emocional de la pandemia COVID-19 en pacientes en hemodiálisis: un estudio transversal analítico / Evaluation Of The Emotional Impact Of The Covid-19 Pandemic On Hemodialysis Patients: An Analytical Cross-Sectional Study

Antecedentes: Los pacientes en hemodiálisis padecen, debido a su diagnóstico y tratamiento, mayores niveles de ansiedad y depresión que la población general. El objetivo de esta investigación es conocer el impacto emocional generado por la COVID-19 en pacientes hemodializados. Método: Estudio transversal analítico en una muestra total de 88 pacientes mayores de 18 años que reciben hemodiálisis entre abril de 2021 y marzo de 2022. Se recogen variables sociodemográficas y clínicas incluyendo aquellas relacionadas con COVID-19. A todos los pacientes se les administran las escalas HADS y Kessler-10. Resultados: La puntuación media de la escala HADS-A fue de 5,3 (±3,732), de la HADS-D de 5,45 (±4,052) y de la Kessler-10 de 20,11(±7,499). Se observaron diferencias significativas entre aislados y no aislados en las escalas clínicas HADS-A (p=,002) y HADS-D (p=,005). Igualmente, aquellos pacientes con antecedentes psicopatológicos fueron significativamente más jóvenes (p=,014) y con una mayor puntuación en las escalas HADS-D (p=,016) y Kessler-10 (p=,035) que aquellos sin antecedentes. Conclusiones: No hubo asociación entre infección por COVID-19 y la clínica ansioso-depresiva en pacientes hemodializados. El aislamiento, en estos pacientes, no se asocia a la aparición de clínica psicopatológica, mientras que el hecho de haber presentado antecedentes psicopatológicos previos se asocia a su desarrollo.(AU)

Background: Hemodialysis patients suffer, due to their diagnosis and treatment, higher levels of anxiety and depression than the general population. The aim of this research is to know the emotional impact generated by COVID-19 in hemodialysis patients. Method: Analytical cross-sectional study in a total sample of 88 patients over 18 years of age receiving hemodialysis between April 2021 and March 2022. Sociodemographic and clinical variables including those related to COVID-19 are collected. All patients were administered the HADS and Kessler-10 scales. Results: The mean score of the HADS-A scale was 5.3(±3.732) of the HADS-D 5.45 (±4.052) and of the Kessler-10 20.11(±7.499). Significant differences were observed between isolated and non-isolated patients in the clinical scales HADS-A (p=.002) and HADS-D (p=.005). Likewise, those patients with a psychopathological history were significantly younger (p=.014) and scored higher on the HADS-D (p=.016) and Kessler-10 (p=.035) scales than those without a history. Conclusions: There was no association between COVID-19 infection and anxious-depressive symptoms in hemodialyzed patients. Isolation, in these patients, was not associated with the appearance of psychopathological symptoms, while the fact of having a previous history of psychopathology was associated with their development.(AU)

Thiol-based mucolytics exhibit antiviral activity against SARS-CoV-2 through allosteric disulfide disruption in the spike glycoprotein

Small molecule therapeutics targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have lagged far behind the development of vaccines in the fight to control the COVID-19 pandemic. Here, we show that thiol-based mucolytic agents, P2119 and P2165, potently inhibit infection by human coronaviruses, including SARS-CoV-2, and decrease the binding of spike glycoprotein to its receptor, angiotensin-converting enzyme 2 (ACE2). Proteomics and reactive cysteine profiling link the antiviral activity of repurposed mucolytic agents to the reduction of key disulfides, specifically, by disruption of the Cys379-Cys432 and Cys391-Cys525 pairs distal to the receptor binding motif (RBM) in the receptor binding domain (RBD) of the spike glycoprotein. Computational analyses provide insight into conformation changes that occur when these disulfides break or form, consistent with an allosteric role, and indicate that P2119/P2165 target a conserved hydrophobic binding pocket in the RBD with the benzyl thiol warhead pointed directly towards Cys432. These collective findings establish the vulnerability of human coronaviruses to repurposed thiol-based mucolytics and lay the groundwork for developing these compounds as a potential treatment, preventative and/or adjuvant against infection.