Outcomes of vaccinated versus unvaccinated COVID-19 patients in Israel during the Omicron and Delta waves—A retrospective cohort study / Resultados de pacientes con COVID-19 vacunados vs. no vacunados en Israel durante las olas de ómicron y delta: Un estudio de cohorte retrospectivo

Introduction Initiation of global vaccination significantly reduced the morbidity and mortality of COVID-19. During the Omicron wave, approximately 70% of the Israeli adult population was fully vaccinated, but the efficacy of the vaccine was questioned. Methods We conducted a retrospective cohort study of all adult patients admitted to the COVID-19 departments in Rabin Medical Center, during the Delta wave and the Omicron wave. Patients were matched in the 2 waves using the inverse probability of treatment weighting (IPTW) method and risk for mechanical ventilation and 30-day all-cause mortality was assessed. Results Vaccination had a significant effect on 30-day mortality in the Delta and Omicron waves with adjusted OR of 0.35 (0.17–0.70) and 0.5 (0.27–0.95) respectively. Nonetheless, the rate of mechanical ventilation was similar between the groups with OR of 0.75 (0.52–1.09) and 0.64 (0.40–1.01). Vaccination status did not change the length of admission in both waves. Conclusion We observed a decreased risk for 30-day mortality among vaccinated patients during the Delta and Omicron waves in Israel. This association, even though consistent, was of a lesser magnitude during the Omicron wave (AU)

Introducción La iniciación de la vacunación global redujo significativamente la morbilidad y la mortalidad de la COVID-19. Durante la ola de ómicron, aproximadamente 70% de la población adulta israelí estaba completamente vacunada, pero se cuestionó la eficacia de la vacuna. Métodos Realizamos un estudio de cohorte retrospectivo de todos los pacientes adultos ingresados en los departamentos de COVID-19 en el Centro Médico Rabin, durante las olas de delta y ómicron. Los pacientes fueron emparejados en las dos olas utilizando el método de ponderación inversa de probabilidad de tratamiento (IPTW) y se evaluó el riesgo de ventilación mecánica y la mortalidad por todas las causas a los 30 días. Resultados La vacunación tuvo un efecto significativo en la mortalidad a los 30 días en las olas de delta y ómicron con odds ratio (OR) ajustadas de 0,35 (0,17-0,70) y 0,5 (0,27-0,95), respectivamente. Sin embargo, la tasa de ventilación mecánica fue similar entre los grupos con OR de 0,75 (0,52-1,09) y 0,64 (0,40-1,01). El estado de vacunación no cambió la duración del ingreso en ambas olas.Conclusión Observamos un menor riesgo de mortalidad a los 30 días entre los pacientes vacunados durante las olas de delta y ómicron en Israel. Esta asociación, aunque constante, fue de menor magnitud durante la ola de ómicron (AU)

Distinct Effects of O-GlcNAcylation and Phosphorylation of a Tau-Derived Amyloid Peptide on Aggregation of the Native Peptide.

Protein phosphorylation and O-GlcNAcylation are very common nucleoplasmic post-translational modifications. Mono-addition of either the phosphate or the O-GlcNAc group were shown to inhibit the self-aggregation of amyloidogenic proteins and peptides, which is the hallmark of various protein misfolding diseases. However, their comparable effect upon co-incubation with a native non-modified amyloid scaffold has not been reported. O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide. These results shed light on the role of post-translational modifications in protein aggregation and suggest a novel therapeutic approach to protein misfolding diseases.

Inhibition of the Aggregation and Toxicity of the Minimal Amyloidogenic Fragment of Tau by Its Pro-Substituted Analogues.

Inhibiting the toxic aggregation of amyloid-ß and the tau protein, the key pathological agents involved in Alzheimer's, is a leading approach in modulating disease progression. Using an aggregative tau-derived model peptide, Ac-PHF6-NH2 , the substitution of its amino acids with proline, a known efficient ß-breaker, is shown to reduce self-assembly. This effect is attributed to the steric hindrance created by the proline substitution, which results in disruption of the ß-sheet formation process. Moreover, several of the proline-substituted peptides inhibit the aggregation of Ac-PHF6-NH2 amyloidogenic peptide. Two of these modified inhibitors also disassemble pre-formed Ac-PHF6-NH2 fibrils and one inhibits induced cytotoxicity of the fibrils. Taken together, these lead ß-breaker peptides may be developed into novel Alzheimer's disease therapeutics.

Selective Inhibition of Aggregation and Toxicity of a Tau-Derived Peptide using Its Glycosylated Analogues.

Protein glycosylation is a ubiquitous post-translational modification that regulates the folding and function of many proteins. Misfolding of protein monomers and their toxic aggregation are the hallmark of many prevalent diseases. Thus, understanding the role of glycans in protein aggregation is highly important and could contribute both to unraveling the pathology of protein misfolding diseases as well as providing a means for modifying their course for therapeutic purposes. Using ß-O-linked glycosylated variants of the highly studied Tau-derived hexapeptide motif VQIVYK, which served as a simplified amyloid model, we demonstrate that amyloid formation and toxicity can be strongly attenuated by a glycan unit, depending on the nature of the glycan itself. Importantly, we show for the first time that not only do glycans hinder self-aggregation, but the glycosylated peptides are capable of inhibiting aggregation of the non-modified corresponding amyloid scaffold.