Sustained Antibody-Dependent NK Cell Functions in Mild COVID-19 Outpatients During Convalescence.

The coronavirus disease 2019 (COVID19) pandemic has left researchers scrambling to identify the humoral immune correlates of protection from COVID-19. To date, the antibody mediated correlates of virus neutralization have been extensively studied. However, the extent that non-neutralizing functions contribute to anti-viral responses are ill defined. In this study, we profiled the anti-spike antibody subtype/subclass responses, along with neutralization and antibody-dependent natural killer cell functions in 83 blood samples collected between 4 and 201 days post-symptoms onset from a cohort of COVID-19 outpatients. We observed heterogeneous humoral responses against the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Overall, anti-spike profiles were characterized by a rapid rise of IgA and sustained IgG titers. In addition, strong antibody-mediated natural killer effector responses correlated with milder disease and being female. While higher neutralization profiles were observed in males along with increased severity. These results give an insight into the underlying function of antibodies beyond neutralization and suggest that antibody-mediated natural killer cell activity is a key function of the humoral response against the SARS-CoV-2 spike protein.

[Efectiveness and safety of switching to raltegravir-based regimen in dyslipidemic HIV-infected patients receiving antiretroviral therapy at Arriaran Foundation]. / Efectividad y seguridad del cambio a esquema basado en raltegravir en pacientes con infección por VIH dislipidémicos bajo terapia anti-retroviral en Fundación Arriarán.

BACKGROUND: The impact of switching antiretroviral therapy (ART) regimen for dyslipidemia management in HIV-infected (HIV+) patients has not been reported in Chile. AIM: To assess effectiveness and safety at 12 months after switching to raltegravir-based regimen for dyslipidemia management. METHODS: Retrospective cohort of HIV+ patients receiving ART at Arriaran Foundation, with dyslipidemia switched to raltegravir-based regimen for lipid management. RESULTS: 73 patients were included, receiving ART based in nonnucleoside reverse transcriptase inhibitor (NNRTI; 50,7%) or protease inhibitor (PI; 49,3%), with mixed dyslipidemia (42,5%) or isolated hypertriglyceridemia (57,5%). At baseline, median total cholesterol (TC) and triglycerides (TG) were 228 mg/dl and 420 mg/dl, respectively; undetectable viral load (VL) was present in 94,5% of patients. Backbone ART was switched in 58,4% and lipid-lowering therapy was used by 89,1% of them. At 12 months, there was a significant decrease in TG (-43,6%) and TC (-19,3%). No cases of virologic failure were observed, although 10,9% of patients had detectable VL at 12 months, mostly transient. CONCLUSIONS: Switching ART to raltegravir-based regimen in dyslipidemic patients receiving NNRTI or PI is associated with a significative decrease in TG and TC at 12 months. This strategy is safe, but VL can be increased temporarily.

Análisis crítico de una revisión sistemática / Critical analysis of a systematic review

In the era in which we face an increasing volume of scientific literature, it is important to analyze the one that answers our clinical questions efficiently and with the best level of evidence. Systematic reviews are especially useful for this purpose. The aim of this article is to give an introduction to the critical assessment of systematic reviews, through the solving of a therapeutic dilemma, which will be addressed through the analysis of a study of this type.

Análisis crítico de un ensayo clínico de no-inferioridad / Critical analysis of a noninferiority trial

In the era of diseases with highly efficacious treatments, the publication of randomized noninferiority clinical trials is increasingly frequent. However, users of medical literature are less familiar with this type of studies. The aim of this article is to give an introduction to the critical assessment of noninferiority clinical trials, through the solving of a therapeutic dilemma, which will be addressed through the analysis of a recently published trial of this type.

Efectividad y seguridad del cambio a esquema basado en raltegravir en pacientes con infección por VIH dislipidémicos bajo terapia anti-retroviral en Fundación Arriarán / Efectiveness and safety of switching to raltegravir-based regimen in dyslipidemic HIV-infected patients receiving antiretroviral therapy at Arriaran Foundation

Resumen Introducción: El impacto del cambio de terapia antiretroviral (TAR) para tratar la dislipidemia en pacientes infectados por VIH no ha sido reportado en Chile. Objetivo: Evaluar la efectividad y seguridad a 12 meses del cambio de TAR a esquema con raltegravir (RAL) para tratar la dislipidemia. Material y Métodos: Cohorte retrospectiva de pacientes con infección por VIH en TAR, atendidos en Fundación Arriarán, con dislipidemia y que cambiaron a esquema con RAL para tratarla. Resultados: Se incluyó 73 casos, en TAR con inhibidores no nucleosídicos de transcriptasa reversa (INNTR; 50,7%) o inhibidores de proteasa (IP; 49,3%), con dislipidemia mixta (42,5%) o hipertrigliceridemia aislada (57,5%). La mediana de colesterol total (CT) y triglicéridos (TG) basales era 228 mg/dl y 420 mg/dl, respectivamente. El 94,5% tenía carga viral (CV) indetectable. Se modificó TAR de base en 58,4%; 89,1% recibía hipolipemiantes. Las concentraciones plasmáticas de lípidos descendieron significativamente a 12 meses (TG= −43,6%; CT= −19,3%). Ningún paciente presentó fracaso virológico, aunque 10,9% tuvo viremia detectable a 12 meses, mayoritariamente transitoria. Conclusiones: El cambio de TAR a RAL en pacientes dislipidémicos tratados con INNTR o IP reduce significativamente las concentraciones plasmáticas de TG y CT a 12 meses. Es una estrategia segura, pero puede observarse viremia transitoria.

Background: The impact of switching antiretroviral therapy (ART) regimen for dyslipidemia management in HIV-infected (HIV+) patients has not been reported in Chile. Aim: To assess effectiveness and safety at 12 months after switching to raltegravir-based regimen for dyslipidemia management. Methods: Retrospective cohort of HIV+ patients receiving ART at Arriaran Foundation, with dyslipidemia switched to raltegravir-based regimen for lipid management. Results: 73 patients were included, receiving ART based in nonnucleoside reverse transcriptase inhibitor (NNRTI; 50,7%) or protease inhibitor (PI; 49,3%), with mixed dyslipidemia (42,5%) or isolated hypertriglyceridemia (57,5%). At baseline, median total cholesterol (TC) and triglycerides (TG) were 228 mg/dl and 420 mg/dl, respectively; undetectable viral load (VL) was present in 94,5% of patients. Backbone ART was switched in 58,4% and lipid-lowering therapy was used by 89,1% of them. At 12 months, there was a significant decrease in TG (-43,6%) and TC (-19,3%). No cases of virologic failure were observed, although 10,9% of patients had detectable VL at 12 months, mostly transient. Conclusions: Switching ART to raltegravir-based regimen in dyslipidemic patients receiving NNRTI or PI is associated with a significative decrease in TG and TC at 12 months. This strategy is safe, but VL can be increased temporarily.

Efectividad y seguridad del tratamiento anticoagulante con acenocumarol en fibrilación auricular no valvular / Effectiveness and safety of oral anticoagulation treatment with acenocoumarol in non-valvular atrial fibrillation

Background: Vitamin K antagonists significantly decrease the incidence of stroke but increase the risk of bleeding. Aim: To assess the effectiveness and risk of bleeding of vitamin K antagonists in non-valvular atrial fibrillation. Material and Methods: Retrospective cohort study of 524 patients, 236 women (45%) and 288 men (55%) with non-valvular atrial fibrillation (NVAF) admitted to the oral anticoagulation treatment (OAT) clinic at four public hospitals, between 2009 and 2012. They were followed until March 2013, measuring the quality of OAT, ischemic and bleeding events. Results: The mean follow-up was 26.1 months, with 1,154.7 person-years of follow-up accrued. The percentage of time in therapeutic range (TTR) was 35.2 ± 18%; this was deemed to represent the quality of OAT. The cumulative incidence of ischemic events, either stroke or systemic embolism, was 2.25/100 person-years, being greater in patients with previous embolism (Risk ratio 5.21, 95% confidence intervals 2.31- 11.73, p < 0.01). The cumulative incidence of major bleeding events-extracranial and intracraneal-was 4.08/100 person-years. The main site of extracranial major bleeding was the gastrointestinal tract (32%). Conclusions: In our clinical practice, the effectiveness of OAT with acenocoumarol in NVAF patients is similar to that published abroad. However, the incidence of bleeding complications is higher. The quality of the OAT measured by the TTR was lower than abroad.