Viral load decrease in SARS-CoV-2 BA.1 and BA.2 Omicron sublineages infection after treatment with monoclonal antibodies and direct antiviral agents

BACKGROUND: The efficacy on the Omicron variant of the approved early- coronavirus disease 2019 (COVID-19) therapies, especially monoclonal antibodies, has been challenged by in vitro neutralization data, while data on in vivo antiviral activity are lacking. MATERIALS AND METHODS: We assessed potential decrease from day1 to day7 viral load (VL) in nasopharyngeal swabs of outpatients receiving Sotrovimab, Molnupiravir, Remdesivir, or Nirmatrelvir/ritonavir for mild-to-moderate COVID-19 due to sublineages BA.1 or BA.2, and average treatment effect (ATE) by weighted marginal linear regression models. RESULTS: A total of 521 patients [378 BA.1 (73%),143 (27%) BA.2] received treatments (Sotrovimab 202, Molnupiravir 117, Nirmatrelvir/ritonavir 84, and Remdesivir 118): median age 66 years, 90% vaccinated, median time from symptoms onset 3 days. Day1 mean viral load was 4.12 log2 (4.16 for BA.1 and 4.01 for BA.2). The adjusted analysis showed that Nirmatrelvir/ritonavir significantly reduced VL compared to all the other drugs, except vs. Molnupiravir in BA.2. Molnupiravir was superior to Remdesivir in both BA.1 and BA.2, and to Sotrovimab in BA.2. Sotrovimab had better activity than Remdesivir only against BA.1. CONCLUSIONS: Nirmatrelvir/ritonavir showed the greatest antiviral activity against Omicron variant, comparable to Molnupiravir only in the BA.2 subgroup. VL decrease could be a valuable surrogate of drug activity in the context of the high prevalence of vaccinated people and low probability of hospital admission. This article is protected by copyright. All rights reserved

Predicting respiratory failure in patients infected by SARS-CoV-2 by admission sex-specific biomarkers

Background: Several biomarkers have been identified to predict the outcome of COVID-19 severity, but few data are available regarding sex differences in their predictive role. Aim of this study was to identify sex-specific biomarkers of severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19. Methods: Plasma levels of sex hormones (testosterone and 17β-estradiol), sex-hormone dependent circulating molecules (ACE2 and Angiotensin1-7) and other known biomarkers for COVID-19 severity were measured in male and female COVID-19 patients at admission to hospital. The association of plasma biomarker levels with ARDS severity at admission and with the occurrence of respiratory deterioration during hospitalization was analysed in aggregated and sex disaggregated form. Results: Our data show that some biomarkers could be predictive both for males and female patients and others only for one sex. Angiotensin1-7 plasma levels and neutrophil count predicted the outcome of ARDS only in females, whereas testosterone plasma levels and lymphocytes counts only in males. Conclusions: Sex is a biological variable affecting the choice of the correct biomarker that might predict worsening of COVID-19 to severe respiratory failure. The definition of sex specific biomarkers can be useful to alert patients to be safely discharged versus those who need respiratory monitoring

A systematic review aimed at studying the influence of educational attainment of HAART compliance

Background The introduction of Highly Active Antiretroviral Therapy (HAART) has definitely improved the quality of HIV patients’ life, although its benefits depend on a strict compliance to therapy. Compliance can be considered as a dynamic process influenced by several variables that include some modifiable determinants such as education. The knowledge of its influence on compliance can lead to change the approach to the HIV patients. The aim of this study is to understand if educational attainment conditions HAART compliance. Methods The present search represents an update of a previous review on the same topic. Studies were selected using Boolean strings in PubMed and Scopus as databases. A snowball analysis was executed too in order to widen the number of articles. Inclusion criteria were: post-HAART era (1996), concerning adult patients ( 18 years), written in English. A data abstraction form was used to abstract and to record study details by two researchers. Methodological quality of studies was furtherly evaluated through Newcastle-Ottawa Scale (NOS). Results Out of 3502 articles, 32 observational studies (10 cohort and 22 cross-sectional) were included in the review. Total sample regarded 19321 people. In 41% of studies adherence was assessed through self-report, in 34% through interviews and in the rest (25%) adherence was measured through other methods or combined ones. 37% of selected studies were conducted in Developing and Emerging Countries (mostly African or Asiatic ones). In 58% of these studies and in 30% of studies set in Developed Countries a low level of education was found to influence HAART compliance. Conclusions Our research suggests that education attainment is an important factor to be considered in strategies aimed at improving HAART compliance in both Developing and Emerging Countries and Developed ones, although educational systems can not be compared completely. Key message: HAART compliance is a complex process in which socioeconomic determinants have to be considered in order to improve i

The role of education in adherence to Highly Active Antiretroviral Therapy (HAART): a systematic review

Background Suboptimal adherence to Highly Active Antiretroviral Therapy (HAART) is an emerging public health priority. There is contrasting evidence about the association between socio- demographic predictors and HAART adherence. The aim of this study was to perform a systematic review of the literature assessing the impact of educational level on adherence to treatment in HIV infected patients from 1999 to 2011. Methods A systematic search was performed using Pubmed and Scopus database. Key search terms used included \u2018\u2018HAART\u2019\u2019, \u2018\u2018adherence\u2019\u2019, \u2018\u2018compliance\u2019\u2019 and \u2018\u2018educational level\u2019\u2019. The inclusion criteria used for each study were: (a) the age of HIV-infected patients was eighteen or older (b) the patient residence was in developed countries. Studies focused on specific behavioral or psychosocial characteristics or HAART na \u308\u131vepatientswereexcluded. Results Among 210 potentially relevant articles, 18 comparative observational studies, concerning an overall population of 7288, were included in the review. Around 60% of research designs were longitudinal. Papers differed by methodological adherence measurement: 10 studies used self-reported ques- tionnaire, 5 individual interview and 3 other tools as pills count. Eight out of 18 papers (39%-including 3692 indivi- duals) showed that subjects with low educational level were less likely to be adherent to HAART than subjects with higher level. Conclusions Educational level seems to be a noticeable factor to consider in policy and practice, in order to improve the HIV treatment adherence

A systematic review of consistency between health literacy and adherence to Highly Active Antiretroviral Therapy (HAART)

Background Health literacy is considered as the degree to which individuals have the capacity to obtain, process and understand basic information and services needed to make appropriate decision regarding their health. Although many studies have examined the association between health literacy and medication adherence in chronic disease context, findings have been contrasting. Medication adherence among people living with HIV remains an important public health challenge, despite recent simplified drug regimens. The main purpose of this study was to review the association between health literacy and adherence to Highly Active Antiretroviral Therapy (HAART). Additionally, this review aimed to clarify whether different adherence measures could influence that relationship. Methods Literature search was performed in PubMed and Scopus for studies regarding health literacy and HAART adherence among individuals HIV infected adult published between 1999 and 2013. Papers focused on drug users, pregnant women and naive patients were excluded. Furthermore, only studies with a measurement of health literacy with validated tools were included. Reporting was conducted in the form recommended in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and checklist. Results There were 57 potentially relevant articles from which a total of 7 studies concerning an overall population of 1274 were included in the systematic review. Adherence was assessed using objective measures (pharmacy refill records, electronic event monitors and unannounced telephone-based pill counts) in three articles; others papers used self-report tools or interview. Two different validated instruments for measuring literacy were reported. In three studies participants with lower health literacy demonstrated poorer adherence compared to individuals with higher literacy (33% of all population, including 416 individuals). The association between health literacy and adherence was not related to different HAART adherence measurement. Conclusions Additional research was needed to pursue a better understanding of the mechanism by which health literacy affects medication adherence. Key message A better understanding of the impact of health literacy on medication adherence is a public health priority in order to safeguard vulnerable communities such as persons living with HIV

Initial antifungal strategy does not correlate with mortality in patients with candidemia

The incidence of Candida bloodstream infections (BSIs) has increased over time, especially in medical wards. The objective of this study was to evaluate the impact of different antifungal treatment strategies on 30-day mortality in patients with Candida BSI not admitted to intensive care units (ICUs) at disease onset. This prospective, monocentric, cohort study was conducted at an 1100-bed university hospital in Rome, Italy, where an infectious disease consultation team was implemented. All cases of Candida BSIs observed in adult patients from November 2012 to April 2014 were included. Patients were grouped according to the initial antifungal strategy: fluconazole, echinocandin, or liposomal amphotericin B. Cox regression analysis was used to identify risk factors significantly associated with 15-day and 30-day mortality. During the study period, 130 patients with candidemia were observed (58 % with C. albicans, 7 % with C. glabrata, and 23 % with C. parapsilosis). The first antifungal drug was fluconazole for 40 % of patients, echinocandin for 57.0 %, and liposomal amphotericin B for 4 %. During follow-up, 33 % of patients died. The cumulative mortality 30 days after the candidemia episode was 30.8 % and was similar among groups. In the Cox regression analysis, clinical presentation was the only independent factor associated with 15-day mortality, and Acute Physiology and Chronic Health Evaluation (APACHE) II score and clinical presentation were the independent factors associated with 30-day mortality. No differences in 15-day and 30-day mortality were observed between patients with and without C. albicans candidemia. In patients with candidemia admitted to medical or surgical wards, clinical severity but not the initial antifungal strategy were significantly correlated with mortality

Sarilumab plus standard of care vs standard of care for the treatment of severe COVID-19: a phase 3, randomized, open-labeled, multi-center study (ESCAPE study)Research in context

Summary: Background: Among interleukin-6 inhibitors suggested for use in COVID-19, there are few robust evidences for the efficacy of sarilumab. Herein, we evaluated the efficacy and safety of sarilumab in severe COVID-19. Methods: In this phase 3, open-labeled, randomized clinical trial, conducted at 5 Italian hospitals, adults with severe COVID-19 pneumonia (excluding mechanically ventilated) were randomized 2:1 to receive intravenous sarilumab (400 mg, repeatable after 12 h) plus standard of care (SOC) (arm A) or to continue SOC (arm B). Randomization was web-based. As post-hoc analyses, the participants were stratified according to baseline inflammatory parameters. The primary endpoint was analysed on the modified Intention-To-Treat population, including all the randomized patients who received any study treatment (sarilumab or SOC). It was time to clinical improvement of 2 points on a 7-points ordinal scale, from baseline to day 30. We used Kaplan Meier method and log-rank test to compare the primary outcome between two arms, and Cox regression stratified by clinical center and adjusted for severity of illness, to estimate the hazard ratio (HR). The trial was registered with EudraCT (2020-001390-76). Findings: Between May 2020 and May 2021, 191 patients were assessed for eligibility, of whom, excluding nine dropouts, 176 were assigned to arm A (121) and B (55). At day 30, no significant differences in the primary endpoint were found (88% [95% CI 81–94] in arm A vs 85% [74–93], HR 1.07 [0.8–1.5] in arm B; log-rank p = 0.50). After stratifying for inflammatory parameters, arm A showed higher probability of improvement than B without statistical significance in the strata with C reactive protein (CRP) < 7 mg/dL (88% [77–96] vs 79% [63–91], HR 1.55 [0.9–2.6]; log-rank p = 0.049) and in the strata with lymphocytes <870/mmc (90% [79–96]) vs (73% [55–89], HR 1.53 [0.9–2.7]; log-rank p = 0.058). Overall, 39/121 (32%) AEs were reported in arm A and 14/55 (23%) in B (p = 0.195), while serious AEs were 22/121 (18%) and 7/55 (11%), respectively (p = 0.244). There were no treatment-related deaths. Interpretation: The efficacy of sarilumab in severe COVID-19 was not demonstrated both in the overall and in the stratified for severity analysis population. Exploratory analyses suggested that subsets of patients with lower CRP values or lower lymphocyte counts might have had benefit with sarilumab treatment, but this finding would require replication in other studies. The relatively low rate of concomitant corticosteroid use, could partially explain our results. Funding: This study was supported by INMI “Lazzaro Spallanzani” Ricerca Corrente Linea 1 on emerging and reemerging infections, funded by Italian Ministry of Health