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Objectives: The immunologic profile and opportunistic viral DNA increase were monitored in Italian patients with COVID-19 in order to identify markers of disease severity. Methods: A total of 104 patients infected with SARS-CoV-2 were evaluated in the study. Of them, 42/104 (40.4%) were hospitalized in an intensive care unit (ICU) and 62/104(59.6%) in a sub-intensive care unit (SICU). Human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV), Parvovirus B19 and Human Herpesvirus 6 virus reactivations were determined by real-time PCR, and lymphocyte subpopulation counts were determined by flow cytometry. Results: Among opportunistic viruses, only EBV was consistently detected. EBV DNA was observed in 40/42 (95.2%) of the ICU patients and in 51/61 (83.6%) of the SICU patients. Comparing the two groups of patients, the EBV DNA median level among ICU patients was significantly higher than that observed in SICU patients. In parallel, a significant reduction of CD8 T cell and NK count in ICU patients as compared with SICU patients was observed (p

Objectives: The first COVID-19 lockdown raised concerns about reduced access to primary care, especially for people with chronic diseases particularly at risk in the absence of follow-up. However, the COVIQuest trial, evaluating the impact of a general practitioner (GP) phone call (intervention) to chronic patients with cardiovascular disease (CVD) or mental health disorder (MHD) concluded that the intervention had no effect at 1 month on the rate of self-reported hospitalisations in the CVD subtrial, whereas the intervention group in MHD subtrial might have a higher rate. This second part of the study aimed to describe the 6 month hospitalisation and specialised consultation rates, using the French health data system ( Système National des Données de Santé ). The secondary objective was to describe these rates during the same period in 2019., Design: A cluster randomised controlled trial, with clusters being GPs., Setting: Primary care, 149 GPs from eight French regions., Participants: Patients ≥70 years old with chronic CVD or ≥18 years old with MHD., Interventions: A standardised GP-initiated phone call aiming to evaluate patient's need for urgent care (vs usual care for control groups)., Primary and Secondary Outcome Measures: The occurrence of at least one hospitalisation at end point 31 October 2020 (randomisation 30 April 2020), excluding those starting on 30 April 2020, was measured as planned. Another main outcome was the occurrence of at least one specialised consultation during the same period. These 6 month effects were studied, using a logistic regression model within a generalised estimating equation framework, for each subtrial., Results: 4640 patients were included: 3274 cardiovascular (mean age 79.9±7.0 years; 57.8% male) and 1366 psychiatric (53.2±7.0; 36.5%). For both subtrials, the intervention patients were significantly more hospitalised than the control patients, respectively, 17.3% versus 14.9% of CVD patients (OR=1.26 (1.05 to 1.52)); 14.4% versus 10.7% of MHD patients (OR=1.40 (1.00 to 1.96)). During the same period in 2019, the hospitalisation rates were, respectively, 16.3%, 18.2%, 15.8% and 14.8%. The proportions of patients with at least one specialised consultation were not different between the intervention and control groups, respectively, 24.6% versus 24.3% for CVD patients (OR=1.06 (0.85 to 1.32)); 26.5% versus 24.4% for MHD patients (OR=1.15 (0.84 to 1.57)). During the same period in 2019, these rates were, respectively, 22.7%, 24.6%, 28.0% and 25.5%., Conclusions: The intervention was associated with higher rates of hospitalisation at 6 months in patients with MHD or CVD. No intervention impact was found in outpatient care. These results are difficult to interpret because of a potential artefact induced by national campaigns promoting medical use during lockdown, overlapping the study inclusion period. This study showed that medico-administrative databases could represent a complementary cost-effective tool to clinical research for long-term and healthcare consumption outcomes., Trial Registration Number: NCT04359875., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: HIV Pre-Exposure Prophylaxis (PrEP) has been used in France since 2016. Its effectiveness is no longer to be demonstrated. However, follow-up and adherence remain the main pitfalls. The main objective of this study was to identify factors associated with persistence or loss of PrEP follow-up., Design: An historic cohort of PrEP users was compiled from the database of consultations in the Indre-et-Loire dedicated sexual health centers (CeGIDD) from June 2016 to June 2021., Methods: Kaplan-Meier curves were performed to compare the group of persistent PrEP users to the discontinuation group. Factors associated with PrEP discontinuation were identified using Cox modelling, considering time-dependent variables. Final variables included in the model were selected based on the Akaike Information Criterion (AIC) and clinical relevance., Results: Over the period, 568 PrEP users were included in the cohort. Median follow-up was 2.3 years. A quarter of users were lost to follow-up within 3 months after PrEP initiation. Sexual risk reduction AIDS community-based support (HR = 0.65[0.42;0.99]), being in a couple (HR = 0.51[0.38;0.68]), and history of syphilis (HR = 0.57[0.40;0.81]) were significantly associated with persistence of follow-up. Remote consultations (HR = 2.74[1.63;4.61]), chemsex practices (HR = 2.01[1.29;3.14]), and side effects (HR=1.72[1.03;2.88]) were significantly associated with a loss of follow-up., Conclusion: These results suggest that more sexual risk reduction AIDS community-based counseling could be a key, necessary for supporting PrEP users in their follow-up pathway. Indeed, AIDS community-based support could be used to build a basis for developing safe pathways. Remote consultations could represent a response to the issue of access to PrEP. To create a significant impact on global HIV incidence, the PrEP offer must be extended, and at-risk PrEP users supported to maintain PrEP use., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In HIV, the polyprotein precursor Gag orchestrates the formation of the viral capsid. In the current view of this viral assembly, Gag forms low-order oligomers that bind to the viral genomic RNA triggering the formation of high-ordered ribonucleoprotein complexes. However, this assembly model was established using biochemical or imaging methods that do not describe the cellular location hosting Gag-gRNA complex nor distinguish gRNA packaging in single particles. Here, we studied the intracellular localization of these complexes by electron microscopy and monitored the distances between the two partners by morphometric analysis of gold beads specifically labeling Gag and gRNA. We found that formation of these viral clusters occurred shortly after the nuclear export of the gRNA. During their transport to the plasma membrane, the distance between Gag and gRNA decreases together with an increase of gRNA packaging. Point mutations in the zinc finger patterns of the nucleocapsid domain of Gag caused an increase in the distance between Gag and gRNA as well as a sharp decrease of gRNA packaged into virions. Finally, we show that removal of stem loop 1 of the 5'-untranslated region does not interfere with gRNA packaging, whereas combined with the removal of stem loop 3 is sufficient to decrease but not abolish Gag-gRNA cluster formation and gRNA packaging. In conclusion, this morphometric analysis of Gag-gRNA cluster formation sheds new light on HIV-1 assembly that can be used to describe at nanoscale resolution other viral assembly steps involving RNA or protein-protein interactions., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021. Published by Elsevier Inc.)

Background: Clinical trials have demonstrated that oral pre-exposure prophylaxis (PrEP) has high efficacy in preventing HIV transmission. In many countries, HIV testing is recommended prior to PrEP initiation, 1 month after and quarterly thereafter. We assessed the uptake of HIV testing and estimated the incidence of HIV infections after oral PrEP initiation, by using the French national health database (SNDS)., Methods: A historic cohort study included every adult person who started oral PrEP between 1 January 2016 and 30 June 2018 in France. HIV infection was tracked in the follow-up, from first PrEP dispensation up to 31 December 2018. Factors associated with adherence to HIV testing in PrEP follow-up were analysed using a generalized linear mixed model., Results: PrEP users (9893) were followed for a median duration of 551 days (IQR 350-769). The first HIV test, 1 month after PrEP initiation, was performed by 64% of users. For subsequent tests, this rate exceeded 81% and remained stable over time. HIV testing was lower among PrEP users without prescription refill (OR 0.15; 99% CI 0.12-0.20), but higher if the last prescription was made by a hospital practitioner (OR 2.03; 99% CI 1.69-2.45). Twenty-nine HIV infections were identified, leading to an incidence of 0.19 cases per 100 person-years (99% CI 0.12-0.30)., Conclusions: We confirmed good adherence to HIV testing and efficacy of PrEP in users, which should help in decreasing HIV incidence in France. This study also revealed that SNDS could be a powerful automated tool for the epidemiological monitoring of PrEP users., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The use of probiotics in critically ill adult and children patients has been growing exponentially over the last 20 years. Numerous factors in pediatriac intensive care unit (PICU) patients may contribute to intestinal dysbiosis, which subsequently promotes the pathobiota's growth. Currently, lactobacillus and bifidobacterium species are mainly used to prevent the development of systemic diseases due to the subverted microbiome, followed by streptococcus , enterococcus , propionibacterium , bacillus and Escherichia coli , Lactobacillus rhamnosus GG , and Lactobacillus reuteri DSM 17938 . The aim of this article is to review the scientific literature for further confirmation of the importance of the usage of probiotics in intensive care unit (ICU) patients, especially in the pediatric population. A progressive increase in nosocomial infections, especially nosocomial bloodstream infections, has been observed over the last 30 years. The World Health Organization (WHO) reported that the incidence of nosocomial infections in PICUs was still high and ranged between 5% and 10%. Petrof et al. was one of the first to demonstrate the efficacy of probiotics for preventing systemic diseases in ICU patients. Recently, however, the use of probiotics with different lactobacillus spp. has been shown to cause a decrease of pro-inflammatory cytokines and an increase in anti-inflammatory cytokines. In addition, in some studies, the use of probiotics, in particular the mix of Lactobacillus and Bifidobacterium reduces the incidence of ventilator-associated pneumonia (VAP) in PICU patients requiring mechanical ventilation. In abdominal infections, there is no doubt at all about the usefulness of using Lactobacillus spp probiotics, which help to treat ICU-acquired diarrhoea episodes as well as in positive blood culture for candida spp. Despite the importance of using probiotics being supported by various studies, their use is not yet part of the standard protocols to which all doctors must adhere. In the meantime, while waiting for protocols to be drawn up as soon as possible for use in PICUs, routine use could certainly stimulate the intestine's immune defences. Though it is still too early to say, they could be considered the drugs of the future.

Since the end of 2019, the medical-scientific community has been facing a terrible pandemic caused by a new airborne viral agent known as SARS-CoV2. Already in the early stages of the pandemic, following the discovery that the virus uses the ACE2 cell receptor as a molecular target to infect the cells of our body, it was hypothesized that the renin-angiotensin-aldosterone system was involved in the pathogenesis of the disease. Since then, numerous studies have been published on the subject, but the exact role of the renin-angiotensin-aldosterone system in the pathogenesis of COVID-19 is still a matter of debate. RAAS represents an important protagonist in the pathogenesis of COVID-19, providing the virus with the receptor of entry into host cells and determining its organotropism. Furthermore, following infection, the virus is able to cause an increase in plasma ACE2 activity, compromising the normal function of the RAAS. This dysfunction could contribute to the establishment of the thrombo-inflammatory state characteristic of severe forms of COVID-19. Drugs targeting RAAS represent promising therapeutic options for COVID-19 sufferers.