Persistence of SARS-CoV-2 infection and viral intra- and inter-host evolution in COVID-19 hospitalized patients.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) persistence in COVID-19 patients could play a key role in the emergence of variants of concern. The rapid intra-host evolution of SARS-CoV-2 may result in an increased transmissibility, immune and therapeutic escape which could be a direct consequence of COVID-19 epidemic currents. In this context, a longitudinal retrospective study on eight consecutive COVID-19 patients with persistent SARS-CoV-2 infection, from January 2022 to March 2023, was conducted. To characterize the intra- and inter-host viral evolution, whole genome sequencing and phylogenetic analysis were performed on nasopharyngeal samples collected at different time points. Phylogenetic reconstruction revealed an accelerated SARS-CoV-2 intra-host evolution and emergence of antigenically divergent variants. The Bayesian inference and principal coordinate analysis analysis showed a host-based genomic structuring among antigenically divergent variants, that might reflect the positive effect of containment practices, within the critical hospital area. All longitudinal antigenically divergent isolates shared a wide range of amino acidic (aa) changes, particularly in the Spike (S) glycoprotein, that increased viral transmissibility (K417N, S477N, N501Y and Q498R), enhanced infectivity (R346T, S373P, R408S, T478K, Q498R, Y505H, D614G, H655Y, N679K and P681H), caused host immune escape (S371L, S375F, T376A, K417N, and K444T/R) and displayed partial or complete resistance to treatments (G339D, R346K/T, S371F/L, S375F, T376A, D405N, N440K, G446S, N460K, E484A, F486V, Q493R, G496S and Q498R). These results suggest that multiple novel variants which emerge in the patient during persistent infection, might spread to another individual and continue to evolve. A pro-active genomic surveillance of persistent SARS-CoV-2 infected patients is recommended to identify genetically divergent lineages before their diffusion.

Quantitative EEG analysis of brivaracetam in drug-resistant epilepsy: A pharmaco-EEG study.

OBJECTIVE: Brivaracetam (BRV) is a recent antiseizure medication (ASM) approved as an add-on therapy for people with focal epilepsy. BRV has a good efficacy and safety profile compared to other ASMs. However, its specific effects on resting-state EEG activity and connectivity are unknown. The aim of this study is to evaluate quantitative EEG changes induced by BRV therapy in a population of adult people with drug-resistant epilepsy (PwE) compared to healthy controls (HC). METHODS: We performed a longitudinal, retrospective, pharmaco-EEG study on a population of 23 PwE and a group of 25 HC. Clinical outcome was dichotomized into drug-responders (i.e., >50% reduction in seizures' frequency; RES) and non-responders (N-RES) after two years of BRV. EEG parameters were compared between PwE and HC at baseline (pre-BRV) and after three months of BRV therapy (post-BRV). We investigated BRV-related variations in EEG connectivity using the phase locking value (PLV). RESULTS: BRV therapy did not induce modifications in power spectrum density across different frequency bands. PwE presented lower PLV connectivity values compared to HC in all frequency bands. RES exhibited lower theta PLV connectivity compared to HC before initiating BRV and experienced an increase after BRV, eliminating the significant difference from HC. CONCLUSIONS: This study shows that BRV does not alter the EEG power spectrum in PwE, supporting its favourable neuropsychiatric side-effect profile, and induces the disappearance of EEG connectivity differences between PwE and HC. SIGNIFICANCE: The integration of EEG quantitative analysis in epilepsy can provide insights into the efficacy, mechanism of action, and side effects of ASMs.

Epstein-Barr virus, Cytomegalovirus, and Herpes Simplex-1/2 reactivations in critically ill patients with COVID-19.

OBJECTIVES: To assess the incidences of Herpes Simplex-1 and 2 (HSV-1, HSV-2), Cytomegalovirus (CMV), Epstein-Barr Virus (EBV) reactivations in critically ill COVID-19 patients. To determine the association between viral reactivation and in-hospital mortality, Intensive Care Unit Bloodstream infection (ICU-BSI), ventilator-associated pneumonia (VAP). DESIGN: Observational retrospective cohort study. SETTING: COVID-19 Intensive Care Unit. PATIENTS: From November 2020 to May 2021, one hundred and twenty patients with COVID-19 severe pneumonia were enrolled and tested for HSV-1, HSV-2, CMV and EBV at the admission in ICU and weekly until discharge or death. The presence of VAP and ICU-BSI was evaluated according to clinical judgement and specific diagnostic criteria. MEASUREMENTS AND MAIN RESULTS: One hundred and twenty patients were enrolled. Multiple reactivations occurred in 75/120 (63%) patients, single reactivation in 27/120 patients (23%). The most reactivated Herpesvirus was EBV, found in 78/120 (65%) patients. The multivariate analysis demonstrated that viral reactivation is a strong independent risk factor for in-hospital mortality (OR = 2.46, 95% CI 1.02-5.89), ICU-BSI (OR = 2.37, 95% CI 1.06-5.29) and VAP (OR = 2.64, 95% CI 1.20-5.82). CONCLUSIONS: Human Herpesviruses reactivations in critically ill patients with COVID-19 severe Pneumonia are associated with mortality and with a higher risk to develop both VAP and ICU-BSI.

Global Measles Surveillance: Trends, Challenges, and Implications for Public Health Interventions.

Measles, a highly contagious disease primarily affecting children, carries serious health risks, including complications and mortality. Vaccination remains the most effective preventive measure against measles transmission. The COVID-19 pandemic has exacerbated challenges in surveillance and immunization efforts, leaving millions of people exposed to preventable diseases such as measles. Globally accelerated immunization campaigns are critical for achieving regional elimination goals and mitigating the risk of outbreaks. Our team has developed an open-access database for global measles monitoring, facilitating standardized data collection and analysis. The analysis of measles cases from 2011 to 2023 reveals fluctuating trends, with notable increases in Africa in 2019 and 2023, indicating potential gaps in control strategies. Using an automated signal detection tool developed by the European Centre for Disease Prevention and Control (ECDC) team, we identified significant variations between World Health Organization (WHO) regions, underscoring the importance of continuous monitoring to detect epidemiological changes early. These results underscore the need for robust surveillance systems and accelerated vaccination efforts to safeguard public health.

On the SARS-CoV-2 Variants.

The evolutionary dynamics of viruses, particularly exemplified by SARS-CoV-2 during the ongoing COVID-19 pandemic, underscore the intricate interplay between genetics, host adaptation, and viral spread. This paper delves into the genetic evolution of SARS-CoV-2, emphasizing the implications of viral variants on global health. Initially emerging from the Wuhan-Hu-1 lineage, SARS-CoV-2 rapidly diversified into numerous variants, each characterized by distinct mutations in the spike protein and other genomic regions. Notable variants such as B.1.1.7 (α), B.1.351 (ß), P.1 (γ), B.1.617.2 (δ), and the Omicron variant have garnered significant attention due to their heightened transmissibility and immune evasion capabilities. In particular, the Omicron variant has presented a myriad of subvariants, raising concerns about its potential impact on public health. Despite the emergence of numerous variants, the vast majority have exhibited limited expansion capabilities and have not posed significant threats akin to early pandemic strains. Continued genomic surveillance is imperative to identify emerging variants of concern promptly. While genetic adaptation is intrinsic to viral evolution, effective public health responses must be grounded in empirical evidence to navigate the evolving landscape of the pandemic with resilience and precision.

Navigating Novel Viral Challenges: Understanding, Tracking, and Mitigating Emerging Threats.

The emergence of new viral threats continues to pose significant challenges to global health security [...].

Mpox: An Overview of Pathogenesis, Diagnosis, and Public Health Implications.

Mpox, caused by viruses of the genus Orthopoxvirus, is an emerging threat to human and animal health. With increasing urbanization and more frequent interaction between humans and wild animals, the risk of Mpox transmission to humans has increased significantly. This review aims to examine in depth the epidemiology, pathogenesis, and diagnosis of Mpox, with a special focus on recent discoveries and advances in understanding the disease. Molecular mechanisms involved in viral replication will be examined, as well as risk factors associated with interspecific transmission and spread of the disease in human populations. Currently available diagnostic methods will also be discussed, with a critical analysis of their limitations and possible future directions for improving the accuracy and timeliness of diagnosis. Finally, this review will explore the public health implications associated with Mpox, emphasizing the importance of epidemiological surveillance, vaccination, and emergency preparedness to prevent and manage possible outbreaks. Understanding the epidemiology and control strategies for Mpox is critical to protecting the health of human and animal communities and mitigating the risk of interspecific transmission and spread of the disease.

Phylodynamic and Evolution of the Hemagglutinin (HA) and Neuraminidase (NA) Genes of Influenza A(H1N1) pdm09 Viruses Circulating in the 2009 and 2023 Seasons in Italy.

The influenza A(H1N1) pdm09 virus, which emerged in 2009, has been circulating seasonally since then. In this study, we conducted a comprehensive genome-based investigation to gain a detailed understanding of the genetic and evolutionary characteristics of the hemagglutinin (HA) and neuraminidase (NA) surface proteins of A/H1N1pdm09 strains circulating in Italy over a fourteen-year period from 2009 to 2023 in relation to global strains. Phylogenetic analysis revealed rapid transmission and diversification of viral variants during the early pandemic that clustered in clade 6B.1. In contrast, limited genetic diversity was observed during the 2023 season, probably due to the genetic drift, which provides the virus with a constant adaptability to the host; furthermore, all isolates were split into two main groups representing two clades, i.e., 6B.1A.5a.2a and its descendant 6B.1A.5a.2a.1. The HA gene showed a faster rate of evolution compared to the NA gene. Using FUBAR, we identified positively selected sites 41 and 177 for HA and 248, 286, and 455 for NA in 2009, as well as sites 22, 123, and 513 for HA and 339 for NA in 2023, all of which may be important sites related to the host immune response. Changes in glycosylation acquisition/loss at prominent sites, i.e., 177 in HA and 248 in NA, should be considered as a predictive tool for early warning signs of emerging pandemics, and for vaccine and drug development.

Changing and evolution of influenza virus: is it a trivial flu?

BACKGROUND: Influenza viruses are etiological agents which cause contagious respiratory, seasonal epidemics and, for Influenza A subtypes, pandemics. The clinical picture of Influenza has undergone continuous change over the years, due to intrinsic viral evolution as well as "reassortment" of its genomic segments. The history of Influenza highlights its ability to adapt and to rapidly evolve, without specific circumstances. This reflects the complexity of this pathology and poses the fundamental question about its assumption as a "common illness" and its impact on public health. SUMMARY: The global influenza epidemics and pandemics claimed millions of deaths, leaving an indelible mark on public health, and showing the need for a better comprehension of the influenza virus. The clear understanding of genetic variations during the Influenza seasonal epidemics is a crucial point for developing effective strategies for prevention, treatment, and vaccine design. The recent advance in Next Generation Sequencing approaches, model systems to virus culture and bioinformatics pipeline played a key role in the rapid characterization of circulating Influenza strains. In particular, the increase of computational power allowed to perform complex tasks in healthcare setting through Machine Learning (ML) algorithms, which analyze different variables, such as medical and laboratory outputs, to optimize medical research and to improve public health systems. The early detection of emerging and re-emerging pathogens is of matter importance to prevent next pandemics. KEY MESSAGES: The perception of influenza as a "trivial flu" or a more serious public health concern is a subject of ongoing debate, reflecting the multifaceted nature of this infectious disease. The variability in the severity of influenza shed the light on the unpredictability of the viral characteristics, coupled with the challenges in accurately predicting circulating strains. This adds complexity to the public health burden of Influenza and highlights the need of targeted interventions.

A One Health Platform for Future Epidemic Preparedness.

Here, we introduce the EpiConnect Intelligence Platform (ECIP), a platform facilitating rapid, transparent data sharing and analysis to support researchers and public health officials in Europe, with a focus on Italy. ECIP provides reliable, concise, machine-readable data to aid in epidemiological understanding, standardize case characteristics, and estimate key parameters. The platform adheres to FAIR (findable, accessible, interoperable, reusable) principles, offering easily accessible and downloadable datasets for researchers' endeavors. Future enhancements include involving national public health authorities, expanding data streams, and fostering collaboration between experts and users for improved epidemic risk monitoring. Shared standards among diverse surveillance systems are advocated to achieve common strategic goals, emphasizing the need for forward-looking policies to empower professionals to analyze disease dynamics in the context of evolving health crises. The recent emergencies underscore the importance of collective efforts towards shared strategic goals, highlighting the necessity for coordinated action to address mutual concerns affecting everyone's lives.

Exploring the Interplay between COVID-19 and Gut Health: The Potential Role of Prebiotics and Probiotics in Immune Support.

The COVID-19 pandemic has profoundly impacted global health, leading to extensive research focused on developing strategies to enhance outbreak response and mitigate the disease's severity. In the aftermath of the pandemic, attention has shifted towards understanding and addressing long-term health implications, particularly in individuals experiencing persistent symptoms, known as long COVID. Research into potential interventions to alleviate long COVID symptoms has intensified, with a focus on strategies to support immune function and mitigate inflammation. One area of interest is the gut microbiota, which plays a crucial role in regulating immune responses and maintaining overall health. Prebiotics and probiotics, known for their ability to modulate the gut microbiota, have emerged as potential therapeutic agents in bolstering immune function and reducing inflammation. This review delves into the intricate relationship between long COVID, the gut microbiota, and immune function, with a specific focus on the role of prebiotics and probiotics. We examine the immune response to long COVID, emphasizing the importance of inflammation and immune regulation in the persistence of symptoms. The potential of probiotics in modulating immune responses, including their mechanisms in combating viral infections such as COVID-19, is discussed in detail. Clinical evidence supporting the use of probiotics in managing long COVID symptoms is summarized, highlighting their role as adjunctive therapy in addressing various aspects of SARS-CoV-2 infection and its aftermath.

Comprehensive Analysis of HIV-1 Integrase Resistance-Related Mutations in African Countries.

The growing emergence of non-nucleoside reverse transcriptase inhibitor (NNRTI) HIV drug resistance in sub-Saharan Africa (SSA) led to the World Health Organization (WHO) recommending, in 2018, a transition to dolutegravir (DTG) as a first-line antiretroviral therapy (ART) in SSA. The broad HIV-1 genetic diversity in SSA could shape DTG effectiveness and the pattern of drug resistance mutations (DRMs) in this region. This study evaluated HIV-1 integrase (IN) DRMs and conserved regions among published groups M, N, O, and P HIV-1 sequences spanning forty years of the HIV epidemic during the transition of DTG-based ART. Overall, we found low levels of integrase strand transfer inhibitor (INSTI)-DRMs (<1%) across HIV groups between the years 1983 and 2023; however, it was unexpected to detect DRMs at statistically significantly higher frequencies in pre-INSTI (1983-2007) than in the INSTI (2008-2023) era. The variability of accessory INSTI-DRMs depended on the HIV subtypes, with implications for susceptibility to DTG. Our findings provide new perspectives on the molecular epidemiology and drug resistance profiles of INSTIs in SSA, emphasizing the need for ongoing surveillance and customized treatment approaches to address the continent's varied HIV subtypes and changing resistance patterns.