Long-COVID - pathophysiology, current concepts and future directions.

Long-COVID, an umbrella term referring to a variety of symptoms and clinical presentations, which emerge in a subset of patients after SARS-CoV-2 infection, has a significant impact on an individual's quality of life and places a substantial burden on healthcare systems worldwide, straining financial and human resources. The pathophysiology of long-COVID remains incompletely understood, though several hypotheses have been proposed to explain different aspects of this complex condition. SARS-CoV-2 persistence, direct organ damage, innate and adaptive immune system pertubation, autoimmunity, latent viruses reactivation, endothelial dysfunction, and microbiome disturbances are among the most relevant avenues for elucidating the evolution, complexity, and mechanisms of long-COVID.

Duration of Antimicrobial Treatment in Adult Patients with Pneumonia: A Narrative Review.

Pneumonia remains a major global health concern, causing significant morbidity and mortality among adults. This narrative review assesses the optimal duration of antimicrobial treatment in adults with community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP). Current evidence about the impact of treatment duration on clinical outcomes demonstrates that shorter antibiotic courses are non-inferior, regarding safety and efficacy, compared to longer courses, particularly in patients with mild to moderate CAP, which is in line with the recommendations of international guidelines.

Mpox and Lessons Learned in the Light of the Recent Outbreak: A Narrative Review.

According to the WHO, more than 90,000 cases of mpox have been reported since the 2022 worldwide outbreak, which resulted in 167 deaths, while a new outbreak in Africa since 2023 has resulted in over 18,000 cases and 617 deaths. Mpox is a zoonosis caused by the monkeypox virus, a double-stranded DNA virus belonging to the Orthopoxvirus genus, which causes smallpox-like illness. Until 2022, cases were predominately located in West and Central Africa, with only sporadic cases and outbreaks reported in other parts of the world.

Effects of long-term corticosteroid use on susceptibility to respiratory viruses: a narrative review.

Background: Synthetic glucocorticoids are among the most commonly administered drugs due to their potent immunomodulatory properties. However, they may put patients at risk for infections. Their effect on the incidence of respiratory viral infections (RVIs) remains unclear.

Breakthrough COVID-19 Infections after Booster SARS-CoV-2 Vaccination in a Greek Cohort of People Living with HIV during the Delta and Omicron Waves.

Introduction: Currently approved SARS-CoV-2 vaccines have been proven effective in protecting against severe COVID-19; however, they show variable efficacy against symptomatic infection and disease transmission. We studied the breakthrough COVID-19 infection (BTI) after booster vaccination against SARS-CoV-2 in people living with HIV (PWH).

Methods: This was a retrospective, single-center, descriptive cohort study involving PWH, who were followed in the HIV Clinic of "Attikon" University Hospital in Athens, Greece.

Cognitive impairment in people living with HIV: mechanisms, controversies, and future perspectives.

Despite the dramatic decrease in HIV-associated neurocognitive impairment (NCI) in the combined antiretroviral treatment (cART) era, subtler neuropsychological complications remain prevalent. In this review, we discuss the changing pathophysiology of HIV-associated NCI, considering recent evidence of HIV neuropathogenesis, and the pivotal role of cART. Furthermore, we address the multifactorial nature of NCI in people living with HIV, including legacy and ongoing insults to the brain, as well as host-specific factors.

Early trajectories of virological and immunological biomarkers and clinical outcomes in patients admitted to hospital for COVID-19: an international, prospective cohort study.

Background: Serial measurement of virological and immunological biomarkers in patients admitted to hospital with COVID-19 can give valuable insight into the pathogenic roles of viral replication and immune dysregulation. We aimed to characterise biomarker trajectories and their associations with clinical outcomes.

Methods: In this international, prospective cohort study, patients admitted to hospital with COVID-19 and enrolled in the Therapeutics for Inpatients with COVID-19 platform trial within the Accelerating COVID-19 Therapeutic Interventions and Vaccines programme between Aug 5, 2020 and Sept 30, 2021 were included.

Multimodal Approach to Neurocognitive Function in People Living with HIV in the cART Era: A Comprehensive Review.

Combination antiretroviral treatment (cART) has revolutionized the management of human immunodeficiency virus (HIV) and has markedly improved the disease burden and life expectancy of people living with HIV. HIV enters the central nervous system (CNS) early in the course of infection, establishes latency, and produces a pro-inflammatory milieu that may affect cognitive functions, even in the cART era. Whereas severe forms of neurocognitive impairment (NCI) such as HIV-associated dementia have declined over the last decades, milder forms have become more prevalent, are commonly multifactorial, and are associated with comorbidity burdens, mental health, cART neurotoxicity, and ageing.

Effect of Neutralizing Monoclonal Antibody Treatment on Early Trajectories of Virologic and Immunologic Biomarkers in Patients Hospitalized With COVID-19.

Background: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood.

Methods: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo.

Endothelial Glycocalyx Integrity in Treatment-Naïve People Living with HIV before and One Year after Antiretroviral Treatment Initiation.

Endothelial glycocalyx (EG) derangement has been associated with cardiovascular disease (CVD). Studies on EG integrity among people living with HIV (PLWH), are lacking. We conducted a prospective cohort study among treatment-naïve PLWH who received emtricitabine/tenofovir alafenamide, combined with either an integrase strand transfer inhibitor (INSTI, dolutegravir, raltegravir or elvitegravir/cobicistat), or a protease inhibitor (PI, darunavir/cobicistat).

New Insights into the Fluid Management in Patients with Septic Shock.

The importance of fluid resuscitation therapy during the early stages of sepsis management is a well-established principle. Current Surviving Sepsis Campaign (SSC) guidelines recommend the early administration of intravenous crystalloid fluids for sepsis-related hypotension or hyperlactatemia due to tissue hypoperfusion, within the first 3 h of resuscitation and suggest using balanced solutions (BSs) instead of normal saline (NS) for the management of patients with sepsis or septic shock. Studies comparing BS versus NS administration in septic patients have demonstrated that BSs are associated with better outcomes including decreased mortality.

Cardiovascular disease and risk assessment in people living with HIV: Current practices and novel perspectives.

Human immunodeficiency virus (HIV) infection represents a major cardiovascular risk factor, and the cumulative cardiovascular disease (CVD) burden among aging people living with HIV (PLWH) constitutes a leading cause of morbidity and mortality. To date, CVD risk assessment in PLWH remains challenging. Therefore, it is necessary to evaluate and stratify the cardiovascular risk in PLWH with appropriate screening and risk assessment tools and protocols to correctly identify which patients are at a higher risk for CVD and will benefit most from prevention measures and timely management.

Switching from Tenofovir Disoproxil to Tenofovir Alafenamide Fumarate: Impact on Cardiovascular Risk and Lipid Profile in People Living with HIV, an Observational Study.

In the era of combination antiretroviral therapy (ART), people living with HIV (PLHIV) still face an increased risk of cardiovascular disease (CVD). Tenofovir alafenamide fumarate (TAF) is superior to its precursor tenofovir disoproxil fumarate (TDF) regarding bone and renal toxicity, but there are concerns about a negative effect on lipid profile. This observational, single-center study investigates the effects on lipid profile and cardiovascular (CVD) risk of the switch from TDF to TAF, in combination with emtricitabine/elvitegravir/cobicistat (FTC/EVG/c), in patients with no exposure to other antiretrovirals.

Performance of point-of care molecular and antigen-based tests for SARS-CoV-2: a living systematic review and meta-analysis.

Background: Molecular and antigen point-of-care tests (POCTs) have augmented our ability to rapidly identify and manage SARS-CoV-2 infection. However, their clinical performance varies among individual studies.

Objectives: The evaluation of the performance of molecular and antigen-based POCTs in confirmed, suspected, or probable COVID-19 cases compared with that of laboratory-based RT-PCR in real-life settings.

Insights into CD24 and Exosome Physiology and Potential Role in View of Recent Advances in COVID-19 Therapeutics: A Narrative Review.

Cluster of differentiation (CD) 24, a long-known protein with multifaceted functions, has gained attention as a possible treatment for Coronavirus Disease 19 (COVID-19) due to its known anti-inflammatory action. Extracellular vesicles (EVs), such as exosomes and microvesicles, may serve as candidate drug delivery platforms for novel therapeutic approaches in COVID-19 and various other diseases due to their unique characteristics. In the current review, we describe the physiology of CD24 and EVs and try to elucidate their role, both independently and as a combination, in COVID-19 therapeutics.

Host immune responses and possible therapeutic targets for viral respiratory tract infections in susceptible populations: a narrative review.

Background: Respiratory viruses are associated with significant global morbidity and mortality, as well as socioeconomic factors. Certain conditions and patient groups are more susceptible to develop severe viral respiratory tract infections (RTIs).

Objectives: To summarise the data on deregulated immune pathways that have been associated with increased susceptibility to severe viral RTIs in certain populations.

Intensity and Dynamics of Anti-SARS-CoV-2 Immune Responses after BNT162b2 mRNA Vaccination: Implications for Public Health Vaccination Strategies.

The aim of our study was to investigate the immunogenicity of the BNT162b2 vaccination according to the age and medical status of vaccinated individuals. A total of 511 individuals were enrolled (median age: 54.0 years, range: 19-105); 509 of these individuals (99.

How to interpret and use COVID-19 serology and immunology tests.

Background: Although molecular tests are considered the reference standard for coronavirus disease 2019 (COVID-19) diagnostics, serological and immunological tests may be useful in specific settings.

Objectives: This review summarizes the underlying principles and performance of COVID-19 serological and immunological testing.

Sources: Selected peer-reviewed publications on COVID-19 related serology and immunology published between December 2019 and March 2021.

Update in Viral Infections in the Intensive Care Unit.

The advent of highly sensitive molecular diagnostic techniques has improved our ability to detect viral pathogens leading to severe and often fatal infections that require admission to the Intensive Care Unit (ICU). Viral infections in the ICU have pleomorphic clinical presentations including pneumonia, acute respiratory distress syndrome, respiratory failure, central or peripheral nervous system manifestations, and viral-induced shock. Besides infections, certain viruses fall into latency and can be reactivated in both immunosuppressed and immunocompetent critically ill patients.

Antibody Response Following Pre-Exposure Immunization Against Rabies in High-Risk Professionals.

Vaccination against rabies and routine antibody testing of subjects participating in programs for the surveillance and control of rabies in animals is strongly recommended. The scope of this study is to describe the antibody level as measured by a commercial enzyme-linked immunosorbent assay (ELISA) after primary and booster intramuscular vaccination with a purified vero-cell rabies vaccine (PVRV) in high-risk professionals and to determine the influence of an array of factors on antibody level, that is, time elapsed since primary immunization series and booster dose, sex, age, pathologic conditions, high-risk occupation, and peak antibody level after initial scheme and booster dose. A primary series of three doses of PVRV was administered and a commercial ELISA was recommended 14 days postimmunization with continuous repetition at 6 months and yearly intervals for the laboratory personnel and the rest of the professionals, respectively.

Predicting protein complexes from weighted protein-protein interaction graphs with a novel unsupervised methodology: Evolutionary enhanced Markov clustering.

Objective: Proteins are considered to be the most important individual components of biological systems and they combine to form physical protein complexes which are responsible for certain molecular functions. Despite the large availability of protein-protein interaction (PPI) information, not much information is available about protein complexes. Experimental methods are limited in terms of time, efficiency, cost and performance constraints.

Which clustering algorithm is better for predicting protein complexes?

Background: Protein-Protein interactions (PPI) play a key role in determining the outcome of most cellular processes. The correct identification and characterization of protein interactions and the networks, which they comprise, is critical for understanding the molecular mechanisms within the cell. Large-scale techniques such as pull down assays and tandem affinity purification are used in order to detect protein interactions in an organism.

Noise reduction in protein-protein interaction graphs by the implementation of a novel weighting scheme.

Background: Recent technological advances applied to biology such as yeast-two-hybrid, phage display and mass spectrometry have enabled us to create a detailed map of protein interaction networks. These interaction networks represent a rich, yet noisy, source of data that could be used to extract meaningful information, such as protein complexes. Several interaction network weighting schemes have been proposed so far in the literature in order to eliminate the noise inherent in interactome data.