Assessment of De-Escalation of Empirical Antimicrobial Therapy in Medical Wards with Recognized Prevalence of Multi-Drug-Resistant Pathogens: A Multicenter Prospective Cohort Study in Non-ICU Patients with Microbiologically Documented Infection.

Antimicrobial resistance poses a major threat to human health worldwide and the implementation of antimicrobial stewardship programs (ASPs), including antimicrobial de-escalation (ADE), is a multifaceted tool for minimizing unnecessary or inappropriate antibiotic exposure. This was a prospective observational study of 142 non-Intensive Care Unit (ICU) patients with microbiologically documented infection who were initially administered empirical antimicrobial therapy and admitted to the medical wards of 6 tertiary-care hospitals in Greece from January 2017 to December 2018. Patients were divided into two groups, the ADE and non-ADE group, based on whether ADE was applied or not, respectively.

Clinical Phenotyping for Prognosis and Immunotherapy Guidance in Bacterial Sepsis and COVID-19.

Objectives: It is suggested that sepsis may be classified into four clinical phenotypes, using an algorithm employing 29 admission parameters. We applied a simplified phenotyping algorithm among patients with bacterial sepsis and severe COVID-19 and assessed characteristics and outcomes of the derived phenotypes.

Design: Retrospective analysis of data from prospective clinical studies.

A Phase III Randomized Controlled Trial of Plitidepsin, a Marine-Derived Compound, in Hospitalized Adults With Moderate COVID-19.

Background: Plitidepsin has shown potent preclinical activity against severe acute respiratory syndrome coronavirus 2 and was generally well tolerated in a phase I trial of hospitalized patients with coronavirus disease 2019 (COVID-19). NEPTUNO, a phase III, multicenter, randomized, controlled trial, was designed to evaluate the efficacy and safety of plitidepsin in the management of moderate COVID-19 in hospitalized adult patients.

Methods: Included patients had documented severe acute respiratory syndrome coronavirus 2 infection, required oxygen therapy, and had adequate organ function.

The Gordian Knot of : If You Cannot Cut It, Prevent It.

Since its first description in 2009, has, so far, resulted in large hospital outbreaks worldwide and is considered an emerging global public health threat. Exceptionally for yeast, it is gifted with a profoundly worrying invasive potential and high inter-patient transmissibility. At the same time, it is capable of colonizing and persisting in both patients and hospital settings for prolonged periods of time, thus creating a vicious cycle of acquisition, spreading, and infection.

The Burden of COVID-19 in Adult Patients With Hematological Malignancies: A Single-center Experience After the Implementation of Mass-vaccination Programs Against SARS-CoV-2.

Background/aim: Despite the widespread mass-vaccination programs worldwide and the continuing evolution of COVID-19 therapeutics, the burden of SARS-CoV-2 infection in patients with hematological malignancies (HM) remains elusive. The aim of the present study was to assess the clinical characteristics, outcomes and therapeutic strategies applied in HM patients hospitalized during the post-vaccine period in Greece.

Patients And Methods: From June 2021 to October 2022, 60 HM patients with COVID-19 were retrospectively analyzed.

Remdesivir: Effectiveness and Safety in Hospitalized Patients with COVID-19 (ReEs-COVID-19)-Analysis of Data from Daily Practice.

Remdesivir was the first antiviral approved for treating COVID-19. We investigated its patterns of use, effectiveness and safety in clinical practice in Greece. This is a retrospective observational study of hospitalized adults who received remdesivir for COVID-19 in September 2020-February 2021.

Dexamethasone attenuates interferon-related cytokine hyperresponsiveness in COVID-19 patients.

Background: Dexamethasone improves the survival of COVID-19 patients in need of supplemental oxygen therapy. Although its broad immunosuppressive effects are well-described, the immunological mechanisms modulated by dexamethasone in patients hospitalized with COVID-19 remain to be elucidated.

Objective: We combined functional immunological assays and an omics-based approach to investigate the and effects of dexamethasone in the plasma and peripheral blood mononuclear cells (PBMCs) of COVID-19 patients.

Efficacy of Tocilizumab in Severely Ill COVID-19 Patients With Rapid Respiratory Deterioration: A Single Center Experience During the Third Pandemic Wave in Greece.

Background/aim: Immunomodulatory therapy with Tocilizumab (TCZ), a monoclonal antibody against interleukin-6 receptor-alpha, has been endorsed by the World Health Organization and other major regulatory bodies, as part of the standard-of-care therapy for severe or critical COVID-19 cases despite discordant trial outcomes. The aim of the present study was to report the experience of our center regarding TCZ routine use in severely ill COVID-19 patients who were hospitalized during the third pandemic wave in Greece.

Patients And Methods: From March 2021 to December 2021, we retrospectively analyzed COVID-19 patients with radiological findings of pneumonia and signs of rapid respiratory deterioration that were treated with TCZ.

Interferon gamma-induced protein 10 (IP-10) for the early prognosis of the risk for severe respiratory failure and death in COVID-19 pneumonia.

Objectives: Elevated concentrations of soluble urokinase plasminogen activator receptor (suPAR) predict progression to severe respiratory failure (SRF) or death among patients with COVID-19 pneumonia and guide early anakinra treatment. As suPAR testing may not be routinely available in every health-care setting, alternative biomarkers are needed. We investigated the performance of C-reactive protein (CRP), interferon gamma-induced protein-10 (IP-10) and TNF-related apoptosis-inducing ligand (TRAIL) for predicting SRF or death in COVID-19.

Ribavirin aerosol in hospitalized adults with respiratory distress and COVID-19: An open-label trial.

There is an unmet medical need for effective treatments for hospitalized patients with coronavirus disease 2019 (COVID-19). Ribavirin is a broad-spectrum antiviral with demonstrated in vitro activity against multiple viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This trial evaluated the potential of ribavirin inhalation solution (ribavirin aerosol) to reduce COVID-19 disease severity in adults with confirmed SARS-CoV-2 infection and a diagnosis of respiratory distress.

Programmed Cell Death Protein 1 Axis Inhibition in Viral Infections: Clinical Data and Therapeutic Opportunities.

A vital function of the immune system is the modulation of an evolving immune response. It is responsible for guarding against a wide variety of pathogens as well as the establishment of memory responses to some future hostile encounters. Simultaneously, it maintains self-tolerance and minimizes collateral tissue damage at sites of inflammation.

New Insights into SARS-CoV-2 and Cancer Cross-Talk: Does a Novel Oncogenesis Driver Emerge?

Since the pandemic's onset, a growing population of individuals has recovered from SARS-CoV-2 infection and its long-term effects in some of the convalescents are gradually being reported. Although the precise etiopathogenesis of post-acute COVID-19 sequelae (PACS) remains elusive, the mainly accepted rationale is that SARS-CoV-2 exerts long-lasting immunomodulatory effects, promotes chronic low-grade inflammation, and causes irreversible tissue damage. So far, several viruses have been causally linked to human oncogenesis, whereas chronic inflammation and immune escape are thought to be the leading oncogenic mechanisms.

Greek Remdesivir Cohort (GREC) Study: Effectiveness of Antiviral Drug Remdesivir in Hospitalized Patients with COVID-19 Pneumonia.

In several randomized studies, remdesivir (RDV) has been reported to shorten the recovery period and improve clinical outcomes in COVID-19 patients, and thus, it is recommended as a standard of care. Nevertheless, controversial reports have been published. The aim of the present study is to evaluate the effectiveness of remdesivir in hospitalized patients with COVID-19 pneumonia at three Greek University Departments of Infectious Diseases with homogenous treatment protocols.

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.

Corrigendum: ACTIVATE-2: A double-blind randomized trial of BCG vaccination against COVID-19 in individuals at risk.

[This corrects the article DOI: 10.3389/fimmu.2022.

A Randomized Trial of Lipid Metabolism Modulation with Fenofibrate for Acute Coronavirus Disease 2019.

Background Abnormal cellular lipid metabolism appears to underlie SARS-CoV-2 cytotoxicity and may involve inhibition of peroxisome proliferator activated receptor alpha (PPARα). Fenofibrate, a PPAR-α activator, modulates cellular lipid metabolism. Fenofibric acid has also been shown to affect the dimerization of angiotensin-converting enzyme 2, the cellular receptor for SARS-CoV-2.

Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial.

Background: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection.

Objective: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone.

Design: Double-blind, randomized, placebo-controlled, clinical trial.

ACTIVATE-2: A Double-Blind Randomized Trial of BCG Vaccination Against COVID-19 in Individuals at Risk.

In a recent study of our group with the acronym ACTIVATE, Bacillus Calmete-Guérin (BCG) vaccination reduced the occurrence of new infections compared to placebo vaccination in the elderly. Most benefit was found for respiratory infections. The ACTIVATE-2 study was launched to assess the efficacy of BCG vaccination against coronavirus disease 2019 (COVID-19).