Omicron variant evolution on vaccines and monoclonal antibodies.

The severe acute respiratory syndrome coronavirus (SARS-CoV)-2 responsible for the global COVID-19 pandemic has caused almost 760 million confirmed cases and 7 million deaths worldwide, as of end-February 2023. Since the beginning of the first COVID-19 case, several virus variants have emerged: Alpha (B1.1.7), Beta (B135.1), Gamma (P.1), Delta (B.1.617.2) and then Omicron (B.1.1.529) and its sublineages. All variants have diversified in transmissibility, virulence, and pathogenicity. All the newly emerging SARS-CoV-2 variants appear to contain some similar mutations associated with greater "evasiveness" of the virus to immune defences. From early 2022 onward, several Omicron subvariants named BA.1, BA.2, BA.3, BA.4, and BA.5, with comparable mutation forms, have followed. After the wave of contagions caused by Omicron BA.5, a new Indian variant named Centaurus BA.2.75 and its new subvariant BA.2.75.2, a second-generation evolution of the Omicron variant BA.2, have recently been identified. From early evidence, it appears that this new variant has higher affinity for the cell entry receptor ACE-2, making it potentially able to spread very fast. According to the latest studies, the BA.2.75.2 variant may be able to evade more antibodies in the bloodstream generated by vaccination or previous infection, and it may be more resistant to antiviral and monoclonal antibody drug treatments. In this manuscript, the authors highlight and describe the latest evidences and critical issues have emerged on the new SARS-CoV-2 variants.

Sex affects immune response capacity against COVID-19 infection.

The genetic variability of each individual may lead to the identification of completely different genetic polymorphisms which are associated with a different sensitivity to infectious diseases in humans. Such genetic variability allows the immune system to respond differently to viral agents, therefore only a fraction of humans develop severe symptoms, as happened with SARS-CoV-2. Such knowledge is critical to enable the development of appropriate pharmacological solutions to prevent the consequences of insufficient immunity in dealing with serious viral diseases such as SARS-CoV-2. For instance, global epidemiological data show that male sex is a risk factor for the severe evolution of SARS-CoV-2 disease. Men, due to higher production of Testosterone (TLT), are more vulnerable than females. Women, due to greater expression of the TLR7 gene found on the X chromosome, a key innate immunity gene that encodes Toll-like proteins, are able to synthesise more antiviral proteins and interferons in dendritic cells, resulting in a more robust immune system capable of preventing severe SARS-CoV-2 viral disease. This manuscript highlights how human genetic variability can lead to severe infectious symptoms in some individuals who must take appropriate prophylactic actions, such as vaccination, to prevent this.

Antifungal Drug Resistance: An Emergent Health Threat.

Fungal infections, named mycosis, can cause severe invasive and systemic diseases that can even lead to death. In recent years, epidemiological data have recorded an increase in cases of severe fungal infections, caused mainly by a growing number of immunocompromised patients and the emergence of fungal pathogenic forms that are increasingly resistant to antimycotic drug treatments. Consequently, an increase in the incidence of mortality due to fungal infections has also been observed. Among the most drug-resistant fungal forms are those belonging to the Candida and Aspergillus spp. Some pathogens are widespread globally, while others are endemic in some areas only. In addition, some others may represent a health threat for some specific subpopulations and not for the general public. In contrast to the extensive therapeutic armamentarium available for the antimicrobial chemotherapeutic treatment of bacteria, for fungal infections there are only a few classes of antimycotic drugs on the market, such as polyenes, azoles, echinocandins, and a few molecules are under trial. In this review, we focused on the systemic mycosis, highlighted the antifungal drug compounds available in the pipeline, and analyzed the main molecular mechanisms for the development of antifungal resistance to give a comprehensive overview and increase awareness on this growing health threat.

Le SARS-CoV-2 a provoqué une augmentation de la consommation d'antibiotiques, provoquant une pandémie silencieuse à l'intérieur de la pandémie. Une analyse rétrospective des données italiennes au premier semestre 2022 SARS-CoV-2 caused a surge in antibiotic consumption causing a silent pandemic inside the pandemic. A retrospective analysis of Italian data in the first half of 2022

Fond. Le phénomène de la résistance aux antibiotiques ne semble pas vouloir s'arrêter, malgré les politiques mondiales de lutte mises en place depuis plusieurs années. Le risque de formes de micro-organismes pathogènes de plus en plus résistants aux antibiotiques courants a conduit les autorités sanitaires du monde entier à porter une plus grande attention au phénomène. La situation préoccupante a conduit à de nouvelles recommandations de l'Organisation mondiale de la santé (OMS) et à des recommandations nationales en Italie à travers le nouveau Plan national de lutte contre la résistance aux antibiotiques 2022-2025 (PNCAR 2022-2025). Avoir pour but. Ce manuscrit vise à sensibiliser tous les professionnels de santé à suivre ce qui est suggéré par les agences réglementaires et les sociétés savantes. Méthode. Nous avons mené une étude rétrospective de la pharmacoutilisation des antibiotiques en Italie, dans la région de Campanie à l'Azienda Sanitaria Locale (ASL) Napoli 3 Sud, sur la consommation au premier semestre 2022 dans une population de plus de 1 million de personnes. Résultat. Les résultats indiquent que la consommation, basée sur des doses journalières définies (DDD), est supérieure à la moyenne nationale. La pandémie de COVID-19 a probablement influencé cette croissance des prescriptions. Conclusions. Notre étude suggère une utilisation informée et appropriée des antibiotiques, afin de s'engager sur une voie vertueuse dans la lutte contre la résistance aux antibiotiques.

Low Molecular Weight Heparin, Anti-inflammatory/Immunoregulatory and Antiviral Effects, a Short Update.

Low molecular weight heparin (LMWH) is a glycosaminoglycan long known for its anticoagulant properties. In recent times, recent evidence has associated this drug with extra pleiotropic anticoagulant effects that have also proven useful in the management of the treatment of COVID-19 infection indicating that heparin may play other roles in the management of the disease in addition to the prevention of thrombosis. Clinical observations and in vitro studies support that heparin has a potential multi-target effect. To date, the molecular mechanisms of these pleiotropic effects are not fully understood. This brief review presents some of the evidence from clinical and animal studies and describes the potential molecular mechanisms by which heparin may exert its anti-inflammatory/immunoregulatory and antiviral effects.

Acute Heart Failure: Diagnostic-Therapeutic Pathways and Preventive Strategies-A Real-World Clinician's Guide.

Acute heart failure (AHF) is the most frequent cause of unplanned hospital admission in patients of >65 years of age and it is associated with significantly increased morbidity, mortality, and healthcare costs. Different AHF classification criteria have been proposed, mainly reflecting the clinical heterogeneity of the syndrome. Regardless of the underlying mechanism, peripheral and/or pulmonary congestion is present in the vast majority of cases. Furthermore, a marked reduction in cardiac output with peripheral hypoperfusion may occur in most severe cases. Diagnosis is made on the basis of signs and symptoms, laboratory, and non-invasive tests. After exclusion of reversible causes, AHF therapeutic interventions mainly consist of intravenous (IV) diuretics and/or vasodilators, tailored according to the initial hemodynamic status with the addition of inotropes/vasopressors and mechanical circulatory support if needed. The aim of this review is to discuss current concepts on the diagnosis and management of AHF in order to guide daily clinical practice and to underline the unmet needs. Preventive strategies are also discussed.

What Do We Know About the Smallpox Virus? A Journey Between Clinic and Therapy.

PURPOSE: Modern research is increasingly focusing on the study of new viruses and the re-emergence of past microbes, such as Coronaviruses, particularly Sars-Cov2 that was responsible for the very recent pandemic. METHODS AND RESULTS: This infection manifested itself and still continues to manifest as a severe respiratory syndrome. The main discriminator of whether or not one succeeds in overcoming this infection may depend on a great many factors, but the main one is definitely determined by vaccination, which has minimized hospitalizations and more severe syndromes. CONCLUSION: Recently, a new virus, the monkeypox virus, which was previously confined to Central and West Africa but is now gradually spreading to more than 30 countries including the United States of America, where such an infection is not endemic, is coming forward again.

Pandemic COVID-19, an update of current status and new therapeutic strategies.

The global COVID-19 pandemic is underway. In recent weeks, several countries throughout the globe, and particularly in Europe, have experienced an exponential increase in the number of individuals infected with COVID-19, probably induced by a new variant of SARS-CoV-2, called the "Omicron variant." Mass vaccination against COVID-19 continues worldwide. Are authorized mRNA vaccines effective against the new Omicron variant? Recently, several pharmaceutical companies have developed oral antiviral pills against SARS-CoV-2, i.e., molnupiravir and paxlovid, that inhibit SARS-CoV-2 viral replication by acting on the RNA polymerase of SARS-CoV. In pre-registration clinical trials, molnupiravir and paxlovid have shown excellent clinical efficacy results, but what impact will these new oral antiviral agents have against pandemic COVID-19? In what specific clinical situations are they preferred over other antivirals such as remdesivir? In this brief review, we explore these important aspects.

Emergency surgical treatment of colonic acute diverticulitis: a multicenter observational study on behalf of the Italian society of colorectal surgery (SICCR) Lombardy committee.

Colonic diverticulitis can be treated conservatively, but some cases require surgery. Patients can undergo Hartmann's procedure (H) or resection with primary anastomosis (RA), with or without diverting stoma. This multicenter observational retrospective study aims to evaluate the adherence to current guidelines by assessing the rate of RA and H in Lombardy, Italy, and to analyze differences in patients' features. This study included data collected from nine surgical units performing emergency surgery in Lombardy, in 2019 and 2021. Data for each year were retrospectively collected through a survey among Italian Society of Colorectal Surgery (SICCR) Lombardy members. Additional data were about: Hinchey's classification, laparoscopic (VLS) or converted procedures, procedures with more than two operators, procedures in which the first operator was older than 40 years, night or weekend procedures, older-than-80 patients, COVID-19 positivity (just 2021). The total number of operations performed was 254, 115 RA and 130 H (45.3% and 51.2%, diff. 12%, p = 0.73), and 9 (3.5%) other procedures. RAs were more frequent for Hinchey 1 and 2 patients, whereas Hs were more frequent for Hinchey 3 and 4. RAs without ileostomy were significantly less than Hs (66 vs. 130, p = 0.04). Laparoscopy was more used for RA compared to H (57 vs. 21, p = 0.03), whereas no difference was found between RA and H with respect to conversion rate, the presence of more than two operators in the team, the presence of a first operator older than 40 years, night or weekend operations, and for older-than-80 patients. This study confirms the adherence to current guidelines for the treatment of acute colonic diverticulitis in Lombardy, Italy. It can be considered as a preliminary survey with interesting results that may open the way to a further prospective observational study to clarify some aspects in the management of this disease.

Long COVID could become a widespread post-pandemic disease? A debate on the organs most affected.

Long COVID is an emerging problem in the current health care scenario. It is a syndrome with common symptoms of shortness of breath, fatigue, cognitive dysfunction, and other conditions that have a high impact on daily life. They are fluctuating or relapsing states that occur in patients with a history of SARS-CoV-2 infection for at least 2 months. They are usually conditions that at 3 months after onset cannot be explained by an alternative diagnosis. Currently very little is known about this syndrome. A thorough review of the literature highlights that the cause is attributable to deposits of tau protein. Massive phosphorylation of tau protein in response to SARS-CoV-2 infection occurred in brain samples from autopsies of people previously affected with COVID-19. The neurological disorders resulting from this clinical condition are termed tauopathies and can give different pathological symptoms depending on the involved anatomical region of the brain. Peripheral small-fiber neuropathies are also evident among patients with Long COVID leading to fatigue, which is the main symptom of this syndrome. Certainly more research studies could confirm the association between tau protein and Long COVID by defining the main role of tau protein as a biomarker for the diagnosis of this syndrome that is widespread in the post-pandemic period.

The direct correlation between microbiota and SARS-CoV-2 infectious disease.

The human microbiota is the good part of the human organism and is a collection of symbiotic microorganisms which aid in human physiological functions. Diseases that can be generated by an altered microbiota are continuously being studied, but it is quite evident how a damaged microbiota is involved in chronic inflammatory diseases, psychiatric diseases, and some bacterial or viral infections. However, the role of the microbiota in the host immune response to bacterial and viral infections is still not entirely understood. Metabolites or components which are produced by the microbiota are useful in mediating microbiota-host interactions, thus influencing the host's immune capacity. Recent evidence shows that the microbiota is evidently altered in patients with viral infections such as post-acute COVID-19 syndrome (PACS). In this review, the associations between microbiota and COVID-19 infection are highlighted in terms of biological and clinical significance by emphasizing the mechanisms through which metabolites produced by the microbiota modulate immune responses to COVID-19 infection.

Mechanisms and Clinical Perspectives of COVID-19-induced Cardiovascular Disease.

COVID-19 infection can cause damage to various systems, such as cardiovascular, respiratory, and neurological, both during the course of the disease and in the period after recovery, caused by the effects of so-called "Long COVID." Cardiovascular complications caused by COVID-19 infection are not yet fully understood and characterized. Cardiovascular complications caused by COVID-19 include pericarditis, myocarditis, dysrhythmias, ischemic and non-ischemic heart disease, and thromboembolic disease. The pathophysiological and molecular mechanisms of cardiovascular damage caused by SARS-CoV-2 are still being studied. More severe COVID-19 cases with the multisystem inflammatory syndrome (MIS) have frequent involvement of cardiovascular damage. In addition, recent evidence shows that months later, individuals who have had a COVID-19 infection may be at a greater risk of suffering heart disease than individuals who have not had the infection. In this brief literature review, we summarize the current evidence in the literature on cardiovascular damage caused by COVID-19, during the period of infection and in the long COVID, and possible concomitant risk factors, which may play an important role.

Overview of pharmacotherapy targeting COVID-19 disease based on ACE-2: current challenges and future directions.

The new Severe acute respiratory syndrome coronavirus 2 (SARS-CoV­2) triggered the pandemic of COVID-19, which is currently still ongoing. In 2021 a worldwide vaccine campaign was launched, and in parallel the lines of research are continuing to target the most effective drug therapies for the treatment of COVID-19 disease. SARS-CoV­2 enters host cells via glycoprotein angiotensin-converting enzyme 2 (ACE-2), which plays a major role in renin-angiotensin system interactions and undergoes changes in expression during metabolic and viral diseases, including COVID-19. It seems that the severe lung damage that occurs in several cases of COVID-19 disease may be connected to a deregulated expression of ACE­2. In this manuscript we focus on the line of research that studies the pharmacological modification of ACE­2 expression, a promising weapon to counter the severe harms caused by COVID-19.

COVID-19 mRNA Vaccines: A Retrospective Observational Pharmacovigilance Study.

BACKGROUND AND OBJECTIVE: Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus has caused millions of deaths worldwide. The mRNA vaccines prevented the figure from being more severe. The objective of this retrospective study is to evaluate the safety of COVID-19 vaccines by analyzing the adverse events following immunization (AEFIs). METHODS: A retrospective observational pharmacovigilance study was conducted, based on the collection of reports of suspected AEFIs reported between 1 January 2021 and 31 December 2021 at the Naples 3 local health authority. AEFIs were stratified and described according to mRNA vaccine, demographics, clinical status, description of AEFI, and degree of severity. In 2021, local health authority Asl Naples 3 South received 1164 reports of suspected adverse events that occurred following the administration of mRNA vaccines. RESULTS: During the reporting period, 746 reports were related to the Comirnaty vaccine (64.1%), 281 to the Vaxzevria vaccine (24.1%), 107 to the Spikevax vaccine (9.2%), and 30 to the Jcovden vaccine (2.6%); 89.3% of the reports were classified as not serious (N = 1039 reports), the remaining 10.7% as serious (N = 125 reports). CONCLUSIONS: This retrospective pharmacovigilance study demonstrates that COVID-19 mRNA vaccines are safe in all population groups.

Pharmacovigilance is an activity that ensures the safety of health care treatments. The COVID-19 pandemic has accelerated the administration of vaccines whose efficacy and safety is to be evaluated. In the year 2021, an analysis of all reported adverse events following immunization (AEFIs) to the vaccine was conducted on a sample of about 1 million people with the aim of understanding efficacy and safety. All adverse events were divided by age, sex, type of reaction, and severity. Serious reactions were divided into subcategories to report the most common critical issues. At the conclusion of the work, it can be seen that COVID-19 mRNA vaccines are safe but can give serious cardiovascular (12% of the total number of serious reports) and neurological (one serious case that led to the development of Guillain Barré syndrome) side effects that need to be monitored by medical personnel.

Miniaturized Real-Time PCR systems for SARS-CoV-2 detection at the Point-of-Care.

Over the past two years, SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus 2) infection has spread globally causing multi-organ disease and severely impacting the healthcare systems of all countries. Accordingly, the development of easy-to-access diagnostic devices has become essential to limit the effect of the virus worldwide. Real-Time PCR is considered the gold standard to identify SARS-CoV-2 infection due to high sensitivity, affordability, and capacity to detect low viral loads at early disease stage. Advances in lab on a chip technology has led to the development of some Point-of-Care (POC) devices using Real-Time PCR and approved by the United States Food and Drug Administration. We provide an overview on recently developed POC tests for the rapid diagnosis of COVID-19 infection. Practical applications of miniaturized devices based on viral genome amplification as well as favorable features such as reduced sample processing time, ease of use by non-specialized personnel, and the potential of PCR-based POC technologies will be highlighted and reviewed.

Nirmatrelvir-remdesivir association for non-hospitalized adults with COVID-19, point of view.

The efforts of the scientific world directed to identifying new antiviral drugs and therapies effective against SARS-CoV-2 continue. New oral antivirals against SARS-CoV-2 such as paxlovid have recently authorized. Evidence shows that these antivirals have good efficacy in reducing the risk of hospitalization in COVID-19 positive patients. Remdesivir is an authorized antiviral for the treatment of SARS-CoV-2 infection. To date, there are still few data in the literature on the safety profile and the risk of generating antiviral-resistant SARS-CoV-2 drug variants. In this manuscript we describe the evidence in the literature on the monotherapy use of paxlovid and monotherapy use of remdesivir, and the scientific hypothesis of using nirmatrelvir and remdesivir in association with the aim of increasing treatment efficacy, reducing the risk of adverse reactions and generating antiviral drug-resistant variants.

Pharmacotherapy Based on ACE2 Targeting and COVID-19 Infection.

The new SARS-CoV-2 coronavirus is responsible for the COVID-19 pandemic. A massive vaccination campaign, which is still ongoing, has averted most serious consequences worldwide; however, lines of research are continuing to identify the best drug therapies to treat COVID-19 infection. SARS-CoV-2 penetrates the cells of the host organism through ACE2. The ACE2 protein plays a key role in the renin-angiotensin system (RAS) and undergoes changes in expression during different stages of COVID-19 infection. It appears that an unregulated RAS is responsible for the severe lung damage that occurs in some cases of COVID-19. Pharmacologically modifying the expression of ACE2 could be an interesting line of research to follow in order to avoid the severe complications of COVID-19.