Respiratory Syncytial Virus (RSV) Hospitalizations in the Elderly in a Tertiary Care Hospital in Southern Italy as a Useful Proxy for Targeting Vaccine Preventive Strategies.

RSV infection causes severe respiratory illness and mortality in the elderly, especially in the presence of comorbidities. Early identification of infection would result in appropriate clinical-therapeutic management, avoiding hospitalizations, the risk of healthcare-associated infections, and inappropriate antibiotic prescriptions, thus reducing healthcare costs and fighting antimicrobial resistance. The aim of this study was to assess RSV hospitalizations in subjects >64 years hospitalized in a large tertiary care hospital in Southern Italy, in order to assess their usefulness as a proxy for targeting a potential vaccination strategy. Fifty-two RSV-positive patients were identified from the 2014-2015 to the 2022-2023 seasons. RSV type B was found in 71.2% of cases. The median age was 78 years (IQR: 72-84) and 40.4% of the subjects had at least one comorbidity; 5.8% needed intensive care. The use of combined rapid tests for SARS-CoV-2/influenza/RSV identification in primary care settings may contribute to an improved definition of the burden of RSV in the elderly. The implementation of an anti-RSV vaccination strategy in the elderly population would reduce direct and indirect infection costs. More robust epidemiological data in Italy are needed for targeted preventive strategies.

Developing recombinant antibodies by phage display technology to neutralize viral infectious diseases.

The use of recombinant antibodies developed through phage display technology offers a promising approach for combating viral infectious diseases. By specifically targeting antigens on viral surfaces, these antibodies have the potential to reduce the severity of infections or even prevent them altogether. With the emergence of new and more virulent strains of viruses, it is crucial to develop innovative methods to counteract them. Phage display technology has proven successful in generating recombinant antibodies capable of targeting specific viral antigens, thereby providing a powerful tool to fight viral infections. In this mini-review article, we examine the development of these antibodies using phage display technology, and discuss the associated challenges and opportunities in developing novel treatments for viral infectious diseases. Furthermore, we provide an overview of phage display technology. As these methods continue to evolve and improve, novel and sophisticated tools based on phage display and peptide display systems are constantly emerging, offering exciting prospects for solving scientific, medical, and technological problems related to viral infectious diseases in the near future.

Development progress and application of monoclonal antibody drugs against respiratory virus / 中国生物制品学杂志

@#Abstract：In recent years，the outbreak and prevalence of respiratory infectious diseases in the world seriously endanger human health，among which the respiratory infectious diseases caused by viral infection account for a large proportion. The use of vaccines and common antiviral drugs is an effective way to fight viral infection，but there are also problems such as lag and drug resistance. Monoclonal antibodies against respiratory viral infections provide a new strategy for clinical treatment. This paper reviews the development of monoclonal antibody against respiratory virus and its application in respiratory viral infectious diseases. Keywords：Respiratory viral infectious diseases；Respiratory syncytial virus（RSV）；Influenza virus（IFV）；Coronavirus （CoV）；Monoclonal antibody

Nanovaccines against Viral Infectious Diseases.

Infectious diseases have always been regarded as one of the greatest global threats for the last century. The current ongoing COVID-19 pandemic caused by SARS-CoV-2 is living proof that the world is still threatened by emerging infectious diseases. Morbidity and mortality rates of diseases caused by Coronavirus have inflicted devastating social and economic outcomes. Undoubtedly, vaccination is the most effective method of eradicating infections and infectious diseases that have been eradicated by vaccinations, including Smallpox and Polio. To date, next-generation vaccine candidates with novel platforms are being approved for emergency use, such as the mRNA and viral vectored vaccines against SARS-CoV-2. Nanoparticle based vaccines are the perfect candidates as they demonstrated targeted antigen delivery, improved antigen presentation, and sustained antigen release while providing self-adjuvanting functions to stimulate potent immune responses. In this review, we discussed most of the recent nanovaccines that have found success in immunization and challenge studies in animal models in comparison with their naked vaccine counterparts. Nanovaccines that are currently in clinical trials are also reviewed.

Monkeypox: A Comprehensive Review.

The 2022 multi-country monkeypox outbreak in humans has brought new public health adversity on top of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The disease has spread to 104 countries throughout six continents of the world, with the highest burden in North America and Europe. The etiologic agent, monkeypox virus (MPXV), has been known since 1959 after isolation from infected monkeys, and virulence among humans has been reported since the 1970s, mainly in endemic countries in West and Central Africa. However, the disease has re-emerged in 2022 at an unprecedented pace, with particular concern on its human-to-human transmissibility and community spread in non-endemic regions. As a mitigation effort, healthcare workers, public health policymakers, and the general public worldwide need to be well-informed on this relatively neglected viral disease. Here, we provide a comprehensive and up-to-date overview of monkeypox, including the following aspects: epidemiology, etiology, pathogenesis, clinical features, diagnosis, and management. In addition, the current review discusses the preventive and control measures, the latest vaccine developments, and the future research areas in this re-emerging viral disease that was declared as a public health emergency of international concern.

Immunomodulatory therapies for COVID-19.

Purpose: As COVID-19 disease progresses, the host inflammatory response contributes to hypoxemia and severe and critical illness. In these latter stages of disease, patients may benefit from immunomodulatory therapies to control the aberrant host inflammatory response. In this review, we provide an overview of these therapies and provide summaries of the studies that led to issuance of FDA Emergency Use Authorization or recommendation by the Infectious Diseases Society of America (IDSA). Materials and methods: We reviewed English-language studies, Emergency Use Authorizations (EUAs), and guidelines from March 2020 to present. Conclusion and relevance: There are several therapies with proposed benefit in severe and critical COVID-19 disease. Few have been issued FDA EUA or recommendation by the Infectious Diseases Society of America (IDSA). Physicians should be familiar with the evidence supporting use of these therapies and the patient populations most likely to benefit from each.

A Comprehensive Review on the Benefits and Problems of Curcumin with Respect to Human Health.

Curcumin is the most important active component in turmeric extracts. Curcumin, a natural monomer from plants has received a considerable attention as a dietary supplement, exhibiting evident activity in a wide range of human pathological conditions. In general, curcumin is beneficial to human health, demonstrating pharmacological activities of anti-inflammation and antioxidation, as well as antitumor and immune regulation activities. Curcumin also presents therapeutic potential in neurodegenerative, cardiovascular and cerebrovascular diseases. In this review article, we summarize the advancements made in recent years with respect to curcumin as a biologically active agent in malignant tumors, Alzheimer's disease (AD), hematological diseases and viral infectious diseases. We also focus on problems associated with curcumin from basic research to clinical translation, such as its low solubility, leading to poor bioavailability, as well as the controversy surrounding the association between curcumin purity and effect. Through a review and summary of the clinical research on curcumin and case reports of adverse effects, we found that the clinical transformation of curcumin is not successful, and excessive intake of curcumin may have adverse effects on the kidneys, heart, liver, blood and immune system, which leads us to warn that curcumin has a long way to go from basic research to application transformation.

Targeting Selective Autophagy as a Therapeutic Strategy for Viral Infectious Diseases.

Autophagy is an evolutionarily conserved lysosomal degradation system which can recycle multiple cytoplasmic components under both physiological and stressful conditions. Autophagy could be highly selective to deliver different cargoes or substrates, including protein aggregates, pathogenic proteins or superfluous organelles to lysosome using a series of cargo receptor proteins. During viral invasion, cargo receptors selectively target pathogenic components to autolysosome to defense against infection. However, viruses not only evolve different strategies to counteract and escape selective autophagy, but also utilize selective autophagy to restrict antiviral responses to expedite viral replication. Furthermore, several viruses could activate certain forms of selective autophagy, including mitophagy, lipophagy, aggrephagy, and ferritinophagy, for more effective infection and replication. The complicated relationship between selective autophagy and viral infection indicates that selective autophagy may provide potential therapeutic targets for human infectious diseases. In this review, we will summarize the recent progress on the interplay between selective autophagy and host antiviral defense, aiming to arouse the importance of modulating selective autophagy as future therapies toward viral infectious diseases.

Therapeutic Mechanism of Xiaoqinglong Decoction against COVID-19 Based on Network Pharmacology and Molecular Docking Technology.

BACKGROUND: A xiaoqinglong decoction (XQLD) has been proven effective in treating severe coronavirus disease 2019 (COVID-19) cases; however, the mechanism remains unclear. OBJECTIVE: In the current study, we used network pharmacology and molecular docking technology to identify the effective components, potential targets, and biological pathways of XQLD against COVID-19. METHODS: Public databases were searched to determine the putative targets of the active compounds of XQLD and COVID-19-related targets. STRING and Cytoscape were used to establish the protein-protein interaction network and drug component, along with the target-pathway network. The DAVID database was used to enrich the biological functions and signaling pathways. AutoDock Vina was used for virtual docking. RESULTS: We identified 138 active compounds and 259 putative targets of XQLD. Biological network analysis showed that quercetin, beta-sitosterol, kaempferol, stigmasterol, and luteolin may be critical ingredients of XQLD, whereas VEGFA, IL-6, MAPK3, CASP3, STAT3, MAPK1, MAPK8, CASP8, CCL2, and FOS may be candidate drug targets. Enrichment analysis illustrated that XQLD could function by regulating viral defense, inflammatory response, immune response, and apoptosis. Molecular docking results showed a high affinity between the critical ingredients and host cell target proteins. CONCLUSION: This study uncovered the underlying pharmacological mechanism of XQLD against COVID-19. These findings lay a solid foundation for promoting the development of new drugs against severe acute respiratory syndrome coronavirus-2 infection and may contribute to the global fight against the COVID-19 pandemic.

Sweeping analysis of transcript profile in dengue virus serotype 3 infection and antibody-dependent enhancement of infection.

Dengue virus infection mainly causes dengue hemorrhagic fever (DHF) and/or dengue shock syndrome (DSS). However, ADE (antibody-dependent enhancement) is one of the main pathogenic factors, and its pathogenic mechanism has not been fully elucidated. Recently, with the development of high-throughput sequencing, an increased number of RNAs have been confirmed to play a vital regulatory role in the process of virus infection. However, there is a lack of research on dengue virus infection and ADE. In this study, we used RNA-Seq to detect differentially expressed RNAs (DE RNAs) profiles in mock-infected, DENV-3-infected, and ADE-infected THP-1 cells. Firstly, we found 69 circRNAs, 259 miRNAs, and 18 mRNAs were differentially expressed in THP-1 vs DENV-3. In THP-1 vs ADE, 94 circRNAs, 263 miRNAs, and 111 mRNAs were differentially expressed. In DENV-3 vs ADE, 68 circRNAs, 105 miRNAs, and 94 mRNAs were differentially expressed. Functional enrichment analysis of these DE RNAs mainly focused on immune system, viral infectious diseases, cytokine-cytokine receptor interactions, and NOD/RIG-I-like receptor signaling pathways. In DENV-3 vs ADE, notably, the expression of HBB was up-regulated, which was a Fcγ Receptor-mediated phagocytosis protein. Additionally, we predicted the encoding ability of DE circRNAs, and it was found that a small peptide was encoded by novel_circ_001562 and that its amino acid sequence was consistent with that of DDX60L, which is a class of interferon-stimulated genes. Finally, we constructed the ceRNA regulatory network pathway. Therefore, our study provides a new strategy for further investigation on DENV-host interactions.

Progress of Plant Medicine Derived Extracts and Alkaloids on Modulating Viral Infections and Inflammation.

Viral infectious diseases are serious threats to human health in both developing and developed countries. Although there is the continued development of new drugs from synthetic sources as antiviral agents, medicinal plants continue to provide the basic raw materials for some of the most important antiviral drugs. Alkaloids are a class of pharmacologically active plant compounds that are usually alkaline in nature. In this review, we tried to summarize recent progress in herb-based antiviral research, the advantages of using active plant compounds as antiviral agents, and the inflammatory responses initiated by alkaloids, based on the literature from 2009 to 2019, for the treatment of conditions, including influenza, human immunodeficiency virus, herpes simplex virus, hepatitis, and coxsackievirus infections. Articles are retrieved from PubMed, Google Scholar, and Web of Science using relevant keywords. In particular, the alkaloids from medicinal plants responsible for the molecular mechanisms of anti-inflammatory actions are identified and discussed. This review can provide a theoretical basis and approaches for using various alkaloids as antiviral treatments. More research is needed to develop alkaloidal compounds as antiviral therapeutic agents and potential regulators of the anti-inflammatory response.

Advances in vaccine delivery systems against viral infectious diseases.

Although vaccines are available for many infectious diseases, there are still unresolved infectious diseases that threaten global public health. In particular, the rapid spread of unpredictable, highly contagious viruses has recorded numerous infection cases and deaths, and has changed our lives socially or economically through social distancing and wearing masks. The pandemics of unpredictable, highly contagious viruses increase the ever-high social need for rapid vaccine development. Nanotechnologies may hold promise and expedite the development of vaccines against newly emerging infectious viruses. As potential nanoplatforms for delivering antigens to immune cells, delivery systems based on lipids, polymers, proteins, and inorganic nanomaterials have been studied. These nanoplatforms have been tested as a means to deliver vaccines not as a whole, but in the form of protein subunits or as DNA or mRNA sequences encoding the antigen proteins of viruses. This review covers the current status of nanomaterial-based delivery systems for viral antigens, with highlights on nanovaccines against recently emerging infectious viruses, such as severe acute respiratory syndrome coronavirus-2, Middle East respiratory syndrome coronavirus, and Zika virus.

A Microfluidic Diagnostic Device Capable of Autonomous Sample Mixing and Dispensing for the Simultaneous Genetic Detection of Multiple Plant Viruses.

As an efficient approach to risk management in agriculture, the elimination of losses due to plant diseases and insect pests is one of the most important and urgent technological challenges for improving the crop yield. Therefore, we have developed a polydimethylsiloxane (PDMS)-based microfluidic device for the multiplex genetic diagnosis of plant diseases and pests. It offers unique features, such as rapid detection, portability, simplicity, and the low-cost genetic diagnosis of a wide variety of plant viruses. In this study, to realize such a diagnostic device, we developed a method for the autonomous dispensing of fluid into a microchamber array, which was integrated with a set of three passive stop valves with different burst pressures (referred to as phaseguides) to facilitate precise fluid handling. Additionally, we estimated the mixing efficiencies of several types of passive mixers (referred to as chaotic mixers), which were integrated into a microchannel, through experimental and computational analyses. We first demonstrated the ability of the fabricated diagnostic devices to detect DNA-based plant viruses from an infected tomato crop based on the loop-mediated isothermal amplification (LAMP) method. Moreover, we demonstrated the simultaneous detection of RNA-based plant viruses, which can infect cucurbits, by using the reverse transcription LAMP (RT-LAMP) method. The multiplex RT-LAMP assays revealed that multiple RNA viruses extracted from diseased cucumber leaves were successfully detected within 60 min, without any cross-contamination between reaction microchambers, on our diagnostic device.

Uncovering the Repertoire of Endogenous Flaviviral Elements in Aedes Mosquito Genomes.

Endogenous viral elements derived from nonretroviral RNA viruses have been described in various animal genomes. Whether they have a biological function, such as host immune protection against related viruses, is a field of intense study. Here, we investigated the repertoire of endogenous flaviviral elements (EFVEs) in Aedes mosquitoes, the vectors of arboviruses such as dengue and chikungunya viruses. Previous studies identified three EFVEs from Aedes albopictus cell lines and one from Aedes aegypti cell lines. However, an in-depth characterization of EFVEs in wild-type mosquito populations and individual mosquitoes in vivo has not been performed. We detected the full-length DNA sequence of the previously described EFVEs and their respective transcripts in several A. albopictus and A. aegypti populations from geographically distinct areas. However, EFVE-derived proteins were not detected by mass spectrometry. Using deep sequencing, we detected the production of PIWI-interacting RNA-like small RNAs, in an antisense orientation, targeting the EFVEs and their flanking regions in vivo The EFVEs were integrated in repetitive regions of the mosquito genomes, and their flanking sequences varied among mosquito populations. We bioinformatically predicted several new EFVEs from a Vietnamese A. albopictus population and observed variation in the occurrence of those elements among mosquitoes. Phylogenetic analysis of an A. aegypti EFVE suggested that it integrated prior to the global expansion of the species and subsequently diverged among and within populations. The findings of this study together reveal the substantial structural and nucleotide diversity of flaviviral integrations in Aedes genomes. Unraveling this diversity will help to elucidate the potential biological function of these EFVEs.IMPORTANCE Endogenous viral elements (EVEs) are whole or partial viral sequences integrated in host genomes. Interestingly, some EVEs have important functions for host fitness and antiviral defense. Because mosquitoes also have EVEs in their genomes, characterizing these EVEs is a prerequisite for their potential use to manipulate the mosquito antiviral response. In the study described here, we focused on EVEs related to the Flavivirus genus, to which dengue and Zika viruses belong, in individual Aedes mosquitoes from geographically distinct areas. We show the existence in vivo of flaviviral EVEs previously identified in mosquito cell lines, and we detected new ones. We show that EVEs have evolved differently in each mosquito population. They produce transcripts and small RNAs but not proteins, suggesting a function at the RNA level. Our study uncovers the diverse repertoire of flaviviral EVEs in Aedes mosquito populations and contributes to an understanding of their role in the host antiviral system.

Mayaro: La cuarta arbovirosis de relevancia médica

La fiebre Mayaro es una arbovirosis aguda que ocasiona un compromiso articular incapacitante. Se identificó por primera vez en Venezuela en un brote epidémico familiar de la región de Barlovento en el edo. Miranda en el año 2000. Los estudios clínicoepidemiológicos y la determinación etiológica identificaron al alfavirus Mayaro como responsable de la enfermedad. Se ha identificado en varias naciones del continente americano, resaltándose su aparición en casos esporádicos y brotes epidémicos, siendo su presentación selvática y rural. Los vectores responsables de la infección son los mosquitos del género Haemagogus. Mayaro es la cuarta arbovirosis de importancia médica descrita en Venezuela, la primera identificada fue la fiebre amarilla, seguida de la encefalitis equina venezolana, el dengue y la quinta el chikungunya, ya que recorrió la geografía nacional como epidemia en 2014. Mediante una revisión de la bibliografía médica disponible y la colaboración de estudiantes del curso regular de Medicina Tropical, siguiendo el programa Docencia en Medicina Tropical centrada en el estudiante se actualizaron los aspectos clínicos, epidemiológicos, etiopatogénicos, diagnósticos, terapéuticos y preventivos de esta enfermedad infecciosa viral. Como su aparición es esporádica y de predominio selvático, debe ser considerada cuando se atienden pacientes con síndrome febril agudo con compromiso articular, sean residentes o viajeros procedentes de áreas endémicas. Por considerar que se mantiene en un ciclo enzoótico en la naturaleza, su prevención debe ser claramente definida.

Mayaro fever is an acute mosquito-borne viral infectious disease that produces disabling joint involvement. It was identified for the first time in Venezuela the year 2000 in a family outbreak in the region of Barlovento of the Miranda State. Clinical and epidemiological studies permitted to identify the Mayaro Alphavirus as responsible for the disease. The virus has been identified in several countries of the American continent, the clinical presentation being as sporadic cases, clusters and outbreaks in the rural and forest areas. Being a mosquito-borne zoonosis, the vectors responsible for the infection are mosquitoes of the Haemagogus genus. Mayaro is the fourth arbovirus infectious disease of medical importance described in Venezuela, being the first identified yellow fever, followed by the Venezuelan equine encephalomyelitis, followed by dengue fever and the fifth is chikungunya that swept over the country as an epidemic in 2014. Through a review of the available medical literature and collaboration of students from the regular course of Tropical Medicine, as part of the Student-based Teaching Tropical Medicine Program, a revision of the epidemiology, etiology, diagnosis, treatment and prevention of this viral disease was updated. As it appears sporadically and occurs predominantly in the rural and forest areas, it should be considered when patients with acute febrile syndromes have also joint involvement, whether they are residents or travellers from endemic areas. Considering the enzootic cycle in nature, prevention must be clearly established.

Risk management of viral infectious diseases in wastewater reclamation and reuse: Review.

Inappropriate usage of reclaimed wastewater has caused outbreaks of viral infectious diseases worldwide. International and domestic guidelines for wastewater reuse stipulate that virus infection risks are to be regulated by the multiple-barrier system, in which a wastewater treatment process composed of sequential treatment units is designed based on the pre-determined virus removal efficiency of each unit. The objectives of this review were to calculate representative values of virus removal efficiency in wastewater treatment units based on published datasets, and to identify research topics that should be further addressed for improving implementation of the multiple-barrier system. The removal efficiencies of human noroviruses, rotaviruses and enteroviruses in membrane bioreactor (MBR) and conventional activated sludge (CAS) processes were obtained by a systematic review protocol and a meta-analysis approach. The log10 reduction (LR) of norovirus GII and enterovirus in MBR were 3.35 (95% confidence interval: 2.39, 4.30) and 2.71 (1.52, 3.89), respectively. The LR values of rotavirus, norovirus GI and GII in CAS processes were 0.87 (0.20, 1.53), 1.48 (0.96, 2.00) and 1.35 (0.52, 2.18), respectively. The systematic review process eliminated a substantial number of articles about virus removal in wastewater treatment because of the lack of information required for the meta-analysis. It is recommended that future publications should explicitly describe their treatment of left-censored datasets. Indicators, surrogates and methodologies appropriate for validating virus removal performance during daily operation of wastewater reclamation systems also need to be identified.

Fiebre amarilla / Yellow fever

La fiebre amarilla representa a una de las fiebres hemorrágicas que adquieren en Venezuela y a una de las cuatro arbovirosis endémicas que tenemos. Revisando la literatura médica nacional e internacional, se actualizan aspectos relevantes de esta endemia rural. Se mencionan en la etiología las características del agente viral, que tiene ARN como componente primordial de su genoma. En la epidemiología, se menciona su prevalencia en el continente americano y africano y se evalúa su modo de transmisión. En la patogenia y la anatomía patológica se describe al hígado como órgano blanco de la infección. Se destacan en las manifestaciones clínicas los trastornos hemorrágicos y de la coagulación sanguínea. El diagnóstico como en Medicina Tropical, corresponde a un diagnóstico integral: la clínica, en primer lugar, asociada a la epidemiología y a la etiología de la enfermedad. Se establece diagnóstico diferencial con otras entidades relacionadas. El tratamiento es de soporte y en terapia intensiva. Se concluye con la profilaxis, evaluando la utilidad que sigue teniendo la vacunación.

The yelow fever represents one of the hemorrhagic fever that can be acquired in Venezuela and one of the four endemic arbovirosis we have. By reviewing the national and international medical literature. Relevant aspects of this endemic rural disease have been updated. In the etiology, several characterictics of the virus are mentioned; including the RNA as a primordial component of its genome. In the epidemiology, its prevalence on the African and American continents is mentioned, and the transmission mode es evaluated. In the pathogenesis and pathological anatomy, the liver is described as the primary organ of infection. Bleeding and blood clotting disorders are the essential clinical manifestations. Like in Tropical Medicina, The corresponding integral diagnosis is required. In the first instance, the clinical aspects, associated to the epidemiology and to the etiology of the disease are analyzed a diffential diagnosis is made with other related entities. The treatment consists of support measures and Intensive Care in the Intensive Care Unit (ICU). For the prophylaxis, we discuss the advantages of vaccination.