Recurrent herpes zoster with IgD deposits, multinucleated keratinocytes and overexpression of galectin and glypican 3 in a patient with SARS-COVID-19 infection

The novel coronavirus disease (COVID-19) that currently plagues the world and caused by SARS-CoV-2, has spread internationally since late 2019. The dermatologic manifestations of this virus are currently being identified. We describe a 73-year-old Caucasian female who presented to many physicians for recurrent Herpes zoster episodes that persisted, despite treatment with multiple antiviral medications. The patient was diagnosed with COVID-19 before an onset of vesicular pustular lesions. The clinical diagnoses were recurrent herpes zoster and recurrent varicella. A skin biopsy was obtained and stained with hematoxylin and eosin to confirm a diagnosis. Immunohistochemical stains for Ki-67, Phospho-Histone H3, galectin 3, glypican and IgD were positive in multinucleated cells of the skin, where the viral lesions were detected. Recidivated herpes zoster and varicella are currently being clinically associated with COVID- 19; the abnormal immune response in patients with COVID-19 may be due to the overexpression of molecules that facilitate the outbreak of these viruses.

NATURAL PRODUCTS WITH ANTI-HERPES ACTIVITIES: IN VIVO STUDIES

Herpes are a group of similar viruses that are responsible for a number of infecting diseases, the most important of which are herpes simplex, herpes zoster and pseudopox. Resistance to traditional antiviral medications is becoming increasingly common, making treatment of such infections even more difficult. For example, the usage of nucleoside analogues like acyclovir to target the DNA-polymerase of the virus on a regular and long-term basis promotes the generation of resistant viruses. As a result, a different treatment is required. Natural products, such as herbal remedies, have been shown to have in vitro and in vivo activity against herpes viruses, and have shown to be a valuable source for new antivirals development and separation. The goal of this review is to highlight the most promising extracts and pure chemicals obtained from plants and marine species that have in vivo anti-herpes simplex virus (HSV-1 and HSV-2) action. Natural products as new anti-HSV medications offer a number of benefits, including fewer side effects, minimal toxicity, and lowered resistance, and a variety ways of deed.

Drug Repurposing Techniques in Viral Diseases

Since the advent of the twentieth century, several severe virus outbreaks have occurred—H1N1 (1918), H2N2 (1957), H3N2 (1968), H1N1 (2009) and recently COVID-19 (2019)—all of which have posed serious challenges to public health. Therefore, rapid identification of efficacious antiviral medications is of ongoing paramount importance in combating such outbreaks. Due to the long cycle of drug development, not only in the development of a “safe” medication but also in mandated and extensive (pre)clinical trials before a drug can be safely licensed for use, it is difficult to access effective and safe novel antivirals. This is of particular importance in addressing infectious disease in appropriately short period of time to limit stress to ever more interlinked societal infrastructures; including interruptions to economic activity, supply routes as well as the immediate impact on health care. Screening approved drugs or drug candidates for antiviral activity to address emergent diseases (i.e. repurposing) provides an elegant and effective strategy to circumvent this problem. As such treatments (in the main) have already received approval for their use in humans, many of their limitations and contraindications are well known, although efficacy against new diseases must be shown in appropriate laboratory trials and clinical studies. A clear in this approach in the case of antivirals is the “relative” simplicity and a high degree of conservation of the molecular mechanisms that support viral replication—which improves the chances for a functional antiviral to inhibit replication in a related viral species. However, recent experiences have shown that while repurposing has the potential to identify such cases, great care must be taken to ensure a rigourous scientific underpinning for repurposing proposals. Here, we present a brief explanation of drug repurposing and its approaches, followed by an overview of recent viral outbreaks and associated drug development. We show how drug repurposing and combination approaches have been used in viral infectious diseases, highlighting successful cases. Special emphasis has been placed on the recent COVID-19 outbreak, and its molecular mechanisms and the role repurposing can/has play(ed) in the discovery of a treatment.

Mini-review: The market growth of diagnostic and therapeutic monoclonal antibodies; SARS CoV-2 an example

BACKGROUND: The emergence of novel viruses poses severe challenges to global public health highlighting the crucial necessity for new antivirals. MAIN BODY: Monoclonal antibodies (mAbs) are immunoglobulins that bind with a single epitope. Mouse mAbs are generated by classic hybridoma technology and are mainly used for immunodiagnostics. For immunotherapy, it is critical to use monoclonal antibodies in the human form to minimize adverse reactions. They have been successfully used to treat numerous illnesses, accordingly, an increasing number of mAbs, with high potency against emerging viruses is the target of every biopharmaceutical company. The diagnostic and therapeutic mAbs market grows rapidly into a multi-billion-dollar business. Biopharmaceuticals are innovative resolutions which revolutionized the treatment of significant chronic diseases and malignancies. Currently, a variety of therapeutic options that include antiviral medications, monoclonal antibodies, and immunomodulatory agents are available in the management of COVID-19. SHORT CONCLUSION: The invasion of mAbs in new medical sectors will increase the market magnitude as it is expected to generate revenue of about 300 billion $ by 2025. In the current mini-review, the applications of monoclonal antibodies in immune-diagnosis and immunotherapy will be demonstrated, particularly for COVID-19 infection and will focus mainly on monoclonal antibodies in the market.

Risk Factors for CMV Viremia and Treatment-Associated Adverse Events among Pediatric Hematopoietic Stem Cell Transplant Recipients

Background Cytomegalovirus (CMV) causes substantial morbidity and mortality after hematopoietic stem cell transplantation (HSCT). There are limited data on risk factors for CMV viremia and the safety of antiviral medications used to treat CMV in children. Methods We conducted a single-center retrospective study of children who underwent HSCT between 2000 and 2016. We used log-logistic regression to evaluate associations between clinical characteristics and CMV-free survival at 100 days after HSCT. We compared the incidences of laboratory-defined adverse events (AEs) during treatment with ganciclovir and foscarnet. Results Among 969 children, median (interquartile range) age was 6.5 (3.1, 11.5) years, and 80% underwent allogeneic HSCT. Two hundred forty-four (25%) children developed CMV viremia. Older age (OR=0.95; 95% CI: 0.92, 0.98), male sex (OR=0.71, 95% CI: 0.51, 0.99), non-Black non-white race (OR=0.56; 95% CI: 0.36, 0.87), umbilical cord blood donor source (OR=0.28; 95% CI: 0.08, 0.97), and CMV-seropositivity (R-/D+, OR=0.17, 95% CI: 0.07, 0.41; R+/D-, OR=0.14, 95% CI: 0.09, 0.21; R+/D+, OR=0.08, 95% CI: 0.04, 0.15) were associated with lower odds of 100-day CMV-free survival. Compared to foscarnet, ganciclovir was associated with lower incidences of thrombocytopenia (IRR: 0.38; 95% CI: 0.15, 0.97), electrolyte AEs (IRR: 0.42; 95% CI: 0.24, 0.75), endocrine AEs (IRR: 0.52; 95% CI: 0.34, 0.79), and renal AEs (IRR: 0.36; 95% CI: 0.19, 0.65). Conclusions CMV viremia occurred commonly among children after HSCT, and ganciclovir and foscarnet were associated with distinct toxicity profiles among children with CMV infection. These findings should be considered when developing CMV prevention and treatment strategies for children after HSCT.

Prevalence, Causes and Management of Encephalitis

Encephalitis is a major cause of morbidity, mortality, and permanent neurological disability in both adults and children. The term "encephalitis" literally means inflammation of part or all of the "brain" or the brain parenchyma. Encephalitis affects people of all ages; however, the incidence is higher in the pediatric population. Although both genders are affected, most studies showed slight dominance in men. There are two main types with different causes: primary or infectious encephalitis can develop when a fungus, virus, or bacteria infects the brain and accounts for approximately 70% of confirmed cases of encephalitis, and secondary or post-infectious encephalitis when the immune system is active and reacts. to a previous infection and mistakenly attacks the brain. The clinical manifestations depend on whether the brain parenchyma or the meninges are predominantly involved and cause an encephalitic or meningitis syndrome. Diagnostic tests should include a lumbar puncture, an MRI of the brain, and an EEG for suspected encephalitis. In encephalitis, a broad differential diagnosis, both infectious and non-infectious, should be considered. These alternatives include malignancy, autoimmune or paraneoplastic diseases (eg, anti-NMDA receptor encephalitis), brain abscess, drug-induced tuberculosis or delirium, neurosyphilis, or bacterial, fungal, protozoal, or helminthic encephalitis. Antiviral medications, such as intravenous acyclovir, are often given at the initial diagnosis of encephalitis before the cause is known. Acyclovir is the best treatment for herpes simplex encephalitis. If medication can be started soon after symptoms appear, the chance of a full recovery is much higher.

A Critical Review on Nanoscience Advancement: In Treatment of Viral Infection

Viral contaminations speak to a general medical issue and one of the main sources of worldwide mortality. A large portion of the antiviral medications have low permeability, low dissolvability and other related physical properties which make them less efficient for the antiviral treatment. To conquer these constraints, different nanomedicine stages have been planned. Nanomaterials offer special physico-chemical properties that have various advantages for medicate conveyance as perfect devices for viral treatment. This review focuses on the currently used medicines used in viral infection, presents a broad overview of the application of nanosized materials for the treatment of common viral infections and shed light on the potential of nanotechnology to provide more effective treatment for HIV, Herpes simplex virus, Influenza virus and Hepatitis C virus. The action of antiviral medications could be improved with nanomedicine formulations. As the physicochemical properties of nanocarriers can empower their capacity to target the specific sites. When it comes to structuring nanocarriers, size is the most important factor and the nanoparticles can permit the controlled delivery kinetics, enhanced bioavailability, altered pharmacokinetics, and less side effects. Nanocarriers that build them appealing candidates for antiviral drug such as Improves bioavailability of the encapsulated actives, controlled release, reduce the toxicity associated with the anti-viral drugs. One of the important physicochemical properties mainly size is the most important design factor for nanocarriers for anti-viral drug delivery to the specific sites. Nanobased drug delivery also leads to enhance the potential of currently approved antiviral drugs. Keywords: Nanotechnology, HIV, Hepatits virus, Influenza, HSV

The beneficial impact of filtration surgery on antiviral therapy cessation in patients with cytomegalovirus-related secondary glaucoma

Purpose Cytomegalovirus (CMV)-related keratouveitis elevates intraocular pressure (IOP). Antiviral therapy does not always control IOP and some patients do not tolerate systemic antiviral therapy because of the side effects. The purpose of this study is to evaluate the clinical characteristics of patients with CMV-related keratouveitis and determine the impact of glaucoma surgeries on the postoperative antiviral therapy regimen. Methods We enrolled twenty-two patients with CMV-DNA-positive keratouveitis between June 2012 and July 2019 in Kobe University Hospital. The following clinical parameters were collected: gender, age, history of previous intraocular surgery, antiviral medications, visual acuity, IOP, glaucoma drug score, corneal endothelial cells density, and the mean deviation of a Humphrey visual field test at the first visit and before and 1 year after glaucoma surgery. Results All twenty-two patients started on oral and/or topical antiviral therapy. Eighteen patients needed glaucoma surgery despite their antiviral medications. Nine patients underwent trabeculotomy (TLO) and nine underwent trabeculectomy (TLE) as the first surgical intervention. Six of patients who initially underwent TLO and two of the patients who initially underwent TLE required additional TLE within 1 year. Each of the 15 patients who underwent at least 1 TLE showed a reduction in the magnitude and variation of IOP and glaucoma drug scores and 13 patients were able to discontinue antiviral therapy. For the remaining 4 patients, IOP and inflammation were controlled but with antiviral medications. Conclusions In patients with CMV-related keratouveitis, TLE decreases and stabilizes IOP and contributes to withdrawal from antiviral medications.

971. Online Medical Education Improves Knowledge of Data on Appropriate and Timely Use of Influenza Antiviral Medications to Patients at High Risk for Influenza-Related Complications and Morbidity

Background Many patients are at a higher risk of influenza complications because of age and comorbidities. We sought to assess whether online education, focused on appropriate and timely use of influenza antiviral medications to patients at high risk for influenza-related complications and morbidity, could improve knowledge, competence, and confidence of clinicians. Methods Primary care physicians (PCPs) and pediatricians participated in a 30-minute video lecture with synchronized slides. Educational effect was assessed using a repeated-pairs design with pre-/post-assessment. Three multiple choice questions assessed knowledge/competence, and 1 question assessed confidence. Statistical tests to assess significance: Paired samples t-test for overall average number of correct responses and for confidence rating; McNemar’s test for individual questions (5% significance level, P < .05). Cohen’s d estimated the effect size impact on number of correct responses (< .20 modest, .20-.49 small, .59-.79 moderate, ≥.80 large). Data were collected from 10/28/20 to 12/23/20. Results Average knowledge/competence improved from 29% to 43% (N=430, P< .001, Cohen’s d = 0.46) among primary care physicians and from 31% to 43% (N=226, P< .001, Cohen’s d = 0.38) among pediatricians. Post participation, 12% more PCPs and pediatricians answered all questions correctly. Relative improvements post-participation in specific areas were as follows (P< .001): (i) 105% improvement among PCPs and 100% improvement among pediatricians in findings associated with the efficacy of treatment with antivirals for influenza in hospitalized patients. (ii) 117% improvement among PCPs and 104% improvement among pediatricians in identifying the antiviral with the greatest activity against influenza B viral strain as reported in a phase 3 clinical trial. (iii) 34% of PCPs and 46% of pediatricians had a measurable improvement in confidence after completing the program. Conclusion This study demonstrated the success of a video lecture with synchronized slides at improving PCPs and pediatricians knowledge, competence and confidence related to appropriate and timely use of influenza antiviral medications to patients at high risk for influenza-related complications and morbidity. Disclosures All Authors: No reported disclosures

Nanotechnology Interventions in the Management of COVID-19: Prevention, Diagnosis and Virus-like Particle Vaccines

SARS-CoV-2 claimed numerous lives and put nations on high alert. The lack of antiviral medications and the small number of approved vaccines, as well as the recurrence of adverse effects, necessitates the development of novel treatment ways to combat COVID-19. In this context, using databases such as PubMed, Google Scholar, and Science Direct, we gathered information about nanotechnology’s involvement in the prevention, diagnosis and virus-like particle vaccine development. This review revealed that various nanomaterials like gold, polymeric, graphene and poly amino ester with carboxyl group coated magnetic nanoparticles have been explored for the fast detection of SARS-CoV-2. Personal protective equipment fabricated with nanoparticles, such as gloves, masks, clothes, surfactants, and Ag, TiO2 based disinfectants played an essential role in halting COVID-19 transmission. Nanoparticles are used not only in vaccine delivery, such as lipid nanoparticles mediated transport of mRNA-based Pfizer and Moderna vaccines, but also in the development of vaccine as the virus-like particles elicit an immune response. There are now 18 virus-like particle vaccines in pre-clinical development, with one of them, developed by Novavax, reported being in phase 3 trials. Due to the probability of upcoming COVID-19 waves, and the rise of new diseases, the future relevance of virus-like particles is imperative. Furthermore, psychosocial variables linked to vaccine reluctance constitute a critical problem that must be addressed immediately to avert pandemic.