Insights for COVID-19 in 2023.

Predictions for a near end of the pandemic by the World Health Organization should be interpreted with caution. Current evidence indicates that the efficacy of a fourth dose of classical mRNA vaccines (BT162b2 or mRNA-1273) is low and short-lived in preventing SARS-CoV-2 infection in its predominant variant (Omicron). However, its efficacy is high against severe symptomatic infection, hospitalization and death. The new vaccines being introduced are bivalent and active against the Omicron variants. Potential new vaccines to be introduced in the coming year include a vaccine based on a recombinant protein that emulates the receptor binding domain of the Spike protein under development by the Spanish company Hipra, as well as vaccines for nasal or oral administration. Available information suggests that vaccines against COVID-19 can be administered in association with influenza vaccination without particular complications. New drugs against COVID-19, both antiviral and anti-inflammatory, are under investigation, but this does not seem to be the case with monoclonal antibodies. The indication to use masks in some circumstances will be maintained next year in view of the accumulation of scientific data on their efficacy. Finally, the long COVID or Post-COVID syndrome may continue to affect a very high proportion of patients who have had the disease, requiring combined diagnostic and therapeutic resources.

Developing a Rapid Response Single IRB Model for Conducting Research During a Public Health Emergency.

Research is foundational for evidence-based management of patients. Clinical research, however, takes time to plan, conduct, and disseminate-a luxury that is rarely available during a public health emergency. The University of Nebraska Medical Center (UNMC) developed a single institutional review board (IRB), with a vision to establish a rapid review resource for a network focused on clinical research of emerging pathogens in the United States. A core aspect of successful initiation of research during a pandemic or epidemic is the ability to operationalize an approach for rapid ethical review of human subject research and conduct those reviews at multiple sites-without losing any of the substantive aspects of ethics review. This process must be cultivated in anticipation of a public health emergency. US guidance for operationalizing IRB review for multisite research in a public health emergency is not well studied and processes are not well established. UNMC sought to address operational gaps and identify the unique procedural needs of rapid response single IRB (RR-sIRB) review of multisite research by conducting a series of preparedness exercises to develop and test the RR-sIRB model. For decades, emergency responder, healthcare, and public health organizations have conducted emergency preparedness exercises to test requirements for emergency response. In this article, we describe 2 types of simulation exercises conducted by UNMC: workshops and tabletops. This effort represents a unique use of emergency preparedness exercises to develop, refine, and test rapid review functions for an sIRB and to validate readiness of regulatory research processes. Such processes are crucial for conducting rapid, ethical, and sound clinical research in public health emergencies.

Robust clinical trials in Ayush systems: compelling necessity

The article focuses on Robust clinical trials in Ayush systems: compelling necessity.

CTSA pharmacies: Contribution to research and public health during the COVID-19 pandemic.

INTRODUCTION: In March 2020, academic medical center (AMC) pharmacies were compelled to implement practice changes in response to the COVID-19 pandemic. These changes were described by survey data collected by the Clinical and Translational Science Awards (CTSA) program which were interpreted by a multi-institutional team of AMC pharmacists and physician investigators. METHODS: The CTSA program surveyed 60 AMC pharmacy departments. The survey included event timing, impact on pharmacy services, and corrective actions taken. RESULTS: Almost all departments (98.4%) reported at least one disruption. Shortages of personal protective equipment (PPE) were common (91.5%) as were drug shortages (66.0%). To manage drug shortages, drug prioritization protocols were utilized, new drug supply vendors were identified (79.3%), and onsite compounding was initiated. PPE shortages were managed by incorporating the risk mitigation strategies recommended by FDA and others. Research pharmacists supported new clinical research initiatives at most institutions (84.0%), introduced use of virtual site visits, and shipped investigational drugs directly to patients. Some pharmacies formulated novel investigational products for clinical trial use. Those AMC pharmacies within networked health systems assisted partner rural and inner-city hospitals by sourcing commercial and investigational drugs to alleviate local disease outbreaks and shortages in underserved populations. Pharmacy-based vaccination practice was expanded to include a wider range of pediatric and adult vaccines. CONCLUSION: The COVID-19 pandemic radically altered hospital pharmacy practice. By adopting innovative methods and adapting to regulatory imperatives, pharmacies at CTSA sites played an extremely important role supporting continuity of care and collaborating on critical clinical research initiatives.

Introduction to the mini special issue on next generation drug discovery and development: rethinking translational pharmacology for accelerated drug development.

The coronavirus disease (COVID-19) pandemic further revealed the barriers to accelerated discovery and development of transformative medicines for life threatening diseases. To effectively and efficiently respond to unmet medical needs, efforts should be directed towards revolutionizing the predictive capability of non-clinical surrogates that inform drug discovery and development programs. I developed this mini special issue amidst the COVID-19 pandemic to evaluate recent advancements and opportunities for four main subthemes that support drug discovery and development including prediction of metabolic pathways, translational pharmacokinetic and pharmacodynamic studies, pharmacogenomics, and trends in bioanalysis. Scientific papers in these areas were covered by investigators from the International Society for the Study of Xenobiotics New Investigator Group and other investigators. Advancement in the predictive capability of in silico, in vitro, and in vivo models used to determine the absorption, distribution, metabolism, excretion, and toxicity profile of investigational drugs can help offset the cost of unexpected safety and/or efficacy issues during clinical studies. Likewise, extensive application of pharmacogenomics in drug development and clinical care can help direct therapeutic benefits to the appropriate patient population with the overall goal of accelerating drug development and mitigating failed drug cost. Finally, I hope that the scientific contributions in this mini special issue will stimulate practical advancements across all aspects of basic science research that support drug discovery and development to help unlock the door to the next generation of drug discovery and development that features reduced failure rates and accelerated development.

Novel insights into the treatment of SARS-CoV-2 infection: An overview of current clinical trials.

The emergence of the global pandemic caused by the novel SARS-CoV-2 virus has motivated scientists to find a definitive treatment or a vaccine against it in the shortest possible time. Current efforts towards this goal remain fruitless without a full understanding of the behavior of the virus and its adaptor proteins. This review provides an overview of the biological properties, functional mechanisms, and molecular components of SARS-CoV-2, along with investigational therapeutic and preventive approaches for this virus. Since the proteolytic cleavage of the S protein is critical for virus penetration into cells, a set of drugs, such as chloroquine, hydroxychloroquine, camostat mesylate have been tested in clinical trials to suppress this event. In addition to angiotensin-converting enzyme 2, the role of CD147 in the viral entrance has also been proposed. Mepolizumab has shown to be effective in blocking the virus's cellular entrance. Antiviral drugs, such as remdesivir, ritonavir, oseltamivir, darunavir, lopinavir, zanamivir, peramivir, and oseltamivir, have also been tested as treatments for COVID-19. Regarding preventive vaccines, the whole virus, vectors, nucleic acids, and structural subunits have been suggested for vaccine development. Mesenchymal stem cells and natural killer cells could also be used against SARS-CoV-2. All the above-mentioned strategies, as well as the role of nanomedicine for the diagnosis and treatment of SARS-CoV-2 infection, have been discussed in this review.