Innovative approaches to COVID-19 medical countermeasure development.

BACKGROUND: The COVID-19 pandemic, while unfortunately notable for immense strain and death throughout the world, has also shown great promise in the development of medical countermeasures. As the global scientific community shifted almost entirely towards vaccines, diagnostics and therapeutics, new trial designs most significantly adaptive platform trials, began to be used with greater speed and broader reach. These designs allowed for deploying and investigating new therapeutics, repurposing currently existing therapeutics and flexibly removing or adding additional medications as data appeared in real-time. Moreover, public-private sector partnering occurred at a level not seen before, contributing greatly to the rapid development and deployment of vaccines. OBJECTIVES: To provide a brief overview of the advances in preventative and therapeutic medical countermeasure development for COVID-19. METHODS: A narrative review of relevant major medical countermeasure trials was conducted using the date range February 2020-December 2022, representing the period of greatest productivity in research to investigate COVID-19. RESULTS: Among the most influential trial designs are the adaptive platform designs, which have been applied to the development of initial COVID-19 antivirals, monoclonal antibodies, repurposing of existing immunomodulatory therapy and assisted in the disproof of ineffective medical therapies. Some of the most prominent examples include the REMAP-CAP, RECOVERY and TOGETHER trials. CONCLUSIONS: Adaptive platform trial designs hold great promise for utility in future pandemics and mass casualty events. Additionally, public-private sectoring is essential for rapid medical countermeasure development and should be further enhanced for future biopreparedness.

Clade X: A Pandemic Exercise.

Clade X was a day-long pandemic tabletop exercise conducted by the Johns Hopkins Center for Health Security on May 15, 2018, in Washington, DC. In this report, we briefly describe the exercise development process and focus principally on the findings and recommendations that arose from this project.

Characteristics of Microbes Most Likely to Cause Pandemics and Global Catastrophes.

Predicting which pathogen will confer the highest global catastrophic biological risk (GCBR) of a pandemic is a difficult task. Many approaches are retrospective and premised on prior pandemics; however, such an approach may fail to appreciate novel threats that do not have exact historical precedent. In this paper, based on a study and project we undertook, a new paradigm for pandemic preparedness is presented. This paradigm seeks to root pandemic risk in actual attributes possessed by specific classes of microbial organisms and leads to specific recommendations to augment preparedness activities.

Infectious Diseases Physicians: Improving and Protecting the Public's Health: Why Equitable Compensation Is Critical.

Infectious diseases (ID) physicians play a crucial role in public health in a variety of settings. Unfortunately, much of this work is undercompensated despite the proven efficacy of public health interventions such as hospital acquired infection prevention, antimicrobial stewardship, disease surveillance, and outbreak response. The lack of compensation makes it difficult to attract the best and the brightest to the field of ID, threatening the future of the ID workforce. Here, we examine compensation data for ID physicians compared to their value in population and public health settings and suggest policy recommendations to address the pay disparities that exist between cognitive and procedural specialties that prevent more medical students and residents from entering the field. All ID physicians should take an active role in promoting the value of the subspecialty to policymakers and influencers as well as trainees.

Biothreat Agents and Emerging Infectious Disease in the Emergency Department.

The challenges faced by the emergency physician with recognizing and treating category A biothreat agents and emerging infectious disease are summarized and reviewed.

Challenges and Opportunities of Nontraditional Approaches to Treating Bacterial Infections.

Due to increasing rates of antimicrobial-resistant infections and the current inadequacy of the antibiotic pipeline, there is increasing interest in nontraditional approaches to antibacterial therapies. We define "traditional" agents as small-molecule agents that directly target bacterial components to exert a bacteriostatic or bactericidal effect, and "nontraditional approaches" as antimicrobial therapeutics that work through other means (ie, not a small molecule and/or utilizes a nontraditional target). Due to their atypical features, such therapies may be less susceptible to the emergence of resistance than traditional antibiotics. They include approaches such as monoclonal antibodies, virulence disruptors, immunomodulators, phage therapies, microbiome-based therapies, antibiotic potentiators, and antisense approaches. This article discusses both the developmental and regulatory advantages and challenges associated with each of these technologies. By identifying existing regulatory and developmental gaps, we hope to provide a sense of where focusing resources may provide the greatest impact on successful product development.

Hospital influenza pandemic stockpiling needs: A computer simulation.

BACKGROUND: A severe influenza pandemic could overwhelm hospitals but planning guidance that accounts for the dynamic interrelationships between planning elements is lacking. We developed a methodology to calculate pandemic supply needs based on operational considerations in hospitals and then tested the methodology at Mayo Clinic in Rochester, MN. METHODS: We upgraded a previously designed computer modeling tool and input carefully researched resource data from the hospital to run 10,000 Monte Carlo simulations using various combinations of variables to determine resource needs across a spectrum of scenarios. RESULTS: Of 10,000 iterations, 1,315 fell within the parameters defined by our simulation design and logical constraints. From these valid iterations, we projected supply requirements by percentile for key supplies, pharmaceuticals, and personal protective equipment requirements needed in a severe pandemic. DISCUSSION: We projected supplies needs for a range of scenarios that use up to 100% of Mayo Clinic-Rochester's surge capacity of beds and ventilators. The results indicate that there are diminishing patient care benefits for stockpiling on the high side of the range, but that having some stockpile of critical resources, even if it is relatively modest, is most important. CONCLUSIONS: We were able to display the probabilities of needing various supply levels across a spectrum of scenarios. The tool could be used to model many other hospital preparedness issues, but validation in other settings is needed.

Clinical management of potential bioterrorism-related conditions.

The agents most likely to be used in bioterrorism attacks are reviewed, along with the clinical syndromes they produce and their treatment.

An estimate of the global health care and lost productivity costs of dengue.

Contemporary cost estimates of dengue fever are difficult to attain in many countries in which the disease is endemic. By applying publicly available health care costs and wage data to recently available country-level estimates of dengue incidence, we estimate the total cost of dengue to be nearly 40 billion dollars in 2011.