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.

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.

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.

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.

Absorbing citywide patient surge during Hurricane Sandy: a case study in accommodating multiple hospital evacuations.

STUDY OBJECTIVE: Hospital evacuations have myriad effects on all elements of the health care system. We seek to (1) examine the effect of patient surge on hospitals that received patients from evacuating hospitals in New York City during Hurricane Sandy; (2) describe operational challenges those hospitals faced pre- and poststorm; and (3) examine the coordination efforts to distribute patients to receiving hospitals. METHODS: We used a qualitative, interview-based method to identify medical surge strategies used at hospitals receiving patients from evacuated health care facilities during and after Hurricane Sandy. We identified 4 hospital systems that received the majority of evacuated patients and those departments most involved in managing patient surge. We invited key staff at those hospitals to participate in on-site group interviews. RESULTS: We interviewed 71 key individuals. Although all hospitals had emergency preparedness plans in place before Hurricane Sandy, we identified gaps. Insights gleaned included improvement opportunities in these areas: prolonged increased patient volume, an increase in the number of methadone and dialysis patients, ability to absorb displaced staff, the challenges associated with nursing homes that have evacuated and shelters that have already reached capacity, and reimbursements for transferred patients. CONCLUSION: Our qualitative, event-based research identified key opportunities to improve disaster preparedness. The specific opportunities and this structured postevent approach can serve to guide future disaster planning and analyses.

Emergency Preparedness in the 10-Mile Emergency Planning Zone Surrounding Nuclear Power Plants.

OBJECTIVES: Each of the nuclear power plants in the US is encircled by an Emergency Planning Zone (EPZ). Within each EPZ, government officials, utility professionals, emergency managers, and public health practitioners collectively conduct extensive planning, exercises, and outreach to better protect their communities in the event of a nuclear accident. Our objective was to conduct a cross-sectional study of off-site public health preparedness within EPZs to better understand the dynamics of nuclear preparedness and uncover lessons for all-hazards preparedness. METHODS: Using a qualitative, interview-based method, we consulted 120 county emergency managers, state health preparedness officers, state radiation health officials, and industry officials from 17 EPZs in ten different states. RESULTS: Interviewees reflected that EPZ emergency preparedness is generally robust, results from strong public-private partnership between nuclear plants and emergency management agencies, and enhances all-hazard preparedness. However, there exist a few areas which merit further study and improvement. These areas include cross-state coordination, digital public communication, and optimizing the level of public education within EPZs. CONCLUSIONS: This first-of-its-kind study provides a cross-sectional snapshot of emergency preparedness in the 10-mile EPZ surrounding nuclear power plants.

Assessment of serosurveys for H5N1.

BACKGROUND: It has been suggested that the true case-fatality rate of human H5N1 influenza infection is appreciably less than the figure of approximately 60% that is based on official World Health Organization (WHO)-confirmed case reports because asymptomatic cases may have been missed. A number of seroepidemiologic studies have been conducted in an attempt to identify such missed cases. METHODS: We conducted a comprehensive literature review of all English-language H5N1 human serology surveys with detailed attention to laboratory methodology used (including whether investigators used criteria set by the WHO to define positive cases), laboratory controls used, and the clades/genotypes involved. RESULTS: Twenty-nine studies were included in the analysis. Few reported using unexposed control groups and one-third did not apply WHO criteria. Of studies that used WHO criteria, only 4 found any seropositive results to clades/genotypes of H5N1 that are currently circulating. No studies reported seropositive results to the clade 2/genotype Z viruses that have spread throughout Eurasia and Africa. CONCLUSIONS: This review suggests that the frequency of positive H5 serology results is likely to be low; therefore, it is essential that future studies adhere to WHO criteria and include unexposed controls in their laboratory assays to limit the likelihood of false-positive results.

Lessons learned during dengue outbreaks in the United States, 2001-2011.

Since 2001, three autochthonous dengue fever outbreaks have occurred in the United States: in Hawaii (2001); Brownsville, Texas (2005); and southern Florida (2009-2011). We sought to characterize and describe the response to these outbreaks from the perspectives of public health and vector control officials. By conducting a medical literature review through PubMed and news media searches through Google, we identified persons involved in managing each outbreak; 26 persons then participated in qualitative, semistructured interviews. After analyzing the 3 outbreaks, we found the following prominent themes in the response efforts: timely detection of illness; communication of up-to-date, correct information; and development of a rapid response that engages the community. We therefore recommend that public health authorities involve the clinical and laboratory community promptly, provide accurate information, and engage the local community in vector control and case identification and reporting.

Actinomyces israelii endocarditis misidentified as "Diptheroids".

Actinomyces is a rare cause of endocarditis, however misidentification as Cornyebacteria often hampers the diagnosis.

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.

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.

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.