Measures to prevent and treat Nipah virus disease: research priorities for 2024-29.

Nipah virus causes highly lethal disease, with case-fatality rates ranging from 40% to 100% in recognised outbreaks. No treatments or licensed vaccines are currently available for the prevention and control of Nipah virus infection. In 2019, WHO published an advanced draft of a research and development roadmap for accelerating development of medical countermeasures, including diagnostics, therapeutics, and vaccines, to enable effective and timely emergency response to Nipah virus outbreaks. This Personal View provides an update to the WHO roadmap by defining current research priorities for development of Nipah virus medical countermeasures, based primarily on literature published in the last 5 years and consensus opinion of 15 subject matter experts with broad experience in development of medical countermeasures for Nipah virus or experience in the epidemiology, ecology, or public health control of outbreaks of Nipah virus. The research priorities are organised into four main sections: cross-cutting issues (for those that apply to more than one category of medical countermeasures), diagnostics, therapeutics, and vaccines. The strategic goals and milestones identified in each section focus on key achievements that are needed over the next 6 years to ensure that the necessary tools are available for rapid response to future outbreaks of Nipah virus or related henipaviruses.

Lassa fever research priorities: towards effective medical countermeasures by the end of the decade.

In 2016, WHO designated Lassa fever a priority disease for epidemic preparedness as part of the WHO Blueprint for Action to Prevent Epidemics. One aspect of preparedness is to promote development of effective medical countermeasures (ie, diagnostics, therapeutics, and vaccines) against Lassa fever. Diagnostic testing for Lassa fever has important limitations and key advancements are needed to ensure rapid and accurate diagnosis. Additionally, the only treatment available for Lassa fever is ribavirin, but controversy exists regarding its effectiveness. Finally, no licensed vaccines are available for the prevention and control of Lassa fever. Ongoing epidemiological and behavioural studies are also crucial in providing actionable information for medical countermeasure development, use, and effectiveness in preventing and treating Lassa fever. This Personal View provides current research priorities for development of Lassa fever medical countermeasures based on literature published primarily in the last 5 years and consensus opinion of 20 subject matter experts with broad experience in public health or the development of diagnostics, therapeutics, and vaccines for Lassa fever. These priorities provide an important framework to ensure that Lassa fever medical countermeasures are developed and readily available for use in endemic and at-risk areas by the end of the decade.

Factors associated with antibody titer levels among an occupational cohort of fully vaccinated individuals and subsequent risk of COVID-19 infection: A cohort study.

This study (1) determined the association of time since initial vaccine regimen, booster dose receipt, and COVID-19 history with antibody titer, as well as change in titer levels over a defined period, and (2) determined risk of COVID-19 associated with low titer levels. This observational study used data from staff participating in the National Football League COVID-19 Monitoring Program. A cohort of staff consented to antibody-focused sub-study, during which detailed longitudinal data were collected. Among all staff in the program who received antibody testing, COVID-19 incidence following antibody testing was determined. Five hundred eighty-six sub-study participants completed initial antibody testing; 80% (469) completed follow-up testing 50-101 days later. Among 389 individuals who were not boosted at initial testing, the odds of titer < 1000 AU/mL (vs. ≥1000 AU/mL) increased 44% (odds ratio [OR] = 1.44, 95% confidence interval [CI]: 1.18-1.75) for every 30 days since final dose. Among 126 participants boosted before initial testing with no COVID-19 history, 125 (99%) had a value > 2500 AU/ml; 86 (96%) of 90 tested at follow-up and did not develop COVID-19 in the interim remained at that value. One thousand fifty-seven fully vaccinated (330 [29%] boosted at antibody test) individuals participating in the monitoring program were followed to determine COVID-19 status. Individuals with titer value < 1000 AU/mL had twice the risk of COVID-19 as those with >2500 AU/mL (HR = 2.02, 95% CI: 1.28-3.18). Antibody levels decrease postvaccination; boosting increases titer values. While antibody level is not a clear proxy for infection immunity, lower titer values are associated with higher COVID-19 incidence, suggesting increased protection from boosters.

A research and development (R&D) roadmap for broadly protective coronavirus vaccines: A pandemic preparedness strategy.

Broadly protective coronavirus vaccines are an important tool for protecting against future SARS-CoV-2 variants and could play a critical role in mitigating the impact of future outbreaks or pandemics caused by novel coronaviruses. The Coronavirus Vaccines Research and Development (R&D) Roadmap (CVR) is aimed at promoting the development of such vaccines. The CVR, funded by the Bill & Melinda Gates Foundation and The Rockefeller Foundation, was generated through a collaborative and iterative process, which was led by the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota and involved 50 international subject matter experts and recognized leaders in the field. This report summarizes the major issues and areas of research outlined in the CVR and identifies high-priority milestones. The CVR covers a 6-year timeframe and is organized into five topic areas: virology, immunology, vaccinology, animal and human infection models, and policy and finance. Included in each topic area are key barriers, gaps, strategic goals, milestones, and additional R&D priorities. The roadmap includes 20 goals and 86 R&D milestones, 26 of which are ranked as high priority. By identifying key issues, and milestones for addressing them, the CVR provides a framework to guide funding and research campaigns that promote the development of broadly protective coronavirus vaccines.

Observed Versus Expected COVID-19 Infections Among National Football League Players During the 2020 Season.

BACKGROUND: The National Football League (NFL) and National Football League Players Association implemented a set of strict protocols for the 2020 season with the intent to mitigate COVID-19 risk among players and staff. In that timeframe, the league's 32 teams completed 256 regular season games and several thousand meetings and practices. In parallel, community cases of COVID-19 were highly prevalent. We assess the risk of holding a 2020 NFL season by comparing community and player COVID-19 infections. METHODS: We used county-level COVID-19 test data from each team to establish baseline distributions of infection rates expected to occur in a population similar in age and sex to NFL players. We used a binomial distribution to simulate expected infections in each community cohort and compared these findings with observed COVID-19 infections in players. RESULTS: Over a 5-month period (1 August 2020 to 2 January 2021), positive NFL player infections (n = 256) were 55.7% lower than expected when compared with simulations from NFL community cohorts. For 30 of 32 teams (94%), observed counts fell at or below expectation, including 28 teams (88%) for which rates were lower. Two teams fell above baseline expectation. CONCLUSIONS: The NFL/NFLPA protocols that governed team facilities, travel, gameday, and activities outside of the workplace were associated with lower infection rates among NFL players compared with the surrounding community. The NFL's 2020-2021 season are consistent with the hypothesis that robust testing and behavioral protocols support a safe return to sport and work.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Dose, Infection, and Disease Outcomes for Coronavirus Disease 2019 (COVID-19): A Review.

The relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dose, infection, and coronavirus disease 2019 (COVID-19) outcomes remains poorly understood. This review summarizes the existing literature regarding this issue, identifies gaps in current knowledge, and suggests opportunities for future research. In humans, host characteristics, including age, sex, comorbidities, smoking, and pregnancy, are associated with severe COVID-19. Similarly, in animals, host factors are strong determinants of disease severity, although most animal infection models manifest clinically with mild to moderate respiratory disease. The influence of variants of concern as it relates to infectious dose, consequence of overall pathogenicity, and disease outcome in dose-response remains unknown. Epidemiologic data suggest a dose-response relationship for infection contrasting with limited and inconsistent surrogate-based evidence between dose and disease severity. Recommendations include the design of future infection studies in animal models to investigate inoculating dose on outcomes and the use of better proxies for dose in human epidemiology studies.

BSAC Vanguard Series: the future of ADVOCACY on AMR.

The COVID public health emergency has brought home how vulnerable we are to forces beyond our control. We are losing our ability to treat infectious diseases for a number of reasons, including antimicrobial resistance (AMR). AMR is a 'slow-moving' threat, which makes it harder to recognize and address. The situation has not been helped by the difficulty we have had in seeing the actions and health of everyone on this planet as interconnected. The COVID pandemic has changed this. Despite the dire predictions of the effect of AMR in the future, we still have time to change course. Advocacy by scientists and health professionals is a powerful tool in this process, but there are pitfalls and it must be used wisely. In this article I suggest a number of ways in which this can be achieved.

A Research and Development (R&D) roadmap for influenza vaccines: Looking toward the future.

Improved influenza vaccines are urgently needed to reduce the burden of seasonal influenza and to ensure a rapid and effective public-health response to future influenza pandemics. The Influenza Vaccines Research and Development (R&D) Roadmap (IVR) was created, through an extensive international stakeholder engagement process, to promote influenza vaccine R&D. The roadmap covers a 10-year timeframe and is organized into six sections: virology; immunology; vaccinology for seasonal influenza vaccines; vaccinology for universal influenza vaccines; animal and human influenza virus infection models; and policy, finance, and regulation. Each section identifies barriers, gaps, strategic goals, milestones, and additional R&D priorities germane to that area. The roadmap includes 113 specific R&D milestones, 37 of which have been designated high priority by the IVR expert taskforce. This report summarizes the major issues and priority areas of research outlined in the IVR. By identifying the key issues and steps to address them, the roadmap not only encourages research aimed at new solutions, but also provides guidance on the use of innovative tools to drive breakthroughs in influenza vaccine R&D.

Optimizing SARS-CoV-2 Surveillance in the United States: Insights From the National Football League Occupational Health Program.

BACKGROUND: Evidence to understand effective strategies for surveillance and early detection of SARS-CoV-2 is limited. OBJECTIVE: To describe the results of a rigorous, large-scale COVID-19 testing and monitoring program. DESIGN: The U.S. National Football League (NFL) and the NFL Players Association (NFLPA) instituted a large-scale COVID-19 monitoring program involving daily testing using 2 reverse transcription polymerase chain reaction (RT-PCR) platforms (Roche cobas and Thermo Fisher QuantStudio), a transcription-mediated amplification platform (Hologic Panther), and an antigen point-of-care (aPOC) test (Quidel Sofia). SETTING: 32 NFL clubs in 24 states during the 2020 NFL season. PARTICIPANTS: NFL players and staff. MEASUREMENTS: SARS-CoV-2 test results were described in the context of medically adjudicated status. Cycle threshold (Ct) values are reported when available. RESULTS: A total of 632 370 tests administered across 11 668 persons identified 270 (2.4%) COVID-19 cases from 1 August to 14 November 2020. Positive predictive values ranged from 73.0% to 82.0% across the RT-PCR platforms. High Ct values (33 to 37) often indicated early infection. For the first positive result, the median Ct value was 32.77 (interquartile range, 30.02 to 34.72) and 22% of Ct values were above 35. Among adjudicated COVID-19 cases tested with aPOC, 42.3% had a negative result. Positive concordance between aPOC test result and adjudicated case status increased as viral load increased. LIMITATIONS: Platforms varied by laboratory, and test variability may reflect procedural differences. CONCLUSION: Routine RT-PCR testing allowed early detection of infection. Cycle threshold values provided a useful guidepost for understanding results, with high values often indicating early infection. Antigen POC testing was unable to reliably rule out COVID-19 early in infection. PRIMARY FUNDING SOURCE: The NFL and the NFLPA.

The relationship of large city out-of-hospital cardiac arrests and the prevalence of COVID-19.

BACKGROUND: Though variable, many major metropolitan cities reported profound and unprecedented increases in out-of-hospital cardiac arrest (OHCA) in early 2020. This study examined the relative magnitude of those increases and their relationship to COVID-19 prevalence. METHODS: EMS (9-1-1 system) medical directors for 50 of the largest U.S. cities agreed to provide the aggregate, de-identified, pre-existing monthly tallies of OHCA among adults (age >18 years) occurring between January and June 2020 within their respective jurisdictions. Identical comparison data were also provided for corresponding time periods in 2018 and 2019.  Equivalent data were obtained from the largest cities in Italy, United Kingdom and France, as well as Perth, Australia and Auckland, New Zealand. FINDINGS: Significant OHCA escalations generally paralleled local prevalence of COVID-19. During April, most U.S. cities (34/50) had >20% increases in OHCA versus 2018-2019 which reflected high local COVID-19 prevalence. Thirteen observed 1·5-fold increases in OHCA and three COVID-19 epicenters had >100% increases (2·5-fold in New York City). Conversely, cities with lesser COVID-19 impact observed unchanged (or even diminished) OHCA numbers. Altogether (n = 50), on average, OHCA cases/city rose 59% during April (p = 0·03). By June, however, after mitigating COVID-19 spread, cities with the highest OHCA escalations returned to (or approached) pre-COVID OHCA numbers while cities minimally affected by COVID-19 during April (and not experiencing OHCA increases), then had marked OHCA escalations when COVID-19 began to surge locally. European, Australian, and New Zealand cities mirrored the U.S. experience. INTERPRETATION: Most metropolitan cities experienced profound escalations of OHCA generally paralleling local prevalence of COVID-19.  Most of these patients were pronounced dead without COVID-19 testing. FUNDING: No funding was involved. Cities provided de-identified aggregate data collected routinely for standard quality assurance functions.

Critical Considerations for COVID-19 Vaccination of Refugees, Immigrants, and Migrants.

As COVID-19 vaccines are distributed across the United States, it is essential to address the pandemic's disproportionate impact on refugee, immigrant, and migrant (RIM) communities. Although the National Academies Press Framework for Equitable Allocation of COVID-19 Vaccine provides recommendations for an equitable vaccine campaign, implementation remains. Practical considerations for vaccine rollout include identifying and overcoming barriers to vaccination among RIM communities. To identify barriers, information regarding vaccine beliefs and practices must be incorporated into the pandemic response. To overcome barriers, effective communication, convenience of care, and community engagement are essential. Taking these actions now can improve health among RIM communities.

Development and deployment of COVID-19 vaccines for those most vulnerable.

Development of safe and effective COVID-19 vaccines is a global priority and the best hope for ending the COVID-19 pandemic. Remarkably, in less than 1 year, vaccines have been developed and shown to be efficacious and are already being deployed worldwide. Yet, many challenges remain. Immune senescence and comorbidities in aging populations and immune dysregulation in populations living in low-resource settings may impede vaccine effectiveness. Distribution of vaccines among these populations where vaccine access is historically low remains challenging. In this Review, we address these challenges and provide strategies for ensuring that vaccines are developed and deployed for those most vulnerable.

Infectious Disease Threats: A Rebound To Resilience.

The US has experienced a series of epidemics during the past five decades. None has tested the nation's resilience like the coronavirus disease 2019 (COVID-19) pandemic, which has laid bare critical weaknesses in US pandemic preparedness and domestic leadership and the nation's decline in global standing in public health. Pandemic response has been politicized, proven public health measures undermined, and public confidence in a science-based public health system reduced. This has been compounded by the large number of citizens without ready access to health care, who are overrepresented among infected, hospitalized, and fatal cases. Here, as part of the National Academy of Medicine's Vital Directions for Health and Health Care: Priorities for 2021 initiative, we review the US approach to pandemic preparedness and its impact on the response to COVID-19. We identify six steps that should be taken to strengthen US pandemic resilience, strengthen and modernize the US health care system, regain public confidence in government leadership in public health, and restore US engagement and leadership in global partnerships to address future pandemic threats domestically and around the world.