The Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Cross-Trial Statistics Group gathered lessons learned from statisticians responsible for the design and analysis of the 11 ACTIV therapeutic master protocols to inform contemporary trial design as well as preparation for a future pandemic. The ACTIV master protocols were designed to rapidly assess what treatments might save lives, keep people out of the hospital, and help them feel better faster. Study teams initially worked without knowledge of the natural history of disease and thus without key information for design decisions. Moreover, the science of platform trial design was in its infancy. Here, we discuss the statistical design choices made and the adaptations forced by the changing pandemic context. Lessons around critical aspects of trial design are summarized, and recommendations are made for the organization of master protocols in the future.

This article discusses the difference between benefit–cost analysis (BCA) and social welfare analysis in the evaluation of pandemic preparedness policies. Two social welfare approaches are considered: utilitarianism and prioritarianism. BCA sums the individuals’ monetary equivalents of the pandemic impacts. Social welfare analysis aggregates individuals’ well-being impacts. The aggregation rule identifies the normative judgments about what is fair. This article shows that the two methods yield very different estimates of the value of avoiding a future pandemic similar to the COVID-19 one. Compared to BCA, considerations about the distribution of the costs of the hypothetical intervention play a major role in the estimate of both utilitarian and prioritarian pandemic burdens: The more progressive the distribution of the costs is, the larger the net benefits of preventing the pandemic. In contrast, the BCA pandemic burden is indifferent to the distribution of the intervention costs. In addition, BCA tends to underestimate the burden suffered by low-income countries compared to social welfare analysis.

As the COVID-19 pandemic took hold in the USA in early 2020, it became clear that knowledge of the prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among asymptomatic individuals could inform public health policy decisions and provide insight into the impact of the infection on vulnerable populations. Two Clinical and Translational Science Award (CTSA) Hubs and the National Institutes of Health (NIH) set forth to conduct a national seroprevalence survey to assess the infection’s rate of spread. This partnership was able to quickly design and launch the project by leveraging established research capacities, prior experiences in large-scale, multisite studies and a highly skilled workforce of CTSA hubs and unique experimental capabilities at the NIH to conduct a diverse prospective, longitudinal observational cohort of 11,382 participants who provided biospecimens and participant-reported health and behavior data. The study was completed in 16 months and benefitted from transdisciplinary teamwork, information technology innovations, multimodal communication strategies, and scientific partnership for rigor in design and analytic methods. The lessons learned by the rapid implementation and dissemination of this national study is valuable in guiding future multisite projects as well as preparation for other public health emergencies and pandemics.

Coronavirus disease 2019 (COVID-19) has placed massive socio-psychological, health, and economic burdens including deaths on countless lives; however, it has disproportionally impacted certain populations. Co-occurring Social Determinants of Health (SDoH) disparities and other underlying determinants have exacerbated the COVID-19 pandemic. This literature review sought to (1) examine literature focused on SDoH and COVID-19 outcomes ie, infectivity, hospitalization, and death rates among marginalized communities; and (2) identify SDoH disparities associated with COVID-19 outcomes. We searched electronic databases for studies published from October 2019 to October 2021. Studies that were selected were those intersecting SDoH indicators and COVID-19 outcomes and were conducted in the United States. Our review underscored the disproportionate vulnerabilities and adverse outcomes from COVID-19 that have impacted racial/ethnic minority communities and other disadvantaged groups (ie, senior citizens, and displaced/homeless individuals). COVID-19 outcomes were associated with SDoH indicators, ie, race/ethnicity, poverty, median income level, housing density, housing insecurity, health-care access, occupation, transportation/commuting patterns, education, air quality, food insecurity, old age, etc. Our review concluded with recommendations and a call to action to integrate SDoH indicators along with relevant health data when implementing intelligent solutions and intervention strategies to pandemic response/recovery among vulnerable populations.

The 2019 Global Health Security Index (GHS Index) assessed the US and the UK as the two countries best prepared to address a catastrophic pandemic. The preparedness rankings of this index have had little correlation with the actual experiences of COVID-19 in various countries. In explaining this disrepancy, the paper argues that better indicators and more data would not have fixed the problem. Rather, the prevailing paradigm of global health security that informs instruments such as the GHS Index needs to be interrogated. This dominant paradigm narrowly conceptualises global health security in terms of the availability of a technical infrastructure to detect emerging infectious diseases and prevent their contagion, but profoundly undertheorises the broader social and political determinants of public health. The neglect of social and political features is amplified in instruments such as the GHS Index that privilege universalised templates presumed to apply across countries but that prove to be inadequate in assessing how individual societies draw on their unique histories to craft public health responses.

Global Health Security Index (GHSI) and Joint External Evaluation (JEE) are two well-known health security and related capability indices. We hypothesised that countries with higher GHSI or JEE scores would have detected their first COVID-19 case earlier, and would experience lower mortality outcome compared to countries with lower scores. We evaluated the effectiveness of GHSI and JEE in predicting countries' COVID-19 detection response times and mortality outcome (deaths/million). We used two different outcomes for the evaluation: (i) detection response time, the duration of time to the first confirmed case detection (from 31st December 2019 to 20th February 2020 when every country's first case was linked to travel from China) and (ii) mortality outcome (deaths/million) until 11th March and 1st July 2020, respectively. We interpreted the detection response time alongside previously published relative risk of the importation of COVID-19 cases from China. We performed multiple linear regression and negative binomial regression analysis to evaluate how these indices predicted the actual outcome. The two indices, GHSI and JEE were strongly correlated (r = 0.82), indicating a good agreement between them. However, both GHSI (r = 0.31) and JEE (r = 0.37) had a poor correlation with countries' COVID-19–related mortality outcome. Higher risk of importation of COVID-19 from China for a given country was negatively correlated with the time taken to detect the first case in that country (adjusted R2 = 0.63–0.66), while the GHSI and JEE had minimal predictive value. In the negative binomial regression model, countries' mortality outcome was strongly predicted by the percentage of the population aged 65 and above (incidence rate ratio (IRR): 1.10 (95% confidence interval (CI): 1.01–1.21) while overall GHSI score (IRR: 1.01 (95% CI: 0.98–1.01)) and JEE (IRR: 0.99 (95% CI: 0.96–1.02)) were not significant predictors. GHSI and JEE had lower predictive value for detection response time and mortality outcome due to COVID-19. We suggest introduction of a population healthiness parameter, to address demographic and comorbidity vulnerabilities, and reappraisal of the ranking system and methods used to obtain the index based on experience gained from this pandemic.

Antivirals are an important defence against novel strains of influenza. However, the impact of widespread drug usage on strain circulation across multiple epidemic waves – via their impact on host immunity – is unknown despite antivirals having the likelihood of extensive use during a pandemic. To explore how drug usage by individuals affects population strain dynamics, we embedded a two-strain model of within-host dynamics within an epidemic model. We found that when 40% of hosts took drugs early during the infectious period, transmission was reduced by 30% and average levels of immunity by 2·9-fold (comparable to antibody concentrations), relative to 14% and 1·5-fold reductions when drugs were taken late. The novel strain was more successful relative to the resident strain when drugs were not taken, and an intermediate level of drug coverage minimized incidence in subsequent waves. We discuss how drug regimens, coverage and R0 could impact pandemic preparedness.

We used a mathematical model to describe a regional outbreak and extrapolate the underlying health-service resource needs. This model was designed to (i) estimate resource gaps and quantities of resources needed, (ii) show the effect of resource gaps, and (iii) highlight which particular resources should be improved. We ran the model, parameterized with data from the 2009 H1N1v pandemic, for two provinces in Thailand. The predicted number of preventable deaths due to resource shortcomings and the actual resource needs are presented for two provinces and for Thailand as a whole. The model highlights the potentially huge impact of health-system resource availability and of resource gaps on health outcomes during a pandemic and provides a means to indicate where efforts should be concentrated to effectively improve pandemic response programmes.