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The test-negative design (TND) is an observational study design to evaluate vaccine effectiveness (VE) that enrolls individuals receiving diagnostic testing for a target disease as part of routine care. VE is estimated as one minus the adjusted odds ratio of testing positive versus negative comparing vaccinated and unvaccinated patients. Although the TND is related to case–control studies, it is distinct in that the ratio of test-positive cases to test-negative controls is not typically pre-specified. For both types of studies, sparse cells are common when vaccines are highly effective. We consider the implications of these features on power for the TND. We use simulation studies to explore three hypothesis-testing procedures and associated sample size calculations for case–control and TND studies. These tests, all based on a simple logistic regression model, are a standard Wald test, a continuity-corrected Wald test, and a score test. The Wald test performs poorly in both case–control and TND when VE is high because the number of vaccinated test-positive cases can be low or zero. Continuity corrections help to stabilize the variance but induce bias. We observe superior performance with the score test as the variance is pooled under the null hypothesis of no group differences. We recommend using a score-based approach to design and analyze both case–control and TND. We propose a modification to the TND score sample size to account for additional variability in the ratio of controls over cases. This work enhances our understanding of the data generating mechanism in a test-negative design (TND) and how it is distinct from that of a case-control study due to its passive recruitment of controls. [ABSTRACT FROM AUTHOR]

Epidemic data are often difficult to interpret due to inconsistent detection and reporting. As these data are critically relied upon to inform policy and epidemic projections, understanding reporting trends is similarly important. Early reporting of the COVID-19 pandemic in particular is complicated, due to changing diagnostic and testing protocols. An internal audit by the State of Florida, USA found numerous specific examples of irregularities in COVID-19 case and death reports. Using case, hospitalization, and death data from the the first year of the COVID-19 pandemic in Florida, we present approaches that can be used to identify the timing, direction, and magnitude of some reporting changes. Specifically, by establishing a baseline of detection probabilities from the first (spring) wave, we show that transmission trends among all age groups were similar, with the exception of the second summer wave, when younger people became infected earlier than seniors, by approximately 2 weeks. We also found a substantial drop in case-fatality risk (CFR) among all age groups over the three waves during the first year of the pandemic, with the most drastic changes seen in the 0 to 39 age group. The CFR trends provide useful insights into infection detection that would not be possible by relying on the number of tests alone. During the third wave, for which we have reliable hospitalization data, the CFR was remarkably stable across all age groups. In contrast, the hospitalization-to-case ratio varied inversely with cases while the death-to-hospitalization ratio varied proportionally. Although specific trends are likely to vary between locales, the approaches we present here offer a generic way to understand the substantial changes that occurred in the relationships among the key epidemic indicators. [ABSTRACT FROM AUTHOR]

Access to COVID-19 vaccines on the global scale has been drastically hindered by structural socio-economic disparities. Here, we develop a data-driven, age-stratified epidemic model to evaluate the effects of COVID-19 vaccine inequities in twenty lower middle and low income countries (LMIC) selected from all WHO regions. We investigate and quantify the potential effects of higher or earlier doses availability. In doing so, we focus on the crucial initial months of vaccine distribution and administration, exploring counterfactual scenarios where we assume the same per capita daily vaccination rate reported in selected high income countries. We estimate that more than 50% of deaths (min-max range: [54−94%]) that occurred in the analyzed countries could have been averted. We further consider scenarios where LMIC had similarly early access to vaccine doses as high income countries. Even without increasing the number of doses, we estimate an important fraction of deaths (min-max range: [6−50%]) could have been averted. In the absence of the availability of high-income countries, the model suggests that additional non-pharmaceutical interventions inducing a considerable relative decrease of transmissibility (min-max range: [15−70%]) would have been required to offset the lack of vaccines. Overall, our results quantify the negative impacts of vaccine inequities and underscore the need for intensified global efforts devoted to provide faster access to vaccine programs in low and lower-middle-income countries. Global COVID-19 vaccine distribution has been inequitable. In this mathematical modelling study, the authors estimate the proportion of deaths that could have been averted in twenty low- and lower-middle-income countries if vaccines had been more widely available early in the pandemic. [ABSTRACT FROM AUTHOR]

Transmission trees can be established through detailed contact histories, statistical or phylogenetic inference, or a combination of methods. Each approach has its limitations, and the extent to which they succeed in revealing a 'true' transmission history remains unclear. In this study, we compared the transmission trees obtained through contact tracing investigations and various inference methods to identify the contribution and value of each approach. We studied eighty-six sequenced cases reported in Guinea between March and November 2015. Contact tracing investigations classified these cases into eight independent transmission chains. We inferred the transmission history from the genetic sequences of the cases (phylogenetic approach), their onset date (epidemiological approach), and a combination of both (combined approach). The inferred transmission trees were then compared to those from the contact tracing investigations. Inference methods using individual data sources (i.e. the phylogenetic analysis and the epidemiological approach) were insufficiently informative to accurately reconstruct the transmission trees and the direction of transmission. The combined approach was able to identify a reduced pool of infectors for each case and highlight likely connections among chains classified as independent by the contact tracing investigations. Overall, the transmissions identified by the contact tracing investigations agreed with the evolutionary history of the viral genomes, even though some cases appeared to be misclassified. Therefore, collecting genetic sequences during outbreak is key to supplement the information contained in contact tracing investigations. Although none of the methods we used could identify one unique infector per case, the combined approach highlighted the added value of mixing epidemiological and genetic information to reconstruct who infected whom. [ABSTRACT FROM AUTHOR]

Detailed characterization of severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) transmission across different settings can help design less disruptive interventions. We used real-time, privacy-enhanced mobility data in the New York City, NY and Seattle, WA metropolitan areas to build a detailed agent-based model of SARS-CoV-2 infection to estimate the where, when, and magnitude of transmission events during the pandemic's first wave. We estimate that only 18% of individuals produce most infections (80%), with about 10% of events that can be considered superspreading events (SSEs). Although mass gatherings present an important risk for SSEs, we estimate that the bulk of transmission occurred in smaller events in settings like workplaces, grocery stores, or food venues. The places most important for transmission change during the pandemic and are different across cities, signaling the large underlying behavioral component underneath them. Our modeling complements case studies and epidemiological data and indicates that real-time tracking of transmission events could help evaluate and define targeted mitigation policies. [ABSTRACT FROM AUTHOR]