skip to main content


Search for: All records

Creators/Authors contains: "Rife Magalis, Brittany"

Note: When clicking on a Digital Object Identifier (DOI) number, you will be taken to an external site maintained by the publisher. Some full text articles may not yet be available without a charge during the embargo (administrative interval).
What is a DOI Number?

Some links on this page may take you to non-federal websites. Their policies may differ from this site.

  1. Background: In the wake of the COVID-19 pandemic, scientists have scrambled to collect and analyze SARS-CoV-2 genomic data to inform public health responses to COVID-19 in real-time. Open-source phylogenetic and data visualization platforms for monitoring SARS-CoV-2 genomic epidemiology have rapidly gained popularity for their ability to illuminate spatial-temporal transmission patterns worldwide. However, the utility of such tools to inform public health decision-making for COVID-19 in real-time remains to be explored. Objective: The objective of this study was to convene experts in public health, infectious diseases, virology, and bioinformatics – many of whom were actively engaged in the COVID-19 response at the time of their participation – to discuss the application of phylodynamic tools to inform pandemic responses. Methods: A series of four virtual focus group discussions were hosted between June 2020 and June 2021, covering the pre- and post-variant and vaccination eras of the COVID-19 crisis. Audio recordings were transcribed verbatim, and an iterative, thematic qualitative framework was used for analysis. Results: Of the 41 individuals invited, 23 total participants (56.1%) agreed to participate. Across the four focus group sessions, 15 (65%) of the participants were female, 17 (74%) were white, and 5 (22%) were black. Participants were described as molecular epidemiologists (ME, n=9), clinician-researchers (n=3), infectious disease experts (ID, n=4), and public health professionals (PH) at the local (n=4), state (n=2), and federal (n=1) levels. Collectively, participants felt that successful uptake of phylodynamic tools relies on the strength of academic-public health partnerships. They called for interoperability standards in sequence data sharing and cited many resource issues that must be addressed, including timeliness and cost, in addition to improving issues related to sampling bias and the translation of phylodynamic findings into public health action. Conclusions: This was the first qualitative study to characterize the perspectives of key experts regarding the utility of phylodynamic tools for the public health response to COVID-19. The focus group participants identified key areas for improvement of existing and future phylogenetic and data visualization platforms for monitoring SARS-CoV-2 genomic epidemiology. This information is critical to both policymakers and developers as they consider how to handle existing and emerging SARS-CoV-2 variants during the ongoing crisis. 
    more » « less
  2. Luigi Martelli, Pier (Ed.)
    Abstract Summary TARDiS is a novel phylogenetic tool for optimal genetic subsampling. It optimizes both genetic diversity and temporal distribution through a genetic algorithm. Availability and implementation TARDiS, along with example datasets and a user manual, is available at https://github.com/smarini/tardis-phylogenetics 
    more » « less
  3. The dynamic nature of the SIV population during disease progression in the SIV/macaque model of AIDS and the factors responsible for its behavior have not been documented, largely owing to the lack of sufficient spatial and temporal sampling of both viral and host data from SIV-infected animals. In this study, we detail Bayesian coalescent inference of the changing collective intra-host viral effective population size ( N e ) from various tissues over the course of infection and its relationship with what we demonstrate is a continuously changing immune cell repertoire within the blood. Although the relative contribution of these factors varied among hosts and time points, the adaptive immune response best explained the overall periodic dynamic behavior of the effective virus population. Data exposing the nature of the relationship between the virus and immune cell populations revealed the plausibility of an eco-evolutionary mathematical model, which was able to mimic the large-scale oscillations in N e through virus escape from relatively few, early immunodominant responses, followed by slower escape from several subdominant and weakened immune populations. The results of this study suggest that SIV diversity within the untreated host is governed by a predator-prey relationship, wherein differing phases of infection are the result of adaptation in response to varying immune responses. Previous investigations into viral population dynamics using sequence data have focused on single estimates of the effective viral population size ( N e ) or point estimates over sparse sampling data to provide insight into the precise impact of immune selection on virus adaptive behavior. Herein, we describe the use of the coalescent phylogenetic frame- work to estimate the relative changes in N e over time in order to quantify the relationship with empirical data on the dynamic immune composition of the host. This relationship has allowed us to expand on earlier simulations to build a predator-prey model that explains the deterministic behavior of the virus over the course of disease progression. We show that sequential viral adaptation can occur in response to phases of varying immune pressure, providing a broader picture of the viral response throughout the entire course of progression to AIDS. 
    more » « less
  4. Abstract We investigated SARS-CoV-2 transmission dynamics in Italy, one of the countries hit hardest by the pandemic, using phylodynamic analysis of viral genetic and epidemiological data. We observed the co-circulation of multiple SARS-CoV-2 lineages over time, which were linked to multiple importations and characterized by large transmission clusters concomitant with a high number of infections. Subsequent implementation of a three-phase nationwide lockdown strategy greatly reduced infection numbers and hospitalizations. Yet we present evidence of sustained viral spread among sporadic clusters acting as “hidden reservoirs” during summer 2020. Mathematical modelling shows that increased mobility among residents eventually catalyzed the coalescence of such clusters, thus driving up the number of infections and initiating a new epidemic wave. Our results suggest that the efficacy of public health interventions is, ultimately, limited by the size and structure of epidemic reservoirs, which may warrant prioritization during vaccine deployment. 
    more » « less
  5. Abstract Background

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant has caused a dramatic resurgence in infections in the United Sates, raising questions regarding potential transmissibility among vaccinated individuals.

    Methods

    Between October 2020 and July 2021, we sequenced 4439 SARS-CoV-2 full genomes, 23% of all known infections in Alachua County, Florida, including 109 vaccine breakthrough cases. Univariate and multivariate regression analyses were conducted to evaluate associations between viral RNA burden and patient characteristics. Contact tracing and phylogenetic analysis were used to investigate direct transmissions involving vaccinated individuals.

    Results

    The majority of breakthrough sequences with lineage assignment were classified as Delta variants (74.6%) and occurred, on average, about 3 months (104 ± 57.5 days) after full vaccination, at the same time (June-July 2021) of Delta variant exponential spread within the county. Six Delta variant transmission pairs between fully vaccinated individuals were identified through contact tracing, 3 of which were confirmed by phylogenetic analysis. Delta breakthroughs exhibited broad viral RNA copy number values during acute infection (interquartile range, 1.2-8.64 Log copies/mL), on average 38% lower than matched unvaccinated patients (3.29-10.81 Log copies/mL, P < .00001). Nevertheless, 49% to 50% of all breakthroughs, and 56% to 60% of Delta-infected breakthroughs exhibited viral RNA levels above the transmissibility threshold (4 Log copies/mL) irrespective of time after vaccination.

    Conclusions

    Delta infection transmissibility and general viral RNA quantification patterns in vaccinated individuals suggest limited levels of sterilizing immunity that need to be considered by public health policies. In particular, ongoing evaluation of vaccine boosters should specifically address whether extra vaccine doses curb breakthrough contribution to epidemic spread.

     
    more » « less