Application of Phylodynamic Tools to Inform the Public Health Response to COVID-19: Qualitative Analysis of Expert Opinions.

BACKGROUND: In the wake of the SARS-CoV-2 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 aim of this study is to convene experts in public health, infectious diseases, virology, and bioinformatics-many of whom were actively engaged in the COVID-19 response-to discuss and report on the application of phylodynamic tools to inform pandemic responses. METHODS: In total, 4 focus groups (FGs) occurred between June 2020 and June 2021, covering both the pre- and postvariant strain emergence and vaccination eras of the ongoing COVID-19 crisis. Participants included national and international academic and government researchers, clinicians, public health practitioners, and other stakeholders recruited through purposive and convenience sampling by the study team. Open-ended questions were developed to prompt discussion. FGs I and II concentrated on phylodynamics for the public health practitioner, while FGs III and IV discussed the methodological nuances of phylodynamic inference. Two FGs per topic area to increase data saturation. An iterative, thematic qualitative framework was used for data analysis. RESULTS: We invited 41 experts to the FGs, and 23 (56%) agreed to participate. Across all the FG sessions, 15 (65%) of the participants were female, 17 (74%) were White, and 5 (22%) were Black. Participants were described as molecular epidemiologists (MEs; n=9, 39%), clinician-researchers (n=3, 13%), infectious disease experts (IDs; n=4, 17%), and public health professionals at the local (PHs; n=4, 17%), state (n=2, 9%), and federal (n=1, 4%) levels. They represented multiple countries in Europe, the United States, and the Caribbean. Nine major themes arose from the discussions: (1) translational/implementation science, (2) precision public health, (3) fundamental unknowns, (4) proper scientific communication, (5) methods of epidemiological investigation, (6) sampling bias, (7) interoperability standards, (8) academic/public health partnerships, and (9) resources. Collectively, participants felt that successful uptake of phylodynamic tools to inform the public health response relies on the strength of academic and public health partnerships. They called for interoperability standards in sequence data sharing, urged careful reporting to prevent misinterpretations, imagined that public health responses could be tailored to specific variants, and cited resource issues that would need to be addressed by policy makers in future outbreaks. CONCLUSIONS: This study is the first to detail the viewpoints of public health practitioners and molecular epidemiology experts on the use of viral genomic data to inform the response to the COVID-19 pandemic. The data gathered during this study provide important information from experts to help streamline the functionality and use of phylodynamic tools for pandemic responses.

Persistence of SARS-CoV-2 omicron variant in children and utility of rapid antigen testing as an indicator of culturable virus.

We screened 65 longitudinally-collected nasal swab samples from 31 children aged 0-16 years who were positive for SARS-CoV-2 omicron BA.1. By day 7 after onset of symptoms 48% of children remained positive by rapid antigen test. In a sample subset we found 100% correlation between antigen test results and virus culture.

Multi-Faceted Approach to COVID-19 Surveillance at a Large University Campus in the Southeastern United States.

The coronavirus disease 2019 (COVID-19) pandemic continues to present unique public health challenges both within the United States and across the globe. Institutions of higher learning are tasked with preventing and responding to COVID-19 on campus while also considering implications for the surrounding communities. The process of re-opening campus, whether at full or partial capacity, has tasked these institutions with overcoming complex challenges associated with balancing the resumption of campus operations while simultaneously protecting university affiliates and surrounding community members from COVID-19 through robust surveillance, contact tracing, and testing efforts. Here, we provide a concise outline related to the development and implementation of the comprehensive and sustainable COVID-19 surveillance program at the University of Florida. We also critically discuss the successes and pitfalls of this program while also providing recommendations for the development of similar programs in the future.

Evaluation of screen, test, & protect: A public health program to control and prevent COVID-19 at a large academic university.

Background: We evaluate the public health surveillance program, Screen, Test, and Protect (STP) designed to control and prevent COVID-19 at a large academic university in the United States. Methods: STP was established at the University of Florida in May 2020. This report details STP's full-time workforce, centralized database, and testing and vaccination programs. We evaluate the program's success in controlling COVID-19 during the 2020-2021 academic school year. Results: COVID-19 cases rose among the campus community in the first few weeks of campus reopening in Fall 2020. Test positivity levels returned to prefall semester levels within one month, however. A few additional, yet smaller, waves occurred during the 2020-2021 school year and were successfully controlled without any campus-wide closures. Conclusions: This program may serve as a framework for other institutions managing the ongoing COVID-19 crisis, in addition to setting the standard for programmatic management of future emerging infectious diseases at universities.

Severe Acute Respiratory Syndrome Coronavirus 2 Delta Vaccine Breakthrough Transmissibility in Alachua County, Florida.

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 ±â€…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.

Low-frequency variants in mildly symptomatic vaccine breakthrough infections presents a doubled-edged sword.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) has raised questions regarding vaccine protection against SARS-CoV-2 infection, transmission, and ongoing virus evolution. Twenty-three mildly symptomatic "vaccination breakthrough" infections were identified as early as January 2021 in Alachua County, Florida, among individuals fully vaccinated with either the BNT162b2 (Pfizer) or the Ad26 (Janssen/J&J) vaccines. SARS-CoV-2 genomes were successfully generated for 11 of the vaccine breakthroughs, and 878 individuals in the surrounding area and were included for reference-based phylogenetic investigation. These 11 individuals were characterized by infection with VOCs, but also low-frequency variants present within the surrounding population. Low-frequency mutations were observed, which have been more recently identified as mutations of interest owing to their location within targeted immune epitopes (P812L) and association with increased replicative capacity (L18F). We present these results to posit the nature of the efficacy of vaccines in reducing symptoms as both a blessing and a curse-as vaccination becomes more widespread and self-motivated testing reduced owing to the absence of severe symptoms, we face the challenge of early recognition of novel mutations of potential concern. This case study highlights the critical need for continued testing and monitoring of infection and transmission among individuals regardless of vaccination status.

Observed Face Mask Use at Six Universities - United States, September-November 2020.

Approximately 41% of adults aged 18-24 years in the United States are enrolled in a college or university (1). Wearing a face mask can reduce transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (2), and many colleges and universities mandate mask use in public locations and outdoors when within six feet of others. Studies based on self-report have described mask use ranging from 69.1% to 86.1% among adults aged 18-29 years (3); however, more objective measures are needed. Direct observation by trained observers is the accepted standard for monitoring behaviors such as hand hygiene (4). In this investigation, direct observation was used to estimate the proportion of persons wearing masks and the proportion of persons wearing masks correctly (i.e., covering the nose and mouth and secured under the chin*) on campus and at nearby off-campus locations at six rural and suburban universities with mask mandates in the southern and western United States. Trained student observers recorded mask use for up to 8 weeks from fixed sites on campus and nearby. Among 17,200 observed persons, 85.5% wore masks, with 89.7% of those persons wearing the mask correctly (overall correct mask use: 76.7%). Among persons observed indoors, 91.7% wore masks correctly. The proportion correctly wearing masks indoors varied by mask type, from 96.8% for N95-type masks and 92.2% for cloth masks to 78.9% for bandanas, scarves, and similar face coverings. Observed indoor mask use was high at these six universities with mask mandates. Colleges and universities can use direct observation findings to tailor training and messaging toward increasing correct mask use.