Phylodynamics of a regional SARS-CoV-2 rapid spreading event in Colorado in late 2020.

Since the initial reported discovery of SARS-CoV-2 in late 2019, genomic surveillance has been an important tool to understand its transmission and evolution. Here, we sought to describe the underlying regional phylodynamics before and during a rapid spreading event that was documented by surveillance protocols of the United States Air Force Academy (USAFA) in late October-November of 2020. We used replicate long-read sequencing on Colorado SARS-CoV-2 genomes collected July through November 2020 at the University of Colorado Anschutz Medical campus in Aurora and the United States Air Force Academy in Colorado Springs. Replicate sequencing allowed rigorous validation of variation and placement in a phylogenetic relatedness network. We focus on describing the phylodynamics of a lineage that likely originated in the local Colorado Springs community and expanded rapidly over the course of two months in an outbreak within the well-controlled environment of the United States Air Force Academy. Divergence estimates from sampling dates indicate that the SARS-CoV-2 lineage associated with this rapid expansion event originated in late October 2020. These results are in agreement with transmission pathways inferred by the United States Air Force Academy, and provide a window into the evolutionary process and transmission dynamics of a potentially dangerous but ultimately contained variant.

Engage, understand, listen and act: evaluation of Community Panels to privilege First Nations voices in pandemic planning and response in Australia.

INTRODUCTION: First Nations Peoples of Australia have not been included in the development nor prioritised in pre-2009 pandemic plans despite being a priority population in Australian health policy. Marginalised groups experience amplified barriers and systemic disadvantage in emergencies, however, their voices have not been heard in past pandemic responses. Through effective engagement with disadvantaged and oppressed groups, health authorities can gain a deeper understanding of how to design and implement pandemic control strategies. There have been limited studies with First Nations Peoples that has focused on pandemic planning and response strategies. Deliberative inclusive approaches such as citizens juries have been a way to uncover public perceptions. METHODS: Qualitative thematic research methods were used to conduct the study. We convened five First Nations Community Panels in three locations in Australia between 2019 and 2020. We used an Indigenist research approach, community-based Participatory Action Research framework and 'yarning' to understand whether Community Panels were an acceptable and appropriate way of engaging First Nations Peoples. Forty First Nations participants were purposively recruited through local and cultural networks. Panels heard evidence supporting various pandemic response strategies, and cross-questioned public health experts. RESULTS: All 40 participants from the 5 panels verbally indicated strong support of the Community Panels approach as an effective way of engaging First Nations Peoples in making decisions about pandemic planning and response strategies. The main theme of 'respect' centred on the overarching principle that First Nations Peoples are important in the context of continuation of culture and ongoing political resistance. CONCLUSION: First Nations Community Panels are a way of enabling active participation of First Nations peoples, increasing knowledge and understanding, and a way for government and policymakers to respectfully listen to First Nations opinions and values.

Host methylation predicts SARS-CoV-2 infection and clinical outcome.

BACKGROUND: Since the onset of the SARS-CoV-2 pandemic, most clinical testing has focused on RT-PCR1. Host epigenome manipulation post coronavirus infection2-4 suggests that DNA methylation signatures may differentiate patients with SARS-CoV-2 infection from uninfected individuals, and help predict COVID-19 disease severity, even at initial presentation. METHODS: We customized Illumina's Infinium MethylationEPIC array to enhance immune response detection and profiled peripheral blood samples from 164 COVID-19 patients with longitudinal measurements of disease severity and 296 patient controls. RESULTS: Epigenome-wide association analysis revealed 13,033 genome-wide significant methylation sites for case-vs-control status. Genes and pathways involved in interferon signaling and viral response were significantly enriched among differentially methylated sites. We observe highly significant associations at genes previously reported in genetic association studies (e.g. IRF7, OAS1). Using machine learning techniques, models built using sparse regression yielded highly predictive findings: cross-validated best fit AUC was 93.6% for case-vs-control status, and 79.1%, 80.8%, and 84.4% for hospitalization, ICU admission, and progression to death, respectively. CONCLUSIONS: In summary, the strong COVID-19-specific epigenetic signature in peripheral blood driven by key immune-related pathways related to infection status, disease severity, and clinical deterioration provides insights useful for diagnosis and prognosis of patients with viral infections.

Viral infections affect the body in many ways, including via changes to the epigenome, the sum of chemical modifications to an individual's collection of genes that affect gene activity. Here, we analyzed the epigenome in blood samples from people with and without COVID-19 to determine whether we could find changes consistent with SARS-CoV-2 infection. Using a combination of statistical and machine learning techniques, we identify markers of SARS-CoV-2 infection as well as of severity and progression of COVID-19 disease. These signals of disease progression were present from the initial blood draw when first walking into the hospital. Together, these approaches demonstrate the potential of measuring the epigenome for monitoring SARS-CoV-2 status and severity.