Faculty at Northern Arizona University (NAU), the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, University of Arizona and Arizona State University launched the ACGU in early April with the express purpose of tracking the causative agent of COVID-19, SARS-CoV-2: How it evolves and how it spreads into, within and out of Arizona.<\/p>\n
The ACGU sequenced the SARS-CoV-2 genomes in as many virus-positive patient samples in Arizona as possible. Working with Arizona\u2019s public health officials, they applied the results toward statewide efforts to test and track patients, as well as provide guidance for Arizona public policymakers.<\/p>\n
Quick action by ASU and Maricopa County public health officials, ACGU scientists agree, likely kept the first identified COVID-19 patient in Arizona\u2014a student who had just returned from Hubei, the Chinese province where the disease originated\u2014from igniting an outbreak, and prevented Arizona from becoming an early epicenter for the contagion.<\/p>\n
\u201cThis is a great example of how a rapid and thorough public health response can be successful in preventing the spread of this disease,\u201d said Paul Keim<\/strong>, ACGU co-founder and director, NAU Regents\u2019 Professor of biological sciences and Cowden Endowed Chair in microbiology and executive director of NAU\u2019s Pathogen and Microbiome Institute<\/a> (PMI). Seven additional PMI scientists also contributed to this study as co-first authors or co-authors.<\/p>\n \u201cSimilar steps could be taken when shaping future efforts to reopen businesses and schools, even though the virus continues to circulate and people remain susceptible,\u201d added Keim, who is also a distinguished professor and co-director of TGen\u2019s Pathogen and Microbiome Division.<\/p>\n Michael Worobey, an ACGU co-founder and the head of University of Arizona\u2019s Department of Ecology and Evolutionary Biology, agrees.<\/p>\n \u201cIt\u2019s a combination of the patient doing the right things to isolate himself and be aware that he possibly had this disease, and public health officials doing all the right things. Stopping an incursion of COVID-19 was a victory for the state of Arizona,\u201d Worobey said.<\/p>\n This bought Arizona valuable time for preparedness efforts. The first reported case of community transmission, which occurred in Arizona in early March, was descended from the Washington state outbreak discovered in February. More than 80 percent of the SARS-CoV-2 genome sequences from Arizona COVID-19 cases descended from at least 11 separate lineages that were initially circulating widely in Europe, and by travel have since dominated the outbreak throughout the U.S. None of the observed transmission clusters are epidemiologically linked to the original travel-related case in the Arizona, suggesting successful early isolation and quarantine.<\/p>\n The ACGU uses state-of-the-art sequencers, custom computational analysis workflows and supercomputers to determine the sequence of the virus\u2019s RNA genome, which is just under 30,000 bases long. In contrast, there are nearly 3 billion bases in the human genome, which determine traits as simple as eye and hair color, and as complex as an individual\u2019s propensity for cancer and other diseases.<\/p>\n TGen has so far sequenced SARS-CoV-2 genomes from almost 3,000 COVID-19 positive samples for the ACGU, and additional sequencing was performed at ASU and UArizona, from among the more than 200,000 positive cases in Arizona, making it one of the most robust efforts in the nation. ACGU receives Arizona samples collected by state, county, tribal and private health care systems.<\/p>\n With the massive amount of data generated through the genomic sequencing, even the most advanced computing resources would not be able to keep pace; custom software was developed to support the ACGU work. Caporaso\u2019s team has released the new software under an open source license, which is free for all use as a contribution to global coronavirus research; see this paper<\/a> describing the software.<\/p>\n \u201cIntegrating the SARS-CoV-2 genomes sequenced from patients in Arizona with those sequenced around the world required us to work quickly to develop new software to support our work,\u201d said Greg Caporaso<\/strong>, NAU associate professor of biology and director of PMI\u2019s Center for Applied Microbiome Science. \u201cOur new software allows us to identify a highly informative subset of the globally available genomes to analyze, which make the analysis more computationally tractable while retaining information that is essential for contextualizing the Arizona sequences.\u201d<\/p>\n ACGU scientists take advantage of small changes or mutations in the virus\u2019 genome, which naturally occur over time as the virus reproduces, to track the spread of the virus. By comparing mutations observed in Arizona to those present in strains circulating across the globe, they can determine when and from where the virus has been introduced to Arizona.<\/p>\n Crystal Hepp<\/strong>, NAU assistant professor in the School of Informatics, Computing, and Cyber Systems<\/a> and assistant director of PMI, noted, \u201cThe rate that mutations accumulate in the virus or viral population can be used as a \u2018molecular clock\u2019 to understand when it arrived in Arizona and to further estimate the magnitude of the outbreak.\u201d The ACGU researchers found that the majority of Arizona sequences are represented by two lineages and several sub-lineages, most of which were likely introduced through domestic travel, but with some evidence for international importation.<\/p>\n Jason Ladner<\/strong>, NAU assistant professor of biology and assistant director of PMI, used similar analysis on the Ebola outbreak in West Africa. He said, \u201cevolutionary analysis of disease outbreaks is one of the most important tools for understanding the origins of new viruses, like this novel coronavirus. Applying this technology to Arizona gives us local insights into how the disease has been spreading and what interventions will likely be most beneficial to control the spread of the virus.\u201d<\/p>\n \u201cThrough the ACGU, we are harnessing expertise in virology, genomics, evolution and bioinformatics from throughout Arizona in order to rapidly distill these genomic data into actionable insights that can complement the state\u2019s public health response,\u201d Keim said. \u201cThese results demonstrate the power of public health contact tracing and self-isolation following a positive test for stemming the tide of infections moving forward.\u201d<\/p>\n David Engelthaler, director of TGen North in Flagstaff, which includes the institute\u2019s infectious disease branch, said the initial ACGU findings show how each community and each state is writing its own story for what is happening in the COVID-19 pandemic.<\/p>\n \u201cWe need to understand all of those plot lines that have led to where we are now,\u201d said Engelthaler, an ACGU co-founder. \u201cOnce this disease was detected in Arizona on Jan. 26, public health officials immediately jumped in to make sure that all contacts were identified, samples were collected and the patient was watched very closely for the next couple of weeks to make sure there were not any more cases.\u201d<\/p>\n In the coming months, he said, it will be necessary to track COVID-19 outbreaks and build epidemiological walls around each case, especially for those most at risk: Persons older than 65, those in long-term care facilities, prisons and those with pre-existing health problems.<\/p>\n \u201cWhen you don\u2019t have eyes on this, when you don\u2019t have contact tracing, then it can really easily move from person-to-person,\u201d Engelthaler said. \u201cIt\u2019s really useful for public policymakers to be making locally informed decisions.\u201d<\/p>\n Efrem Lim, a virologist who leads the ASU team, said the SARS-CoV-2 genome sequence data can give health care providers and public policy makers an edge in fighting the pandemic.<\/p>\n \u201cTracking the transmission of the virus and its mutations ensures that therapeutics and vaccines being developed are on the right course,\u201d said Lim, an assistant professor at ASU\u2019s Biodesign Institute. \u201cWe now have a handle on what the SARS-CoV-2 virus in our communities looks like at the sequence level.\u201d<\/p>\n This study, \u201cAn Early Pandemic Analysis of SARS-CoV-2 Population Structure and Dynamics in Arizona<\/a>,\u201d was supported by The NARBHA Institute, Flinn Foundation, The Virginia G. Piper Charitable Trust, Blue Cross and Blue Shield of Arizona, the National Institutes of Health, the David and Lucile Packard Foundation, the University of Arizona College of Science and Office of Research Innovation and Impact and BIO5 Institute.<\/p>\n The authors acknowledge the critical role the Arizona Department of Health Services and multiple county and tribal health departments play in directing samples to the ACGU to be sequenced. Computational analyses were run on Northern Arizona University\u2019s Monsoon high-performance computing cluster, funded by Arizona\u2019s Technology and Research Initiative Fund. Software development efforts were funded in part by the Chan-Zuckerberg Initiative and the Alfred P. Sloan Foundation. Additional analysis effort was funded under the State of Arizona Technology and Research Initiative Fund (TRIF), administered by the Arizona Board of Regents, through NAU. The Cowden Endowment for Microbiology provided funds to support salaries.<\/p>\n
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