Genomics researchers at Northern Arizona University, University of Arizona and the Translational Genomics Research Institute (TGen) have formed the Arizona COVID-19 Genomics Union to track the coronavirus's origins and impacts.
The collaboration offers unique advantages in studying such a stealthy pathogen.
"You start to get this picture of how these viruses are moving, spreading, starting local epidemics, how often new things are jumping to a new area and taking off, how often you just have a sort of one-off dead end," said Michael Worobey, who heads UA's Ecology and Evolutionary Biology department.
Genomics experts study the structure, function and evolution of an organism's complete set of genes, or genome.
Tools that allow researchers to sequence large quantities of DNA or RNA at once have transformed genomics over the past 15 years into an epidemiological powerhouse. From its time in the wings studying rare conditions, the field has moved to center stage, offering better estimates of heritability and environmental risk factors.
Indeed, genomic epidemiology was instrumental in tracking the family tree and transmission paths of the severe acute respiratory syndrome virus (SARS), and researchers have applied related methods to bird flu and human influenza.
As an expert in using evolutionary biology to study viruses like influenza and HIV, Worobey knows firsthand the value of genomic epidemiology in tracing their timing, relationships and spread.
"These genomes are telling us, before we took really extensive measures statewide, this virus was already established and transmitting successfully in a transmission chain," he said.
COVID-19's ability to spread while people lack symptoms means traditional epidemiological methods, like monitoring hospitalizations and deaths, can lag weeks behind.
Genomics can fill in important blanks, provided researchers have the computational power.
"And so, the investment that the state of Arizona has put into that infrastructure is really critical in this crisis," said pathogen genomics expert Paul Keim of NAU and TGen North.
It also takes a lot of data.
"We are receiving samples regularly, multiple times a week, coming in from the state lab and also from other testing labs," said David Engelthaler, who co-directs TGen's Pathogen and Microbiome Division with Paul Keim.
COVID-19 uses RNA as its genetic material. Unlike DNA, which consists of the nucleotide bases adenine, thymine, cytosine and guanine (A-T-C-G), RNA comprises adenine, uracil, cytosine and guanine (A-U-C-G).
Researchers extract this genetic material to spell out and encode the virus's base alphabet. This process often involves a PCR thermal cycler, which uses polymerase chain reactions to copy genic material multiple times — a process known as amplification.
The structure is then summarized, or sequenced.
"It's digitizing the RNA; it's turning that A's, G's, C's and U's, in this case, into ones and zeros," said Engelthaler.
The union shares their results with other researchers, including the Centers for Disease Control and Prevention and other partners around the country and the world.
Keim emphasized the importance of such collaboration — and transparency.
"You know, the last thing we want is for the Chinese government to tell us about what's happening. We want to be able to look at the data and understand it ourselves," he said.
For example, we now know the virus didn't roll across Arizona as a single strain.
"It's coming in in spurts and starts in different places. And we can track what states they're coming from, or what countries they seem to be most related to," said Engelthaler.
That differs from what occurred in Washington state. There, a single strain persisted and infected new hosts six weeks after the first COVID-19 case in the U.S. — well after the first host should no longer have been contagious.
Arizona has multiple transmission chains besides the main one.
"It's come in independently, and it looks like ultimately it has its roots in the European outbreak," said Worobey.
Such information can potentially improve public health responses, as Engelthaler explained.
"Public health is actually able to use that to see, do we need to put resources around this because there's a growing cluster? Or do we see that this a one-off case that didn't have any other subsequent cases tied to it?" he said.
Genomic methods also can help gauge the effectiveness of strategies like social distancing.
"So we're going to be able to look back and say, 'OK, over this last March, when things were growing without much social distancing, how fast was this epidemic moving?'" said Worobey.
Data describing the diverse virus strains in circulation also informs the development of therapies and vaccines. Currently, differences remain small — just a dozen or so mutations across 30,000 RNA nucleotide "letters" — but that could change.
"We're watching for it to see if these mutations are going to change our ability of our diagnostic tests to work and whether they have the potential to affect our vaccine strategies in the future," said Keim.
That's the upside of working with such a recently emerged virus.
"We're in this sweet spot where, if we do get to develop a vaccine, it's likely to work across every lineage and in the world," said Worobey.
But the window is closing.
"It's still not impossible that we could drive this thing into extinction. But it's getting less and less likely — and more likely that will establish itself as another virus like influenza that we have to be concerned about year to year," said Worobey.
If so — and if, as many experts believe, we'll see a fall or winter resurgence, with 80-90 percent of people lacking resistance — then officials will need to know as much as possible about the virus and its variants.
It sounds dire. But the researchers said we are lucky this virus struck at a time when we're equipped with the genomic methods needed to effectively analyze it.
Indeed, Engelthaler says we're witnessing "the creation of 21st century medicine."
"We're bringing genomics in to be able to empirically understand relationships between pathogens that before we were just using the best information to really guess at," he said.
For years, genomics has promised to revolutionize medicine. The coronavirus pandemic shows how it is already transforming our understanding, and response, to infectious disease.
