Minnesota's disease detectives are using the changing genomics of the coronavirus that causes COVID-19 to track outbreaks across the state to identify their sources.

Mutations in the SARS-CoV-2 virus create genomic fingerprints, which have been used to show that a single person likely sparked a COVID-19 outbreak at a bar in Minneapolis, and another started the spread of virus at a campground concert in southwestern Minnesota. Working backward, the state public health lab also found that outbreaks at a correctional facility and long-term care center were linked to employees at each who lived together.

"It provides the ultimate viral mutation surveillance and it can provide clearer answers to understand outbreaks," said Sean Wang, a sequencing and bioinformatics supervisor at the state's lab in St. Paul.

State epidemiologists hope to advance the science of genomic sequencing — the ordering of genetic material that makes up an organism's unique DNA — so they can provide the same kind of real-time information about COVID-19 outbreaks as they can about the causes of foodborne illnesses.

Genetic information from lab samples of salmonella-infected patients, for example, traced a national outbreak with 18 Minnesota cases this summer to red onions.

Genomic sequencing already can answer historical questions about how SARS-CoV-2 arrived here after it was discovered in Wuhan, China, last winter. Sequencing showed that the virus split into subtypes, or clades, that spread across Asia and Europe.

Wang said the United States has "a little bit of everything," but that the virus arrived in Minnesota via Europe, New York, California, and Washington state. Wang said studies have found the Europe version spreads faster but doesn't cause more severe illness.

Long-term care clusters

Minnesota's sequencing work was highlighted Friday by the U.S. Centers for Disease Control and Prevention for detailing how the virus wreaked havoc in two Twin Cities long-term care facilities.

The report validated universal testing of all residents and staff to help get control of outbreaks — as sequencing revealed infection clusters of residents but also support workers who had little contact with them. Testing between the two facilities found infections in 64% of 259 residents, and 33% of 341 workers.

The state has reported 1,963 COVID-19 deaths and 88,721 infections confirmed by diagnostic testing. That includes 13 deaths — eight of whom were residents of long-term care and assisted-living facilities — and 924 infections reported on Saturday.

Practical obstacles prevent the complete mapping of viral spread in Minnesota with genomic sequencing. Some labs don't save nasal or throat swab samples from infected patients, which are needed to conduct sequencing. The state lab uses samples from its testing, and from the University of Minnesota and Mayo Clinic.

Beyond that, many people carry the virus and spread it in the absence of symptoms that would motivate them to seek testing. If an asymptomatic and untested person starts an outbreak, "then you're missing the initial link for the transmission chain," Wang said.

Sequencing is important for understanding how individual outbreaks start, said Dr. Nick Lehnertz, a medical director for infectious disease epidemiology at the Minnesota Department of Health. In a long-term care facility, it's helpful to know if an outbreak starts with one person or if the virus finds its way in through multiple entry points.

"It's adding another layer of understanding so that we can say, 'Hey, it's not like multiple exposures are needed in long-term care facilities,' " he said. "You can have these outbreaks with a single exposure. It provides supportive evidence to say, 'Hey, keep vigilant. It only takes a single individual to result in these horrible outbreaks.' "

One long-term care outbreak in the Twin Cities primarily involved staff members who were identified early and quarantined at home.

One became symptomatic along with a housemate who worked in a correctional facility. Sequencing then found identical genomic signatures in their COVID-19 infections and those of roughly 30 people at the correctional facility.

The campground concert outbreak in July was interesting to health officials because so much viral transmission occurred in the outdoors despite good airflow to reduce that threat.

Identical genomic sequences in a dozen cases revealed what was likely a "superspreader event" of one highly infectious person spreading the virus to others in proximity who weren't wearing masks, Lehnertz said.

Fall surge concerns

The level at which genetic mutations are taking place bodes well for vaccine development, because mutations so far appear to be "neutral," Wang said, affecting the genetic building blocks of the virus but not its proteins or behaviors. That means one vaccine could work against the virus that has also showed a slow rate of mutation.

"It is definitely a good thing for us in terms of vaccine design and vaccine development," Wang said, "that we do not have to deal with a fast-mutating virus, which could be disastrous."

State health officials have noted a surprising level of steady but manageable growth in COVID-19 cases over the past month, but remain concerned about a delayed surge after the Labor Day weekend and the resumption of K-12 and college classes.

A particular concern is that 36% of infections in communities come from unknown sources that can't be traced as part of contact investigations to notify others of exposure risks. That is a key rate for state health officials and Gov. Tim Walz as he weighs decisions about business and social distancing restrictions — because it indicates a level of viral spread that is beyond the state's tracking.

Genomic sequencing isn't as helpful in the current scenario, because identifying one chain of transmission doesn't reduce risks when the virus is so widespread, said Sara Vetter, interim assistant director of the state public health lab.

When testing resources are abundant, and COVID-19 cases are coming in individual flare-ups, then sequencing could become a valuable real-time tool to prevent further exponential growth of outbreaks.

For now, Wang said its value is taking a foggy picture of a local outbreak and making it clear for state epidemiologists.

"They know there are cases out there, but they don't know what's going on exactly," he said. "Whole genomic sequencing can change the foggy glass to a clear glass."