Susie Ning was vaccinated for COVID-19. So she was frustrated when, in August, she came down with a fever, chills and intense fatigue that lasted for two weeks.
Despite her two shots of Pfizer, she had been infected, a classic example of what experts call a breakthrough case.
While she was grateful that the vaccine kept her from being hospitalized, Ning still wanted to know which version of the virus was to blame for her serious symptoms.
“Since I was vaccinated, I was curious if it really was delta,” she said.
Other people have wondered the same thing. Dr. David Engelthaler, director of the Pathogen Genomics Division at the Translational Genomics Research Institute (TGen), said he has received “dozens” of phone calls from patients wanting to know the COVID-19 variant behind their positive test results.
For now, Ning and curious COVID-19 patients like her will have to wait for definitive answers. Arizonans are not yet able to see a test result that tells them which variant they have. That’s because researchers don’t tie any of the data about variants to individual results; it’s all anonymous. But an individual variant diagnosis may not be far off.
The technology researchers use to assess the landscape of COVID-19 variants across the region may one day allow doctors to provide more precise and personalized care. It may also help physicians and researchers to fight misinformation and increase transparency when they communicate with patients.
In the meantime, the population-level data almost certainly reveals the answers to Ning’s question.
After a summer of rising cases, TGen’s variant tracker shows that the delta variant has become dominant. Delta currently accounts for 99% of all the samples that TGen has tested.
“SARS-CoV-2 essentially can be called the delta virus right now,” Engelthaler said. “You could bet money that you have delta if you get infected.”
At the TGen North facility in Flagstaff, researchers use machines called sequencers to turn the thousands of letters of genetic code into data that can be analyzed outside the lab, a process Engelthaler calls “digitizing biology.”
Once the samples are digitized, computer scientists and mathematicians can analyze the specific makeup of each case. Every virus has a unique set of genetic instructions, spelled out in a long sequence of letters that stand for different molecular compounds. By lining up those letters in a computer program, researchers can compare thousands of positive COVID-19 tests to one another.
Dr. Angie Hinrichs maintains a database of about 4 million unique COVID-19 sequences and works on computer programs that help scientists make decisions about categorizing new samples, including Pangolin, which is used by TGen. Hinrichs, a bioinformatics professor at the University of California, Santa Cruz, explained that the computer scientists and epidemiologists who track variants watch the evolution of the virus in real time.
Each time the virus mutates, it creates a new branch on the COVID-19 family tree.
“That’s the same idea as the trees that Darwin sketched in his notebooks to show how different bird species were related by common ancestry,” Hinrichs said.
Unlike Darwin’s finches, the biggest challenge for Hinrich and her teams has been keeping up with the volume of data. One coronavirus sample contains about 30,000 letters of genetic code, and tens of thousands of those sequences are released by COVID-19 testing centers every day.
The process of sequencing a single genome used to take days, Hinrichs said. TGen North now sequences about a thousand virus samples per week (Arizona has been seeing about 2,500 new positive tests per day, according to a tracker from Johns Hopkins University). Machine learning allows researchers to place a particular sequence with its closest genetic relatives in seconds.
That information shows that while the delta variant is now almost universal in many parts of the world, most individual cases of delta show slight differences from one another. Eventually, if allowed to spread, those minor tweaks could give rise to an even stronger version of the variant.
The future of COVID-19 tracking: public health and personalized care
There are three ways variants can get stronger: They can grow deadlier, spread more easily (like delta), or evade vaccines, explained Dr. Erik McLaughlin, who is the medical director of Cochise Health and Social Services and an expert on variants and vaccine efficacy.
McLaughlin says it’s only a matter of time before a mutation gives the virus better abilities in one of those three areas — or worse, in all three areas.
The possibility of a new variant with higher mortality, transmission and breakthrough cases “keeps me up at night,” McLaughlin said.
Engelthaler believes that using genomic surveillance to keep watch on the variants will be a vital way to prevent future deadly outbreaks. He worries that from a public health perspective, “as the cases drop off, and we move on to some other emergency, that everything is going to be forgotten around (variant tracking).”
On a personalized level, the possibilities for using genomic sequencing as a tool for precision medicine are just beginning. Since the version of the virus does not affect which symptoms appear or which treatment patients receive, the FDA has not yet approved such variant tracking as a diagnostic tool. But McLaughlin believes that as the pandemic evolves, that will change.
“I know we’re going to see more variants, and I think this will be the norm of trying to identify what strain (people) have — a mild strain, a deadly strain,” said McLaughlin, adding that pockets of more dangerous variants may become endemic to certain regions. “I expect COVID testing to begin to include the specific strain or variant you have by the end of the year.”
Engelthaler also sees the applications for this technology in diseases beyond COVID-19.
“We’re hoping that pretty soon this becomes the standard of care, that we just sequence every single patient’s pathogen,” Engelthaler said.
In the meantime, said McLaughlin, communities need to reduce the number of chances the virus has to mutate.
“The best way to avoid all these variants that are scary and bad is to get vaccinated, wash your hands, wear your mask and stay far away from sick people,” he said.
Variants, vaccines, and vulnerable people
Dr. Sudha Nagalingam cares for vulnerable populations at El Rio Health, a non-profit health center with a network of clinics serving both insured and uninsured patients in Tuscon. Nagalingam, an infectious disease physician by training, runs the largest HIV clinic in Southern Arizona. When the pandemic hit, she found herself on the front lines of the clinic’s COVID-19 response, working as a partner with the state to support homeless and refugee populations.
Most days, she spends visit after visit trying to persuade people to take the vaccine. With the rise of the delta variant, the mission feels more urgent than ever, especially for her patients who are already immunocompromised. But trying to explain that urgency, she said, has been difficult.
“When it comes to the nuances of what the variants look like, I try to push that discussion, but sometimes I just get blank stares,” Nagalingam said. She tries to drive home that delta is a thousand times more transmissible than the original COVID-19 strain, but said there is a need for better information in the communities she serves.
While some of her colleagues’ patients are hyper-aware of variants and boosters, Nagalingam said that her patients are still on the level of “basic survival” when it comes to COVID-19. She described educating some to wear masks and to stay home when they are exhibiting symptoms, especially if they work in high-exposure areas like warehouses or commute to work on public transportation.
Some of her patients ask, “‘What’s the point (of getting vaccinated) if there’s another variant coming?’” Others express a sense of distrust in the government and in vaccines.
“I had to have that conversation, like, ‘Hey, this virus is disproportionately affecting people of color like you and me,’” Nagalingam said.
She partly blames social media misinformation for contributing to vaccine hesitancy, an issue McLaughlin also described. McLaughlin said that for some patients, he has had to debunk the idea that vaccines give rise to new variants when in reality widespread use of the vaccines decreases the probability of new variants arising.
“The potential (for mutation) is there every time (the virus) replicates in a new person,” he said.
McLaughlin said he and many of his colleagues hope individualized genomic sequencing tests will be approved by the FDA for direct patient care because he believes empowering patients with information is a key way to foster their trust in physicians. “As doctors, we always want to educate our patients, because an informed patient is the best kind of patient,” McLaughlin said.
But Nagalingam said even if precision COVID-19 testing becomes mainstream, ingrained systemic issues will remain the largest barrier. While community health clinics like El Rio have received funding to help support their COVID-19 testing and treatment, many patients still struggle to find transportation to get to appointments or lack WiFi for telehealth visits.
For now, she said she will continue to educate patients in her efforts to keep delta — and any of its future variations — at bay.
“I think it’s really important that healthcare providers sit down and talk with patients because there’s that level of trust,” Nagalingam said.
Independent coverage of bioscience in Arizona is supported by a grant from the Flinn Foundation.
Melina Walling is a bioscience reporter who covers COVID-19, health, technology, agriculture and the environment. You can contact her via email at firstname.lastname@example.org, or on Twitter @MelinaWalling.