Tracing the genetic evolution of SARS-CoV-2, the virus that causes COVID-19, is crucial for detecting and responding to emerging variants. A team of scientists within Mayo Clinic's COVID-19 Sequencing Command Center is at the forefront of the extensive research and surveillance operation, conducting nearly 750 sequences of the COVID-19 virus each week.
"Our overarching goal is to conduct impactful scientific research through genomic sequencing to improve patient care, inform the development of therapeutics, advise hospital epidemiology, and serve our communities and people around the world," says Bobbi Pritt, M.D., who oversees the COVID-19 Sequencing Command Center and directs Mayo Clinic's Division of Clinical Microbiology.
Dr. Pritt says the genetic sequencing data gives her team insight for:
In addition, Dr. Pritt says sharing sequencing information into publicly available databases can help public health officials better understand outbreaks and make informed decisions.
"COVID-19, like the flu, is an RNA virus, which means it's more prone to mutating as it makes copies of itself and injects those copies into other cells in the body," Dr. Pritt explains. "It is likely to continue its evolution as it infects people and replicates. But that doesn't mean those variants are all going to be important, and it doesn't mean they're going to stick around."
Mayo Clinic's COVID-19 Biobank boosts genomic research
A key resource in the ongoing investigation is Mayo Clinic's COVID-19 biobank, which was quickly mobilized at the pandemic's start. The vast library of COVID-19-positive biospecimens, which were contained with patient consent ― including nasal swabs, serum, plasma, blood, urine and stool samples, as well as corresponding clinical and patient-provided data ― is helping scientists advance the understanding of the virus.
For Dr. Pritt and her team, the biobank is essential for analyzing samples in real time and going back in time to scour the virus's genetic code from early on in the pandemic.
Overseeing the sequencing process and deciding which samples to analyze is Andrew Norgan, M.D., Ph.D., a Mayo Clinic pathologist and medical microbiologist.
"In our lab-intensive process, we extract the RNA genetic code, inactivate it and make millions of copies using polymerase chain reaction, or PCR," Dr. Norgan explains. "Next, we sequence those millions of small pieces of the virus and use computer algorithms to put them together into one viral sequence. We can then look for changes from the first original sequence strain of the virus to determine if it's an existing strain or if it might be something completely new."
Dr. Norgan says the emergence of the new and highly transmissible omicron variant, with its significant mutations, shows the power of the virus.
"As the virus tries to find a way to survive in an environment where some people are vaccinated and some people are not, and more people are moving around and traveling, we're finding the virus is less and less predictable," Dr. Norgan says.
Biospecimens provide clues on COVID-19 disease severity
The COVID-19 biobank serves dozens of other Mayo Clinic scientists who are working to improve patient outcomes by identifying and understanding the unique factors contributing to disease severity.
Each biosample, stored in large, minus 80 degree Fahrenheit freezers, holds potentially valuable information about SARS-CoV-2 and the pathology of COVID-19. For example, blood contains DNA, antibodies, serum and plasma that could provide information about a person's immune response and susceptibility.
Konstantinos Lazaridis, M.D., the Carlson and Nelson Endowed Executive Director for Mayo Clinic's Center for Individualized Medicine, is leading his team in exploring which genes influence disease outcomes.
"Our aim is to answer questions about the potential genetic predisposition of developing the infection and the long-term outcomes of the disease," Dr. Lazaridis says. "We may be in a position to say why some patients with COVID-19 develop blood clots or a severe inflammatory reaction. Or why some patients have neurologic impairment while others show no symptoms at all."
The team is studying stool samples to possibly reveal how the virus is affected by the microbiome — the trillions of microbes living inside the digestive system that regulate various bodily functions.
"The microbiome may be an important determinant in severity of symptoms, as well as the pace and degree of recovery, explains Purna Kashyap, M.B.B.S., the Bernard and Edith Waterman co-director of Mayo Clinic's Center for Individualized Medicine Microbiome Program.
The ongoing COVID-19 research efforts are expected to continue until the pandemic ends, according to Dr. Pritt.
"We're not out of the woods yet. We need to get as many people vaccinated as possible, and we have to maintain those preventive measures: mask-wearing, social distancing, not gathering in large groups," Dr. Pritt says. "We haven't seen this scale of a pandemic in more than a century, and we need people to understand that."
The ability to scale sequencing so quickly involved teamwork from the Advanced Diagnostics Laboratory led by Benjamin Kipp, MD, the Medical Genome Facility led by Eric Wieben, PhD, and the Hepatitis and HIV Laboratory led by Dr. Joseph Yao, MD.
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Tags: center for individualized medicine, covid-19, Dr. Konstantinos Lazaridis, Dr. Purna Kashyap, Genetic Sequencing, genomic medicine, Multi-omics, Precision Medicine, Research, sequencing