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Detecting, Sequencing and Monitoring SARS-CoV-2 Virus Variants

Four scientists look at SARS-CoV-2 sequencing data.

By Melissa Schraeder, writer

Sequencing viruses has many purposes, two of which are for surveillance of circulating strains and for analyzing clusters. During the first several months of the COVID-19 pandemic, scientists were not focused on identifying potential variant strains partially because SARS-CoV-2—the virus that causes COVID-19—has a relatively slow mutation rate. That changed when variants of the virus began to appear in December 2020. Several public health laboratories, however, were already doing the important work of mapping the genomic baseline of the virus in order to analyze clusters and were fully prepared to pivot in the application of whole genome sequencing work to detect virus variants.

At the Minnesota Department of Health Public Laboratory Division (MDH), SARS-CoV-2 sequencing was performed from the very beginning of the COVID-19 pandemic. The first confirmed case of COVID-19 in the state of Minnesota was on March 6, 2020 and Sean Wang, PhD, DVM, supervisor of Sequencing and Bioinformatics, began sequencing SARS-CoV-2 samples on March 13, 2020. This early effort made Minnesota one of the first public health laboratories in the country to begin this process and share data with the public.

Initially, the goal of genetic sequencing was to analyze clustering and determine where the first cases had originated from geographically. Starting this process early provided valuable information about the spread of virus in the state but it also led to some tension as the need for Minnesota’s public health laboratory to do diagnostic testing continued to grow. Sara Vetter, PhD, D(ABMM), interim assistant laboratory director & CLIA director, indicated that it was crucial at this point to protect staff time devoted to sequencing work.

“We had to prioritize at the beginning of the pandemic,” Vetter explained. She remembers thinking and saying, “Yes, everything is going on around us and we have every excuse not to sequence, but we had a hunch that even though we didn’t have time, this would help us in the long run.”

Having the support of leadership who saw the value of genetic sequencing allowed Wang to ultimately identify the nation’s first case of the P.1 variant of the virus on January 25, 2021—the same day he was scheduled for his first COVID-19 vaccination.

Sean Wang, Minnesota Department of Health Public Laboratory Division, works in the laboratory.

“I felt surprised and excited, but I also needed to double-check to be sure that the data were correct,” Wang recalled. Vetter felt a sense of relief from anticipation.

“When we look for things, we find things,” she explained. “We were eager to take the next steps in communicating our findings and concerns with the public.”

At the Colorado Department of Public Health and Environment Laboratory (CDPHE), sequencing was not performed on SARS-CoV-2 virus until early September 2020, when there was finally sufficient staff capacity for both diagnostic testing and sequencing for surveillance. Initially, the goal was to look at cases of reinfected individuals as well as to examine the introduction and spread of the virus across the state.

Sarah Totten, DrPH, M(ASCP), CIC, CDPHE microbiology program manager,  explained that setting up sequencing processes in their lab was challenging. “Sequencing was always part of our plan,” she said. “But how to execute it in a laboratory that felt like it was full of chaos was a challenge.”

The sequencing team was built out of the diagnostic team as they became more efficient and processes were streamlined. Despite these staffing challenges, Shannon Matzinger, PhD, lead microbiology scientist, explained that very quickly her laboratory leadership, “recognized the value of analysis” through sequencing and informing the public about these findings.

Having just begun sequencing less than three months prior, on December 29, 2020 Matzinger identified the first case of the B.1.1.7 virus variant in the US. Matzinger was working from home examining results on her computer via Google Cloud Computing Resources funded by the US Centers for Disease Control and Prevention (CDC), thinking “it is just a matter of time” when she discovered the B.1.1.7 variant.

“I stared at the picture with a sense of trepidation and fascination,” she remembered. She then texted Totten and Emily Travanty, PhD, CDPHE’s scientific director, an image of the gene tree for the mutated virus with a simple caption: It’s here.

Travanty emphasized how important the timing of Matzinger’s discovery proved as many people were still participating in holiday celebrations, spending time with extended family, and feeling ready to move on from 2020 and into the new year. “The timely discovery of the B.1.1.7. variant allowed health department leadership in Colorado to bolster communication and get out the critical message that everyone needed to keep wearing masks and exercising caution.”

Strong communication networks proved invaluable to both MDH and CDPHE staff. Wang specified tight and frequent communication between epidemiologists and the laboratory as a key to success of his project. Travanty similarly pointed to a high level of coordination and engagement where her laboratory participates in daily meetings for real-time sharing of data with epidemiologists in Colorado. “Hospitals and clinical settings are now contacting CDPHE to participate in sequencing,” Totten added.

Minnesota and Colorado are continuing the use of sequencing for surveillance and detection of SARS-CoV-2 variants. Both laboratories have a target goal to sequence 5% of all positive cases in their state, although this will prove challenging if cases surge again and the need for diagnostic testing significantly increases.

So what have the public health laboratory teams in these two states learned from this experience with sequencing as a way to identify and monitor variants? Both lab teams have championed the value of devoting time to surveillance and analysis in the early stages of the pandemic and continuing to evolve the goals of their analyses.

“It is important to follow your gut and know when something matters,” Vetter said.  “We had a hunch and so we carved and stretched [our time and resources] and we’ve learned a lot through sequencing. It has paid off.”

“Being able to look at WGS very holistically has allowed us to use it as a way to ask ‘Are these variants of concern? What’s next? What don’t we yet know?’,” Totten added.


Melissa Schraeder is a freelance writer and educator.

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