Research: “Tremendous genomic diversity” discovered across SARS-COV-2 in Delaware

Team publishes SARS-COV-2 genome sequencing research following ACCEL COVID-19 Rapid Science Grant

Delaware Clinical and Translational Research (DE-CTR) ACCEL Program investigators recently published their research findings regarding the diversity and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) genomes throughout the state of Delaware revealing the rapid change and extensive diversity in the virus’s genomic sequencing.

In 2020, the team of researchers received a DE-CTR ACCEL COVID-19 Two-Step Rapid Science Grant, which enabled immediate clinical and translational research specific to the coronavirus. The team used this award to gain a deeper understanding of the spread of SARS-CoV-2 strains within Delaware and surrounding areas.

SARS-CoV-2 is the highly contagious coronavirus that emerged in late 2019, causing a pandemic of the of the acute respiratory disease, named coronavirus disease 2019 (COVID-19).

“My area of expertise was next-generation sequencing and people were trying to quicky develop and assess techniques for diagnostic purposes,” Erin Crowgey, PhD, Nemours Children’s Health Pediatric Genomics Laboratory Director of Medical Bioinformatics, and DE-CTR ACCEL Program Management Information System Director, said. “So, I was interested in the COVID grant, being the PI and running that grant because I wanted to see how we could apply those techniques to studying COVID.”

The research team and paper’s authors included:

  • Karl R. Franke, PhD, Nemours Children’s Health Pediatric Genomics Laboratory Bioinformatician;
  • R. Benjamin Isett, MB, Nemours Children’s Health Pediatric Genomics Laboratory Research Lab Manager;
  • Alan Robbins, MSc, Nemours Children’s Health Pediatric Genomics Laboratory Research Lab Manager;
  • Carrie Paquette-Straub, MS, Nemours Children’s Health Transplant Molecular Diagnostics Lab Clinical Research Assistant;
  • Craig A. Shapiro, MD, Nemours Children’s Health Division of Infectious Diseases Department of Pediatrics;
  • Mary M. Lee, MD, FAAP, Nemours Children’s Health Executive Vice President, Enterprise Chief Scientific Officer, Physician-in-Chief for Delaware Valley;
  • Erin L. Crowgey, PhD, Nemours Children’s Health Pediatric Genomics Laboratory Director of Medical Bioinformatics, and DE-CTR ACCEL Program Management Information System Director

The team analyzed a total of 1,459 high-quality positive SARS-CoV-2 test samples from across the state of Delaware. From the genome sequencing of those samples, they were able to identify a great genetic diversity in the virus.

Fig 1. Lineage analysis of SARS-CoV2 genome from samples collected in the state of Delaware. Panel A: Pangolin lineages calculated from 1,459 samples. The x-axis is the lineage ID and the y-axis is the number of samples within that lineage. Panel B: The distribution of the NextClade Clades for all samples analyzed. Panel C: The major lineages over time in Delaware. The x-axis is the date, ranging from 6/20-5/21 and the y-axis is the percentage of that lineage in the total cohort analyzed. Panel D: The major lineages over time in Pennsylvania. Data Source—GISAID. Panel E: Results of COVID-19 PCR testing performed at Nemours Children’s Hospital Delaware. 

“Not only are we seeing a lot of genetic diversity in SARS-CoV-2, but we saw B.1.1.7, the alpha variant – which was essentially the first variant of concern – take over Delaware in a matter of weeks,” Dr. Franke said. “And when we were doing this research, Delta was on the horizon – we were just hearing about Delta and it was just starting to enter the United States. … The take-home message [of the paper] was: Delta is going to hit us fast and hard. And it did.”

“[Next-generation sequencing] turned out to be a pretty powerful technique for studying the genomic landscape of the virus,” Dr. Crowgey said.

Typically, the team does not work with genetic sequencing of viruses, so this was a first for their team.

“Being able to literally see the virus evolve as we’re sequencing it and seeing it mutate and start to see another variant take form – seeing that process happen in real-time” was new and interesting, Dr. Franke said.

Unfortunately, the paper was not published until January 2022, when the next variant, Omicron, had emerged and become widespread, following the devastation of the Delta variant.

Despite the delay in publishing, the work helped the team develop metagenomics sequencing techniques at the bench and data analyses which can be applied broadly to other viruses or scientific problems.

Furthermore, this research is enabling the team to seek out a larger grant in which they would work with the Delaware State Public Laboratory to analyze and sequence over 10,000 positive SARS-CoV-2 test samples.

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