Intermountain Healthcare is a Utah-based, not-for-profit system of 24 hospitals that provide numerous healthcare services to their populations. Additionally, Intermountain Healthcare has a long and distinguished history of leading cutting-edge clinical research studies. After becoming responsible for SARS-CoV-2 testing, Intermountain Healthcare came across the TaqMan SARS-CoV-2 Mutation Panel, which can identify known mutations in SARS-CoV-2 positive samples, and added it to their portfolio. Dr. John Carlquist, Intermountain Healthcare’s Technical Director of Molecular Diagnostics, spoke to us about the hows and whys of choosing the TaqMan SARS-CoV-2 Mutation Panel for surveillance studies.
Why did you choose the TaqMan SARS-CoV-2 Mutation Panel?
Carlquist puts it simply: “I think it was just timing.” Intermountain Healthcare was in the process of developing their own assays for detecting SARS-CoV-2 variants and mutations, but Thermo Fisher Scientific’s assay became available before their work was complete. In Dr. Carlquist’s words, “We put our project on hold and decided to go ahead with the assays [from Thermo Fisher Scientific].”
Intermountain Health had been sending select samples to health departments for several months for the purpose of sequencing and epidemiological surveillance. These findings would then be passed on to the United States Centers for Disease Control and Prevention (CDC) to guide national efforts. Carlquist and his team recognized that the TaqMan SARS-CoV-2 Mutation Panel could generate similar information without the sizable lag time of their old process. In particular, the TaqMan mutation panel could rapidly and efficiently recognize whether a variant had a particular mutation, whereas full sequences are more important at other levels of study.
Sequencing will remain a critical part of epidemiological surveillance and provide more complete information than a PCR assay ever could, but its relative slowness makes it tricky for Intermountain Healthcare’s needs. The TaqMan SARS-CoV-2 Mutation Panel can provide more information than other PCR-based assays and is faster than sequencing, and this combination helps improve upon Intermountain Healthcare’s previous process.
Where does the TaqMan SARS-CoV-2 Mutation Panel fit into your workflow?
For Dr. Carlquist’s team, this question is still in flux. His team is currently using the TaqMan SARS-CoV-2 Mutation Panel as a primary screening tool, starting their analyses with it and passing on interesting samples, such as those that show S-dropout mutations, for more detailed examination with other testing tools.
“We’ll probably develop a screening panel and use that as a first pass,” Dr. Carlquist explains. This general model of using a preliminary test and directing unusual results for more extensive study seems likely to hold for them: “I don’t really see that we will ever re-test all positives. I think that’s going to be expensive and a lot of work and I’m not sure that the information we gain will be all that valuable,” especially with the state still performing sequencing on samples of interest.
Which mutations did you choose for your panel and why?
Dr. Carlquist started with the first five available mutations: P681H, N510Y, K417N, E484K and del 69/70. As more mutations have become available, Dr. Carlquist’s team has begun re-evaluating their selection. At the moment, the Intermountain Healthcare team is particularly interested in the E484K and L452R mutations, alongside the more famous del69/70, which causes S-gene dropout with some tests, and the 501Y mutation, particularly as the Alpha variant (B.1.1.7) continues to gain prevalence. The team is trying to use a parsimonious scheme, attempting to maximize the number of variants detected with the minimum number of different mutations tested, to keep their assay simple and easy to process with minimal negative impact on their results.
To stay apprised of variants of interest, Dr. Carlquist and his team maintain frequent literature searches and alerts on information networks where new variants are mentioned as soon as they are discovered, as well as receiving communication from the CDC and other regulatory bodies. Knowing which variants are in circulation and what distinguishes them from others is important because variants may differ in transmissibility, virulence and disease pathology.
What is your favorite feature of the TaqMan SARS-CoV-2 Mutation Panel?
“It’s convenient, but I’ll tell you honestly, it’s the availability.” Dr. Carlquist’s lab urgently needs assays that cover currently circulating mutations, and that means prioritizing a solution that works and is easy for his team to acquire. An assay that does not include the necessary mutations or have stock available to ship is small comfort to a facility whose needs are far more immediate. Thermo Fisher Scientific can manufacture the TaqMan SARS-CoV-2 Mutation Panel in large quantities, with additional customization as needed, making it ideal for Dr. Carlquist and Intermountain Healthcare. Dr. Carlquist additionally appreciates Thermo Fisher Scientific’s responsive customer service, which is able to address his needs quickly and effectively.