As the novel coronavirus began to rapidly spread in early 2020, Children’s Hospital Colorado infectious disease specialist Samuel Dominguez, MD, PhD, and his team knew it was likely only a matter time before it became a global pandemic. The hospital would need to quickly bring its own assay online to effectively manage its patients. It was the first clinical lab in Colorado to do so and one of the first in the nation.
Assessing the situation
Dr. Dominguez has a clinical interest in emerging pathogens. In fact, before he took over as medical director of the Children’s Colorado microbiology lab in 2016, he worked on basic science research related to coronaviruses.
“Our whole team had been watching this scenario closely since late 2019,” he says. “In early January 2020, we went to hospital leadership and expressed how we needed to start thinking about what our response was going to be and how we could prepare, including what it would take to bring an assay online.”
Then, on January 20, 2020, Washington State reported the U.S.’s first confirmed case of COVID-19. That accelerated an already unprecedented preparation timeline.
Evaluating the options
Dr. Dominguez and his team could try to build an assay from scratch — what’s known as a laboratory developed test, or LDT. Historically, though, it takes months to progress through necessary government approvals. Labs have to prove the test meets appropriate standards for sensitivity, specificity and limits of detection. Was that even possible in weeks?
The other option was to use the assay already in development by the Centers for Disease Control and Prevention, or CDC, but at the time, it was only available for use by state public health labs.
“It really left clinical labs in a bind,” says. Dr. Dominguez. “So we went back to hospital leadership and asked for guidance on how to proceed.”
Hospital leadership connected the epidemiology team with the Children’s Colorado legal and government affairs teams to find a way to fast track the process.
The government affairs team lobbied the governor of Colorado and members of congress to speak with the FDA about lifting regulatory barriers. As it turned out, other labs across the country were doing the same in their respective states.
Mounting pressure led the FDA to issue an emergency use authorization allowing high-complexity, CLIA-certified labs to use the CDC assay, provided those labs had particular reagents, extraction kits, probes and enzymes to run the assay. That was another roadblock.
“We got approval to move forward, but there were supply chain barriers,” says Dr. Dominguez. “We didn’t have access to those resources and neither did other labs.” But they had plenty of the reagents they typically use, which meant that the government affairs team needed to lobby for additional approval.
“We were willing to do our own validation and verification to show that the extraction agents we had on hand were equivalent,” he says. “We’d do whatever was necessary to get this assay up and running.”
That determination paid off. They secured quick approval, and on March 16, Children’s Colorado was the first hospital in Colorado to have an assay up and running. Not only could they run samples from team members and patients in-house, it was a service they began to offer community hospitals around the region — including some from Wyoming and Montana.
Preserving turnaround time
From the outset, the lab has maintained a 24-hour turnaround time for samples. “The health department’s initial turnaround time was one to three days, but they got backlogged really quickly and that turned into five to seven days,” says Dr. Dominguez. “In the clinical realm, that timeline isn’t useful because we’re making decisions in real time about patient placements and use of protective equipment.”
Waiting days for results would spend resources. A perpetually fast turnaround time was crucial, so they built efficiencies into their process.
“It’s about how many runs you can do in a day,” he says. “We had to repurpose some instruments. We had to rethink our workflow in the lab. We had to retrain people and reorganize shifts, even ask part-time people to come in. It was a new way of thinking so we could run the assay multiple times a day and get results out as quickly as we possibly could. Our team really stepped up, and I’m so proud of them.”
Adding additional assays
Diversifying their platform portfolio was also key. In other words, they acquired additional assays so they could run more samples and keep operation steady if they ran into a supply chain issue with one of the platforms.
On March 26, they brought a second platform online through a company they’d already been in contact with when they were initially evaluating their LDT options. It’s a smaller platform, says Dr. Dominguez, running about eight samples at once. But it has a quicker turnaround time, so they’re able to run it 24 hours a day.
On April 7, they brought a third platform online. It’s a higher throughput system, running about 94 samples at a time. But it’s a longer turnaround, roughly six hours from start to finish.
“That one is really useful for the samples we’re getting from other hospitals,” he says. “We can batch those and run them all once and do a couple of runs a day if we need to.”
A week later, they added a fourth platform.
Coronavirus testing capacity and its impact on care
As testing capacity increased, it helped the hospital enhance patient workflow so providers could continue to isolate and cohort patients and then quickly move those patients out of isolation when appropriate.
There were ultimately three phases of testing, each linked to when the assays were brought online.
Launch of the CDC assay was the start of Phase 1. All patients admitted to the hospital with respiratory symptoms or a fever received a respiratory pathogen panel, or RPP. If that was negative, the patient was flexed to the SARS-COV-2 test. While pending, that patient was a person under investigation and was cohorted on the hospital’s 9th floor.
“While the number of patients coming in was still relatively low, that strategy helped us quickly rule out or isolate,” says Dr. Dominguez, “which meant we could reserve full PPE — gowns, masks, face shields — for those patients who were flexed.”
As more patients came in that fit the criteria, though, they needed to morph the strategy.
In Phase 2, they started testing everyone who had respiratory symptoms, regardless of RPP results, because coinfection was an increasing concern.
“That raised the number of tests, but as we had more assays available, we could maintain our turnaround time and still efficiently manage the flow of patients in and out of the hospital. We kept them off that special floor and could get them out of those special isolations sooner, which further decreased our use of PPE.”
On April 9, two days after they launched the third assay, Phase 3 went into effect. Every single patient who is admitted to the hospital, even if they don’t have respiratory symptoms, receives the SARS-COV-2 test. They also now screen patients who are set to have procedures or who are undergoing anesthesia. That way, providers and their teams can know if those patients are positive and can don the appropriate PPE.
Ongoing process enhancements
Led by Dr. Dominguez and his team, Children’s Colorado continues to make adjustments to processes as necessary to limit the spread of infection and ensure the safety of team members, patients and the broader community.
For example, they no longer test healthcare workers in the hospital. Instead, they’ve fashioned a drive-thru testing site. Perioperative and immunocompromised outpatients use that site too.
There was also a critical shortage of nasal swabs — one of the main ways to collect a specimen. So Dr. Dominguez and his team got creative.
“With children, we often do nasopharyngeal washes, which is where you squirt some saline into the nose and then collect it as the specimen,” he says. “You don’t need swabs for those because it’s a different procedure, and you achieve the same results. It’s been a great workaround.”
The ability to be proactive instead of reactive has made the entire process easier, he says.
“The idea of ‘What we do today prepares us for tomorrow’ has really carried us through. None of this would have been possible without the incredible work of our government affairs team, the strong support we’ve received from the very top teams at Children’s Colorado, and the knowledge and early input of everyone on our microbiology team, all of whom continue to work tirelessly day in and day out. With no real end in sight, we’re grateful to have accomplished so much in such a short amount of time.”