CEO SUMMARY: After seeing the novel coronavirus spread quickly in China, staff in the Department of Pathology and Laboratory Medicine developed a test to identify the pathogen in patients in Chicago and its suburbs. With the CDC’s assay in hand, it started work on its own lab-developed test. In early April, the lab tested more than 10,000 patients and approximately 20% were positive and 5% needed immediate care.
IN JANUARY, NEWS OF AN OUTBREAK OF THE NOVEL CORONAVIRUS caught the attention of the staff in the Department of Pathology and Laboratory Medicine at NorthShore University HealthSystem outside Chicago. As the number of infections and deaths rose quickly in China, the lab staff began to worry that the virus was likely to spread worldwide.
“That news reminded us of the swine flu outbreak in 2009, so we began to think about how we could prepare our lab—just in case,” said Karen L. Kaul, MD, PhD, Chairman of the department. Just as lab professionals were doing worldwide, Kaul and her staff recognized that the epidemic in China had the potential to become a pandemic.
Based on the experience gained from testing for swine flu (also known as H1N1) and other pathogens, Kaul and the staff in the molecular lab knew they would need to take steps early to prepare for an influx of patients. Only accurate tests done in large enough quantities would help clinicians understand how quickly the virus was spreading and to identify infection hot spots.
For NorthShore, the early steps the lab took proved to be the proper course. Within weeks, the lab had begun testing patients and by the first week in April was running more than 10,000 tests per day.
In an interview with The Dark Report, Kaul explained how foresight and planning allowed the NorthShore lab to increase testing volume just as the infection rate was rising in the Chicago metropolitan area. Since then, the lab has expanded test capacity and throughput to serve more patients.
“When the CDC published the details of its assay for the virus and its primer sequences, we ordered that test and prepared to do the necessary validation,” said Kaul, a specialist in molecular medicine who leads the Molecular Diagnostics Laboratory in NorthShore’s Mark R. Neaman Center for Personalized Medicine. At the time, the lab staff was preparing to develop its own test for the SARS-CoV-2 pathogen.
Early in February, the Food and Drug Administration issued an emergency use authorization (EUA) allowing CDC-designated and CLIA-certified laboratories to apply for approval to validate and run the CDC’s 2019-Novel Coronavirus (2019-nCoV) Real-Time Reverse Transcriptase (RT)-PCR Diagnostic Panel. At the time, only a small number of labs were allowed to do the validation, one of which was the lab at NorthShore.
“Once we had the CDC’s assay, we ordered PCR primers and decided to develop our own test in house, meaning a lab-developed test (LDT),” she explained.“Because of the FDA’s regulatory stance,we thought the fastest way to get our test approved for emergency use was to duplicate the CDC test in our lab.
CDC’s COVID-19 Test
But first, we contacted the CDC to ask if they would distribute their test to us,” she added. “They said no. They couldn’t distribute that test to labs in hospitals. They can distribute those tests only to public health laboratories.
“Next, we tried to determine if we could be certified to become a public health laboratory, but that avenue was not available to us either,” said Kaul. “So, we decided to duplicate the CDC test and validate it in-house.
“For that process, the biggest challenge was getting the reference materials, and initially there weren’t any available,” she explained. “We tried our regular sources, and, over time, found a couple of commercial sources. One of those was BEI Resources in Washington D.C.” The National Institute of Allergy and Infectious Diseases established BEI to provide reagents to research and other labs studying pathogens and emerging infectious disease.
“The Illinois state public health lab and other labs sent us viral RNA—material that is not infectious,” Kaul explained. “We are part of a network of laboratories that share resources to help each other when needed. That’s how we were able to develop our test.
“In that way, we were like every lab that was scrambling to get the reagents and other needed supplies,” she said. “Those other labs have helped us and we’ve helped other labs too.
“For any LDT, we have to follow the validation rules under CLIA and CAP to verify accuracy, reproducibility, detection limits, and other values,” she said. “Ultimately we want to look at a panel of positive and negative patient samples to evaluate our own processes and to ensure the LDT performs accurately,” she added.
The lab then compared its results against those the state public health lab reported. “We did parallel testing with the laboratory at the Illinois Department of Public Health,” she said. “They were running their version of the CDC’s test, and the two assays performed identically. With their okay, we went live March 12.
“The next step was to submit our findings and the data we collected to the FDA for our EUA authorization,” Kaul said. “On Feb. 29, the FDA outlined a more streamlined process for its lab-developed test review. That streamlined process makes it more feasible than it would be normally for hospital laboratories to pursue an approval for an LDT.
“The FDA’s usual approach for LDT approvals is geared toward independent laboratory companies,” she commented. “That method can be expensive and time consuming. The new streamlined approach is better for us as a health system laboratory.”
Respiratory Virus Testing
Before developing its LDT to identify the SARS-CoV-2 infection, the lab was using a molecular respiratory virus panel (RVP) to identify patients with a variety of respiratory viruses, including the flu and other coronaviruses. By the time the LDT was ready for use, the lab could use the RVP and follow up with the LDT, if appropriate.
“We used the RVP because we were still seeing a fair amount of flu in the community,” Kaul explained. “Using the RVP first means we can avoid wasting the coronavirus tests when they wouldn’t be appropriate for those patients.”
If the RVP was negative for a symptomatic patient, the next step was to use the LDT that NorthShore developed for the SARS-CoV-2 infection. “The coronavirus test is something new and separate in the clinical community. Therefore, we are prescreening those patients by taking a nasopharyngeal swab and testing that specimen using the RVP,” she said. “If that test is negative, then we test for SARS-CoV-2.
“At first, our goal was to report results in a day or two and we met that standard,” she said. “This turnaround time is important for hospital inpatients because a positive test result has implications for discharge and other reasons.
Are Patients Positive, or Not?
“For example, it’s important for bed control, meaning whether those patients get isolated or not,” she added. “Our care teams need to know the status of whether patients are positive or negative and they need to know that quickly.”
“By the end of the first week in April, we passed the 10,000 mark for the number of tests run in NorthShore’s lab,” Kaul reported. “Approximately 20% of those patients tested positive and about 5% of that group needed immediate care. “Since April 11, our lab has been processing COVID-19 tests for the state testing location on West Forest Preserve Drive in Chicago,” she noted. “The criteria that state health officials set for that site is the testing is for first responders, healthcare workers, and people over 65 who have respiratory symptoms.
“Our goal is to return results within 24 to 48 hours,” Kaul added. “The National Guard will drop off the specimen collections to NorthShore Evanston Hospital daily for processing. Reporting test results quickly was a challenge because running the SARSCoV-2 test required some manual processing at first. “To address that problem, we’re adding some automated platforms because we want to be able to bring in tests from the other laboratories,” she added. “For that work, big automated instruments are very helpful.”
Contact Karen Kaul, MD, PhD at KKaul@northshore.org.