Interviews

Dr. Kimia Sobhani describes how the laboratory has been handling COVID19 testing as the pandemic broke out and through July of he first wave.

COVID19 in La La Land: The Cedars-Sinai experience

Interview conducted in July 2020

For more than 8 years Dr. Kimia Sobhani, PhD, has directed the Core laboratories at Cedars Sinai Medical Center. She also directs the ER and Cancer Center Laboratories and serves as an associate professor of Pathology and Laboratory Medicine. She completed her undergraduate, graducate and doctoral work at the University of Washington.  Between 2017 and 2019 she was the chair of the Southern California chapter of the AACC.

When did you know you needed to bring in COVID19 testing and when did you bring on PCR method(s)?
We knew we would need testing in-house at least in February 2020, if not earlier. Our molecular pathology team went live with a PCR method in early March after a fast-paced but thorough validation, approximately 2 weeks before the official California state shelter-in-place order went out.

When did you bring on rapid testing?
Rapid PCR testing via Abbott IDnow went live in early May. At the moment we only use rapid PCR testing on patients who are coming in same-day for surgery and other types of on-site care, and not for suspected SARS-CoV-2 infection.

When did you bring on serology?
Serology testing started with RUO kits from EDI in early April. We found that the cutoffs were not well validated, which was not surprising. We also validated Healgen lateral flow qualitative immunoassay cartridges after looking at a few companies. Healgen ended up being one of the few companies with a lateral flow assay that later received EUA approval from the FDA. And finally, when semi-quantitative Abbott IgG became available in late April/early May, we moved to this test. And we are planning to bring up a separate IgM assay from Abbott to complement IgG, which should be available shortly.

See even more stories about COVID-19 Laboratory Challenges...

For serology and PCR testing, what kind of volumes are you seeing, and how have they changed over time? What kind of positivity rates have you seen?
We are now running approximately 300-400 PCR tests per week in our molecular pathology division for confirmation of current/active infection. Volume for serology testing was initially limited to a large-scale employee health study we were conducting at Cedars Sinai. We ran over 6000 employee samples over about a 3-4 week period. We then made serology testing available to outpatient orders and will soon allow inpatient use. Outpatient volume is low but steady. We have a COVID taskforce that has been approving the use of testing for specific patient populations, and the last holdout was use of serology on inpatients due to a perceived limited utility in this patient population, which is true from an initial diagnostic perspective, but there is certainly utility in monitoring the evolution of antibody levels overtime in these patients with a semi-quantitative set of assays, which is what we will have once IgM is validated.

What methods you have evaluated (and what are your validation protocols, 30 and 30 for clinical agreement, what other studies do you perform?), and which methods have you found wanting?
I mentioned some of the assays we validated or evaluated previously. Speaking specifically to the serology, we have validated at least 20 positive (as confirmed by PCR testing on nasopharyngeal swab samples) and 20 negative samples for each assay, as is consistent with current guidelines. Furthermore, the FDA now stipulates that only assays with EUA approval should be used. However, we have in fact run far more than this; particularly, far more negatives (in the hundreds range) on samples that were collected pre-emergence of COVID in our region in order to demonstrate the specificity of the assay(s) and show that false positives due to exposure to other pathogens (respiratory or otherwise) is extremely rare. The CDC states that serology assays with ≥ 99.5% specificity in low prevalence populations (i.e., <5%) should be used, and the Abbott IgG assay, as an example, has demonstrated this.

What your architecture of testing is (screening - confirmatory? use of
PCR vs use of Serology)?
We only use PCR testing to confirm infection in patients who are symptomatic or high-risk. Serology testing is used in outpatient populations at this time to evaluate prior exposure (e.g., ≥ 2 weeks prior) at the time of testing.

What’s your experience with PCR tests and serology tests? How are you using serology, if at all?
Positivity of PCR testing depends on which patient populations we’re discussing. For example, for patients presenting to our ED with high clinical suspicion (but not necessarily confirmed COVID symptoms) who are tested ~25% test positive by PCR. As for seroprevalence in LA county, that can also fluctuate a bit from town to town, but studies have shown that seroprevalence hovers in the ~3.5-4% range, and we have observed a similar range locally.

What kind of supply challenges with swabs, reagents, and other supplies have you experience?
Initially there was some concern about not supply chain for primers and swabs for PCR testing. The supply chain for PCR reagents was determined to be strong and we could pretty adequately estimate our ability to test specific volumes of patients from week to week. However, access to viral transport media (VTM) for swabs was questionable for a while, so we started to make our own, which is easy to do. Since the end of May supply chain for all reagents has been fairly stable.

What are your plans for the immediate future? Do you have predictions?
I anticipate that both PCR testing access will increase (we had been protecting testing access to high clinical suspicion and symptomatic patients for some time) and serology testing will increase as time goes on. Longer term I expect that serology testing will be very useful in evaluating the ambulatory patient population who were/are asymptomatic or mildly symptomatic and would like to confirm exposure (or likelihood thereof). Insurance coverage, however, for repeated testing is another issue. Furthermore, for evaluation of the ambulatory population with no current illness, lower cutoffs for semi-quantitative serology assays may be needed as the current cutoffs are geared towards high specificity in patients with SARS-CoV-2 infection confirmed by PCR, who were obviously all symptomatic. Also, as vaccines become available looking at antibody levels in the general population will be of great interest for studies and for ongoing efficacy evaluations.

How Los Angeles has been doing in the pandemic and how do you fit in with the public
health plans – do you interact or collaborate with other hospitals in Los Angeles?
The Cedars-Sinai health system (which consists of two hospitals, affiliates, and a medical group of physicians and clinics) has been highly collaborative. My team has also been collaborating with University of Southern California (USC) researchers and the LA Fire Department on a study to evaluate prevalence and transmission of SARS-CoV-2 in our first responders. We also have a similar study planned for children in the community via our USC collaboration.

Any advice you’d like to impart to a laboratory manager facing an upward curve?
If you have the laboratory resources to do it, I would highly suggest using semi-quantitative SARS-CoV-2 serology assays, over qualitative assays (e.g., lateral flow). It’s also much easier to start testing, and choose amongst available methods now, both for PCR testing for virus and serology, as there are several publications in the last couple of months validating the use of specific tests. Also, selection should be limited to those tests that have received EUA approval. Go to the FDA EUA approval page to start: https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas