CEO SUMMARY: This intelligence briefing provides a valuable look inside a clinical laboratory that is at ground zero in a city and state that is experiencing the nation’s most intense and fastest-moving incidence of COVID-19, the novel coronavirus. Lab leadership granted The Dark Report access to its strategies and how it supports health system administrators, physicians and patients, and state andlocal health officials. Northwell’s lab team wants the lab profession to understand how the Clinical Lab 2.0 model delivers significant value and makes the lab an essential contributor during a pandemic.
DURING THE LAST DAYS OF MARCH, Northwell Health Laboratories’ data from confirmed positive test results for the COVID-19 illness allowed lab executives to make a serious and troubling prediction. “The prospects for the coming week or more are daunting,” warned James M Crawford, MD, PhD, Northwell’s Senior Vice President of Laboratory Services.
“Both at the level of New York State, and at Northwell Health alone, documented COVID-19 incidence (meaning positivity, or the rate of confirmed COVID-19 tests) continues increasing at the rate of 10-fold every 13 days, even if down from every 6.5 days just the week before.”
From its base in Lake Success, N.Y., just north of New York City, Northwell is in an unusually strong position to issue such warnings, because, as Crawford commented, “We are at the epicenter of the epicenter.”
Northwell’s service area stretches from Long Island to the five boroughs of New York City and into Westchester County. Its lab test result data show that demand for testing will likely outstrip supply, he predicted.
“If unabated, our region may rapidly run out of testing capacity to document this continued increase,” he said. “That means these logarithmic curves will flatten simply because we won’t be able to keep up with Covid-19 testing.”
In addition, lab test results support New York State’s urgent demand for an increase in regional hospital beds and intensive care units. Such heavy demand is a significant concern for regional healthcare providers, especially those at the front lines, and it remains to be seen if more stringent “social distancing” practices would help to reduce this demand in the coming weeks, he warned.
By March 28, Northwell Labs had confirmed COVID-19 positivity for 9,301 Northwell patients, which represents 18% of the number of cases statewide, 7% of the number nationwide, and 1.4% of the world’s total. In the United States that day, New York had the highest number of confirmed cases of the new coronavirus with 52,318, including 5,039 patients hospitalized and 728 deaths.
Unique Vantage Point
The outbreak of the virus in New York has put the clinical laboratory of Northwell Health in the center of intense efforts to document the spread of the disease and to help healthcare administrators and public health officials identify trends and design strategies to mitigate its spread. For example, on March24, the lab projected that, without mitigation, the number of confirmed positive tests statewide for SARS-CoV-2 could race past 100,000 by the end of the month.
In recent weeks, the Northwell Laboratories have gathered test-result data under circumstances that are perhaps more challenging and intense than labs have experienced in any other region of the country. As one of the largest clinical laboratories within a health system in the United States, the Northwell Labs have an opportunity to showcase the role of a lab working under the Clinical Lab 2.0 model in delivering an unprecedented level of value by reporting real-time clinical data gleaned from lab results and delivered to health system leadership and front-line providers.
In a March 24 interview with The Dark Report, Crawford outlined the role he serves as a member of the federal Centers for Disease Control and Prevention’s Laboratory Response Network (LRN). In this role Northwell is a sentinel laboratory, meaning it reports lab test results to the New York State Department of Health (NYSDOH), which forwards those results to the CDC.
“Our high COVID-19 test volume, linked with data streams from the clinical practice environment, give the health system the information it needs to guide the emergency response for prioritization of diagnostic testing, and to help inform deployment of supplies, hospital beds, ventilators, personal protective equipment, and swabs for nasopharyngeal specimen collections,” commented Crawford. “By the hour—and sometimes by the minute—these lab test results are critical in the management of this crisis.”
Since March 8, when Northwell Labs ran its first test for the new coronavirus, it has added new assays and instruments to increase test volume from 90 tests per day during the week of March 9 to a capacity of more than 2,000 tests each day by the third week of the month, with further increases planned for the final days of March.
“Lab test results are among the very first starting points for managing the response to any threat, such as the coronavirus,” Crawford said. “Our lab test results provide an immediate data feed to the health system, to civic authorities, and to the public. Each day, we now document COVID-19 positivity in more than 1,000 sickened patients in our regional population. And, we find that our positivity rates are now in excess of 50% of tests performed.”
This intelligence briefing outlines the steps the Northwell Labs took to increase COVID-19 test volume and how data from those tests provide insight into what New York’s hospitals and health systems can expect in the days and weeks to come. Clinical laboratory directors and pathologists will find the results of Northwell’s efforts to date to be instructive about how clinical lab data provide insights into how hospital and health systems can manage their response to the pandemic.
Boosting Test Volume
The Dark Report previously reported on the steps Northwell followed when it validated tests for the SARS-CoV-2 virus and increased testing volume to meet an unknown level of demand. (See “Northwell Lab Team Validates COVID-19 Test on Fast Timeline,” TDR, March 9.)
Since then, the lab has added new assays and analyzers to support patient care throughout the 23 hospitals in its system. “We now have multiple platforms running,including the CDC test for sputum,the semi-automated GenMark machines—which we are deploying to our system hospitals—and additional platforms from other manufacturers,” Crawford said.
“Within three days of standing up the CDC assay on March 8 in the core lab, COVID-19 testing was also brought up on GenMark systems in the core lab on March 11. “A week later, we started COVID-19 testing on March 18 using the core lab’s Hologic Panther Fusion machines,” he said. “Using the Hologic instruments allowed us to redirect the GenMark COVID-19 testing supplies to system hospitals for on-site COVID-19 testing, a step that let us use the GenMark machines already onsite in those facilities for routine respiratory virus testing.
Automating COVID-19 Tests
“Currently, we run two automated Hologic Panther machines in the core lab, and we plan to add two more Panther machines soon,” he said. “We also plan to acquire other automated platforms.
“Taken together, the two Hologic Panthers and the semi-automated platforms increased our testing capacity to just shy of 3,000 results per day,” Crawford explained. “That’s a 30-fold increase in the 14 days since we were running 90 tests a day on March 9 using the manual CDC assay.
“But now we’re back to a linear rate of growth with each new Panther that we add, not logarithmic.”
As soon as Northwell began running COVID-19 testing, the data analytics team of Tylis Y. Chang, MD, who heads the lab’s Clinical Informatics division, could show patterns that allow Crawford and Northwell’s lab team to alert physicians and other clinicians to adjust testing order priorities as conditions allow.
At one point, for example, blood culture testing rates rose dramatically because of the number of hospitalized patients with fever. For this reason, blood culture orders momentarily exceeded the surge capacity in Northwell’s clinical microbiology lab, Crawford commented. Reporting detailed blood culture test utilization data to clinical leadership enabled quick readjustmentof health system guidelines for blood culture ordering.
“We messaged strongly to our physician workforce that they should not be ordering blood cultures at the same time that they order a COVID-19 test,” Crawford said in the report to staff. “Blood cultures should be ordered when there is concern about a super-infection, such as bacteremia or sepsis.”
Another alert the lab sent to physicians and lab personnel addressed the shortage in nasal swabs for specimen collection. “We instructed that one swab is sufficient for testing both the rapid respiratory virus panel (the RVP from GenMark) and COVID-19 polymerase chain reaction (PCR) test,” he explained. “These real-time adjustments in health system management of COVID-19 patients were essential for ensuring that our health system could optimize use of both laboratory and system resources.”
Many hospitals and health systems are running the RVP first to identify patients who have flu-like symptoms but may not have the novel coronavirus. Before the Hologic Panthers went live, Northwell took the opposite approach. “We stated that when a patient is suspected of having COVID-19 and when test positivity rates in hospitalized patients exceed 50%, ordering the COVID-19 PCR test first was preferable,” Crawford reported to staff. “The Rapid RVP could follow if the COVID-19 PCR test was negative.
“Now that COVID-19 testing is being pushed out to system hospital sites the same concern applies because routine Rapid RVP testing takes up local capacity for COVID-19 PCR testing on our semi-automated machines. “That said, we constantly adjust our testing recommendations,” he commented. “When core lab testing capacity expanded, we could then run the Rapid RVP and COVID-19 tests on different platforms, meaning both tests could be ordered and resulted again without canceling any tests. We monitor such load-balancing daily and have constant communication among clinical leadership about test ordering recommendations.”
One important way that lab test result data are used is to understand the epidemiology of how the virus spreads. “Since March 1, the lab test results we’re reporting have been pushed out into the community to inform public health activities,” Crawford commented. “The first confirmed case in New York was March 1, through public health laboratory testing.
SARS CoV-2 Assay
“One week later, the Northwell lab was ready to run its CDC assay for SARSCoV-2,” he added. “On Sunday, March 8, our lab reported its first positive test result from the Northwell Health system.
“At our lab’s command meeting the next morning, we activated our Laboratory Incident Command, reporting up to the health system Incident Command,” noted Crawford. “As our 10-person laboratory command group divvied up these tasks, I took on the responsibility for laboratory-driven epidemiologic reporting.
“Once you test people who are symptomatic, that data can guide how the health system responds to care for the most critically-ill patients,” he said. “We hope the day will come when we can provide testing for a broader portion of our regional population. But for the time being, our testing is for the patients with the greatest need-to-know, whether they are COVID-19 positive or not.
Analyzing Lab Data
“We are doing health services research by linking the test results from symptomatic patients with clinical, demographic, and geographic information,” he added. “For example, we want to identify the indications for repeat testing. We also want to identify patients who convert from negative to positive and what it means when they convert in that way. We have some interesting leads, but we’re not ready to publish them yet.
“Also, we found that the rate of patient tests that are positive for the new coronavirus varies depending on the clinical siteordering the test,” he said. “If the COVID-19 test originates from one of our hospitals (meaning an emergency department, inpatient admission, or intensive care), the test positivity rate is now almost 70%.
“By comparison, if the test comes from one of our urgent care centers, the positivity rate is 57%, and if it is from a physicians’office, the rate of positivity is 48%,” Crawford explained. “What this means for physicians treating symptomatic hospital-based patients is that their illness is caused by COVID-19 until the laboratory test indicates otherwise.
“Although the probability of a positive result is lower if a patient presents at an urgent care center or in a physician’s office, at this time, each of those sites still has a staggeringly high positivity rate in our regional population,” he added.
“To me, these are incredible numbers that document the penetration of the virus into our community,” he reported. “In addition, when we combine our COVID-19 test results with results from the tests we do with our routine respiratory virus panel, we see a trend in that data that helps us know what we can expect in the coming weeks.”
Predictive Value of Results
From their position in clinical informatics, Chang and Samuel Reichberg, MD, PhD, a pathologist and informaticist, have shown that—since March 6—the many patients who are symptomatic for the flu and are tested using the Rapid RVP get a negative test result over 80% of the time. In other words, these patients do not have any of the 14 respiratory virus types or subtypes that the GenMark panel identifies and yet they have flu-like symptoms. “That means that the many patients who get the Rapid RVP test and a negative result are a leadindicator of entry of the new coronavirus into our population,” Crawford observed.
Charting RVP, COVID-19
Reichberg showed this pattern by creating a chart showing the number of positive tests with the Rapid RVP panel against the total number of RVP tests performed, noted Crawford. “The gap between positive and negative tests was an indication of the presence of COVID-19,” he said. That data showed RVP results from Feb. 17 through March 29. (See sidebar below, “COVID-19 Testing by Laboratory at Northwell Health Detects Large Proportion of Cases in New York State.”)
“We call the difference between the RVP positive tests and the total tests the COVID-19 Gap,” Crawford explained.“That gap is significant because that’s where the coronavirus lives before it’s detected with the SARS-CoV-2 test.”
After Northwell Lab’s first testing for COVID-19 on March 8, the gap widened considerably, an indication that some patients who had tested negative with the RVP were in high likelihood positive for the SARS-CoV-2 virus, he said.
“Beginning after March 8, the number of completed COVID-19 tests in our lab began to rise,” he noted. “On about March 10, physicians also ordered more tests using the RVP. Yet results for the vast majority of their patients came up negative. “The chart (below) shows that on March 13, there are 500 or so symptomatic patients who were tested using theRVP and yet those tests were negative, versus about 100 patients who tested positive,” explained Crawford. “That’s a fivefold increase in negatives.
“A few days later, on March 17, about 700 symptomatic patients were tested with the RVP and those tests were negative and again there were about 100 cases of flu that the RVP detects,” he said. “That’s a seven-fold increase in the number of RVP tests that were negative.
“These increased test volumes were a sign that something was happening because physicians were testing patients who had flu-like symptoms, but the RVP tests were negative,” he noted. “This was a lead indication of a new respiratory illness, which Northwell had been expecting.”
Lab Data Reporting
The Northwell lab team reported these findings to the health system and to ordering physicians, Crawford said. “To create the data to track the epidemiology of the disease, we put a lot of work into analyzing changes in both the volume and results of RVP tests, and the rapidly-emerging COVID-19 positive test results,” Crawford reported.
“To do that, we assembled a team of six people in the laboratory to crunch the numbers for the lab,” he continued. “We were essentially on a 24-hour cycle. In addition, we were working with dozens of data scientists at the system level in our health services research department.
“These numbers show how the disease spread over a four-week period, and we disseminate these data as quickly as possible so that we can guide our practice community and our health system administrators about what’s going on with this disease outbreak,” noted Crawford.
“Also, I’ve sent these data to my national peer group of academic pathology chairs to help them prepare for what’s coming their way,” he reported. “Basically we’re talking about urgent, real-time lab data science. Every day, we demonstrate the value of lab data that we can track, analyze, and disseminate.
“We’ve spent the last four years developing our skills as Clinical Lab 2.0 providers, and, in many ways, this is the new religion with our laboratory,” concluded Crawford. “Given the extraordinary events that are happening now, ourprovider community and our health systemleadership need no convincing of thevalue of Northwell Labs as their laboratory provider.”
COVID-19 Testing by Laboratory at Northwell Health Detects Large Proportion of Cases in New York State
Chart A (above): Showing the cumulative daily total of positive cases of COVID-19 for New York State and as resulted by Northwell Health Laboratories. Data show that a large proportion of positive test results in New York State are from the region served by Northwell. Cumulative state deaths also are shown.
Chart B (above): Shows how testing patients with a respiratory virus panel will miss identifying patients positive for COVID-19 and why, during this outbreak, the COVID-19 test may be the more appropriate first test that a physician should order.
Boosting the Number of COVID-19 Tests the Laboratory Could Perform Required Multiple Steps, Automation
SINCE THE NOVEL CORONAVIRUS WAS IDENTIFIED AT THE END OF LAST YEAR, all clinical laboratories have faced the challenge of determining the fastest and most effective ways to meet an unknown level of testing demand.
At Northwell Laboratories, Stefan Juretschko, PhD, D(ABMM), Northwell’s Senior Director of the Division of Infectious Disease Diagnostics, has led the lab’s efforts to increase capacity to test for the virus that causes the COVID-19 illness.
On March 8, the lab resulted its first run of COVID-19 clinical tests, after having worked with the New York State Department of Health over the prior three days to validate the test kit from the federal Centers for Disease Control and Prevention (CDC), according to James M. Crawford, MD, PhD, Northwell Health’s Senior Vice President of Laboratory Services.
Juretschko’s lab completed validating the test on Saturday, March 7. That evening, he submitted to the state the data needed to support the lab’s request for emergency use authorization (EUA), under the FDA guidelines. The state approved Northwell’s request and the lab proceeded with the CDC assay the next day, Sunday, March 8. On that first day of testing, the lab ran nine of the manual COVID-19 tests. During the next three days, the lab ran about 90 such tests per day for the highest priority patients at Northwell Health system.
On March 11, the state gave Juretschko approval for the core lab to go live with a semi-automated qualitative multiplex assay to detect SARS-CoV-2 nucleic acid from specimens collected from nasopharyngeal swabs. That test from GenMark Diagnostics runs on GenMark’s ePlex Sample-to-Answer System. Using that test, Northwell boosted coronavirus test volume to about 150 to 200 tests each day, Crawford reported.
Juretschko went live on March 18 with a fully automated assay from Hologic (the Panther Fusion SARS-CoV-2 test), which detects genetic material from the virus in less than three hours. The FDA approved Hologic’s EUA for that test on March 16. Using two Hologic Panther machines allowed Northwell to run more than 2,000 tests per day.
Contact James M. Crawford, MD, PhD, at 516-719-1060 or email@example.com.